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PurposeSGLT2, the sodium glucose cotransporter two, is expressed in human pancreatic, prostate and brain tumors, and in a mouse cancer model SGLT2 inhibitors reduce tumor glucose uptake and growth. In this study we have measured the effect of a specific SGLT2 inhibitor, Jardiance® (Empagliflozin), on glucose uptake into astrocytomas in patients.MethodsWe have used a specific SGLT glucose tracer, α-methyl-4-[18F]fluoro-4-deoxy-α-D-glucopyranoside (Me4FDG), and Positron Emission Tomography (PET) to measure glucose uptake. Four of five patients enrolled had WHO grade IV glioblastomas, and one had a low grade WHO Grade II astrocytoma. Two dynamic brain PET scans were conducted on each patient, one before and one after treatment with a single oral dose of Jardiance, a specific SGLT2 inhibitor. As a control, we also determined the effect of oral Jardiance on renal SGLT2 activity.ResultsIn all five patients an oral dose (25 or 100 mg) of Jardiance reduced Me4FDG tumor accumulation, highly significant inhibition in four, and inhibited SGLT2 activity in the kidney.ConclusionsThese initial experiments show that SGLT2 is a functional glucose transporter in astocytomas, and Jardiance inhibited glucose uptake, a drug approved by the FDA to treat type 2 diabetes mellitus (T2DM), heart failure, and renal failure. We suggest that clinical trials be initiated to determine whether Jardiance reduces astrocytoma growth in patients.

BACKGROUND: To investigate the individual profile of each SGLT2 (sodium-glucose cotransoporter-2) inhibitor in patients with different backgrounds. METHODS AND RESULTS: This study included 21 placebo-controlled randomized controlled trials with a total of 96 196 participants, investigating empagliflozin, ertugliflozin, dapagliflozin, canagliflozin, and sotagliflozin. The primary efficacy end point was the composite of cardiovascular death and hospitalizations for heart failure. The secondary efficacy end points were all-cause death, cardiovascular death, hospitalizations for heart failure, kidney disease progression, and acute kidney injury. We conducted subgroup analyses based on the underlying comorbidities, including diabetes and chronic kidney disease. Safety end points were also assessed among SGLT2 inhibitors in the overall cohort. In the overall cohort, there were no significant differences in the primary efficacy outcome among the SGLT2 inhibitors, while empagliflozin (hazard ratio [HR], 0.70 [95% CI, 0.53-0.92]) and dapagliflozin (HR, 0.73 [95% CI, 0.56-0.96]) were associated with lower risk of acute kidney injury than sotagliflozin. The presence or absence of diabetes did not alter the results. In patients with chronic kidney disease, there were no differences in the efficacy outcomes among SGLT2 inhibitors, while in patients without chronic kidney disease, empagliflozin was associated with lower risk of the primary outcome compared with ertugliflozin (HR, 0.77 [95% CI, 0.60-0.98]). For safety outcomes, no significant differences were observed in amputation, urinary tract infection, genital infection, hypoglycemia, and diabetic ketoacidosis. CONCLUSIONS: The differences in reducing cardiovascular and kidney outcomes as well as safety profiles across SGLT2 inhibitors were not consistently significant, although empagliflozin might be preferred in patients without chronic kidney disease. Further investigations are needed to better understand the mechanism and clinical effectiveness of each SGLT2 inhibitor in certain populations.

Phytochemical investigation of Staehelina uniflosculosa Sibth. & Sm. resulted in the isolation of twenty-two natural products: eleven sesquiterpene lactones, artemorin (1), tamirin (2), tanachin (3), reynosin (4), baynol C (5), desacetyl-β-cyclopyrethrosin (6), 1β-hydroxy-4α-methoxy-5α,7α,6β-eudesm-11(13)-en-6,12-olide (7), 1β,4α,6α-trihydroxyeudesm-11-en-8α,12-olide (8), 1β-hydroxy-arbusculin A (9), methyl-1β,4α,6α-trihydroxy-5α,7αH-eudesm-11(13)-en-12-oate (10) and methyl-1β,6α,8α-trihydroxy-5α,7αH-eudesma-4(15),11(13)-dien-12-oate (11); one lignan, pinoresinol (12); one norisoprenoid, loliolide (13); six flavonoids (four genins and two glycosides), hispidulin (14), nepetin (15), jaceosidin (16), eriodictyol (17), eriodictyol-3′-O-β-D-glucoside (18) and eriodictyol-7-O-β-D-glucuronide (19); and three phenolic derivatives (one phenolic acid and two phenolic glucosides), protocatechuic acid (20), arbutin (21) and nebrodenside A (22). From the isolated compounds, only nepetin (15) has been reported previously from the Staehelina genus and, to the best of our knowledge, it is the first time that compound (18) has been identified in Asteraceae. A number of these substances were tested for (a) inhibition of lipoxygenase and acetylocholinesterase, (b) their antioxidant activity using the DPPH (1,1-Diphenyl-2-picrylhydrazyl) method or/and (c) inhibition of lipid peroxidation. The tested components exhibited low antioxidant activity with the exception of 5 and 22, while the effectiveness of these compounds in the inhibition of acetylocholinesterase is limited. Furthermore, Molinspiration, an online computer tool, was used to determine the bioactivity ratings of the isolated secondary metabolites. The compounds' bioactivity ratings for potential therapeutic targets were very promising. [ABSTRACT FROM AUTHOR]

From the MeOH residue of Barringtonia macrocarpa branches and leaves, one new isoryanodane diterpene, barringisol (1), and two new isoryanodane diterpene glucosides, barringisosides A and B (2 and 3), were obtained using various chromatographic isolations. The structural characterization was confirmed by spectroscopic methods including 1D, 2D NMR and HR-ESI-QTOF-MS. This is the first isolation of isoryanodane diterpene derivatives from Barringtonia species. Moreover, the in vitro cytotoxicity of 1−3 on three human cancer cell lines (HepG2, LNCaP and MCF7) was also accessed using SRB assays. [ABSTRACT FROM AUTHOR]

This research examines the anti‐aging potential of the flavonoid derivative of isoquercitrin known as enzymatically modified isoquercitrin (EMIQ). Initial HPLC analyses showed that EMIQ used in the study contained 1–12 glucosides and 10.7% pentahydroxyflavonoids, promising potent antioxidant properties. In subsequent in‐vitro studies with UVA‐exposed human dermal fibroblasts (HDFa), EMIQ demonstrated protective properties by reducing collagen damage. It modulated both the TGFβ/Smad pathway and the MMP1 pathway, contributing to collagen preservation. This protective effect was further confirmed using the T‐Skin™ model, a reconstructed full‐thickness human skin model, which illustrated that EMIQ could defend the physiological structures of both the epidermis and dermis against UV radiation. A 28‐day clinical trial with 30 volunteers aged 31–55 years highlighted EMIQ's effectiveness. Participants using EMIQ‐containing Essence displayed reduced facial trans‐epidermal water loss and skin roughness, alongside improved skin elasticity. This study emphasizes EMIQ's potential as an anti‐photoaging ingredient in cosmetics, warranting further research. The findings pave the way for developing innovative skincare products addressing photoaging effects. [ABSTRACT FROM AUTHOR]

Gingerols are phenolic biomedical compounds found in ginger (Zingiber officinale) whose low aqueous solubility limits their medical application. To improve their solubility and produce novel glucosides, an α -glucosidase (glycoside hydrolase) from Agrobacterium radiobacter DSM 30147 (Ar G) was subcloned, expressed, purified, and then confirmed to have additional α -glycosyltransferase activity. After optimization, the Ar G could glycosylate gingerols into three mono-glucosides based on the length of their acyl side chains. Compound 1 yielded 63.0 %, compound 2 yielded 26.9 %, and compound 3 yielded 4.37 %. The production yield of the gingerol glucosides optimally increased in 50 mM phosphate buffer (pH 6) with 50 % (w/v) maltose and 1000 mM Li+ at 40 °C for an 24-h incubation. The structures of purified compound 1 and compound 2 were determined as 6-gingerol-5- O - α -glucoside (1) and novel 8-gingerol-5- O - α -glucoside (2), respectively, using nucleic magnetic resonance and mass spectral analyses. The aqueous solubility of the gingerol glucosides was greatly improved. Further assays showed that, unusually, 6-gingerol-5- O - α -glucoside had 10-fold higher anti-inflammatory activity (IC 50 value of 15.3 ± 0.5 μM) than 6-gingerol, while the novel 8-gingerol-5- O - α -glucoside retained 42.7 % activity (IC 50 value of 106 ± 4 μM) compared with 8-gingerol. The new α -glucosidase (Ar G) was confirmed to have acidic α -glycosyltransferase activity and could be applied in the production of α -glycosyl derivatives. The 6-gingerol-5- O - α -glucoside can be applied as a clinical drug for anti-inflammatory activity. [Display omitted] [ABSTRACT FROM AUTHOR]

(1) Background: Salix species occurring in Finland have not been well studied for their antimicrobial potential, despite their frequent use for lung and stomach problems in traditional medicine. Thus, twig extracts of three species of Salix that are found naturally in Finland and one cultivated species were screened for their antimicrobial properties against human pathogenic bacteria. S. starkeana and S. x pendulina were screened for antibacterial effects for the first time. (2) Methods: An agar diffusion and a microplate method were used for the screenings. Time-kill effects were measured using a plate-count and a microplate method. A DPPH-method using a qualitative TLC-analysis was used to detect antioxidant compounds in antimicrobial extracts. Metabolites from a S. myrsinifolia extract showing good antibacterial effects were identified using UPLC/QTOF-MS. (3) Results: A methanol extract of S. starkeana was particularly active against B. cereus (MIC 625 µg/mL), and a methanol extract of S. myrsinifolia showed good activity against S. aureus and B. cereus (MIC 1250 µg/mL) and showed bactericidal effects during a 24 h incubation of B. cereus. Moreover, a decoction of S. myrsinifolia resulted in good growth inhibition against P. aeruginosa. Our UPLC/QTOF-MS results indicated that proanthocyanidins (PAs), and especially the dimer procyanidin B1 (m/z 577) and other procyanidin derivatives, including highly polymerized proanthocyanidins, were abundant in S. myrsinifolia methanol extracts. Procyanidin B1 and its monomer catechin, as well as taxifolin and p-hydroxycinnamic acid, all present in S. myrsinifolia twigs, effectively inhibited B. cereus (MIC 250 µg/mL). (4) Conclusions: This study indicates that Finnish Salix species contain an abundance of antibacterial condensed tannins, phenolic acids and other polyphenols that deserve further research for the antibacterial mechanisms of action. [ABSTRACT FROM AUTHOR]

Rinse-off cosmetic products, primarily shampoos, are frequently implicated in the onset of allergic contact dermatitis (ACD) caused by alkyl glucosides (AGs). AGs are increasingly popular surfactants and known contact allergens. Glucoside-induced ACD was most frequently observed with shampoos and skin-cleansing products in both consumer and occupational settings. Thereby, studies have shown that atopic individuals are the most susceptible to ACD. Also, several investigations have indicated that individuals with sensitive skin might be more prone to skin allergies. This is why the presence of AGs was investigated in shampoos and body cleansers marketed as hypoallergenic or for sensitive skin. For this purpose, the website of Amazon.com was surveyed. Four groups of cosmetics were obtained by using the following keywords: "hypoallergenic shampoo for adults," "sensitive skin shampoo for adults," "hypoallergenic body cleanser for adults," and "sensitive skin body cleanser for adults." The first 30 best-selling cosmetics in each group were investigated for the presence of AGs, by analyzing the product information pages. The results showed that as much as 56.7% of hypoallergenic shampoos contained AGs, as ingredients, whereas the percentage was somewhat lower for other product categories. Even though decyl and lauryl glucoside were nearly ubiquitously used AGs in cosmetics over the past decade, the most commonly present AG in our analysis was coco-glucoside. The results of this study indicated a necessity to include coco-glucoside in the baseline series of patch testing allergens. Industry, regulators, and healthcare providers should be made aware of the frequent presence of AGs in rinse-off cosmetic products marketed as hypoallergenic or for sensitive skin to ensure the safety and well-being of consumers and patients. [ABSTRACT FROM AUTHOR]

Background: The total glucoside of paeony (TGP) is recognized for its immunomodulatory properties and anti‐inflammatory effects. This study evaluates the efficacy of TGP combined with oral mini‐pulse therapy (OMP) and narrow‐band ultraviolet B (NB‐UVB) in treating active nonsegmental vitiligo (NSV). Materials and methods: The combination therapy was contrasted against those from a group treated solely with OMP and NB‐UVB. Data from 62 patients undergoing TGP combination treatment and 55 without were analyzed over a 3‐month period. After 6 months, the differences in recurrence rate were investigated by follow‐up. Results: The findings indicate that integrating TGP may yield superior outcomes compared to OMP + NB‐UVB alone. Moreover, the patient's oxidative stress makers were significantly reduced after the treatment. The majority of patients in the TGP cohort exhibited enhanced skin pigmentation over the duration. Notably, no increase in side effects or recurrence was observed in this group. Especially, patients with vitiligo on their head and neck experienced pronounced improvements. Conclusion: The efficacy of the combination treatment group was better than that of the control group at 2 and 3 months, and there was no difference in recurrence rate and side effects, suggesting that TGP may continue to show efficacy in NSV for a longer period of time by reducing the level of oxidative stress, and is especially suitable for patients with head and neck lesions. [ABSTRACT FROM AUTHOR]

Background: Recurrent aphthous ulcer (RAU) had high prevalence and lacked widely recognized treatment. Total glucosides of paeony (TGP) was used in the treatment of RAU in recent years. This study was to summarize the efficacy and safety of TGP in the treatment of RAU. Methods: We searched eight commonly used databases for relevant studies that published before 1 November 2023. Primary outcome was visual analogue scale (VAS). Secondary outcomes included overall response rate, significant response rate, ulcer healing time, interval, number of ulcers, and serum inflammatory factors. We conducted the meta-analysis, assessed risk of bias and the confidence of the evidence, by using Stata 15.0, Review Manager 5.4, and Gradepro. Results: Nine randomized controlled trials (RCTs) encompassing 883 patients with RAU were included in the final analysis. The VAS in the TGP group was lower than that in the control group (MD = -1.18, 95% CI = -1.58 to -0.78, p < 0.001, moderate-certainty evidence), subgroup analysis suggested longer (>8 weeks) medication and observation led to a more significant reduction in pain (p = 0.02). Moreover, TGP had higher overall response rate (RR = 1.18, 95% CI = 1.04 to 1.33, p = 0.008, very low-certainty evidence) and significant response rate (RR = 1.72, 95% CI = 1.38 to 2.14, p < 0.001, very low-certainty evidence), accelerated ulcer healing (MD = -1.79, 95% CI = -2.67 to -0.91, p < 0.001, low-certainty evidence), and extended intervals (MD = 23.60, 95% CI = 14.17 to 33.03, p < 0.001, very lowcertainty evidence). The efficacy of TGP in reducing the number of ulcers showed no significant difference compared to the control group (MD = -1.66, 95% CI = -3.60 to 0.28, p = 0.09, low-certainty evidence). Moreover, TGP treatment was associated with a higher incidence of abdominal symptoms (RR = 3.27, 95% CI = 1.62 to 6.60, p < 0.001). Conclusion: TGP appears to hold promise as a widely-used clinical therapeutic option for treating RAU. Nevertheless, further rigorous studies of high quality are required to validate its effectiveness. [ABSTRACT FROM AUTHOR]

Enzymatic malonylation of natural glycosides provides a promising alternative method for drug-like malonylated glycosides supply. However, the catalytic potential and structural basis of plant malonyltransferase are far from being fully elucidated. This work identified a new malonyltransferase CtMaT1 from Cistanche tubulosa. It displayed unprecedented mono- and/or di-malonylation activity toward diverse glucosides with different aglycons. A "one-pot" system by CtMaT1 and a malonyl-CoA synthetase was established to biosynthesize nine new malonylated glucosides. Structural investigations revealed that CtMaT1 possesses an adequately spacious acyl-acceptor pocket capable of accommodating diverse glucosides. Additionally, it recognizes malonyl-CoA through strong electrotactic and hydrogen interactions. QM/MM calculation revealed the H167-mediated S N 2 reaction mechanism of CtMaT1, while dynamic simulations detected the formation of stable hydrogen bonds between the glucose-6-OH group and H167, resulting in its high malonylation regiospecificity. Calculated energy profiles of two isomeric glycosides highlighted lower reaction energy barriers towards glucoside substrates, emphasizing CtMaT1's preference for glucosides. Furthermore, a mutant CtMaT1 H36A with notably increased di-malonylation activity was obtained. The underlying molecular mechanism was illuminated through MM/GBSA binding free energy calculation. This study significantly advances the understanding of plant acyltransferases from both functional and protein structural perspectives, while also providing a versatile tool for enzymatic malonylation applications in pharmacology. CtMaT1, a plant malonyltransferase with both unprecedented substrate promiscuity and malonylation regiospecificity, was functionally and structurally identified, and employed in universal enzymatic synthesis of diverse malonylated glycosides with potential druggabilities. [Display omitted] [ABSTRACT FROM AUTHOR]

Two new sesquiterpene glucosides, 1α,6β,9β-trihydroxy-eudesm-4(15)-en-1,6-O-β-diglucopyranoside (1) and 1α,6β,9β-trihydroxy-eudesm-3-en-1,6-O-β-diglucopyranoside (2) were obtained along with the 1α,6β,9β-trihydroxy-5,10-bis-epi-eudesm-3-en-6-O-β-D-glucopyranoside (3), chlorogenic acid (4), luteolin 7-O-rutinoside (5) and luteolin 7-O- glucoside (6) from the whole plant parts of Lecokia cretica. Their structures were determined on the basis of 1 D, 2 D NMR and HRMS analyses. The in vitro cytotoxic activity of compounds 1-3 against human lung cancer cells (A549) and normal human lung cells (BEAS-2B) was determined using the MTT colorimetric assay. All the tested eudesmane derivatives were found to be inactive. [ABSTRACT FROM AUTHOR]

Astaxanthin, a versatile C40 carotenoid prized for its applications in food, cosmetics, and health, is a bright red pigment with powerful antioxidant properties. To enhance astaxanthin production in Corynebacterium glutamicum, we employed rational pathway engineering strategies, focused on improving precursor availability and optimizing terminal oxy-functionalized C40 carotenoid biosynthesis. Our efforts resulted in an increased astaxanthin precursor supply with 1.5-fold higher β-carotene production with strain BETA6 (18 mg g−1 CDW). Further advancements in astaxanthin production were made by fine-tuning the expression of the β-carotene hydroxylase gene crtZ and β-carotene ketolase gene crtW, yielding a nearly fivefold increase in astaxanthin (strain ASTA**), with astaxanthin constituting 72% of total carotenoids. ASTA** was successfully transferred to a 2 L fed-batch fermentation with an enhanced titer of 103 mg L−1 astaxanthin with a volumetric productivity of 1.5 mg L−1 h−1. Based on this strain a pathway expansion was achieved towards glycosylated C40 carotenoids under heterologous expression of the glycosyltransferase gene crtX. To the best of our knowledge, this is the first time astaxanthin-β-d-diglucoside was produced with C. glutamicum achieving high titers of microbial C40 glucosides of 39 mg L−1. This study showcases the potential of pathway engineering to unlock novel C40 carotenoid variants for diverse industrial applications. [ABSTRACT FROM AUTHOR]

Tumors have a huge impact on human life and are now the main cause of disease-related deaths. The main means of treatment are surgery and radiotherapy, but they are more damaging to the organism and have a poor postoperative prognosis. Therefore, we urgently need safe and effective drugs to treat tumors. In recent years, Chinese herbal medicines have been widely used in tumor therapy as complementary and alternative therapies. Medicinal and edible herbs are popular and have become a hot topic of research, which not only have excellent pharmacological effects and activities, but also have almost no side effects. Therefore, as a typical medicine and food homology, some components of Paeoniae Radix Alba (PRA, called Baishao in China) have been shown to have good efficacy and safety against cancer. Numerous studies have also shown that Paeoniae Radix Alba and its active ingredients treat cancer through various pathways and are also one of the important components of many antitumor herbal compound formulas. In this paper, we reviewed the literature on the intervention of Paeoniae Radix Alba in tumors and its mechanism of action in recent years and found that there is a large amount of literature on its effect on total glucosides of paeony (TGP) and paeoniflorin (PF), as well as an in-depth discussion of the mechanism of action of Paeoniae Radix Alba and its main constituents, with a view to promote the clinical development and application of Paeoniae Radix Alba in the field of antitumor management. [ABSTRACT FROM AUTHOR]

Trichothecenes produced by Fusarium species are commonly detected in oats. However, the ratios of the concentrations of free trichothecenes and their conjugates and how they are impacted by different interacting environmental conditions are not well documented. This study aims to examine the effect of water activity (0.95 and 0.98 aw) and temperature (20 and 25 °C) stress on the production of T-2 and HT-2 toxins, deoxynivalenol and their conjugates, as well as diacetoxyscirpenol (DAS). Multiple mycotoxins were detected using liquid chromatography–tandem mass spectrometry from 64 contaminated oat samples. The highest concentrations of HT-2-glucoside (HT-2-Glc) were observed at 0.98 aw and 20 °C, and were higher than other type A trichothecenes in the natural oats' treatments. However, no statistical differences were found between the mean concentrations of HT-2-Glc and HT-2 toxins in all storage conditions analysed. DAS concentrations were generally low and highest at 0.95 aw and 20 °C, while deoxynivalenol-3-glucoside levels were highest at 0.98 aw and 20 °C in the naturally contaminated oats. Emerging mycotoxins such as beauvericin, moniliformin, and enniatins mostly increased with a rise in water activity and temperature in the naturally contaminated oats treatment. This study reinforces the importance of storage aw and temperature conditions in the high risk of free and modified toxin contamination of small cereal grains. [ABSTRACT FROM AUTHOR]

As a part of our systematic study on Castanopsis genus (Fagaceae), one new triterpene hydrolysable tannin (1) and two new phenol glucosides (2 and 3) were isolated from the leaves of Castanopsis eyrei (Champ. ex Benth.) Hutch. Compound 1 was identified as a triterpene hexahydroxydiphenoyl (HHDP) ester. This type of compounds has only been isolated from Castanopsis genus. The structures of 1-3 were elucidated by the combination of spectroscopic analysis (MS, 1 D and 2 D NMR) and chemical evidence. [ABSTRACT FROM AUTHOR]

The isoflavone aglycone (IA) contents of commercial fermented soybean products in Korea, such as cheonggukjang and doenjang, and the IA-producing ability of the Bacillus subtilis strains isolated from the products were examined. Among three commercial products, product C (doenjang), which is produced using a long fermentation method, showed the highest conversion rate of isoflavone glucosides to aglycones. Of all eight B. subtilis strains isolated from the products, four strains had the same or higher level of IA production than B. subtilis (natto), with the C-3 strain showing the highest level. Hence, the difference in the conversion rate among the products might be attributed not only to fermentation time during the manufacturing process, but also the IA-producing ability of the B. subtilis strains. Moreover, the C-3 strain produced IA during the early stage of culture with soybean liquid medium, and the IA-producing ability of the C-3 strain in the fermentation with soybean solid medium was higher than that of B. subtilis (natto). Thus, the rapid IA production by the B. subtilis C-3 strain might contribute to the high IA content of product C. [ABSTRACT FROM AUTHOR]

The aim of the present research was the development and validation of a selective and reliable method for the indirect and direct determination of acidic herbicide glucosides. Enzymatic deconjugation was investigated as a mild alternative to harsh alkaline hydrolysis. Various enzymatic options for deconjugation were exploited. One out of nine tested specific enzymes proved to be practical and repeatable for different matrices and concentration ranges, leading to the complete deconjugation of the glucosides. The method was validated according to the SANTE/11312/2021 guideline for cereals and oilseeds and for a rice-based infant formula. Additionally, for four acidic herbicide glucosides available on the market, a quantitative method for direct determination of the intact glucosides was optimized and validated. In both methods, the average recoveries were within 70–120%. The limits of quantification (LOQ) achieved were 10 µg kg−1 and 2.5 µg kg−1 for the intact glucosides and the free acids in cereal and oilseeds. For the rice-based infant formula, the LOQ was 1 µg kg−1 (3 µg kg−1 for dichlorprop). To confirm its applicability, the deconjugation approach was tested for fifteen samples (cereals, oilseeds, and citrus) with incurred residues. Comparisons were made between the method without deconjugation, and two methods with deconjugation, the here proposed enzymatic deconjugation and the more commonly used alkaline hydrolysis. The inclusion of enzymatic deconjugation during sample preparation led to an increase up to 2.7-fold compared to analysis without deconjugation. Enzymatic deconjugation resulted in comparable results to alkaline hydrolysis for 13 out of 15 samples. [ABSTRACT FROM AUTHOR]

The current body of research on the health implications of isoflavone phytoestrogens still presents unsolved matters pertaining to absorption, metabolism, and bioavailability. To conduct research in this particular domain, it is important to possess the means to obtain samples of both isoflavone 7-O-glucosides, which are naturally occurring in plants, and 7-O-glucuronides, which are major metabolites present in mammals. To comprehensively examine the potential health advantages, it is important to precisely measure the concentrations of phytoestrogens present in various food sources and bodily fluids. The use of C-labeled isoflavones was critical to the development of a methodology that allows for precise measurement. 2,3,4-13C-Labeled isoflavone 7-O-glucosides, namely 2,3,4-13C-labeled daidzin, genestin and glycitin, were efficiently prepared via BF3·Et2O catalyzed glycosylation at the 7-O-position of 13C-labeled 4′-O-hexanoyldaidzein, 4′-O-hexanoylglycitein and 5,4′-O-dihexannoylgenestein with 2,2,2-trifluoro-N-(p-methoxyphenyl)acetamidates as glycosyl donors. It was found that protecting all of the OH groups in the isoflavones with hexanoyl groups, with the exception of the 7-OH group, resulted in an increase in both their solubility in organic solvents and the reaction efficiency. [ABSTRACT FROM AUTHOR]

A new isocoumarin glucoside, 3S-6-methoxy-8-hydroxy 3-(4-hydroxyphenylethyl)-3,4-dihydroisocoumarin- 8-O-β-D-glucopyranoside (1), along with seven known compounds (2–8) were isolated from the aerial parts of Aruncus sylvester, and their structures were elucidated based on IR, HR-ESI-MS, 1D and 2D NMR spectroscopic data, and XSA. This is the first report of compounds 5–8 from Aruncus sylvester. [ABSTRACT FROM AUTHOR]

Cassava (Manihot esculenta) is a long tuberous starch-containing root crop that stands as a significant staple food globally. Its adaptability to various climates has increased its commercial growth. However, challenges such as toxic cyanogenic glucosides and rapid perishability in cassava demand its processing for safety and extended shelf-life. In Sri Lanka, where cassava is widely consumed, surplus production can be a highly prospective revenue. This review summarizes the utilization of cassava flour as a potential alternative for wheat flour emphasizing the Sri Lankan scenario. The cassava flour production process involves cleaning, peeling, slicing, drying, grinding, and sieving. Nutritional composition varies among cultivars, with variations in starch, amylase, fiber, protein, and ash. The cyanogenic levels also depend on the cultivars. Cassava flour emerges as a promising wheat flour substitute due to its abundance, effortless cultivation practices, nutritional profile, and unique functional properties. Furthermore, cassava flour is gluten-free and considered as the most comparable gluten-free substitute to wheat flour in terms of texture and taste. The incorporation of cassava flour into bakery products shows an opportunity to reduce the massive dependence on costly wheat flour imports in developing countries, which improves the country’s revenues. This review focuses on diverse food applications of cassava flour, including cookies, crackers, biscuits, and commercial products, highlighting cassava flour's market potential in Sri Lanka amidst the increasing demand for gluten-free products. [ABSTRACT FROM AUTHOR]

Glycosylated volatiles are considered as hidden aroma precursors that affect fruit flavor and are involved in plant defense response. Several uridine-diphosphate (UDP)-glycosyltransferase (UGT) members related to the glycosylation of volatiles have been identified from grapevine berries. Although grapevine leaves produced much higher levels of glycosylated volatiles than berries, UGTs responsible for the production of glycosylated volatiles in leaves have not yet been identified. Here, eight novel UGT genes were cloned, among these four members that belong to UGT85A family (named UGT85A24, UGT85A25, UGT85A26, and UGT85A27) were localized in the cytoplasm and their recombinant proteins showed activity toward volatiles detected in grapevine, with geraniol as the preferred substrate in vitro. Two UGT genes with 98.1% homology differ in R/S-linalool selection. The UGT85A26-catalyzed substrate showed enrichment in S-linalool, whereas UGT85A27 showed a strong preference for R-linalool. UGT85A24 and UGT85A25 were expressed mainly in berries, and UGT85A26 and UGT85A27 were expressed predominantly in grapevine mature leaves and correlated with the highest content of glycosylated volatiles in the mature leaves. Methyl jasmonate (MeJA) induced the expression of UGT85A26 and UGT85A27 as well as the production of linalyl-b-glucoside, citronellyl-b-glucoside and phenethyl-b-glucoside. Transient overexpression of UGT85A26 and UGT85A27 in tobacco leaves led to the accumulation of linalyl-b-glucoside and an increase in citronellyl-b-glucoside in vivo. These results indicate that the expression of UGT85A26 and UGT85A27 is a major regulator affecting the content of glycosylated volatiles in grapevine. [ABSTRACT FROM AUTHOR]

Rudbeckia hirta L. (Compositae: Heliantheae: Rudbeckinae) is described and illustrated. Material in Wakehurst's North American Prairie planting would key out to the widespread Rudbeckia hirta L. var. pulcherrima Farw., in that it is a perennial, leafy in the upper half of the stem and with narrow-lanceolate leaves. The issue of the rank of the currently recognized infraspecific taxa is highlighted and the cluttering of the synonymy with the recognition of minor, often horticultural variants discussed. A commonly cultivated species, this is one of several late-season flowerers in the American Prairie at RBG, Kew atWakehurst Place. Cultivars are commonly cultivated, offering a considerable colour variation in the ray limbs, but it appears that the true species is relatively uncommon, possibly having come in and gone out of fashion since it was first brought into cultivation. Statements of the species' distribution, habitat and ecological preferences, phenology, conservation status, and the etymology of both generic and specific epithets are given, along with an impressive array of vernacular names, reflecting its wide distribution and long cultivation. Comments are provided on the nectar, or honey, guides seen (under UV light) in Rudbeckia hirta. The guides are due to the presence of flavonol glucosides, these present only in the upper surface of the ray limbs. Historical uses of the species are noted, and phytochemical analyses have provided evidence that the antiinflammatory properties have a factual basis. [ABSTRACT FROM AUTHOR]

Marrubium species have been used since ancient times as food additives and curative treatments. Their phytochemical composition and various pharmacological activities were the focus of a number of scientific investigations but no comprehensive metabolome profiling to identify the numerous primary and secondary metabolites has been performed so far. This study aimed to generate a comprehensive picture of the total metabolite content of two Marrubium species—M. peregrinum and M. friwaldskyanum—to provide detailed information about the main primary and secondary metabolites. In addition, the elemental composition was also evaluated. For this purpose, non-targeted metabolomic analyses were conducted using GC-MS, UPLC-MS/MS and ICP-MS approaches. Nearly 500 compounds and 12 elements were detected and described. The results showed a strong presence of phenolic acids, flavonoids and their glucosides, which are generally of great interest due to their various pharmacological activities. Furthermore, tissue-specific analyses for M. friwaldskyanum stem, leaves and flowers were carried out in order to outline the sources of potentially important bioactive molecules. The results generated from this study depict the Marrubium metabolome and reveal its dual scientific importance—from one side, providing information about the metabolites that is fundamental and vital for the survival of these species, and from the other side, defining the large diversity of secondary substances that are a potential source of phytotherapeutic agents. [ABSTRACT FROM AUTHOR]

Escherichia coli, a well-known prokaryotic organism, has been widely employed as a versatile host for heterologous overexpression of proteins/biocatalysts and the production of pharmaceutically important intermediates/small molecules. However, some E. coli endogenous enzymes showing substrate promiscuity may disturb the heterologous metabolic flux, which will result in the reduction of substrates, intermediates, and target products. Here we reported an unexpected E. coli-catalyzed regioselective O-acetylation of various glucosides. The regioselectively O-acetylated products, 6′-O-acetyl-loganin and 6′-O-acetyl-loganic acid, were obtained and characterized from the enzymatic reaction in which the supernatants of E. coli expressing either CaCYP72A565 and CaCPR, the key enzymes involved in camptothecin biosynthesis, or empty vector were used as catalyst and loganin and loganic acid as independent substrate. An alkaloidal glucoside strictosamide was converted into the regioselectively O-acetylated product 6′-O-acetyl-strictosamide, implying substrate promiscuity of the E. coli-catalyzed O-acetylation reaction. Furthermore, 8 glucosides, including 5 iridoid glucosides and 3 flavonoid glucosides, were successfully converted into the regioselectively O-acetylated products by E. coli, indicating the wide substrate range for the unexpected E. coli-catalyzed O-acetylation. E. coli maltose O-acetyltransferase was demonstrated to be responsible for the mentioned regioselective O-acetylation at the 6-OH of the glucopyranosyl group of multiple classes of natural product glucosides through candidate acetyltransferase-encoding gene analysis, gene knock-out, gene complementation, and the relevant enzymatic reaction activity assays. The present study not only provides an efficient biocatalyst for regioselective O-acetylation but also notifies cautions for metabolic engineering and synthetic biology applications in E. coli. Key points: • 6-OH of glucosyl of multiple glucosides was regioselectively O-acetylated by E. coli. • Endogenous EcMAT is responsible for the regioselective O-acetylation reaction. [ABSTRACT FROM AUTHOR]

Objective of this study was to investigate the effects of GIG on bile acid enterohepatic circulation and explore the underlying mechanism in cholestatic rats.Methods: In order to identify key pathways associated with cholestasis, we conducted Gene Ontology (GO) Enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. In vivo experiments were then performed on alpha-naphthylisothiocyanate (ANIT)-treated rats to assess the impact of GIG. We measured bile flow and various biomarkers including total bilirubin (TB), total bile acids (TBA), total cholesterol (TC), malondialdehyde (MDA), glutamic-pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), and total superoxide dismutase (T-SOD) in the serum. We also examined the expression levels of bile salt export pump (BSEP), ATP-binding cassette subfamily B member 4 (ABCB4), far-nesoid X receptor (FXR), small heterodimer partner (SHP), cholesterol 7α-hydroxylase (CYP7A1), and sodium taurocholate cotransporting polypeptide (NTCP) in liver tissue. In vitro experiments were conducted on primary hepatocytes to further investigate the mechanism of action of GIG on the expression of SHP, CYP7A1, NTCP, and FXR.Results: Our in vivo experiments demonstrated that GIG significantly increased bile flow and reduced the levels of TB, TBA, TC, MDA, GPT, and GOT, while increasing T-SOD levels in ANIT-treated rats. Addi-tionally, GIG ameliorated liver tissue damage induced by ANIT, upregulated the expression of BSEP and ABCB4, and modulated the protein expression of FXR, SHP, CYP7A1, and NTCP in model rats. In vitro experiments further revealed that GIG inhibited the expression of SHP, CYP7A1, and NTCP by suppressing the expression of FXR.Conclusion: This study provides new insights into the therapeutic potential of GIG for the treatment of cholestasis. GIG demonstrated beneficial effects on bile acid enterohepatic circulation and liver biomarkers in cholestatic rats. The modulation of FXR and its downstream targets may contribute to the mechanism of action of GIG. These findings highlight the potential of GIG as a therapeutic intervention for cholangitis. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and joint damage with complex pathological mechanisms. In recent years, many studies have shown that the dysregulation of intestinal mucosal immunity and the damage of the epithelial barrier are closely related to the occurrence of RA. Total glucosides of paeony (TGP) have been used clinically for the treatment of RA in China for decades, while the pharmacological mechanism is still uncertain. The purpose of this study was to investigate the regulatory effect and mechanism of TGP on intestinal immunity and epithelial barrier in RA model rats. The results showed that TGP alleviated immune hyperfunction by regulating the ratio of CD3+, CD4+ and CD8+ in different lymphocyte synthesis sites of the small intestine, including Peyer's patches (PPs), intraepithelial lymphocytes (IELs), and lamina propria lymphocytes (LPLs). Specially, TGP first exhibited immunomodulatory effects on sites close to the intestinal lumen (IELs and LPLs), and then on PPs far away from the intestinal lumen as the administration time prolonged. Meanwhile, TGP restores the intestinal epithelial barrier by upregulating the ratio of villi height (V)/crypt depth (C) and expression of tight junction proteins (ZO-1, occludin). Finally, the integrated analysis of metabolomics-network pharmacology was also used to explore the possible regulation mechanism of TGP on the intestinal tract. Metabolomics analysis revealed that TGP reversed the intestinal metabolic profile disturbance in CIA rats, and identified 32 biomarkers and 163 corresponding targets; network pharmacology analysis identified 111 potential targets for TGP to treat RA. By intersecting the results of the two, three key targets such as ADA, PNP and TYR were determined. Pharmacological verification experiments showed that the levels of ADA and PNP in the small intestine of CIA rats were significantly increased, while TGP significantly decreased their ADA and PNP levels. In conclusion, purine metabolism may play an important role in the process of TGP improving RA-induced intestinal immune imbalance and impaired epithelial barrier. [ABSTRACT FROM AUTHOR]

The aim of the study is to investigate the differences in the interaction of three structurally diverse anthocyanidins, namely peonidin, petunidin, and delphinidin, as well as their glucosides with model biological membranes, human albumin, and plasmid DNA in order to look into their structure–activity relationships. Fluorimetric studies, as well as ATR-FTIR analyses, were jointly used in order to determine the changes observed in both the hydrophilic and hydrophobic layers of cell-mimic membranes (MM) which reflected the membrane lipid composition of tumour cells and red blood cell membranes (RBCM). Our results showed that anthocyanins and anthocyanidins can cause an increase in the packing order of the polar heads of lipids, as well as interact with their deeper layers by reducing the fluidity of lipid chains. The results presented here indicate that all compounds tested here possessed the ability to bind to human serum albumin (HSA) and the presence of a glucose molecule within the structures formed by anthocyanidin reduces their ability to bind to proteins. Using fluorescence correlation spectroscopy, it was demonstrated that the compounds tested here were capable of forming stable complexes with plasmid DNA and, particularly, strong DNA conformational changes were observed in the presence of petunidin and corresponding glucoside, as well as delphinidin. The results we obtained can be useful in comprehending the anthocyanins therapeutic action as molecular antioxidants and provide a valuable insight into their mechanism of action. [ABSTRACT FROM AUTHOR]

Two new dihydrochalcone glucosides, phloretin-4′-O-(4′′-O-galloyl)-β-D-glucoside (1) and phloretin-4′-O-(3′′-O-galloyl)-β-D-glucoside (2), were isolated from the fresh aerial part of Balanophora subcupularis P.C.Tam, together with eight known flavonoid glycosides, phloretin-4′-O-(6′′-O-galloyl)-β-D-glucoside (3), trilobatin (4), 3-hydroxyphloretin-4′-O-β-D-glucoside (5), phloretin-4′-O-(4′′,6′′-O-Sa-hexahydroxydiphenoyl)-β-D-glucoside (6), naringenin-7-O-β-D-glucoside (7), eriodictyol-7-O-β-D-glucoside (8), kaempferol-7-O-β-D-glucoside (9), and quercetin-7-O-β-D-glucoside (10). All of the compounds were elucidated by spectroscopic methods. Their antioxidant activities were examined by DPPH and ABTS assay. Compounds 1–3, 5, 6, and 10 showed significant radical scavenging activities compared with ascorbic acid. [ABSTRACT FROM AUTHOR]

Three new glucosides, ziberthinosides A–C (1–3), and six known compounds, cleomiscosins A–D (4–7), sporogen AO-2 (8) and sapinofuranone A (9), were isolated from a methanol extract of Durio zibethinus fruit peels. Their chemical structures were elucidated by analyses of their 1 D/2D NMR and HR-ESI-MS data as well as by comparison with the literature values. The absolute configuration of sporogen AO-2 (8) was confirmed by ECD calculation. Of the isolates, compounds 8 and 9 were cytotoxic toward all MCF7, HepG2 and SK-LU-1 cell lines, with IC50 values ranging from 10.7 to 34.9 μM. Our results contribute to better understanding of the chemical constituents of the high valued durian fruit and their pharmacological effect, such as cytotoxicity. [ABSTRACT FROM AUTHOR]

Individuals with type 1 diabetes have an impaired glucagon counterregulatory response to hypoglycemia. Sodium-glucose cotransporter (SGLT) inhibitors increase glucagon concentrations. We evaluated whether SGLT inhibition restores the glucagon counterregulatory hormone response to hypoglycemia. Adults with type 1 diabetes (n = 22) were treated with the SGLT2 inhibitor dapagliflozin (5 mg daily) or placebo for 4 weeks in a randomized, double-blind, crossover study. After each treatment phase, participants underwent a hyperinsulinemic-hypoglycemic clamp. Basal glucagon concentrations were 32% higher following dapagliflozin versus placebo, with a median within-participant difference of 2.75 pg/mL (95% CI 1.38-12.6). However, increased basal glucagon levels did not correlate with decreased rates of hypoglycemia and thus do not appear to be protective in avoiding hypoglycemia. During hypoglycemic clamp, SGLT2 inhibition did not change counterregulatory hormone concentrations, time to recovery from hypoglycemia, hypoglycemia symptoms, or cognitive function. Thus, despite raising basal glucagon concentrations, SGLT inhibitor treatment did not restore the impaired glucagon response to hypoglycemia. We propose that clinical reduction in hypoglycemia associated with these agents is a result of changes in diabetes care (e.g., lower insulin doses or improved glycemic variability) as opposed to a direct, physiologic effect of these medications on α-cell function.

Ischemia/reperfusion (I/R) injury of the lung can lead to extensive pulmonary damage. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are insulin-independent, oral antihyperglycemic agents used for treating type 2 diabetes mellitus (T2DM). Although their cardioprotective properties have been reported, their potential roles in pulmonary protection in vivo are poorly characterized. Here, we tested a hypothesis that empagliflozin, an SGLT2 inhibitor, can protect lungs in a mouse model of lung I/R injury induced by pulmonary hilum ligation in vivo. We assigned C57/BL6 mice to sham-operated, nonempagliflozin-treated control, or empagliflozin-treated groups. Pulmonary I/R injury was induced by 1-hour left hilum ligation followed by 2-hour reperfusion. Using quantitative polymerase chain reaction (q-PCR) and Western blot analysis, we demonstrate that SGLT2 is highly expressed in mouse kidney but is weakly expressed in mouse lung (n = 5-6 per group, P < 0.01 or P < 0.001). Empagliflozin improved respiratory function, attenuated I/R-induced lung edema, lessened structural damage, inhibited apoptosis, and reduced inflammatory cytokine production and protein concentration in bronchoalveolar lavage (BAL) fluid [P < 0.05 or P < 0.001 versus control group (CON)]. In addition, empagliflozin enhanced phosphorylation of pulmonary extracellular signal-regulated kinases 1 and 2 (ERK1/2) post-I/R injury in vivo (P < 0.001, versus CON, n = 5 per group). We further showed that pharmacological inhibition of ERK1/2 activity reversed these beneficial effects of empagliflozin. In conclusion, we showed that empagliflozin exerts strong lung protective effects against pulmonary I/R injury in vivo, at least in part via the ERK1/2-mediated signaling pathway. SIGNIFICANCE STATEMENT: Pulmonary ischemia-reperfusion (I/R) can exacerbate lung injury. Empagliflozin is a new antidiabetic agent for type 2 diabetes mellitus. This study shows that empagliflozin attenuates lung damage after pulmonary I/R injury in vivo. This protective phenomenon was mediated at least in part via the extracellular signal-regulated kinases 1 and 2-mediated signaling pathway. This opens a new avenue of research for sodium-glucose cotransporter-2 inhibitors in the treatment of reperfusion-induced acute pulmonary injury.

The cryptic β-glucoside GFB (bglGFB) operon in Escherichia coli (E. coli) can be activated by mutations arising under starvation conditions in the presence of an aromatic β-glucoside. This may involve the insertion of an insertion sequence (IS) element into a "stress-induced DNA duplex destabilization" (SIDD) region upstream of the operon promoter, although other types of mutations can also activate the bgl operon. Here, we show that increased expression of the bglG gene, encoding a well-characterized transcriptional antiterminator, dramatically increases the frequency of both IS-mediated and IS-independent Bgl+ mutations occurring on salicin- and arbutin-containing agar plates. Both mutation rates increased with increasing levels of bglG expression but IS-mediated mutations were more prevalent at lower BglG levels. Mutations depended on the presence of both BglG and an aromatic β-glucoside, and bglG expression did not influence IS insertion in other IS-activated operons tested. The N-terminal mRNA-binding domain of BglG was essential for mutational activation, and alteration of BglG's binding site in the mRNA nearly abolished Bgl+ mutant appearances. Increased bglG expression promoted residual bgl operon expression in parallel with the increases in mutation rates. Possible mechanisms are proposed explaining how BglG enhances the frequencies of bgl operon activating mutations.

BackgroundEmpagliflozin is a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor used to lower blood sugar in adults with type 2 diabetes. Empagliflozin also exerts cardioprotective effects independent from glucose control, but its benefits on arrhythmogenesis and sudden cardiac death are not known. The purpose of this study was to examine the effect of empagliflozin on myocardial ischemia/reperfusion-provoked cardiac arrhythmia and sudden cardiac death in vivo.MethodsMale Sprague Dawley rats were randomly assigned to sham-operated, control or empagliflozin groups. All except for the sham-operated rats were subjected to 5-min left main coronary artery ligation followed by 20-min reperfusion. A standard limb lead II electrocardiogram was continuously measured throughout the experiment. Coronary artery reperfusion-induced ventricular arrhythmogenesis and empagliflozin therapy were evaluated. The hearts were used for protein phosphorylation analysis and immunohistological assessment.ResultsEmpagliflozin did not alter baseline cardiac normal conduction activity. However, empagliflozin eliminated myocardial vulnerability to sudden cardiac death (from 69.2% mortality rate in the control group to 0% in the empagliflozin group) and reduced the susceptibility to reperfusion-induced arrhythmias post I/R injury. Empagliflozin increased phosphorylation of cardiac ERK1/2 after reperfusion injury. Furthermore, inhibition of ERK1/2 using U0126 abolished the anti-arrhythmic action of empagliflozin and ERK1/2 phosphorylation.ConclusionsPretreatment with empagliflozin protects the heart from subsequent severe lethal ventricular arrhythmia induced by myocardial ischemia and reperfusion injury. These protective benefits may occur as a consequence of activation of the ERK1/2-dependent cell-survival signaling pathway in a glucose-independent manner.

This article discusses the importance of cassava as a staple crop, particularly in sub-Saharan Africa, and the issue of cyanogenic glucosides (CGs) accumulating in cassava roots, which can be toxic to humans if not properly processed. Researchers have successfully used gene editing to reduce CG levels in cassava, but there is evidence that this may lead to increased herbivory and potentially lower yields. The article also explores the transport of CGs in cassava, suggesting that they are synthesized in the roots rather than transported from the shoot apex. The findings have implications for improving the safety of cassava and understanding the movement of CGs within the plant. [Extracted from the article]

Objective: To explore the effect of total glucosides of paeony （TGP） on airway remodeling in mice with bronchial asthma and its underlying mechanism. Methods: Fifty mice were randomly divided into control group （Control group）, model group （OVA group）, TGP low-dose group （TGP-L, 460 mg/kg）, TGP high-dose group （TGP-H, 920 mg/kg）, TGP+ML385 group （TGP 920 mg/kg+ML385 30 mg/kg）, with 10 mice in each group. Two stages of ovalbumin（ OVA） sensitization and stimulation were used to establish mice model of asthma. One hour before each stimulation, the TGP groups were given a corresponding dose of TGP suspension by gavage, and TGP+ML385 group was given 30 mg/kg of ML385 and 920 mg/kg TGP by gavage, administered continuously for 8 weeks. Behavioral changes of mice in each group were observed during the experiment, bronchoalveolar lavage fluid （BALF） was collected 24 hours after the last challenge, levels of TGF-β1, cysteyl leukotriene 1（ CysLT1） and cysteyl leukotriene receptor 1（ CysLTR1） in BALF were detected by ELISA; total antioxidant capacity（ T-AOC）, superoxide dismutase（ SOD）, glutathione peroxidase（ GSH-Px） and catalase （CAT） activities in lung homogenate were detected; pathological changes of lung tissues were observed by HE and AB-PAS staining; expressions of lung tissue TGF-β1, matrix metalloproteinase 9 （MMP-9） and tissue inhibitor of metalloproteinase 1 （TIMP-1） mRNA were detected by RT-qPCR; expressions of TGF-β1/Nrf-2/HO-1 pathway related proteins in lung tissues were detected by Western blot. Results: Compared with control group, mice in OVA group showed typical asthma symptoms, such as sneezing, restlessness and wheezing, levels of TGF-β1, CysLT1, CysLTR1, lung inflammation and mucus secretion scores, expressions of TGF-β1 mRNA and protein, and MMP-9 mRNA in BALF were significantly increased （P<0.05）, T-AOC, SOD, GSH-Px, CAT activity and expression of TIMP-1 mRNA in lung tissues were significantly reduced （P<0.05）, expressions of Nrf-2 and HO-1 proteins in lung tissues were increased, while the difference was not statistically significant （P>0.05）; compared with OVA group, mice in TGP-L and TGP-H groups had significantly reduced asthma symptoms, levels of TGF-β1, CysLT1, CysLTR1, lung inflammation and mucus secretion scores, expressions of TGF-β1 mRNA and protein, and MMP-9 mRNA in BALF were significantly reduced （P<0.05）, T-AOC, SOD, GSH-Px, CAT activity and expressions of TIMP-1 mRNA, Nrf-2 and HO-1 proteins in lung tissues were significantly increased （P<0.05）; using Nrf2 inhibitor ML385 to block the activation of Nrf-2/HO-1 pathway could significantly attenuate the inhibitory effect of TGP on lung tissue oxidative stress and airway remodeling in asthmatic mice. Conclusion: TGP can regulate airway remodeling in mice with bronchial asthma induced by oxidative stress and inflammation, and its mechanism may be related to reducing the expression of TGF-β1 and activating the Nrf-2/HO-1 pathway. [ABSTRACT FROM AUTHOR]

A well-known herb Barleria lupulina is traditionally used as a medicinal and decorative plant. The various parts of this plant are reported to contain a range of phytoconstituents, including terpenes and terpenoidal compounds, iridoid glucosides, iridoid diglucosides, phenylpropanoid glucosides, and phenylethanoid glucosides. Antibacterial, antiarthritic, CNS depressive, antiosteoporotic, antioxidant, anti-diabetic, and anti-inflammatory effects are present in isolated components and extract of B. lupulina. This in-depth analysis covers the traditional uses, phytochemistry, pharmacological use, and mechanism of action of B. lupulina. [ABSTRACT FROM AUTHOR]

Continued improvement of yields of rice, a primary nutrient for much of humanity, in the future to feed a growing population will benefit from greater knowledge of the plant's function at the molecular level, including the roles of various enzymes and how their gene expression levels contribute to traits that can increase crop yields. One group of enzymes of interest are the β-glucosidases, which release single glucose residues from glucosides and oligosaccharides, due to their multiplicity and involvement in various functions. Known β-glucosidases fall in 4 sequence-similaritybased glycoside hydrolase (GH) families in plants, GH1, GH3, GH5 and GH116. Of these the GH1 family encodes the most known β-glucosidases and related enzymes, with 34-35 active genes in rice. These enzymes contribute to cell wall recycling, lignification, glycolipid recycling, release of phytohormones and their precursors, including response to biotic and abiotic stress, defense, and metabolic homeostasis, among other roles. In the past 20 years, numerous studies have teased out various aspects of rice β-glucosidase function using biochemical, cell biological and genetic approaches. Clear roles have been elucidated for certain isoenzymes, although most remain poorly understood. Efficient transglycosylation activities of certain enzymes affords production of novel glucoconjugates, including phytohormone glucosyl esters for identification of enzymes catalyzing related functions. Here, we provide an overview of what has been learned about rice β-glucosidase functions and what remains to be clearly understood. [ABSTRACT FROM AUTHOR]

Objective: To assess the effectiveness and safety of the total glucosides of paeony (TGP) combined with hydroxychloroquine (HCQ) on the treatment of primary Sjögren's syndrome (pSS) by conducting a meta‐analysis. Methods: Eight databases were searched for randomized controlled trials (RCTs) reporting the use of TGP combined with HCQ for pSS, which are before May 10, 2022. Meta‐analyses were performed on disappeared clinical symptoms (dry mouth and dry eyes), Schirmer's test, saliva flow test, erythrocyte sedimentation rate (ESR), index of immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), and adverse events (AEs). The Revman 5.4 software was used for this meta‐analysis. Results: Seven RCTs which included 632 participants were identified. The pooled results showed significant differences in clinical symptoms disappear (dry mouth and dry eyes) (p =.0004), IgM (p <.00001), IgA (p <.00001), salivary flow rate (p <.00001) and Schirmer's test (p =.02) in the comparison of TGP combined with HCQ and HCQ alone. For the IgG and ESR, both pooled and subgroup analyses showed that TGP + HCQ was superior to HCQ alone. For the safety analysis, no significant differences in AEs (p =.39) was revealed. The more frequently seen adverse reactions were diarrhea, vomit and there was no severe adverse events were reported in TGP + HCQ group. Conclusion: Therefore, TGP + HCQ can be considered to be a potentially valid and safe combination for the treatment of pSS in the clinic. [ABSTRACT FROM AUTHOR]

Thioxopyrimidines are an important class of compounds in the fields of biology and chemistry that play significant roles in drug discovery, nucleic acid chemistry, enzyme inhibition, and various other fields of science and technology. Their structural diversity and potential bioactivities make them valuable tools for researchers. This work presents a thorough synthesis and analysis and bio-functional assessment of a variety of isoxazole C-Nucleoside, and thioxopyrimidine derivative. The structural characterization of the synthesized compounds was achieved through spectral analyses, including IR, 1H NMR, and mass spectra and also deals with its antibacterial and antifungal activity. [ABSTRACT FROM AUTHOR]

Purslane (Portulaca oleracea L., Portulacaceae) is a widespread edible plant with significant ethnobotanical and ethnopharmacological importance. The plant is characteristic for the presence of a class of indoline amide glucoside alkaloids, called cyclo-dopa amides, or oleraceins. Additionally, a new, structurally similar to oleraceins, class of indole amides have been discovered recently, called oleraindoles. These compounds have been evaluated to possess antiinflammatory and anticholinesterase activities. Herein, utilizing UHPLC-Orbitrap-MS with MS² filtering by diagnostic ion filtering (DIF), and diagnostic difference filtering (DDF) using different data analysis tools, eight compounds with oleraindole structure were tentatively identified. [ABSTRACT FROM AUTHOR]

Aglaia foveolata Pannell (A. foveolata) is a type of plant that has many benefits, including the skin, leaves, roots, and seeds as medicinal ingredients. The potential of this plant is inseparable from the content of various bioactive compounds. This study aims to isolate, characterize the active compound from the stem bark of A. foveolata and test its activity as an antioxidant with the ABTS method, cytotoxic (MCF-7 cancer cells) with the MTT method, and antibacterial (bacterial strains ATCC and MDR) with the MIC. There are four isolated compounds obtained, namely (1) 17,24-epoxy-25-hydroxybaccharan-3-one, (2) β-stigmasterol glucoside, (3) Eichlerianic acid, and (4) 17,24-epoxy-25 -hydroxy-3- oxobaccharan-21-oic acid, which is a class of triterpenoid and steroid compounds. The best activity as an antioxidant was compound 3 (25.68 µg/mL); cytotoxic activity against MCF-7 cells namely compound 4 (94.59 µg/mL); antibacterial activity against ATCC strains: (1) P. aeruginosa namely compound 3 (29.4 µg/mL), (2) E. coli, (3) S. aureus, (4) B. subtilis for compounds 1, 2, and 4 have the same activity (62.5 µg/mL) while compound 3 was not active; MDR bacterial strains: (1) P. aeruginosa namely compound 4 (62.5 µg/mL), (2) E. coli namely compound 3 (62.5 µg/mL), (3) S. aureus namely compound 4 (62 .5 µg/mL), (4) B. subtilis namely compound 4 (62.5 µg/mL) and (5) K. pneumoniae namely compound 1 (125 µg/mL). [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the two Tabernaemontana species (Apocynaceae) T. peduncularis Wall. and T. divaricata (L.) R.Br. ex Roem. & Schult. indicated closely related biosynthetic pathways leading to lipophilic and hydrophilic alkaloids. In total, 18 specialized metabolites comprising indole-derived alkaloid aglycones, three oxindole-derived alkaloid glycosides, and two iridoid glucosides could be identified in the studied species. Among the alkaloids, the two Iboga-type alkaloids 3,7-coronaridine isoindolenine, coronaridine 3,4-iminium and a javaniside derivative bearing a glucuronic acid, named javanuronic acid, could be described by spectroscopic and spectrometric methods for the first time. A docking experiment using alpha-fold was performed to generate a protein model of the enzyme 7-deoxyloganetic acid glucosyl transferase. Performed bioassays exhibited a growth reduction of neonate Spodoptera littoralis larvae and reduced cell viability of HepG2 cells of the extracts containing Iboga alkaloids, whilst the javaniside derivatives containing hydrophilic fraction did not show any effects. These findings indicate a high flexibility in the formation of bioactive indole alkaloid aglycones by Tabernaemontana species and also evidence similar accumulation trends in both species as well as indicate that biosynthetic routes leading to oxindole alkaloids like javanisides are more widespread than reported. Furthermore, the incorporation of the three novel compounds into potential biosynthetic pathways is discussed. [ABSTRACT FROM AUTHOR]

Four previously undescribed terpenoid glucosides, including one sesquiterpenoid di-glucoside (1), two new iridoid glucosides (2, 3), and a new triterpenoid tri-glucoside (4), were isolated from a 70% ethanol extract of the root of Gentiana macrophylla (Gentianaceae), along with eight known terpenoids. Their structures were determined by spectroscopic techniques, including 1D, 2D NMR, and HRMS (ESI), as well as chemical methods. The absolute configuration of compound 1 was determined by quantum chemical calculation of its theoretical electronic circular dichroism (ECD) spectrum. The sugar moieties of all the new compounds were confirmed to be D-glucose by GC analysis after acid hydrolysis and acetylation. Anti-pulmonary inflammation activity of the iridoids were evaluated on a TNF-α induced inflammation model in A549 cells. Compound 2 could significantly alleviate the release of proinflammatory cytokines IL-1β and IL-8 and increase the expression of anti-inflammatory cytokine IL-10. [ABSTRACT FROM AUTHOR]

2-(2-Phenylethyl)chromones (PECs) are the main bioactive components of agarwood which showed diverse pharmaceutical activities. Glycosylation is a useful structural modification method to improve compounds' druggability. However, PEC glycosides were rarely reported in nature which largely limited their further medicinal investigations and applications. In this study, the enzymatic glycosylation of four naturally separated PECs 1 − 4 was achieved using a promiscuous glycosyltransferase UGT71BD1 identified from Cistanche tubulosa. It could accept UDP-Glucose, UDP- N -acetylglucosamine and UDP-xylose as sugar donors and conduct the corresponding O -glycosylation of 1 − 4 with high conversion efficiencies. Three O -glucosylated products 1a (5-hydroxy-2-(2-phenylethyl)chromone 8- O - β -D-glucopyranoside), 2a (8-chloro-2-(2-phenylethyl)chromone 6- O - β -D-glucopyranoside) and 3a (2-(2-phenylethyl)chromone 6- O - β -D-glucopyranoside) were prepared and structurally elucidated as novel PEC glucosides based on NMR spectroscopic analyses. Subsequent pharmaceutical evaluation found that 1a showed remarkably improved cytotoxicity against HL-60 cells, whose cell inhibition rate was 19 times higher than that of its aglycon 1. The IC 50 value of 1a was further determined to be 13.96 ± 1.10 μM, implying its potential as a promising antitumor-leading candidate. To improve the production of 1 , docking, simulation and site-directed mutagenesis were performed. The important role of P15 in the glucosylation of PECs was discovered. Besides, a mutant K288A with a two-fold increased yield for 1a production was also afforded. This research reported the enzymatic glycosylation of PECs for the first time, and also provide an eco-friendly pathway for the alternative production of PEC glycosides for leading compounds discovery. [Display omitted] • It is the first report of enzymatic glycosylation of 2-(2-phenylethyl)chromone (PECs). • UGT71BD1 can catalyze glycosylation of PECs using UDP-Glc/GlcNAc/Xyl as sugar donors. • Three novel PECs glucosides were prepared. 1a showed cytotoxicity against HL-60 cells. • Molecular docking, dynamic simulation and mutagenesis studies were carried out. • Pro15 is important for glycosylation. K288A showed increased production yield of 1a. [ABSTRACT FROM AUTHOR]

Objective: Although many painkillers can be used to relieve the symptoms of osteoarthritis (OA), these drugs do not address joint bone degeneration and muscle wasting, highlighting the need for alternative treatments. This study evaluated the ability of various plant extracts to inhibit joint destruction, focusing on the total glucosides of peony (TGP) obtained from the normal Chinese medication white peony. Methods: A rabbit OA model was established by anterior cruciate ligament resection (ACLT) and TGP treatment was initiated for 3 months. The morphologies of the skeletal muscle fibers, articular cartilage, and subchondral bone of the knee joint were histologically observed via X-ray and micro-computed tomography scan. Results: TGP significantly reduced the histopathological changes associated with skeletal muscle atrophy and inflammation, and alleviated cartilage degeneration. In addition, TGP treatment significantly improved the bone density and microstructure of subchondral bone in rabbit knee joints compared with the model group. Conclusion: The results suggested that TGP treatment may alleviate the progression of osteoarthritis and reduce the destruction of joint cartilage and bone in ACLT. [ABSTRACT FROM AUTHOR]

Introduction: There has been a lack of treatments available to lower the frequency of recurrent aphthous ulcers (RAUs) until now. Total glucosides of paeony (TGP) is a botanical drug extracted from the dried roots of Paeonia lactiflora Pall. [Ranunculaceae; Paeoniae Radix Alba]. This study aims to evaluate the efficacy and safety of TGP in the treatment of RAU. Methods: This study was registered with the Chinese Clinical Trial Registry (ChiCTR1900025623). Patients were randomly assigned to the TGP or placebo group and treated with 1.8g/day for 24 weeks. Participants were observed for a total of36 weeks and were asked to record ulcer severity, medication, and adverse reactions in the form of diaries or apps every day. The primary outcome was the monthly ulcer-free interval. Results: A total of 79 individuals were enrolled, with 40 assigned to the TGP group and 39 to the placebo group. The dropout rate was 18.18%. In the TGP group, the monthly ulcer-free interval was significantly longer than baseline (median, 9.6 days) since weeks 13-24 (median, 18.5 days) (p < 0.05), and after discontinuation, it was further prolonged (median, 24.7 days) than in weeks 13-24 (p < 0.05). In addition, the monthly ulcer-free interval was longer in the TGP group than in the placebo group (median, 15.9 days) at weeks 25-36 (p < 0.001). There were better improvements in the monthly number of ulcers and monthly area of ulcers, and visual analog scoring in the TGP group at weeks 25-36 (p < 0.001). Conclusion: TGP had a good long-term therapeutic effect on RAU with frequent occurrence. Systematic Review Registration: www.chictr.org.cn, identifier ChiCTR1900025623. [ABSTRACT FROM AUTHOR]

Objective: To investigate effect of total glucosides of paeoniae on immune balance of Treg/Th17 in mice with henoch purpura via janus kinase 1/signal transducer and activator of transcription3 （JAK1/STAT3） signal pathway. Methods: Animal experiments were divided into control group, model group, experimental group and inhibitor group. Mice in model group, experimental group and inhibitor group were injected with Indian ink in tail vein and gavaged ergotin to replicate allergic purpura model. Mice in experimental group and inhibitor group were given 0.1 g/kg total glucosides of paeoniae and AG490 daily for 4 weeks. ELISA was used to determine serum IL-10 and IL-17 levels of mice in each group; flow cytometry was used to detect changes of serum Treg and Th17 in each group; Western blot was used to detect expressions of p-JAK1 and p-STAT3 of skin and kidney tissues in each group of mice. Results: Compared with control group, proportion of Treg in CD4+T cells and content of IL-10 in serum of mice in model group, experimental group and inhibitor group were decreased significantly, proportion of Th17 in CD4+T cells and content of serum IL-17, expressions of p-JAK1 and p-STAT3 in skin and kidney tissues were significantly increased （all P<0.05）. Compared with model group, proportion of Treg in CD4+T cells and content of serum IL-10 of mice in experimental group and inhibitor group were increased significantly, proportion of Th17 in CD4+T cells and content of IL-17 in serum, expressions of p-JAK1 and p-STAT3 in skin and kidney tissues were decreased significantly （all P<0.05）. Conclusion: Total glucosides of paeoniae can regulate immune balance of Treg/Th17 in henoch purpura mice by inhibiting JAK2/STAT3 signal pathway. [ABSTRACT FROM AUTHOR]