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Phyllanthus emblica L. offers promising therapeutic potential for inflammatory diseases. This study revealed the molecular structure of a homogeneous polysaccharide purified from Phyllanthus emblica L. (PEP-1) and evaluated its anti-inflammatory effects on ulcerative colitis (UC) in mice. In the in vivo experiment, administered in varying dosages to dextran sulfate sodium (DSS)-induced UC models, PEP-1 significantly alleviated colonic symptoms, histological damages and reshaped the gut microbiota. Notably, it adjusted the Firmicutes/Bacteroidetes ratio and reduced pro-inflammatory species, closely aligning with shifts in the fecal metabolites and metabolic pathways such as the metabolism of pyrimidine, beta-alanine, and purine. These findings underscore the potential of PEP-1 as a therapeutic agent for UC, providing insights into the mechanisms through gut microbiota and metabolic modulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This work studied the effects of C. longa extract as a dietary supplement for Macrobrachium rosenbergii. Shrimp juvenile (n = 960, initial average weight 0.06 ± 0.042 g and initial stocking density 0.4 animals/L) received diets with different concentrations of turmeric extract (0.05, 0.2, 1%) for 60 days, and zootechnical (weight gain, specific growth rate, initial and final condition factor) and metabolic (activities of digestive enzymes, amino acid metabolism enzymes, and energy metabolism enzymes) parameters were evaluated. A transport simulation (TS) test was conducted and, in challenged animals, survival and antioxidant status were studied. Phenolic compound content and in vitro antioxidant potential of the turmeric extract were evaluated. Turmeric extract (0.05%) significantly increased weight gain and the activity of digestive enzymes. An increase in citrate synthase activity for all concentrations of turmeric was also observed. The glutamate dehydrogenase activity in the 0.05% group was also increased by turmeric extract. The in vitro antioxidant activity of the turmeric extract was like butylated hydroxytoluene (BHT), a common antioxidant, and the total phenolic content was 0.98 ± 0.02 mmolAG/g. In animals from the TS test, turmeric extract promoted a dose-dependent increase in animal survival. Furthermore, turmeric supplementation increased the activity of the enzymes catalase, glutathione reductase, glutathione peroxidase, glutathione S-transferase, and it reduced glutathione (GSH) content. A reduction in the levels of lipid peroxidation (TBARS) and protein carbonyl was also observed in the hepatopancreas of all experimental groups. The addition of low concentrations of turmeric extract to the diet of M. rosenbergii juvenile presents great potential for application in commercial shrimp farming, since the extract (at concentrations as low as 0.05 to 1%) increased weight gain and improved the physiological and metabolic conditions of the animals, improving the use of nutrients and consequently the animals' responses to stressful conditions, such as transport., Competing Interests: Declarations. Ethical approval: This declaration is not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Rubusoside─a high-sweetened, nonsugar sweetener─is mainly extracted from Rubus chingii var. suavissimus (S. Lee) L. T. Lu or Rubus suavissimus S. Lee (Chinese sweet leaf tea). We previously reported that rubusoside regulates lipid metabolism disorder in Syrian golden hamsters on a high-fat diet (HFD). This study aimed to reveal the underlying mechanisms through which rubusoside alleviates lipid metabolism disorder in vivo and in vitro. First, we analyzed the therapeutic properties of rubusoside in alleviating HFD-induced lipid metabolism disorder in C57BL/6J mice. Then, we analyzed the adipogenic effect of rubusoside in normal and Lgals3/Mknk2-overexpressing 3T3-L1 cells by exploring the mechanisms on peroxisome proliferator-activated receptor-γ/α (PPARγ/α), galectin-3 (Lgals3), mitogen-activated protein kinase interacting serine/threonine kinase-2 (Mknk2), p38 mitogen-activated protein kinase (p38MAPK), and extracellular regulated protein kinases 1/2 (ERK1/2) with RT-qPCR and Western blot. Our results showed a rubusoside-mediated reduction of HFD-induced weight gain, dyslipidemia, and decelerated hepatic steatosis and adipose tissue expansion in mice as well as improved adipogenesis in 3T3-L1 cells. Mechanistically, rubusoside up-regulated the PPARγ/α expression while down-regulating Lgals3 and Mknk2 expression in vivo and in vitro. Furthermore, rubusoside attenuated the adipogenic activity of PPARγ through increasing its site-specific phosphorylation mediated by p38MAPK and ERK1/2. Taken together, our findings suggest that rubusoside alleviates lipid metabolism disorder through multiple pathways and thus holds potential for future development.

Background and Purpose: Nearly 95% of women treated with radiotherapy for breast cancer experience some degree of radiodermatitis. Radiation therapy's most frequent side effect is skin damage. Managing radiation-induced skin reactions while maintaining treatment continuity is a challenging issue. The chicory plant has known anti-inflammatory properties. This study aimed to assess the effect of chicory root extract gel on the incidence and severity of radiodermatitis in breast cancer patients., Materials and Methods: This three-blind clinical trial was conducted in the radiation therapy department of Ayatollah Yasrebi Hospital in Kashan from September 2022 to February 2023. Forty-four breast cancer patients undergoing radiation therapy with a linear accelerator were randomly assigned to either the intervention group (n = 21) or the placebo group (n = 20). Participants applied topically chicory root extract gel or placebo twice daily, starting with their radiation therapy. The incidence and severity of dermatitis were assessed using the Radiation Therapy Oncology Group (RTOG) scale. Participants' characteristics were collected through a researcher-designed questionnaire. Data analysis was performed using chi-square tests, Fisher's exact test, independent t-tests, Mann-Whitney U tests, and generalized linear models with a Poisson distribution, using SPSS version 16 software., Results: No significant differences were found between the two groups regarding individual and clinical characteristics at the beginning of the study. The results indicated that the number of patients who did not develop dermatitis in later weeks was higher in the intervention group compared to the placebo group (P < 0.001). In the second and third weeks, grade 1 and 2 dermatitis incidence was higher in the placebo group than in the intervention group (P < 0.001). A comparison of the incidence of dermatitis between the two groups, in terms of the number of days to develop grade 1 dermatitis, showed that the average duration was longer in the intervention group than in the placebo group (P > 0.05). This comparison was insignificant for grade 3 dermatitis in either group. Additionally, when considering body mass index (BMI) as a confounding variable and adjusting for its effect, the results revealed that the intervention group developed grade 1 dermatitis significantly later than the placebo group (P < 0.001)., Discussion and Conclusion: Chicory root extract gel offers an effective, low-risk option for managing radiodermatitis in breast cancer patients. This aligns with the goals of supportive cancer care, which emphasize minimizing side effects, maintaining treatment efficacy, and improving the patient's quality of life., Trial Registration: The study was registered in the Clinical Trials Center of Iran ( https://irct.behdasht.gov.ir ) with the number cod: IRCT20220601055055N1 on July 2, 2023., Competing Interests: Declarations Ethics approval and consent to participate The Institutional Review Board and the Research Ethics Committee of Kashan University of Medical Sciences (Ethical Code: IR.KAUMS.NUHEPM.REC.1401.017) approved the study protocol. All participants signed informed written consent before participating in the study.  All procedures were carried out in accordance with approved protocols and all relevant local, and national research guidelines and regulations. Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Osteoarthritis (OA) is a prevalent joint disease affecting the spine, hands, hips, knees, and feet. However, definitive drugs for OA are lacking, and current treatments are limited owing to inconvenient administration, inadequate functional improvement, and long-term side effects including gastrointestinal and cardiovascular adverse events. Therefore, in this study, we aimed to assess the pharmacokinetics and safety profiles of PK101, a fixed-dose combination (FDC) comprising PG201, a 12-herb extract used in OA treatment in traditional East Asian medicine, and celecoxib, a selective cyclooxygenase-2 inhibitor, by comparing its administration as an FDC and the corresponding individual formulations in healthy subjects., Patients and Methods: A randomized, open-label, single-dose, 2 × 2 crossover design with a cohort of healthy participants. All subjects received a single FDC tablet (405.4 mg PG201 and 100 mg celecoxib) or the individual formulations, with 7-day washout period between administrations. The estimation of maximum plasma concentration and area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration of celecoxib involved determining the geometric mean ratios and 90% confidence intervals of the FDC compared to its individual formulations., Results: Forty-six participants were enrolled; however, only 44 completed the study. The geometric mean ratios (90% confidence intervals) for the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration and maximum plasma concentration of celecoxib were 1.1124 (1.0601-1.1672) and 1.2788 (1.1708-1.3969), respectively. The time of maximum plasma concentration range was 1.0 to 4.0 hours and 1.0 to 6.0 hours (minimum-maximum) for the FDC and individual formulations, respectively. Seven adverse events occurred in 6 subjects., Conclusion: The systemic exposure and safety profiles of the individual and FDC formulations were similar, supporting their potential as an innovative and effective therapeutic approach for OA treatment. All relevant data are within the paper and its Supporting Information files., Competing Interests: HK and H-YM are employees of the PMG Pharm Co., Ltd. All the other authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Carthamus tinctorius L. (Safflower) is extensively used as a functional food and herbal medicine, with its application closely associated with hydroxysafflor yellow A (HSYA). However, the low oral bioavailability of HSYA in safflower extract (SFE) limits its health benefits and application. Our study found that co-administration of 250, 330, and 400 mg/kg peach kernel oil (PKO) increased the oral bioavailability of HSYA in SFE by 1.99-, 2.11-, and 2.49-fold, respectively. The enhanced bioavailability is attributed to improved lipid solubility and intestinal permeability of HSYA in SFE due to PKO. PKO is believed to modify membrane fluidity and tight junctions, increase paracellular penetration, and inhibit the expression and function of P-glycoprotein, enhancing the transcellular transport of substrates. These mechanisms suggest that PKO is an effective absorption enhancer. Our findings provide valuable insights for developing functional foods with improved bioavailability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Sea buckthorn ( Hippophaë rhamnoides L.) known as the deciduous shrub has been reported to have effects of antioxidant, anti-inflammatory, and immunomodulatory activities. Tropomyosin (TM) induced a regulatory immune response associated with food allergy. In this study, a mouse model of food allergy sensitized to tropomyosin (TM) was established to assess the antiallergic properties of sea buckthorn flavonoid extract (SBF). SBF alleviated mice's allergic symptoms and exhibited a significant reduction in the levels of IgE and histamine. Meanwhile, SBF repaired the allergic Th2 cell overpolarization generated by TM, via downregulating the IL-4 production and upregulating IFN-γ production to restore the balance of Th1/Th2 cells. Furthermore, the 16S RNA analysis showed that SBF primarily restored the gut microbiota via increasing the abundance in Chitinophilidae and decreasing in Burkholderiaceae, Pneumatobacteriaceae , and Sphingomonadaceae . Gut metabolomes determined by liquid chromatography-mass spectrometry (LC-MS) suggested that TM upregulated PE (14:0/22:1(13Z)) and SBF decreased formimino-l-glutamic acid and urocanic acid levels. According to the KEGG pathway analysis, SBF treatment has been shown to modulate glycerophospholipid and histidine metabolism to improve allergic reactions. SBF holds great promise as a novel potential agent for the treatment of food allergies.

Although the association between high-sugar diets and depression has been verified, few studies have explored the antidepressant mechanisms of apple polyphenol extracts (APE). Therefore, fifty-four C57BL/6 male mice aged 5 weeks were randomly assigned into five groups: the control group with the standard diet (CON), the constant high-sucrose diet group (HSD), the "2 + 5" alternate diet group (A-HSD), and the 500 mg/(kg·bw) APE treatment for the HSD group (APE) and the A-HSD group (A-APE), respectively. The data of hypothalamic-pituitary-adrenal (HPA) axis function and behavioral experiments confirmed the success in the establishment of depression-like mouse models in both HSD and A-HSD groups, which were significantly alleviated after APE treatment. Meanwhile, APE reduced serum levels of corticosterone and adrenocorticotrophic hormone, alleviated histopathological damage of the liver, colon, and brain, respectively, elevated the protein expressions of Occludin, ZO-1, and MUC-2, and decreased Firmicutes/Bacteroidota ratio and Dubosiella abundance with the increased microbiota of Tannerellaceae&#95;unclassified , Muribaculum , and Lachnospiraceae&#95;unclassified . Moreover, APE treatment reduced Farnesoid X receptor (FXR) protein levels along with the increased expressions of CYP7A1 and TGR5, lowered the contents of serum and fecal total bile acids, and modulated fecal BA compositions, particularly glycocholic acid (GCA) and isolithocholic acid (ILCA). Thus, both the constant and alternate high-sucrose diets successfully induced depression-like behaviors in mice, and APE might be a potential nutraceutical to attenuate high-sucrose diet-induced depression by regulating BAs circulation within the liver-gut-brain axis mediated by FXR.

Background: With advancing age among older adults, the associated debilities increase, indicating a deteriorating health status as there is a gradual loss of muscle mass, strength, and functionality. Ayush Rasayana A and B are coded Ayurvedic medicines developed from herbal extracts. This study has been planned to prevent debilitating conditions and improve the quality of life (QOL) in older adults., Objective: This study aimed to assess the effectiveness of Ayush Rasayana A and B on the QOL, quality of sleep, and functionality of older adults, along with the tolerability of the intervention., Methods: This was a multicenter, open-label, cluster randomized controlled trial conducted with 720 participants aged 60 to 75 years. The participants were divided into 2 groups (intervention and control), with both receiving Ayurvedic ancillary treatment for 3 months. The intervention group additionally received 10 g of Ayush Rasayana A orally once daily at bedtime for 6 days, followed by 1.5 g of Ayush Rasayana B orally twice daily before food for the remaining 84 days. The assessment criteria included the Older People's Quality of Life Questionnaire Brief, Katz Index of Independence in Activities of Daily Living, Pittsburgh Sleep Quality Index, Five Times Sit-to-Stand Test, and shoulder and scapular movements. Any change in hematological and biochemical parameters and occurrence of treatment-emergent adverse events were also assessed during the study period., Results: The recruitment of the participants started in December 2023, and the final follow-up was completed in April 2024. Out of the total 720 enrolled participants, 686 (95.3%) completed the study up to the last follow-up., Conclusions: This study may provide evidence-based data to establish preventive treatment protocols for enhancing the QOL and functionality among older adults. The study results may also be helpful for the planning of interdisciplinary health policies for improving the health conditions of different populations., International Registered Report Identifier (irrid): DERR1-10.2196/58186., (©Pallavi Mundada, Deepa Makhija, Sunita Mata, Kalpana Kachare, Aparna Manathottathil, Abha Sharma, Bhogavalli Chandra Sekhara Rao, Rakesh Rana, Arunabh Tripathi, Kiran Rana, Vandana Joshi, Ashish Raturi, Anukampa Singh, N Srikanth, Rabinarayan Acharya. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 11.11.2024.)

The modulation of intestinal flora by various polysaccharides has been shown to mitigate disease progression. Recent research reveals a significant link between intestinal flora and the progression of mastitis. This study demonstrates that the oral administration of Angelica sinensis polysaccharide (ASP) reduces mammary inflammation and blood-milk barrier (BMB) damage induced by Staphylococcus aureus in mice, primarily through the modulation of intestinal flora. The beneficial effects of ASP were negated when antibiotics disrupted the gut microbiota in mice. Furthermore, fecal microbiota transplantation (FMT) from ASP-treated mice to recipients markedly alleviated symptoms of S. aureus -induced mastitis. Oral ASP not only enhances gut microbial diversity but also shifts its composition, increasing the abundance of Lachnospiraceae&#95;NK4A136 while reducing Erysipelatoclostridium . Metabolomic analysis revealed that ASP alters intestinal metabolic pathways, elevating levels of metabolites, such as tabersonine and riboflavin. Notably, tabersonine was found to ameliorate S. aureus -induced mastitis. These results suggest that targeting intestinal flora and metabolism through polysaccharides could serve as a promising strategy for mastitis intervention and potentially for other infectious diseases, as well.

Alcoholic liver disease (ALD) is one of the causes of hepatocellular carcinoma, accompanied by intestinal leakage and microbial changes. Pueraria has protective effects on liver injury. The aim of this study was to investigate the mechanism of pueraria in the treatment of ALD. UPLC-Q/TOF-MS was used to analyze the composition of the pueraria extract (PUE). Acute and chronic ALD models were established to evaluate the antialcoholic and hepatoprotective effects of PUE. As a result, PUE treatment reduced the serum levels of ALT, AST, TC, and TG and inflammatory factors and alleviated liver inflammation and drunk state. PUE decreased the gene expression of ADH1 and the serum level of acetaldehyde (ACH) to inhibit the generation of ACH from ethanol metabolism, increased the gene level of ALDH2 to accelerate the decomposition of ACH, and thereby alleviated liver inflammation and intestinal barrier damage. Meanwhile, 16 S rDNA revealed that PUE altered the microbiota composition, reduced the amount of Proteobacteria and Desulfobacterota , and thus inhibited the generation of lipopolysaccharide and its downstream-like TLR4/MyD88/NF-κB pathway. PUE also increased the abundance of Bacteroides , Ruminococcus , and Prevotella and producted short-chain fatty acids to protect the intestinal wall. Treatment with fecal microbiota transplantation further confirmed that PUE gut microbiota dependently alleviated ALD. Therefore, PUE regulated gut microbiota and inhibited ethanol metabolism to alleviate ALD through the liver-gut-brain axis. It has good prospects in the future.

Restriction of lipid uptake and absorption from the diet is regarded as an efficient strategy for the management of obesity, while lipase inhibition could successfully block the digestion of dietary lipids. Mume Fructus (MF) and Schisandrae Chinensis Fructus (SCF) were used as fruits, the biological effect of which on obesity desired more attention. Herein, the extracts of MF and SCF displayed significant efficacy in managing obesity in mice fed with a high-fat diet, via the inhibition of hydrolase activity of lipase in the digestive tract. Using the bioactivity guidance strategy, citric acid and malic acid were identified as the major lipase inhibitors from MF and SCF, respectively, which could prevent body weight gain, along with adipose tissue formation, and alleviate hyperlipidemia and hepatic steatosis in obese mice. Above all, MF and SCF could be used for the management of obesity via the lipase inhibition by citric acid and malic acid, displaying potential applications in healthy foods, nutritional supplements, and pharmaceutical materials.

Ulcerative colitis (UC) is a common chronic, relapsing inflammatory bowel condition. Procyanidins (PC) are known for their antiangiogenic, anti-inflammatory, antioxidant, and antimetastatic properties. However, there is comparatively limited information on how PC interacts with UC. In this study, 5 mg/10 mL/kg body weight of PC was administered to mice with dextran sulfate sodium (DSS)-induced colitis mice. PC treatment prolonged the survival period of mice, ameliorated UC symptoms, reduced damage to the intestinal mucosal barrier, and increased the protein expression of ZO-1 and occludin in the DSS-treated mice. Importantly, PC treatment significantly reduced gene expression related to Th17 cell differentiation, including STAT3, SMAD3, TGF-β, and JAK1. The results of the flow cytometry analysis indicated significant increase in the number of Treg cells and a concomitant decrease in the proportion of Th17 cells in the colon following PC treatment. Additionally, PC increased the abundance of gut microbiota such as Bacteroidota , Oscillospiraceae , Muribaculaceae, and Desulfovibrionaceae , as well as the concentrations of acetate acid, propionate acid, and butyrate acid in the feces. PC also activated short-chain fatty acid receptors, such as G-protein coupled receptor 43 in the colon, which promoted the proliferation of Treg cells. The depletion of gut microbiota and subsequent transplantation of fecal microbiota demonstrated that PC's effects on gut microbiota were effective in improving UC and restoring intestinal Th17/Treg homeostasis in a microbiota-dependent manner. This suggests that PC could be a promising functional food for the prevention and treatment of UC in the future.

Objective: To investigate the effects of licorice functional ingredient intake on blood pressure, explore its potential mechanisms of action, and provide safety information for personalized nutritional interventions in special populations and for the application of licorice-derived functional foods., Methods: PubMed, Cochrane Library, Medline, Embase, EBSCO, ScienceDirect, and Web of Science databases were searched from inception to 31 August 2024. Randomized controlled trials (RCTs) investigating the intake of licorice or its functional components were included. The range of continuous variables was assessed using the weighted mean difference (WMD) with 95% confidence intervals. Genes associated with hypertension were screened using an online database. Machine learning, receiver operating characteristic(ROC) curve analysis, molecular docking, and gene set enrichment analysis (GSEA) were employed to explore the potential mechanisms underlying licorice-induced blood pressure fluctuations., Results: Eight RCTs (541 participants) were included in the meta-analysis, which indicated interventions containing glycyrrhizic acid (GA) as the main component increased systolic blood pressure (SBP) and diastolic blood pressure (DBP) (SBP: WMD [95% CI ] = 3.48 [2.74, 4.21], p < 0.001; DBP: WMD [95% CI ] = 1.27 [0.76, 1.78], p < 0.001). However, interventions dominated by licorice flavonoids(LF) had no significant effect on SBP or DBP (SBP: WMD [95% CI ] = 0.58 [-1.15, 2.31], p = 0.511; DBP: WMD [95% CI ] = 0.17 [-1.53, 1.88], p = 0.843). Three machine learning algorithms identified five biomarkers associated with hypertension: calmodulin 3 (CALM3), cluster of differentiation 9 (CD9), growth factor independence 1B transcriptional repressor (GFI1B), myosin light chain kinase (MYLK), and Ras suppressor-1 (RSU1). After removing biomarkers with lower validity and reliability, GFI1B, MYLK, and RSU1 were selected for subsequent analysis. The network toxicology results suggested that GA and its metabolite glycyrrhetinic acid may act on GFI1B, MYLK, and RSU1, influencing blood pressure fluctuations by modulating nitrogen metabolism signaling pathways., Conclusions: There were distinct differences in the effects of licorice functional components on blood pressure. Functional constituents dominated by GA were shown to increase both SBP and DBP, whereas those dominated by LF did not exhibit significant effects on blood pressure. The hypertensive mechanism of GA may involve the modulation of GFI1B, MYLK, and RSU1 to regulate nitrogen metabolic pathways.

Background: Breast milk is essential for the development of a newborn's neurological, gastrointestinal, and immune systems and helps reduce the risk of infections and infant mortality. Banana flowers, often combined with additives such as ginger, are commonly included in the country's local diets because they are believed to enhance postpartum lactation. We aimed to investigate the impact of banana blossom extract pills on breast milk volume (BMV) in mothers of preterm newborns. Methods: A randomized, double-blind, placebo-controlled trial was conducted; it involved eligible preterm mothers, who were divided into two groups: a banana blossom group, which received banana blossom extract pills (36 mg/day), and a control group, which received placebo pills. All participants were given identical-looking tablets and were required to chew two tablets four times a day for 14 days. The primary outcome was the total BMV expressed (in milliliters) on the seventh day using an electric breast pump. Results: A total of 70 mothers of premature newborns were randomly allocated in equal numbers to either the banana blossom intervention group or the control group. There was no significant difference between the groups with respect to the median BMV on the seventh day postpartum (333 versus 350 mL, p = 0.73). A similar trend was observed on the 14th day postpartum (331 versus 510.0 mL, p = 0.6). Additionally, no significant differences were observed regarding maternal and neonatal adverse events. Conclusions: The administration of banana blossom extract pills (36 mg/day) to mothers with preterm infants did not increase the BMV on the seventh day postpartum.

Background: After cardiovascular disease, cancer is one of the leading causes of death due to uncontrolled cell growth. Breast cancer is among the most prevalent types of cancer. Zingiber officinale Roscoe. rich in phenolic compounds, which can stimulate and function as endogenous antioxidants., Purpose: Investigation of the in vivo chemopreventive has the potential of nano Z. officinale Roscoe (Zo-NPs) in breast cancer., Study Design: Using female Mus musculus Balb/c induced with benzo[α]pyrene, the chemopreventive action of Z. officinale Roscoe. nanoencapsulated using κ-carrageenan was assessed., Results: Z. officinale Roscoe Extract. contains 58 compounds, with the main component being [6]-gingerol with [6]-gingerol content being 697.65 ± 8.52 mg/g extract. Nanoencapsulation of Z. officinale Roscoe. has been successfully prepared with a particle size of 483.30 ± 11.23 nm. Zo-NPs are generally resistant to pH, temperature, and salt content variations. Compared to group C 1 , which underwent ductular dilatation, the administration of Zo-NPs (group T 2 ) to female Mus musculus Balb/c, induced by benzo[α]pyrene, revealed no histological alterations in breast tissue. Moreover, administering Zo-NPs can raise blood serum levels of CAT, GSH, and SOD. In addition, it showed a greater ability to lower TNF-α levels than the T 1 group, which received Z. officinale Roscoe extract. (Zo)., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Wardana et al.)

Background: Developing interventions for older adults with subjective cognitive decline (SCD) has the potential to prevent dementia in this at-risk group. Preclinical models indicate that Citrus-derived phytochemicals could benefit cognition and inflammatory processes, but results from clinical trials are still preliminary. The aim of this study is to determine the effects of long-term supplementation with Citrus peel extract on cognitive performance and inflammation in individuals with SCD., Methods: Eighty participants were randomly assigned to active treatment (400 mg of Citrus peel extract containing 3.0 mg of naringenin and 0.1 mg of auraptene) or placebo at 1:1 ratio for 36 weeks. The primary endpoint was the change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score across the 36-week trial period. Other cognitive outcomes included tests and scales evaluating verbal memory, attention, executive and visuospatial functions, and memory concerns. The secondary endpoint was the change of interleukin-8 (IL-8) levels over the 36-week trial period in a subsample of 60 consecutive participants. An Intention-to-treat approach with generalized linear mixed models was used for data analysis., Results: The RBANS total score showed significant improvement in both Citrus peel extract and placebo groups at 36 weeks (p for time < .001, d = 0.36, p time x treatment = .910). Significant time effects were also found in cognitive domains of short- and long-term verbal memory (p < .001) and scales of subjective memory (p < .01), with no significant time x treatment interaction. The largest effect sizes were observed in verbal memory in the placebo group (d = 0.69 in short-term, and d = 0.78 in long-term verbal memory). Increased IL-8 levels were found at 36-week follow-up in both Citrus peel extract and placebo groups (p for time = .010, d = 0.21, p time x treatment = .772). Adverse events were balanced between groups., Conclusions: In this randomized clinical trial, long-term Citrus peel extract supplementation did not show cognitive benefits over placebo in participants with SCD, possibly due to high placebo response. These findings might have specific implications for designing future nutraceutical trials in individuals experiencing SCD., Trial Registration: The trial has been registered at the United States National Library of Medicine at the National Institutes of Health Registry of Clinical Trials under the code NCT04744922 on February 9th, 2021 ( https://www., Clinicaltrials: gov/ct2/show/NCT04744922 )., (© 2024. The Author(s).)

This study aimed to determine the antimicrobial effects of ethanolic extracts of Ulva sp. and garlic (Allium sativum) powder ethanolic extracts against Vibrio harveyi in vitro. The stimulatory effects of Ulva sp. extract (UE) and garlic powder extract (GPE) on the growth performance and innate immune responses of white-leg shrimp, Litopenaeus vannamei, and their challenge against V. harveyi infection were also investigated. A commercial shrimp diet (36.1% protein) was enriched with 0.5, 1.0 and 2.0 g UE/kg diet and 2, 4 and 6 g GPE/kg diet, whereas the control group was free of any supplement. Health juveniles of L. vannamei (average weight 2-3 g) were distributed in 21 fiberglass reinforced plastic (FRP) tanks (500-L capacity) at a stocking density of 300 animals/tank to represent each treatment in triplicate. The animals were fed ad libitum on the experimental diets up to satiety four times daily for 60 days. The phytochemical analysis of ethanolic extracts of Ulva sp. and garlic powder evoked their richness of several bioactive compounds showing significant antibacterial activity against V. harveyi. The GPE exhibited a higher inhibition zone than that of the UE. The supplemented diets did not significantly affect weight gain %, final weight, feed conversion ratio, specific growth rate and survival rates of white shrimp compared to those fed on the control diet. Significant increases were observed in total haemocyte count, phagocytosis and phagocytic index of all treatments compared with the control group. There were significant increases in serum total protein, acid phosphatase activity, alkaline phosphatase, lysosomal enzyme activity, phenoloxidase activity and superoxide dismutase activity with offered diets with increasing the levels of ethanolic extracts of Ulva sp. and garlic powder up to 2.0 g UE/kg diet and 6 g GPE/kg diet, respectively. The ethanolic extraction of Ulva sp. and garlic powder-supplemented diet groups, particularly at treatments of 2.0 and 6 g GPE/kg diet, respectively, significantly reduced the shrimp mortality induced by V. harveyi infection when compared with the control group. The net results evoked that ethanolic extraction of Ulva sp. (2.0 g UE/kg) and garlic powder (6 g GPE/kg diet) enhanced the immune response and disease resistance of the white-leg shrimp, L. vannamei. It is also noted that the GPE is more efficient than the UE in vitro and in vivo investigations., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Background: Adult tendon tissue has limited and slow regenerative capacity. Sambucus nigra plant possesses antioxidant and anti-inflammatory attributes., Objectives: This study aimed to evaluate the effect of hydroalcoholic extract of this plant's fruit on superficial digital flexor tendon repair in rabbits (SDFT)., Methods: Twenty-five male New Zealand white rabbits weighing 1.5-2 kg were selected, quarantined and randomly divided into four groups of six. By performing a partial left posterior limb tenotomy, differentiating the SDFT and creating multiple scrapes were performed. During 3 consecutive days post-surgery, the positive control group was injected with 0.5 mg/kg dexamethasone, whereas the treatment groups received extract doses of 200 and 400 mg/kg, respectively. The negative control group did not receive any medication. Evaluation of sonographic and histopathological parameters was conducted on days 0, 7 and 28 post-surgeries. Findings were analysed and compared using SPSS22., Results: Both treatment groups showed significant differences in echogenicity, and collagen fibre alignment compared to the control and positive control groups, in sonographic evaluation. Histopathological examination revealed fewer inflammatory cells and increased collagen fibre formation in the treatment groups compared to the other two groups. No significant difference in angiogenesis was observed among the groups on days 7 and 28 (p value <0.05)., Conclusions: The results indicate that the S. nigra fruit extract, by stimulating collagen synthesis and reducing inflammation, effectively accelerates the healing process of injured tendons., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Type 2 diabetes mellitus (T2DM) involves insulin resistance and elevated blood sugar levels, causing complications. Red ginseng extract powder (RGEP) from Panax ginseng Meyer shows promise for diabetes treatment. However, its efficacy in managing T2DM remains unclear. Therefore, this study aims to evaluate the effectiveness of RGEP in a mouse model of T2DM. The efficacy of RGEP in treating T2DM was assessed in db/db mice. Mice were divided into seven groups: control, db/db, metformin, and RGEP at 50, 100, 200, and 400 mg/kg. Administered orally for 9 weeks, RGEP effects on glucose regulation and insulin sensitivity were assessed through various metabolic parameters. In addition, mRNA expression levels of genes associated with hepatic gluconeogenesis and insulin sensitivity were examined. Fasting blood sugar showed a significant decrease in all RGEP concentration groups, but OGTT and insulin tolerance test showed a significant decrease at the RGEP concentration of 400 mg/kg, indicating enhanced glycemic control. Moreover, RGEP dose-dependently decreased serum glucose, HbA1c levels, and homeostatic model assessment of insulin resistance values, suggesting its effectiveness in reducing insulin resistance in db/db mice. Furthermore, RGEP downregulated mRNA expression of key components in the gluconeogenesis pathway ( G6Pase , FOXO1 , GLUT4 , and PEPCK ), insulin sensitivity ( leptin , insulin1 , PTP1B , GLP-1 , and DPP-4 ), and mitochondria energy metabolism ( PGC1 ) in either the liver or pancreas, while simultaneously upregulating GLP-1 expression. In conclusion, these findings highlight the potential of RGEP as a complementary therapy for T2DM, indicating therapeutic efficacy in managing diabetic complications through improved metabolic parameters.

Currently, developing nonantibiotic growth promoters is a broad consensus in broiler industry, which is one of the effective ways to reduce drug-resistant strains. Chuanminshen violaceum is a traditional Chinese medicinal herb that is commonly used for its roots, while the stems and leaves are often discarded, resulting in a huge amount of waste. This study optimized the preparation process of water extract of Chuanminshen violaceum stems and leaves (CVSLE) by response surface analysis based on the yields of polysaccharide and protein. The CVSLE and herbal powder (CVSL) were then processed into granules before being used as feed additives. The Macleaya cordata powder was used as positive control. The results showed that the addition of CVSLE (0.5% of the feed) showed the highest growth-promoting activity than other CVSLE groups (0.2% and 1%), 1% CVSL group and positive control (0.05%). CVSLE at the dosage of 0.5% could significantly increase the ADG and reduce the FCR from d 21 to 42, d 0 to 42. The HI antibody titers against Newcastle disease virus and avian influenza virus were significantly enhanced at 21, 28 and 42 d. CVSLE did not affect the slaughtering performances, but could significantly elevate the spleen, thymus and bursa of Fabricius indices and the transcriptional levels of IL-2, IL-4, IL-10 and IFN-γ in spleen. The intestinal barrier function of broilers was significantly enhanced by increased levels of immune barrier (sIgA), physical barrier (ZO-1, OCL and Muc-2) and flora barrier (Lactobacillus and Bifidobacterium). These results suggest that CVSLE was a promising herbal additive candidate for broilers., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Our aim in the current study was to determine the in vitro and in vivo synergistic antiinflammatory and antiallergic effect associated with the IL-12 production of guaijaverin and epigallocatechin gallate (EGCG) complex (GEC) and ILS-F-2301 (2:8 extract of Psidium guajava and Camellia sinensis ). Compared to EGCG alone, GEC showed synergistic inhibition of nitric oxide (NO), inducible NO synthase, and cyclooxygenase-2 by 3.8, 5.1, and 4.1%, respectively. The downregulation of interleukin-12 (IL-12) by 2,4-dinitrophenyl-human serum albumin conjugate/DNP-immunoglobulin E or ovalbumin (OVA) was synergistically increased by GEC by about 7.5% or 5.4% compared to EGCG alone. The level of downregulation of IL-12 in plasma increased by 100 mg/kg with ILS-F-2301 (28.7%) when compared to the OVA/Alu-treated group. Also, GEC synergistically increased by GEC by about 7.5% or 5.4% compared to EGCG alone. The level of down and cyclooxygenase C synergistically inhibited p-Akt, PI3K, mTOR, p-STAT6, and GATA3 by 4.9%, 4.1%, 19.2%, 23.8%, and 35.3%, respectively, while increasing the expressions of p-STAT1 and T-bet (showing 53.3% and 9.4% activation) when compared to EGCG alone. In an allergenic rhinitis mouse model, 100 mg/kg of ILS-F-2301 was shown to inhibit p-Akt, PI3K, mTOR, p-c-Jun N-terminal kinase (p-JNK), p-extracellular signal-regulated kinase (p-ERK), and p-p38 by 23.3%, 43.8%, 17.2%, 32.2%, 29.1%, and 41.8% when compared to the OVA/Alu-sensitized group. Taken together, our findings suggest that ILS-F-2301 may have potential as a functional food for alleviating antiallergic rhinitis.

Excessive and prolonged alcohol consumption can lead to a serious health condition known as alcohol-related liver disease (ARLD). This ailment represents a significant worldwide health challenge, affecting populations across various demographics. ARLD has a multifactorial pathogenesis involving oxidative stress, inflammation, dysregulated lipid metabolism, and apoptosis. In this study, we investigated the hepatoprotective effects of Laurus nobilis L. leaf water extract (LLE) against ARLD in alcohol-treated hepatocytes and mice. LLE exhibited antioxidant and anti-inflammatory properties by enhancing antioxidant enzyme activities and suppressing proinflammatory cytokines and CYP2E1 expression in ethanol-treated hepatocytes. Moreover, LLE mitigated lipogenesis by modulating the expression of lipogenic factors in ethanol-treated hepatocytes. In vivo , LLE administration attenuated liver injury, oxidative stress, inflammation, and lipid accumulation induced by alcohol consumption in mice. Additionally, LLE suppressed apoptosis signaling pathways implicated in alcohol-induced hepatocyte apoptosis. These findings suggest that LLE functions as a multifaceted therapeutic agent for ARLD by modulating multiple cellular mechanisms, including the reduction of oxidative damage, mitigation of inflammatory responses, alleviation of lipid-mediated toxicity, and regulation of programmed cell death pathways.

This study was conducted to explore effects of Lonicerae flos and Rhomoma curcumae longae extracts (LR) on intestinal function of broilers. Three hundred broiler chickens were randomly assigned to the following 5 groups. The control group were fed the basal diet; the antibiotic group were fed the basal diet supplemented with spectinomycin hydrochloride (50 million units/ton) + lincomycin hydrochloride (25 g/ton); the LRH, LRM and LRL groups were fed the basal diet supplemented with a high dose (750 g/ton of feed), normal dose (500 g/ton of feed), or low dose (250 g/ton of feed) of LR, respectively. The changes of intestinal structure, intestinal digestive enzyme activities, antioxidant enzyme activities, inflammatory cytokines, and bacterial abundances in the colon and cecum contents were determined. The results indicated that compared with the control group and the antibiotic group, LR significantly increased the villus length/crypt depth (VCR) of the intestine, and significantly inhibited oxidative stress and inflammatory responses in the broiler intestine. In addition, LR regulated intestinal function by increasing the abundance of the intestinal microorganisms in broilers. In conclusion, LR improved antioxidant capacity, intestinal morphology, and microorganisms, and inhibited inflammatory response. The effect of high and medium doses of LR was better than lower doses., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study was conducted to evaluate the effects of walnut green husk extract (WGHe) on the growth performance, meat quality, antioxidative status, gut morphology, and microbiota diversity of broilers. A total of 216 one-day-old broilers were divided into 4 groups, each consisting of 9 replicates (6 birds per replicate) as follows: 1) control group, basal diet; 2) antibiotic group, basal diet supplemented with enduracidin and colistin sulfate; 3) low-dose group, basal diet supplemented with 5.0 g/kg WGHe; and 4) high-dose group, basal diet supplemented with 10.0 g/kg WGHe. The results revealed that the percentage of abdominal fat decreased, and the ratio of the duodenal villus length to crypt depth (V/C), as well as the α-diversity of the ileal microbiota, increased with 10.0 g/kg WGHe supplementation (P < 0.05). The shear force of the breast muscle and plasma malondialdehyde (MDA) concentration decreased, whereas the plasma peroxidase (POD) activity, Trolox equivalent antioxidant capacity (TEAC), and jejunal villus length increased in response to WGHe supplementation (P < 0.05). Compared with the antibiotic diet, the addition of 5.0 g/kg WGHe resulted in a significant increase in the relative abundances of Candidatus Arthromitus, Eubacterium coprostanoligenes, and Ruminococcaceae UCG-014 (P < 0.01). Furthermore, the addition of 10.0 g/kg WGHe increased the relative abundances of Candidatus Arthromitus and Lachnoclostridium, whereas the relative abundance of unidentified Chloroplast decreased (P < 0.05). In conclusion, dietary supplementation with 10.0 g/kg WGHe is advantageous for intestinal health, meat quality, and antioxidant status in broilers, suggesting its potential as a functional additive in poultry production., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Mercuric chloride (HgCl 2 ) is poisonous to humans and animals and typically damages the nervous system and other organs. Mercuric chloride exposition disclosed to initiation of oxidative stress pathway can result in a defect in male fertility and testis tissue. Synthesized selenium nanoparticles (SeNPs) were characterized with a diameter range minimal than 100 nm, having the effective sets of the biological matter. The present study aimed to evaluate the effect of biosynthesized SeNPs, prepared by leek extract on Wistar rats' testicles and brain., Methods: Thirty-five Wistar male rats (120-150 g) were randomly split into five groups (n = 7), orally ingested with leek aqueous extract loaded on SeNPs, and then the animals were administered with mercury II chloride (HgCl 2 ) to induce testis injury and damage the nervous system., Results: The used dose of mercuric chloride led to oxidative stress damage in the testis of the rats which was evidenced by a decrease in testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and proliferating cell nuclear antigen (PCNA) levels, and an increase in nuclear factor-kappa B (NF-κB) and caspase-3. Also, HgCl 2 decreased the levels of dopamine (DA), serotonin (5-HT), norepinephrine (NE) and brain-derived neurotrophic factor (BDNF) in the brains of rats. In addition, A decrease was observed in the levels of antioxidant markers, B-cell lymphoma-2 (Bcl-2), as well as an increase in malondialdehyde (MDA), nitric oxide (NO), NF-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and Bax in both testes and brains. Pre-treatment with leek extract loaded on SeNPs significantly ameliorated testosterone, LH, FSH, PCNA and caspase-3 levels in the testis and DA, 5-HT, NE and BDNF in brains. Although the contents of MDA, NO, TNF-α, IL-1β, NF-κB and Bax decreased significantly in both. glutathione, glutathione peroxidase, glutathione reductase, catalase, superoxide dismutase and Bcl-2 levels were significantly improved in both organs., Conclusion: Our findings suggest that treatment with aqueous leek extract loaded on SeNPs may offer promising prospects for the advancement of anti-inflammation activity against testis injury and also have a very key role in neurobehavioral alterations as a result of mercury toxicity. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Aim: To develop turmeric extract-loaded chitosan microparticles for treating gastrointestinal disorders., Methods: The microparticles were prepared using a spray-drying process, optimised the characteristics by biomarker loading, and encapsulation efficiency, and assessed for bioactivities related to gastrointestinal diseases., Results: The optimised microparticles were spherical, with a mean diameter of 2.11 ± 0.34 µm, a SPAN of 4.46 ± 0.68, a zeta potential of +37.6 ± 0.2 mV, loading of 15.7% w/w curcuminoids, 5.4% w/w ar-turmerone, and encapsulation efficiency of 63.26 ± 1.62% w/w curcuminoids and 43.75 ± 1.33% w/w ar-turmerone. Encapsulation of turmeric extract improved release at 6 h by 20 times and mucoadhesion by 3.6 times. The microparticles exhibited high acid-neutralising capacity (1.64 ± 0.34 mEq/g) and inhibited nitric oxide production about twice as effectively as the turmeric extract, while maintaining antioxidant and antibacterial activities., Conclusion: Encapsulation of turmeric extract in chitosan microparticles effectively enhanced therapeutic potential for gastrointestinal disorders.

Background: Dendrobium officinale flos (DOF), a novel food raw material, is used in Chinese folk medicine to nourish the stomach. However, there is still no available study to evaluate the effects of DOF on animal models of acute gastric injury and its mechanism by modern pharmacological research., Results: Herein, we characterized the major components of an aqueous extract of DOF and assessed its potential ameliorative effects in a rat model of acute gastric mucosal injury. The DOF water extract showed significant protective effects on the gastric mucosa and exhibited excellent antioxidant and anti-inflammatory activities. Acute gastric injury rat models induced by ethanol (6 mL kg -1 ) were pretreated with different doses of DOF water extract (50-100 mg kg -1  day -1 ), and the biological effects of DOF extract in gastric tissues were evaluated. DOF extract alleviated the symptoms of ethanol-stimulated acute gastric mucosal injury, as evidenced by a significant reduction in gastric injury index and the degree of gastric pathological changes. Additionally, treatment with DOF extract upregulated mucin expression in the gastric mucosa, attenuated oxidative stress, decreased the release of inflammatory mediators (TNF-α, IL-6), suppressed the expression of key proinflammatory enzymes (COX-2 and iNOS), reduced the phosphorylation of p38 MAPK and p65 NF-κB and increased the level of PGE2 in gastric tissues., Conclusion: DOF exerts protective effects against ethanol-induced acute gastric mucosal injury, mainly by inhibiting inflammation and oxidative stress. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

A 50-day feeding trial was conducted to evaluate the effects of mulberry leaf powder water extract (MLE) on the growth performance, immunity, antioxidant, meat quality and intestinal microbiota of yellow feather broilers. A total of 720 birds (initial body weight 40.07 ± 0.05 g) were randomly distributed into four groups with six replicates per group and 30 birds per replicate. Four diets were formulated with 0% (CON), 200 mg/kg MLE (MLE200), 400 mg/kg MLE (MLE400) and 600 mg/kg MLE (MLE600) supplementation. Results showed that the addition of 200-600 mg/kg MLE to the diet significantly increased the body weight (BW) and average daily weight gain (ADG), but feed to gain ratio (F/G) were linearly decreased (p = 0.045) as dietary MLE increased. Birds fed MLE400 had higher (p < 0.05) total antioxidant capacity (T-AOC), interleukin-10 (Il-10), secretory immunoglobulin A (SIgA) and complement 3 (C3) contents than those fed CON, whereas MLE400 had lower malondialdehyde (MDA) content than CON (p < 0.05). Analysis of 16 S rDNA indicated that supplementation with 200 mg/kg MLE increased the Shannon indices in the caecum (p < 0.05). Supplementation with MLE decreased the abundance of the phylum Proteobacteria and genus Helicobacter, and increased the abundance of the phylum Bacteroidetes in the caecum in broiler chickens (p < 0.05). The drip loss rate in the MLE600 was significantly diminished (p < 0.05), whereas the shear force was significantly elevated (p < 0.05). In summary, dietary supplementation with MLE can effectively improve growth performance, intestinal immunity, serum antioxidant capacity, meat quality and intestinal microbiota of yellow feather broilers. The most appropriate MLE supplementation level was 400 mg/kg. This study provides a practical strategy for the dietary application of MLE in yellow feather broilers., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Objective: This study assessed whether polyphenolic rich supplement containing Bacopa monnieri (BM: 300 mg), Panax quinquefolius ginseng (PQ: 100 mg) and whole coffee fruit extract (WCFE: 100 mg) could enhance cognitive performance, affect and cerebral-cortical activation over 28-days of intervention. Method: A randomised, double-blind, placebo-controlled, between-group study of 52 healthy adults between 35 and 65 years (M = 50.20, SD = 9.37) was conducted. Measures of cognition, affect and brain activity were measured at three time points: baseline, 28 days post intervention and 14 days post washout. At each time point, haemodynamic response in the prefrontal cortex (PFC) was measured using functional near-infrared spectroscopy (fNIRS), and serum brain-derived neurotrophic factor (BDNF). Results: The polyphenolic-rich supplement reliably improved positive affect and delayed recall compared to placebo following 28 days of supplementation. For the brain, those in the active condition showed greater PFC activation on performance of the 2-back tasks post supplementation compared to placebo ( p  < .05, d = 0.6). Discussion: This is the first report of a 28-day supplement intervention and 2-week follow-up study to assess changes in affect, cognition, cerebral haemodynamic response and BDNF in healthy middle-aged adults. The potential synergistic effects of polyphenolic compounds on neurocognitive function in middle-aged adults through emotional-cognitive processing and cognitive reserve are important for promoting brain and cognitive health.

This study investigated the impact of Hypericum attenuatum Choisy extract (HYG) on immunological function and the cecum microflora in broilers. A total of 240 one-day-old AA broilers were randomly divided into 5 groups with 6 replicates of 8 broilers each: 1) the CN group, in which broilers were injected with saline and fed a basal diet; 2) the PC group, in which broilers were injected with lipolyaccharide (LPS) and fed a basal diet; 3) the HYG1 group, in which broilers were injected with LPS and fed a 400 mg/kg HYG-supplemented diet; 4) the HYG2 group, in which broilers were injected with LPS and fed a 800 mg/kg HYG-supplemented diet; 5) the HYG3 group, in which broilers were injected with LPS and fed a 1,200 mg/kg HYG-supplemented diet. Broilers were injected with 1 mg/kg LPS or the same amount saline 12 hours before sampling on d 21 and 42. The results revealed that dietary 400 mg/kg HYG supplementation alleviated spleen index and thymus index abnormalities, balanced the disturbance of serum immunoglobulin (Ig)M and IgA levels, and regulated the cytokine balance in the serum, liver, spleen and jejunum tissues included induced by LPS. Dietary supplementation with 400 mg/kg HYG also downregulated the relative expression of the inhibitor of kappa B kinase alpha (IKKα) and interleukin (IL)-6 mRNAs in the liver and upregulated the relative expression of the inhibitor kappa B alpha (IκBα) and IL-10 mRNAs in the spleen. Dietary HYG improved the cecal microflora balance at 42 d by increasing the relative abundance of beneficial bacteria, such as Alistipes and Phascolarctobacterium, while reducing the relative abundance of harmful bacteria, such as Helicobacter and Colidextribacter. Spearman correlation analysis revealed a negative correlation between activation of the NF-κB inhibitory pathway in the liver and the presence of Phascolarctobacterium, Erysipelatoclostridium, Subdoligranulum and Parabacteroides. Conclusions: The incorporation of 400 mg/kg HYG into the diet was optimal in improving broiler immunological function., Competing Interests: DISCLOSURES The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Annona senegalensis Pers., (wild custard apple), is a shrub used traditionally to treat respiratory and skin diseases. Previous studies have demonstrated its anti-malaria, anti-snake envenomation and anti-cancer activities. However, its toxicological profile remains limited, particularly in male and female animals. This study aims to evaluate the safety of crude aqueous methanol extract of Annona senegalensis stem bark (AMEAS) through acute and sub-chronic toxicity studies. The stem bark of A. senegalensis was collected, air-dried, pulverized, and extracted using 70% methanol. Phytochemical screening, elemental analysis, and acute toxicity evaluation were carried out on AMEAS. Sub-chronic toxicity study was conducted on Wistar rats of both sexes at different doses administered orally for 28 days. Elemental analysis revealed the presence of heavy metals and essential mineral elements with the highest contents being calcium (59.88%) and potassium (25.39%). Acute toxicity testing showed no mortality up to 5000 mg/kg, suggesting an LD 50 greater than 5000 mg/kg. In the sub-chronic toxicity study, no mortality or significant harmful effects were observed. The blood glucose decreased from 13.68 mMol/L at 250 mg/kg to 10.71 mMol/L at 1000 mg/kg, much lower than the distilled water group (17.06 mMol/L). In conclusion, the extract appeared to be well-tolerated, with no obvious adverse effects. AMEAS is rich in Calcium (Ca) and potassium (K). It has been shown to have LD 50 greater than 5000 mg/kg and is assumed to be safe. On repeated use, AMEAS may cause hypoglycemia and weight loss which may be useful in managing diabetes and obesity respectively.

There are concerns about residues of drugs in meat that are used to prevent coccidiosis in chickens. Natural compounds are an alternative to drugs. Two studies investigated the effect of an extract of Enterolobium cyclocarpum fruits (EEC) in the feed of male Leghorn chickens exposed to Eimeria spp. In the first experiment, the administration of EEC after infection with Eimeria spp. was investigated over 16 days. One thousand chickens were randomly housed in 20 pens of 1 m 2 each. The pens were randomly assigned to each treatment. Five treatments were administered, containing 150, 300 and 450 mg/kg of EEC in the feed, the fourth treatment (C) contained 0.5 g/kg of a commercial anticoccidial, and the fifth treatment provided no treatment (WA). The second experiment lasted 18 days. Administration of the EEC began five days before the chickens were infected with Eimeria spp. Four hundred and eighty chickens were randomly allocated to 24 pens of 1 m 2 . The pens were randomly assigned to each treatment. In the second experiment, the same five treatments were tested and one additional treatment containing 300 mg EEC plus 1 g of polyethylene glycol (PEG)/kg of feed (E300PEG). In the experiment one chickens in the EEC treatments had lower faecal oocyst excretion (OE) on day 14 post infection with Eimeria spp., than chickens in the WA treatment (P < 0.05). A reduction in live weight gain (LWG) was observed in the EEC treatments (P < 0.05). In the second experiment, the excretion of oocysts in chickens from the EEC and E300PEG treatments on day 13 post-infection with Eimeria spp. was the same as in the C treatment and lower than in the WA treatment (P < 0.05). LWG was lower in the EEC treatments than in the C treatment (P < 0.05). However, the Chickens in the E300PEG and C treatments had similar LWG (P > 0.05) suggesting that PEG inhibits the negative effect of EEC tannins on LWG. In conclusion, the addition of EEC to chicken feed reduced both OE and LWG. Treatment with EEC and PEG (E300PEG) reduced the excretion of oocysts without negative effects on LWG., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

A previous study showed that kiwifruit polysaccharide (KFP) has benefits in relieving intestinal inflammation, while the underlying mechanism remains unresolved. The objective of this study was to investigate the regulatory effect of KFP on the gut microbiota metabolism and intestinal barrier of ulcerative colitis (UC) mice induced by dextran sulfate sodium (DSS). KFP significantly improved the UC symptoms including weight loss, shortened colon length, splenomegaly, diarrhea, hematochezia, and colon inflammation of mice. In addition, KFP could alleviate DSS-caused gut microbiota dysbiosis and increase the levels of short-chain fatty acids in the cecal contents of mice. Furthermore, the results of nontargeted and targeted metabolomics analysis combined with antibiotic treatment revealed that KFP could regulate gut microbiota-dependent tryptophan metabolism, activate the aryl hydrocarbon receptor (AhR) in colon cells, and enhance interleukin-22 production and tight junction proteins' (ZO-1, occludin, and claudin3) expression to repair the intestinal barrier in UC mice. Immunofluorescence results showed that KFP significantly upregulated the conjunction of lectin WGA and UEA1 in the UC mouse colon, implying that KFP promoted fucosylation in the colon. These results suggest that KFP alleviates UC primarily via targeting the gut microbiota involved in the AhR pathway and upregulating colon fucosylation.

Green tea polyphenols (GTP) have been shown to ameliorate lipid metabolic disorders by regulating intestinal bacteria. Given the significant role of intestinal bacteriophages in shaping the gut microbiota, this study investigates GTP's influence on gut bacteriophage-bacteria interactions and lipid metabolism using metagenomics and metabonomics. The research results indicated that GTP significantly reduced body weight, serum triglycerides, leptin, insulin resistance, interleukin-6, and TNF-α levels while increasing adiponectin in ob/ob mice fed high-fat diet, aiding intestinal repair. GTP improved gut health by decreasing Enterobacter, Siphoviridae and Enterobacteria&#95;phage&#95;sfv, increasing Bifidobacterium and intestinal metabolites SCFA and hippuric acid. Correlation analysis showed negative correlations between Enterobacter sp. 50,588,862 and Enterobacteria&#95;phages, Shigella&#95;phages with 4-hydroxyphenylpyruvate and hippuric acid. Bifidobacterium choerinum and Bifidobacterium sp. AGR2158 were positively correlated with fatty acids and bile acids. In conclusion, GTP reduced fat accumulation and inflammation, enhanced gut barrier function in obese mice, closely associated with changes in the gut bacteriophage community., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Lindera aggregata (Sims) Kosterm is a common traditional herb that has multiple bioactivities. Radix Linderae (LR), the dry roots of Lindera aggregata (Sims) Kosterm, is a traditional Chinese herbal medicine with antioxidant, anti-inflammatory and immunomodulatory properties, first found in Kaibao Era. Norboldine (Nor) is an alkaloid extracted from LR and is one of the primary active ingredients of LR. However, the pharmacological functions and mechanism of Nor in Alzheimer's disease (AD) are still unknown., Aim of the Study: This study aims to investigate the effect and mechanism of Nor therapy in improving the cognitive impairment and pathological features of 3 × Tg mice., Materials and Methods: 3 × Tg mice were treated with two concentrations of Nor for one month and then the memory and cognitive abilities of mice were assessed by novel object recognition experiment and Morris water maze. The impact of Nor on the pathology of ADwere examined in PC12 cells and animal tissues using western blotting and immunofluorescence. Finally, western blotting was used to verify the anti-apoptotic effect of Nor by activating AMPK/GSK3β/Nrf2 signaling pathway at animal and cellular levels., Results: In this study, we showed that Nor treatment improved the capacity of the learning and memory of 3 × Tg mice and alleviated AD pathology such as Aβ deposition. In addition, Nor restored the abnormalities of mitochondrial membrane potential, significantly reduced the production of intracellular ROS and neuronal cell apoptosis. Mechanistically, we combined network pharmacology and experimental verification to show that Nor may exert antioxidant stress and anti-apoptotic through the AMPK/GSK3β/Nrf2 signaling pathway., Conclusion: Our data provide some evidence that Nor exerts a neuroprotective effect through the AMPK/GSK3β/Nrf2 pathway, thereby improving cognitive impairment in AD model mice. Natural products derived from traditional Chinese medicines are becoming increasingly popular in the process of new drug development and discovery, and our findings provide new perspectives for the discovery of improved treatment strategies for AD., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The sap of Angelica keiskei (Miq). Koidz. has been reported for its abundance of chalcone contents. Chalcones have been known for their effective nephroprotective activity toward cisplatin-induced renal cells and mice., Purpose: To investigate the effect of A. keiskei sap extract (ASEE) on kidney function parameters (serum creatinine, urea nitrogen, and kidney injury molecule-1) and the expression of NF-kappaB p65 and COX-2 in cisplatin-induced Wistar rats., Methods: In vivo nephroprotective activity of ASEE at 1000 and 1500 mg/kg BW/day doses for 10 days on cisplatin (5 mg/kg BW) induced nephrotoxicity was evaluated on Wistar rats. Quercetin 20 mg/kg BW/day was used as the control drug. Cisplatin inducement was given on day 7. The BW was measured every day. On day 11, the rats were euthanized, and their blood was taken intracardially for creatinine and urea nitrogen analysis. Histopathological analysis was carried out on the right kidney, and KIM-1 levels in the left kidney were measured. The Western blot technique evaluated the NF-kappaB p65 and COX-2 expression in the kidney. All data obtained were compared to the cisplatin group (negative control). The total flavonoids and chalcones in ASEE were also determined., Results: Pretreatment with ASEE reduces the BW of Wistar rats, and significantly reduces creatinine and KIM-1 levels, but does not significantly reduce the levels of urea nitrogen, the expression of NF-kappaB p65, and COX-2 in the kidney of cisplatin-induced Wistar rats. The total flavonoid content in ASEE is 8.755 g QE/100 g extract and the total chalcone content is 5.532 g IBCE/100 g extract., Conclusion: The sap of Angelica keiskei (Miq). Koidz. reveal the potential to protect the kidneys against cisplatin-induced toxicity. The nephroprotective activity may be attributed to the antioxidant and anti-inflammatory properties of the flavonoids and the chalcones contained in the sap of Angelica keiskei (Miq). Koidz., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Wahyuni et al.)

Codonopsis Radix (CR), a traditional tonic medicinal material in China, has been proven to possess a variety of bioactive functions. However, its chemical composition and in vivo metabolic pattern have not been fully elucidated. In this study, AB-8 macroporous resin column chromatography was employed for the enrichment of small molecular components in CR. Furthermore, a method combining ultra-performance liquid chromatography-quadrupole-orbitrap mass spectrometry with Acquire X intelligent data acquisition technology software was developed for the preliminary screening and identification of the chemical composition of CR in vitro and their metabolites in vivo. As a result, a total of 116 components were preliminarily characterized in the CR extract, including 28 polyacetylenes, 33 organic acids, 4 amino acids, 23 alkaloids, 9 phenylpropanoids, 6 terpenoids, 2 nucleosides, and 11 others. Additionally, a total of 84 compounds, including 37 prototype components and 47 metabolites, were identified in the plasma, urine, and feces of rats after oral administration of CR. Specifically, 11, 24, 19, 32, and 25 constituents were identified in the heart, liver, spleen, lung, and kidney, respectively. Of note, the lung and spleen are the organs with the highest distribution of CR compounds. These findings will serve as valuable data for future research on the correlation between the chemical composition and pharmacological effects of CR., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gnetum montanum Markgr. (Gnetaceae) is a commonly used traditional herbal medicine among the Yao ethnic group, with potential effects in preventing and treating tumors. However, the substance basis of its anti-tumor properties remains unclear. This study utilized ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) to identify the chemical components of G. montanum extract (GME) and its absorbed prototypes in cynomolgus monkey plasma after oral administration. A total of 57 compounds were detected in the GME, with 14 compounds in positive ion mode and 43 compounds in negative ion mode. In the cynomolgus monkey plasma, 17 compounds were identified, with 3 compounds in positive ion mode and 14 compounds in negative ion mode. Subsequently, we utilized high content screening technology to investigate the anti-tumor effects of GME on colon cancer, lung cancer, breast cancer, gastric cancer, liver cancer, and esophageal cancer. We found that the GME exhibited significant proliferation inhibition on colon cancer cells SW480, with an IC 50 value of 50.77 μg/mL. Further research using component separation and pharmacological tracking revealed that the F2 component of the GME demonstrated notable anti-tumor effects. Through UPLC-MS identification, the chemical components in the F2 fraction were identified as pinoresinol diglucoside, (+)-pinoresinol-4-O-beta-D-glucopyranoside, ursolic acid, and gnetol. In conclusion, this study contributes to elucidating the anti-tumor pharmacological basis of GME and provides robust support for future drug design and development., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Sorafenib-resistant (SR) hepatocellular carcinoma (HCC) is a current serious problem in liver cancer treatment. Numerous phytochemicals derived from plants exhibit anticancer activity but have never been tested against drug-resistant cells., Methods: Avocado seed extract (APE) isolated by maceration was analysed for its phytochemical composition and anticancer activity. Novel design charge-switchable pH-responsive nanocarriers of aminated mesoporous silica nanoparticles with conjugated galactose (GMSN) were synthesised for delivering APE and their physicochemical properties were characterized. The drug loading efficiency (%LE) and entrapment efficiency (%EE) were evaluated. Anticancer activity of APE loaded GMSN was measured against HCC (HepG2, Huh-7) and SR-HCC (SR-HepG2)., Results: Anticancer activity of APE against non-resistant HepG2 (IC 50 50.9 ± 0.83 μg mL -1 ), Huh-7 (IC 50 42.41 ± 1.88 μg mL -1 ), and SR-HepG2 (IC 50 62.58 ± 2.29 μg mL -1 ) cells was confirmed. The APE loaded GMSN had a diameter of 131.41 ± 14.41 nm with 41.08 ± 2.09%LE and 44.96 ± 2.26%EE. Galactose functionalization (55%) did not perturb the original mesoporous structure. The GMSN imparted positive surface charges, 10.3 ± 0.61mV at acidic medium pH 5.5 along with rapid release of APE 45% in 2 h. The GMSN boosted cellular uptake by HepG2 and SR-HepG2 cells, whereas the amine functionalized facilitated their endosomal escape. Their anticancer activity was demonstrated in non-resistant HCC and SR-HCC cells with IC 50 values at 30.73 ± 3.14 (HepG2), 21.86 ± 0.83 (Huh-7), 35.64 ± 1.34 (SR-HepG2) μg mL -1 , respectively, in comparison to the control and non-encapsulated APE., Conclusion: APE loaded GMSN is highly effective against both non-resistant HCC and SR-HCC and warrants further in vivo investigation., Competing Interests: The authors declare no competing interests over the publication of this manuscript., (© 2024 Basu et al.)

Objective: To identify the polar parts in Rhubarb that cause hepatotoxicity and explore the underlying mechanisms., Methods: The rat model of liver cancer was established by gavage of diethylnitrosamine (DEN; 0.002 g/rat) for 14 weeks. Starting from the 11th week, Rhubarb granule (4 g/kg), aqueous, ethyl acetate and n-butanol extract of Rhubarb or Rhein equivalent to a dose of 4 g/kg Rhubarb granule were administered intragastrically for 4 consecutive weeks. Liver tissues from rats treated with DEN and Rhubarb granules were used for non-targeted metabolomics analysis. The correlation between pyruvate kinase isozyme type M2 (PKM2) expression level and the progress and prognosis of hepatocellular carcinoma (HCC) was evaluated through bioinformatics analysis based on TCGA database. Liver tissues and blood samples from rats treated with DEN and aqueous, ethyl acetate and n-butanol extract of Rhubarb were used for the screening of hepatotoxic polar parts of Rhubarb. The liver injuries were evaluated by the changes in pathology, liver function, and the expression levels of proliferating cell nuclear antigen (PCNA) and transforming growth factor beta1 (TGF-β1). The mechanism studies focus on PKM2 expression, and the metabolic reprogramming via detecting the activities of lactate dehydrogenase A (LDHA) and isocitrate dehydrogenase (ICDH). Furthermore, molecular docking analysis was performed to validate the target interaction between Rhein and PKM2, and the hepatotoxicity of Rhein was evaluated by testing liver function in the DEN-induced liver cancer model., Results: The non-targeted metabolomics analysis revealed that Rhubarb promoted aerobic glycolysis in the rat model of DEN-induced liver cancer. And bioinformatics analysis revealed that high PKM2 expression was closely related to the progression and poor prognosis of HCC. In vivo studies indicated that the aqueous extract of Rhubarb, but not ethyl acetate and n-butanol extract, promoted the liver injuries induced by DEN. The mechanism study showed that the aqueous extract of Rhubarb increased the expression of PKM2 and promoted aerobic glycolysis. Moreover, Rhein had a strong binding affinity for PKM2 and aggravated liver injury in the DEN-induced liver cancer model., Conclusion: Aqueous extract of Rhubarb promoted hepatotoxicity via facilitating PKM2-mediated aerobic glycolysis in the rat model of DEN-induced liver cancer., Competing Interests: The authors declare that there are no conflicts of interest in this work. This paper has been uploaded to SSRN as a preprint: https://ssrn.com/abstract=4736236 or http://dx.doi.org/10.2139/ssrn.4736236, (© 2024 Zhao et al.)

Delayed thrombolytic therapy with tissue plasminogen activator (tPA), the only FDA-approved drug for ischemic stroke, can cause catastrophic hemorrhagic transformation (HT) after ischemic stroke. However, it remains largely unknown how microglial polarization dynamically changes in HT. Poria cocos is a widely used functional edible fungus in Asia and has been used for more than 2000 years as a food and medicine in China. Our preliminary study found that P. cocos extract (PCE) significantly reduced the volume of cerebral infarction. We performed the effects of PCE on tPA-induced HT in rat models of autologous thromboembolism middle cerebral artery occlusion in vivo and BV-2 cells injured by oxygen-glucose deprivation/reperfusion in vitro. Hemorrhage test and triphenyltetrazolium chloride staining were performed to examine the efficiency of PCE. The expression level of proteins associated with microglia polarization was detected using Western blotting and immunofluorescence staining. Small interfering RNA transfection reveals the regulatory mechanism of PCE on microglia polarization. PCE plus tPA reduced hemorrhage and infarct volumes after ischemic stroke. During tPA-induced HT, M1 microglia increased over time from 3 days onward and remained high for at least 7 days, reaching the peak at 7 days, M2 microglia gradually increased after 3 days and continued to increase for at least 14 days. Furthermore, PCE inhibited the secretion of pro-inflammatory cytokines in M1 microglia and improved the secretion of anti-inflammatory cytokines in M2 microglia, which related to the regulation of the IRF5-IRF4 axis. This current study indicates that PCE alleviates tPA-induced HT after ischemic stroke by modulating microglia M1/M2 phenotype polarization.

Heat stress, low mango yields and inconsistent fruit quality are main challenges for growers. Recently, licorice-root extract (LRE) has been utilized to enhance vegetative growth, yield, and tolerance to abiotic stresses in fruit trees. Potassium sorbate (PS) also plays a significant role in various physiological and biochemical processes that are essential for mango growth, quality and abiotic stress tolerance. This work aimed to elucidate the effects of foliar sprays containing LRE and PS on the growth, yield, fruit quality, total chlorophyll content, and antioxidant enzymes of 'Osteen' mango trees. The mango trees were sprayed with LRE at 0, 2, 4 and 6 g/L and PS 0, 1, 2, and 3 mM. In mid-May, the mango trees were sprayed with a foliar solution, followed by monthly applications until 1 month before harvest. The results showed that trees with the highest concentration (6 g/L) of LRE exhibited the maximum leaf area, followed by those treated with the highest concentration (3 mM) of PS. Application of LRE and PS to Osteen mango trees significantly enhanced fruit weight, number of fruits per tree, yield (kg/tree), yield increasing%, and reduced number of sun-burned fruits compared to the control. LRE and PS foliar sprays to Osteen mango trees significantly enhanced fruit total soluble solids ˚Brix, TSS/acid ratio, and vitamin C content compared to the control. Meanwhile, total acidity percentage in 'Osteen' mango fruits significantly decreased after both LRE and PS foliar sprays. 'Osteen' mango trees showed a significant increase in leaf area, total chlorophyll content, total pigments, and leaf carotenoids. Our results suggest that foliar sprays containing LRE and PS significantly improved growth parameters, yield, fruit quality, antioxidant content, and total pigment concentration in 'Osteen' mango trees. Moreover, the most effective treatments were 3 mM PS and 6 g/L LRE. LRE and PS foliar spray caused a significant increase in yield percentage by 305.77%, and 232.44%, in the first season, and 242.55%, 232.44% in the second season, respectively., Competing Interests: The authors declare that they have no competing interests., (© 2024 Al-Saif et al.)

Recently, the anti-tumor effects of cannabis extract on various cancers have attracted the attention of researchers. Here, we report a nanoemulsion (NE) composition designed to enhance the delivery of two active components in cannabis extracts (∆9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD)) in an animal model of glioblastoma. The efficacy of the NE containing the two drugs (NED) was compared with the bulk drugs and carrier (NE without the drugs) using the C6 tumor model in rats. Hemocompatibility factors (RBC, MCV, MCH, MCHC, RDW, PPP, PT and PTT) were studied to determine the potential in vivo toxicity of NED. The optimized NED with mean ± SD diameter 29 ± 6 nm was obtained. It was shown that by administering the drugs in the form of NED, the hemocompatibility increased. Cytotoxicity studies indicated that the NE without the active components (i.e. mixture of surfactants and oil) was the most cytotoxic group, while the bulk group had no toxicity. From the in vivo MRI and survival studies, the NED group had maximum efficacy (with ~4 times smaller tumor volume on day 7 of treatment, compared with the control. Also, survival time of the control, bulk drug, NE and NED were 9, 4, 12.5 and 51 days, respectively) with no important adverse effects. In conclusion, the NE containing cannabis extract could be introduced as an effective treatment in reducing brain glioblastoma tumor progression., (© 2024. The Author(s).)

The use of agricultural waste in animal production has gained global interest. An eight-week trial was conducted to investigate the impacts of adding ethanolic guava leaf extract (GLE) as a feed supplement on the growth, feed utilization, immune response, nutrient digestibility, redox regulation, and blood health of growing rabbits. Ninety weaned growing rabbits were randomly assigned to three groups. The first group was fed a basal diet (GLE0), while the other two groups were fed the control diet fortified with 15 mg (GLE15) or 20 mg (GLE20) of GLE per kg of diet for 8 weeks. The HPLC analysis of GLE exhibited the presence of gallic acid, ferulic acid, catechin, and caffeic acid in significant amounts. The results indicated that final body weight, daily body weight, daily feed intake and nutrient digestibility were significantly higher in the GLE-treated groups compared to the un-treated group (p < 0.05). Dietary supplementation of GLE significantly reduced lipid contents including triglycerides, total cholesterol, LDL, HDL, and VLDL (P < 0.05), with the most significant results observed when adding 20 mg/kg to the diet. AST and ALT levels as well as cortisol hormone in rabbits fed GLE were lower than those in the GLE0 group (P < 0.05). Immunoglobulins (IgG and IgA), antioxidant biomarkers (SOD and TAC) and T3 hormone were significantly improved by GLE supplementation (P < 0.001). Rabbits fed with GLE had lower levels of ROS and MDA compared to those in the GLE0 group (P < 0.001). Moreover, the hepatic and intestinal architectures were maintained in all rabbits fed diets with GLE. The results suggest that GLE supplementation (20 mg/kg diet) in fattening rabbit diets could efficiently improve growth, health status, blood physiology, antioxidant capacity and tissue histology., (© 2024. The Author(s).)

Objectives: Withania somnifera (WS) is a valuable medicinal plant that has been used against several ailments. The medicinal properties of WS are ascribed to existence of secondary metabolites which are in great demand in herbal nutraceutical industry. Despite well-known therapeutic effects of WS, it is necessary to assess preclinical toxicity of WS plant on rats and further explore its potential application against treatment of various disorders in humans. The existing study assessed oral acute and sub-chronic toxicities of WS root extract in Sprague Dawley (SD) rats (male and female) for 14 and 90 days, respectively under OECD-423 and -408 guidelines as well as GLP compliance., Methods: In acute toxicity, rats of either sex were orally fed a dose of 2,000 mg/kg. In sub-chronic toxicity, animals were orally administered repeated doses of WS root extract at 250, 500, 1,000 mg/kg for 90 days with an additional 14-day recovery period. Two more groups (n=5 animals each) receiving vehicle and 1,000 mg/kg of WS root extract for 90 days were also observed., Results: In acute toxicity, the results revealed that LD 50 of WS root extract in SD rats was higher than 2,000 mg/kg. In sub-chronic toxicity, oral administration of extract for 90 days showed no significant toxicological changes in rats. Haematological and serum chemistry markers were found within normal range. Terminal necropsy showed no gross or histopathological outcomes., Conclusions: The no-observed-adverse-effect level (NOAEL) of WS root extract was 1,000 mg/kg body weight, and safe to use at this dose in rats., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

The present study aimed to investigate the effects of ( R )-(-)-1-isothiocyanato-6-(methylsulfinyl)-hexane [( R )-6-HITC], the major isothiocyanate present in wasabi, in an ex vivo model of inflammation using lipopolysaccharide-stimulated murine peritoneal macrophages. ( R )-6-HITC improved the immune response and mitigated oxidative stress, which involved suppression of reactive oxygen species, nitric oxide, and pro-inflammatory cytokines (IL-1β, IL-6, IL-17, IL-18, and TNF-α) production and downregulation of pro-inflammatory enzymes such as inducible nitric oxide synthase, COX-2, and mPGES-1. In addition, ( R )-6-HITC was able to activate the Nrf2/HO-1 axis while simultaneously inhibiting key signaling pathways, including JAK2/STAT3, mitogen-activated protein kinases, and canonical and noncanonical inflammasome pathways, orchestrating its potent immunomodulatory effects. Collectively, these findings demonstrate the potential of ( R )-6-HITC as a promising nutraceutical for the management of immuno-inflammatory diseases and justify the need for further in vivo validation studies.

Background: Mammary gland carcinoma is a malignant type of cancer that occurs in mammae tissue. Dimethylbenzene (α) anthracene (DMBA) is a carcinogenic agent that causes mammary cancer by damaging cellular DNA. Flavonoids found in the black soybean ( Glycine max L. Merr) exhibit anti-carcinogenic effects., Aim: This study evaluated the anticarcinogenic effects of black soybean extract., Methods: The activity of flavonoid compounds in black soybean was determined in silico . Five groups of rats, four in each group, were established, consisting of a negative control, a positive control, and three treatment groups. Treatment included black soybean extract administration (i.e., T1 = 200, T2 = 400, and T3 = 800 mg of black soybean extract/kg body weight for 10 days). The observed parameters included the immunohistochemical analysis of Breast Cancer 1(BRCA1) and TNF-α., Results: Based on an in silico study, compounds from black soybeans are non-toxic. Functional annotation analysis revealed that most of the target proteins have a role in biological processes associated with cancer development. An in vivo analysis using an animal mammae cancer model indicated that black soybean extracts inhibited mammae cancer progression by attenuating TNF-α and BRCA1 expression., Conclusion: The most effective dosage of black soybean extract was 200 mg/kg body weight. An increase in BRCA1 and TNF-α expression may be related to the effects of catechin, daidzein, genistein, and glycitein, which are present in black soybeans., Competing Interests: The authors have no conflicts of interest regarding this study.

Background: Type 2 diabetes mellitus (T2DM) is a chronic condition characterized by insulin resistance and impaired insulin production, leading to elevated blood glucose levels. Curcumin, a polyphenolic compound from Curcuma longa, has shown potential in improving insulin sensitivity and reducing blood glucose levels, which may help mitigate type 2 diabetes progression., Objective: To assess the efficacy of improving type 2 diabetes (T2DM)., Study Design: This randomized, double-blind, placebo-controlled trial included subjects (n = 272) with criteria for type 2 diabetes., Methods: All subjects were randomly assigned to receive curcumin (1500 mg/day) or placebo with blind labels for 12 months. To assess the improvement of T2DM after curcumin treatments body weight and body mass index, fasting plasma glucose, glycosylated hemoglobin A 1c, β-cell function (homeostasis model assessment [HOMA-β]), insulin resistance (HOMA-IR), insulin, adiponectin, and leptin were monitored at the baseline and at 3-, 6-, 9-, and 12-month visits during the course of intervention., Results: After 12 months of treatment, the curcumin-treated group showed a significant decrease in fasting blood glucose (115.49 vs.130.71; P < 0.05), HbA 1c (6.12 vs. 6.47; P < 0.05). In addition, the curcumin-treated group showed a better overall function of β-cells, with higher HOMA-β (136.20 vs. 105.19; P < 0.01) The curcumin-treated group showed a lower level of HOMA-IR (4.86 vs. 6.04; P < 0.001) and higher adiponectin (14.51 vs. 10.36; P < 0.001) when compared to the placebo group. The curcumin-treated group also showed a lower level of leptin (9.42 vs. 20.66; P < 0.001). Additionally, body mass index was lowered (25.9 4 vs.29.34), with a P value of 0.001., Conclusions: A 12-month curcumin intervention in type 2 diabetes patients shows a significant glucose-lowering effect. Curcumin treatment appeared to improve the overall function of β-cells and reduce both insulin resistance and body weight, with very minor adverse effects. Curcumin intervention in obese patients with type 2 diabetes may be beneficial., Trial Registration: Thai clinical trials regentrify no.20140303003., (© 2024. The Author(s).)

Objective: To investigate the efficacy and safety of a repairing mask as an adjunctive treatment for skin barrier maintenance of mild to moderate rosacea., Methods: Patients with rosacea were recruited in this dual center randomized controlled trial from November 2019 to December 2021. A total of 64 patients were included and randomized into two groups at a ratio of 3:1 into a mask group (n = 47) and a control group (n = 17). Patients in the mask group received treatment with Dr. Yu Centella asiatica repairing facial mask three times weekly for a duration of 6 weeks. All participants were instructed to continue their regimen of 50 mg oral minocycline twice daily and to apply Dr. Yu Intensive Hydrating Soft Cream twice daily. The primary endpoint of this study was the Investigator Global Assessment (IGA) score., Results: A total of 54 patients completed this trial, with 41 in the mask group and 13 in the control group. After using this facial mask for 3 and 6 weeks, the IGA, facial skin dryness, facial flushing, and severity of skin lesion in the mask group showed significantly improvement (p < 0.05). Moreover, the change in the delta degree of skin flushing was significantly higher than that in the control group (p = 0.037). Throughout the study, no adverse events were reported in either group of participants., Conclusion: The Dr. Yu Centella asiatica repairing facial mask, as an adjunctive treatment of rosacea, appears to effectively repair and protect the skin barrier, alleviate cutaneous symptoms of rosacea, and is both efficacious and safe for patient use., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)