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BACKGROUND: With the proven ability of traditional Chinese medicine such as icariin and berberine to promote bone regeneration by regulating various mechanisms and targets, researchers have combined active ingredients of traditional Chinese medicine with bone tissue engineering and found that they have unique advantages in treating bone defects. OBJECTIVE: Starting from the active ingredients of traditional Chinese medicines that promote bone formation, to screen cases of their effective combination with different drug-carrying scaffold materials, and summarize the active ingredients of traditional Chinese medicines that have the potential to be applied to bone tissue engineering. METHODS: CNKI, WanFang, PubMed, and Web of Science were searched for relevant literature published from 2000 to 2023, using the keywords of “bone tissue engineering, bone tissue-engineered scaffold materials, bone defect, bone repair, bone regeneration, traditional Chinese medicine” in Chinese and English. According to the inclusion and exclusion criteria, 87 papers were finally included for review. RESULTS AND CONCLUSION: There are various kinds of active ingredients of traditional Chinese medicine to promote bone regeneration, mainly including flavonoids, non-flavonoid polyphenols, alkaloids, glycosides. These active ingredients have anti-inflammatory and analgesic effects, promote osteoblasts, inhibit osteoclasts and promote early angiogenesis. The combination of active ingredients of traditional Chinese medicine with bone tissue engineering is effective in anti-inflammation, accelerating collagen and bone formation, and promoting the expression of osteogenic genes, which provides a theoretical basis for the application of traditional Chinese medicine in bone tissue regeneration, and at the same time provides a new idea for the repair of bone defects. [ABSTRACT FROM AUTHOR]

BACKGROUND: The implant osseointegration rate of patients with diabetes is low, and the failure rate is high, which seriously affects the quality of life. It is urgent to improve the implant osseointegration of patients with diabetes by effective means to elevate the success rate. Exploring the effect of berberine on the osteogenic differentiation of bone marrow mesenchymal stem cells under a high-glucose environment and its specific mechanism will provide effective theoretical support for solving the above problems. OBJECTIVE: To explore the effect of natural extract berberine on the osteogenic differentiation of rat bone marrow mesenchymal stem cells under the high)glucose microenvironment. METHODS: Bone marrow mesenchymal stem cells of SD rats were cultured by the whole bone marrow adherence method. CCK-8 assay was used to detect the effects of different concentrations of berberine on the proliferation of bone marrow mesenchymal stem cells under the high-glucose environment and to screen out the optimal berberine concentration. The expressions of Runx2 and Osx were detected by alkaline phosphatase activity, alicarin red staining and PCR to determine the effect of berberine on osteogenic differentiation of bone marrow mesymal stem cells under the high-glucose environment. To further explore the underlying mechanism, we introduced the AMPK-specific inhibitor Dorsomorphin and used a DCFH-DA reactive oxygen species fluorescent probe to examine reactive oxygen species levels. The p-AMPK expression was also determined by western blot assay. RESULTS AND CONCLUSION: (1) 10 µmol/L was the optimal concentration of berberine to promote bone marrow mesenchymal stem cell proliferation. (2) Alberberine promoted alkaline phosphatase viability of bone marrow mesenchymal stem cells and mineralized nodule formation in a high-glucose microenvironment. (3) Alberberine promoted the expression of Runx2 and OSx in a high-glucose microenvironment. (4) Alberensine effectively inhibited the reactive oxygen species level of bone marrow mesenchymal stem cells in a high-glucose environment. (5) The effects of berberine on promoting bone marrow mesenchymal stem cell osteogenesis and inhibition of reactive oxygen species were reversed by the AMPK inhibitor. (6) Berberine activated AMPK and promoted p-AMPK expression. (7) The above results indicate that berberine (10 µmol/L) promotes the osteogenic differentiation of bone marrow mesenchymal stem cells in a high-glucose environment by activating AMPK and reducing intracellular reactive oxygen species levels. [ABSTRACT FROM AUTHOR]

Introduction: Berberine (BBR) is an alkaloid found in plants. It has neuroprotective, anti‐inflammatory and lipid‐lowering activity. However, the efficacy of treatment with BBR and the mechanisms through which it acts need further study. Aims: This study investigated the therapeutic effects and the mechanism of action of BBR on obesity‐induced insulin resistance in peripheral tissues. Methods: High‐fat‐fed C57BL/6J mice and low‐fat‐fed C57BL/6J mice with miR‐27a overexpression were given BBR intervention (100 mg/kg, po), and the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed. Palmitic acid‐stimulated hypertrophic adipocyte models were treated with BBR (10 μM). Related indicators and protein expression levels were examined. Results: The AUCs of the OGTT and the ITT in the BBR intervention group were reduced significantly (p < 0.01) (p < 0.05), and the serum biochemical parameters, including FBG, TC, TG and LDL‐C were significantly reduced after BBR intervention. In the in vitro experiments, the triglyceride level and volume of lipid droplets decreased significantly after BBR intervention (p < 0.01) (p < 0.05). Likewise, BBR ameliorates skeletal muscle and pancreas insulin signalling pathways in vivo and in vitro. Discussion: The results showed that BBR significantly ameliorated insulin resistance, reduced body weight and percent body fat and improved serum biochemical parameters in mice. Likewise, BBR reduced triglyceride level and lipid droplet volume in hypertrophic adipocytes, BBR improved obesity effectively. Meanwhile, BBR ameliorated the histomorphology of the pancreas, and skeletal muscle and pancreas insulin related signalling pathways of islets in in vitro and in vivo experiments. The results further demonstrated that BBR inhibited miR‐27a levels in serum from obese mice and supernatant of hypertrophic adipocytes. miR‐27a overexpression in low‐fat fed mice indicated that miR‐27a caused insulin resistance, and BBR intervention significantly improved the miR‐27a induced insulin resistance status. Conclusion: This study demonstrates the important role of BBR in obesity‐induced peripheral insulin resistance and suggest that the mechanism of its effect may be inhibition of miR‐27a secretion. [ABSTRACT FROM AUTHOR]

Background: The development of smart nanocarriers that enable controlled drug release in response to internal and external triggers is an emerging approach for targeted therapy. This study focused on designing pH-sensitive, ultrasound-responsive gelatin/perfluorohexane (PFH) nanodroplets loaded with berberine chloride as a model drug. Results: The nanodroplets were prepared using an emulsion technique and optimized by varying process parameters like homogenization rate, polymer concentration, surfactant, drug, and perfluorocarbon content. The optimal formulation yielded nanodroplets with a particle size of 281.7 nm, a drug encapsulation efficiency of 66.8 ± 1.7%, and a passive drug release of 15.4 ± 0.2% within 24 h. Characterization confirmed successful encapsulation and pH-responsive behavior. Ultrasound stimulation significantly enhanced drug release, with 150 kHz being more effective than 1 MHz in triggering acoustic droplet vaporization while minimizing heat generation. After 10 min of radiation, the optimal formulation showed 89.4% cumulative drug release. The nanodroplets displayed stability over 1 month at 4°C. Conclusions: Overall, the dual-triggered nanodroplets demonstrate excellent potential for controlled delivery and targeted release of berberine chloride. [ABSTRACT FROM AUTHOR]

Biofilms produced by Candida albicans present a challenge in treatment with antifungal drug. Enhancing the sensitivity to fluconazole (FLC) is a reasonable method for treating FLC-resistant species. Moreover, several lines of evidence have demonstrated that berberine (BBR) can have antimicrobial effects. The aim of this study was to clarify the underlying mechanism of these effects. We conducted a comparative study of the inhibition of FLC-resistant strain growth by FLC treatment alone, BBR treatment alone, and the synergistic effect of combined FLC and BBR treatment. Twenty-four isolated strains showed distinct biofilm formation capabilities. The antifungal effect of combined FLC and BBR treatment in terms of the growth and biofilm formation of Candida albicans species was determined via checkerboard, time-kill, and fluorescence microscopy assays. The synergistic effect of BBR and FLC downregulated the expression of the efflux pump genes CDR1 and MDR, the hyphal gene HWP1, and the adhesion gene ALS3; however, the gene expression of the transcriptional repressor TUP1 was upregulated following treatment with this drug combination. Furthermore, the addition of BBR led to a marked reduction in cell surface hydrophobicity. To identify resistance-related genes and virulence factors through genome-wide sequencing analysis, we investigated the inhibition of related resistance gene expression by the combination of BBR and FLC, as well as the associated signaling pathways and metabolic pathways. The KEGG metabolic map showed that the metabolic genes in this strain are mainly involved in amino acid and carbon metabolism. The metabolic pathway map showed that several ergosterol (ERG) genes were involved in the synthesis of cell membrane sterols, which may be related to drug resistance. In this study, BBR + FLC combination treatment upregulated the expression of the ERG1, ERG3, ERG4, ERG5, ERG24, and ERG25 genes and downregulated the expression of the ERG6 and ERG9 genes compared with fluconazole treatment alone (p < 0.05). [ABSTRACT FROM AUTHOR]

Rotenone (RTN) induces neurotoxicity and motor dysfunction in rats, mirroring the pathophysiological traits of Parkinson's disease (PD), including striatal oxidative stress, mitochondrial dysfunction, and changes in neural structure. This makes RTN a valuable model for PD research. Berberine (BBR), an isoquinoline alkaloid recognized for its antioxidative, anti-inflammatory, and neuroprotective properties, was evaluated for its ability to counteract RTN-induced impairments. Rats received subcutaneous RTN at 0.5 mg/kg for 21 days, resulting in weight loss and significant motor deficits assessed through open-field, bar catalepsy, beam-crossing, rotarod, and grip strength tests. BBR, administered orally at 30 or 100 mg/kg doses, one hour prior to RTN exposure for the same duration, effectively mitigated many of the RTN-induced motor impairments. Furthermore, BBR treatment reduced RTN-induced nitric oxide (NO) and lipid peroxidation (LPO) levels, bolstered antioxidative capacity, enhanced mitochondrial enzyme activities (e.g., succinate dehydrogenase (SDH), ATPase, and the electron transport chain (ETC)), and diminished striatal neuroinflammation and apoptosis markers. Notably, the co-administration of trigonelline (TGN), an inhibitor of the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway, significantly attenuated BBR's protective effects, indicating that BBR's neuroprotective actions are mediated via the Nrf2 pathway. These results underscore BBR's potential in ameliorating motor impairments akin to PD, suggesting its promise in potentially delaying or managing PD symptoms. Further research is warranted to translate these preclinical findings into clinical settings, enhancing our comprehension of BBR's therapeutic prospects in PD. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a common digestive tract tumor, with incidences continuing to rise. Although modern medicine has extended the survival time of CRC patients, its adverse effects and the financial burden cannot be ignored. CRC is a multi‐step process and can be caused by the disturbance of gut microbiome and chronic inflammation's stimulation. Additionally, the presence of precancerous lesions is also a risk factor for CRC. Consequently, scientists are increasingly interested in identifying multi‐target, safe, and economical herbal medicine and natural products. This paper summarizes berberine's (BBR) regulatory mechanisms in the occurrence and development of CRC. The findings indicate that BBR regulates gut microbiome homeostasis and controls mucosal inflammation to prevent CRC. In the CRC stage, BBR inhibits cell proliferation, invasion, and metastasis, blocks the cell cycle, induces cell apoptosis, regulates cell metabolism, inhibits angiogenesis, and enhances chemosensitivity. BBR plays a role in the overall management of CRC. Therefore, using BBR as an adjunct to CRC prevention and treatment could become a future trend in oncology. Significance statement: Berberine (BBR) is the main alkaloid compound found in coptidis rhizome (Huanglian in Chinese). BBR has been proven to have anti‐inflammatory and antitumor therapeutic effects. This article summarizes the specific mechanism of BBR prevention and treatment of colorectal cancer (CRC) from four aspects: intestinal microbiome, inflammation, precancerous lesions, and CRC. The findings indicate that BBR regulates gut microbiome homeostasis and controls mucosal inflammation to prevent CRC. In the CRC stage, BBR inhibits cell proliferation, invasion, and metastasis, blocks the cell cycle, induces cell apoptosis, regulates cell metabolism, inhibits angiogenesis, and enhances chemosensitivity. BBR plays a role in the overall management of CRC. [ABSTRACT FROM AUTHOR]

Berberine (BBR) is used to treat cancer, inflammatory conditions, and so on. But the side effects of BBR causing constipation should not be ignored. In clinical application, the combination of Amomum villosum Lour. (AVL) and BBR can relieve it. However, the effective ingredients and molecular mechanism of AVL in relieving constipation are not clear. A small intestine propulsion experiment was conducted in constipated mice to screen active ingredients of AVL. We further confirmed the molecular mechanism of action of the active ingredient on BBR-induced constipation. Quercetin (QR) was found to be the effective ingredient of AVL in terms of relieving constipation. QR can efficiently regulate the microbiota in mice suffering from constipation. Moreover, QR significantly raised the levels of substance P and motilin while lowering those of 5-hydroxytryptamine and vasoactive intestinal peptide; furthermore, it also increased the protein expression levels of calmodulin, myosin light-chain kinase, and myosin light chain. The use of QR in combination with BBR has an adverse effect-reducing efficacy. The study provides new ideas and possibilities for the treatment of constipation induced by BBR. [ABSTRACT FROM AUTHOR]

We investigated the pharmacokinetic pathway of berberine and its metabolites in vitro, in Caco-2 cells, and in human participants following the administration of dihydroberberine (DHB) and micellar berberine (LipoMicel®, LMB) formulations. A pilot trial involving nine healthy volunteers was conducted over a 24 h period; blood samples were collected and subjected to Ultra High-Performance Liquid Chromatography–High Resolution Mass Spectrometry (UHPLC-HRMS) analyses to quantify the concentrations of berberine and its metabolites. Pharmacokinetic correlations indicated that berberrubine and thalifendine follow distinct metabolic pathways. Additionally, jatrorrhizine sulfate appeared to undergo metabolism differently compared to the other sulfated metabolites. Moreover, berberrubine glucuronide likely has a unique metabolic pathway distinct from other glucuronides. The human trial revealed significantly higher blood concentrations of berberine metabolites in participants of the DHB treatment group compared to the LMB treatment group—except for berberrubine glucuronide, which was only detected in the LMB treatment group. Similarly, results from in vitro investigations showed significant differences in berberine metabolite profiles between DHB and LMB. Dihydroberberine, dihydroxy-berberrubine/thalifendine and jatrorrhizine sulfate were detected in LMB-treated cells, but not in DHB-treated cells; thalifendine and jatrorrhizine-glucuronide were detected in DHB-treated cells only. While DHB treatment provided higher blood concentrations of berberine and most berberine metabolites, both in vitro (Caco-2 cells) and in vivo human studies showed that treatment with LMB resulted in a higher proportion of unmetabolized berberine compared to DHB. These findings suggest potential clinical implications that merit further investigation in future large-scale trials. [ABSTRACT FROM AUTHOR]

This review aims to analyse the efficacy of dietary supplements in reducing plasma cholesterol levels. Focusing on evidence from meta-analyses of randomised controlled clinical trials, with an emphasis on potential mechanisms of action as supported by human, animal, and cell studies. Certain dietary supplements including phytosterols, berberine, viscous soluble dietary fibres, garlic supplements, soy protein, specific probiotic strains, and certain polyphenol extracts could significantly reduce plasma total and low-density lipoprotein (LDL) cholesterol levels by 3–25% in hypercholesterolemic patients depending on the type of supplement. They tended to be more effective in reducing plasma LDL cholesterol level in hypercholesterolemic individuals than in normocholesterolemic individuals. These supplements worked by various mechanisms, such as enhancing the excretion of bile acids, inhibiting the absorption of cholesterol in the intestines, increasing the expression of hepatic LDL receptors, suppressing the activity of enzymes involved in cholesterol synthesis, and activating the adenosine monophosphate-activated protein kinase signalling pathway. [ABSTRACT FROM AUTHOR]

Polymeric thin films based on polylactide with an addition of poly(ethylene glycol) as a plasticizer and flavonoids in the form of quercetin and berberine were subjected to tests that were particularly relevant from the point of view of contact with food. A comparative analysis of the effect of individual flavonoids on the antioxidative properties of tested films and blueberry storage was carried out. The influence of active compounds on the water vapor permeability, as well as UV protection, of the obtained materials was investigated. Also, the specific migration of individual flavonoids from obtained materials to food simulants in the form of acetic acid and ethyl alcohol was determined. The crucial point of this study is the storage of blueberries. The obtained results indicate that the selection of packaging, containing individual active compounds, depends on the purpose and requirements that the packaging must meet for particular types of food. [ABSTRACT FROM AUTHOR]

Berberine (Ber) as a natural isoquinoline alkaloid, with a wide range of biological activities, mainly suffers from low bioavailability, decreasing its therapeutic efficacy. In this study, two novel conjugates of Ber with self-assembly property, Ber–polyethylene glycol (B–PEG) and Ber–diethylene glycol monomethyl ether (B–DG), were synthesized to investigate the effect of the anchoring part on the CMC, morphology as well as antioxidant and neuroprotective properties of the nanomicelles. The CMC increased from 1.2 μmol in B–DG to 3.0 μmol in B–PEG, measured by pendant drop. The anchored part affected greatly the shape and CMC of the self-assembled nanomicelles. A mixture of semi-spherical and cubic nanomicelles in the average hydrodynamic size of 93 nm was achieved for B–PEG, while B–DG nanomicelles were just in semispherical morphology with the hydrodynamic size of 64 nm. The antioxidant property of the nanomicelles was studied by DPPH scavenging and ferric reducing antioxidant power assays, exhibiting improved antioxidant activity of B–PEG and B–DG conjugates compared to free Ber. The neuroprotection potency of Ber was improved significantly after conjugation compared to free Ber against H2O2-induced cell death and B–PEG showed activity as level as that of the standard drug, Quercetin. Owing to the self-assembly property and interesting biological activities of the introduced amphiphilic Ber–PEG conjugate, we propose application of this nanomicelle alone, or as a promising bioactive carrier of the poorly water-soluble drugs, against neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Thermoresponsive drug delivery systems have been used to treat diseases that cause hyperthermia or elevated body tissue temperatures, viz., rheumatoid arthritis and different cancers. The aim of the study was to enhance berberine (BER) release using thermosensitive nanostructured lipid carriers (TNLCs) through intra-articular administration for the management of arthritis. TNLCs were prepared using binary mixtures of stearic acid and decanoic acid as solid and liquid lipids, respectively. Lipid mixtures with an optimum melting point were assessed using differential scanning calorimetry studies. In vitro characterization of the BER TNLCs included particle size, zeta potential, entrapment efficiency, and drug release at 37 °C and 41 °C. Joint diameter measurement, real-time polymerase chain reaction (RT-PC) analysis, enzyme-linked immunosorbent assay (ELISA) for inflammatory markers, and histological evaluation of the dissected joints were all performed in vivo on rats with adjuvant-induced arthritis. In vitro characterization revealed negatively charged BER-loaded TNLCs with a spherical shape, particle size less than 500 nm, BER entrapment efficiency up to 79%, and a high drug release rate at an elevated temperature of 41 °C. In silico studies revealed the affinity of BER to different formula components and to the measured biomarkers. In vivo assessment of the optimum TNLCs showed that BER TNLCs were superior to the BER solution suspension regarding their effect on inflammatory biomarkers, joint diameter, and histological studies. [ABSTRACT FROM AUTHOR]

Background: Huanglian (HL), also known as Coptis chinensis Franch., was initially documented in "Sheng Nong's Herbal Classic" as a high-quality product used to cure ailments such as fever, indigestion, bloating, nausea, dysentery, diarrhea, abdominal pain, and tuberculosis. Nowadays, it is extensively employed in clinical settings to alleviate pulmonary diseases, like tuberculosis, lobular lung disease, and pulmonary abscess, and is worth exploring further. Nevertheless, there is limited research on the precise advancements of anti-lung adenocarcinoma (LUAD). Objectives: Using biological experiments and network pharmacology, the objective of this research was to investigate the most effective parts and chemical constituents of C. chinensis against LUAD and ascertain the probable targets and pathways. Materials and Methods: First, an MTT experiment verified the impact of each part on A549 and BEAS-2B cells. High performance liquid chromatography (HPLC) was then used to identify the chemical components of the effective substance in C. chinensis against LUAD. Then, network pharmacology was used to screen potential pathways and binding target proteins. Finally, a subcutaneous tumor model was established in mice using LLC cells to observe the effects of the effective components of C. chinensis against LUAD in tumor-bearing mice. Results: The MTT assay demonstrated the efficacy of oxyepiberberine (OPB) as an anti-LUAD compound with minimal toxicity and side effects. According to the results of network pharmacology and molecular docking, SRC appears to be the primary target of C. chinensis active substance against LUAD. In vivo experiments revealed that the OPB group exhibited lowered toxicity and side effects. Additionally, the density of tumor cells decreased and the nuclei were destroyed in OPB groups of tumor tissues. Finally, OPB could regulate apoptosis, migration, and protein expression significantly related to the SRC pathway in tumor cells. Conclusion: Our research reveals the anti-LUAD properties of C. chinensis through a combination of experimentation and network analysis. These findings establish a theoretical foundation for C. chinensis as a clinical antitumor agent. Furthermore, our work provided an essential groundwork for further investigations into the medicinal properties of C. chinensis. [ABSTRACT FROM AUTHOR]

Allergic rhinitis is a prevalent inflammatory condition that impacts individuals of all age groups. Despite reports indicating the potential of berberine in alleviating allergic rhinitis symptoms, the specific molecular mechanisms and therapeutic targets of berberine remain unclear. This research aims to explore the pharmacological mechanism of berberine in the treatment of allergic rhinitis through bioinformatic analyses and experimental validation. The research utilized public databases to identify potential targets of berberine. Furthermore, differentially expressed genes (DEGs) related to allergic rhinitis were pinpointed from the GSE52804 dataset. Through bioinformatics techniques, the primary targets were discovered and key KEGG and GO-BP pathways were established. To confirm the therapeutic mechanisms of berberine on allergic rhinitis, an OVA-induced allergic rhinitis model was developed using guinea pigs. We identified 32 key genes responsible for the effectiveness of berberine in treating allergic rhinitis. In addition, five central genes (Alb, Il6, Tlr4, Ptas2, and Il1b) were pinpointed. Further examination using KEGG and GO-BP pathways revealed that the main targets were primarily involved in pathways such as NF-kappa B, IL-17, TNF, and inflammatory response. Molecular docking analysis demonstrated that berberine exhibited strong affinity towards these five key targets. Furthermore, the expression levels of IL-6, TLR4, PTGS2, and IL-1β were significantly upregulated in the model group but downregulated following berberine treatment. This research has revealed the mechanism through which berberine combats allergic rhinitis and has identified its potential to regulate pathways linked to inflammation. These discoveries provide valuable insights for the development of novel medications for the treatment of allergic rhinitis. [ABSTRACT FROM AUTHOR]

Background: Thalictrum foliolosum, a member of the Ranunculus family, is recognized for its therapeutic potential in addressing gastric issues, dyspepsia, tooth pain, abdominal colic pain, and piles. The diverse array of secondary metabolites present in the plant contributes to these therapeutic applications. This study aims to uncover and quantify the bioactive secondary metabolites found in the unexplored leaves, stems, and roots of T. foliolosum. Additionally, we also aimed to evaluate the antibacterial activity and MIC values of these extracts against a panel of pathogenic bacteria, such as pathogenic strains, including Escherichia coli, Pseudomonas aeruginosa, Streptococcus mutant and Staphylococcus aureus. Result: HPLC analysis suggested all examined compounds were found significantly more in root parts of plant. To determine the potential antimicrobial activity of different plant parts result suggested chloroform fraction of root most effective with variable potency against each examined pathogen at 25–100 µg/ml extracts which indicated rich content of berberine in this fraction. Minimum MIC (121.26 µg/mL) of the chloroform fraction of the root was also supported the results. Fatty acid methyl ester analysis by gas chromatography revealed that the stem contained high levels of fatty acids, such as palmitic acid, stearic acid, and linolenic acid, all of which have antibacterial properties. Conclusion: The potential antimicrobial activity of extracts of various plant parts strongly supports the T. foliolosum plant's widespread use in folk medicine for the treatment of various chronic diseases and adulterants with various associated medicinal plant species. [ABSTRACT FROM AUTHOR]

A Cp*Ir‐catalyzed C−H arylation of 1‐isoquinolinone and 2‐pyridones with N‐2‐pyridyl as a directing group to afford 6‐phenylpyridin‐2(1H)‐ones and 3‐phenylisoquinolin‐1(2H)‐ones by using arylsilanes is described in this paper. This method tolerates a series of functional groups, such as halide, trifluoromethyl, C=C double bond and offers a synthetic approach to the core structure of protoberberine alkaloids. Several experiments on mechanism studies were conducted to reveal the possible process of this Cp*Ir‐catalytic cycle. [ABSTRACT FROM AUTHOR]

One of the important issues for RNA-targeting drugs is to improve their binding properties. Herein, we modified berberine, which interacts with structured RNAs, with the guanidine moiety. Protein expression from target mRNA was efficiently reduced by the modification, suggesting a simple strategy to improve the therapeutic activity. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine (TCM) serves as a significant adjunct to chemical treatment for chronic diseases. For instance, the administration of Baitouweng decoction (BTWD) has proven effective in the treatment of ulcerative colitis. However, the limited understanding of its pharmacokinetics (PK) has impeded its widespread use. Chinese Bama miniature pigs possess anatomical and physiological similarities to the human body, making them a valuable model for investigating PK properties. Consequently, the identification of PK properties in Bama miniature pigs can provide valuable insights for guiding the clinical application of BTWD in humans. To facilitate this research, a rapid and sensitive UPLC-MS/MS method has been developed for the simultaneous quantification of eleven active ingredients of BTWD in plasma. Chromatographic separation was conducted using an Acquity UPLC HSS T3 C18 column and a gradient mobile phase comprising acetonitrile and water (containing 0.1% acetic acid). The methodology was validated in accordance with the FDA Bioanalytical Method Validation Guidance for Industry. The lower limit of quantitation fell within the range of 0.60–2.01 ng/mL. Pharmacokinetic studies indicated that coptisine chloride, berberine, columbamine, phellodendrine, and obacunone exhibited low C max , while fraxetin, esculin, fraxin, and pulchinenoside B 4 were rapidly absorbed and eliminated from the plasma. These findings have implications for the development of effective components in BTWD and the adjustment of clinical dosage regimens. [ABSTRACT FROM AUTHOR]

The objective of this study was to create a liquid chromatographic method that could accurately and simultaneously quantify the amount of Quercetin, Berberine, and Phytosterol present in lyophilized liposome used to treat metabolic syndrome. To achieve this goal, the team utilized a Shim‐pack GIST C8 column with a gradient elution of 0.1% (V/V) triethylamine buffer: acetonitrile at 30°C. They analyzed the phytoconstituents using an eluent flow rate of 1 mL/min and ultraviolet detection at 205 nm. The method was linear within a range of 25–77 μg/mL, which had excellent correlation coefficients (R2) of 0.9998, 0.9998, and 0.9996 for Quercetin, Berberine, and Phytosterol, respectively. The %RSD for precision and robustness of the method were also less than 2%, and the recovery values for Quercetin, Berberine, and Phytosterol were 99.5%, 100.5%, and 99.8%, respectively. The assay values of were found to be 100.2%, 101.6%, and 100.5% for Quercetin, Berberine, and Phytosterol, loaded lyophilized liposomes, respectively. As a result, this specific, accurate, and precise method can be employed for the routine analysis of Quercetin, Berberine, and Phytosterols in QC laboratories. [ABSTRACT FROM AUTHOR]

Berberis vulgaris (L.) has remarkable ethnopharmacological properties and is widely used in traditional medicine. The present study investigated B. vulgaris stem bark (Berberidis cortex) by extraction with 50% ethanol. The main secondary metabolites were quantified, resulting in a polyphenols content of 17.6780 ± 3.9320 mg Eq tannic acid/100 g extract, phenolic acids amount of 3.3886 ± 0.3481 mg Eq chlorogenic acid/100 g extract and 78.95 µg/g berberine. The dried hydro-ethanolic extract (BVE) was thoroughly analyzed using Ultra-High-Performance Liquid Chromatography coupled with High-Resolution Mass Spectrometry (UHPLC–HRMS/MS) and HPLC, and 40 bioactive phenolic constituents were identified. Then, the antioxidant potential of BVE was evaluated using three methods. Our results could explain the protective effects of Berberidis cortex EC50FRAP = 0.1398 mg/mL, IC50ABTS = 0.0442 mg/mL, IC50DPPH = 0.2610 mg/mL compared to ascorbic acid (IC50 = 0.0165 mg/mL). Next, the acute toxicity and teratogenicity of BVE and berberine—berberine sulfate hydrate (BS)—investigated on Daphnia sp. revealed significant BS toxicity after 24 h, while BVE revealed considerable toxicity after 48 h and induced embryonic developmental delays. Finally, the anticancer effects of BVE and BS were evaluated in different tumor cell lines after 24 and 48 h of treatments. The MTS assay evidenced dose- and time-dependent antiproliferative activity, which was higher for BS than BVE. The strongest diminution of tumor cell viability was recorded in the breast (MDA-MB-231), colon (LoVo) cancer, and OSCC (PE/CA-PJ49) cell lines after 48 h of exposure (IC50 < 100 µg/mL). However, no cytotoxicity was reported in the normal epithelial cells (HUVEC) and hepatocellular carcinoma (HT-29) cell lines. Extensive data analysis supports our results, showing a significant correlation between the BVE concentration, phenolic compounds content, antioxidant activity, exposure time, and the viability rate of various normal cells and cancer cell lines. [ABSTRACT FROM AUTHOR]

Cardiac disorders in cancer patients pose significant challenges to disease prognosis. While it has been established that these disorders are linked to cancer cells, the precise underlying mechanisms remain elusive. In this study, we investigated the impact of cancerous ascites from the rat colonic carcinoma cell line RCN9 on H9c2 cardiomyoblast cells. We found that the ascites reduced mitochondrial volume, increased oxidative stress, and decreased membrane potential in the cardiomyoblast cells, leading to apoptosis and autophagy. Although the ascites fluid contained a substantial amount of high-mobility group box-1 (HMGB1), we observed that neutralizing HMGB1 with a specific antibody mitigated the damage inflicted on myocardial cells. Our mechanistic investigations revealed that HMGB1 activated both nuclear factor κB and phosphoinositide 3-kinases-AKT signals through HMGB1 receptors, namely the receptor for advanced glycation end products and toll-like receptor-4, thereby promoting apoptosis and autophagy. In contrast, treatment with berberine (BBR) induced the expression of miR-181c-5p and miR-340-5p while suppressing HMGB1 expression in RCN9 cells. Furthermore, BBR reduced HMGB1 receptor expression in cardiomyocytes, consequently mitigating HMGB1-induced damage. We validated the myocardial protective effects of BBR in a cachectic rat model. These findings underscore the strong association between HMGB1 and cancer cachexia, highlighting BBR as a promising therapeutic agent for myocardial protection through HMGB1 suppression and modulation of the signaling system. [ABSTRACT FROM AUTHOR]

This study aims to explore the impact of ADME on the Oral Bioavailability (OB) of drugs and to construct a machine learning model for OB prediction. The model is then applied to predict the OB of modified berberine and atenolol molecules to obtain structures with higher OB. Initially, a drug OB database was established, and corresponding ADME characteristics were obtained. The relationship between ADME and OB was analyzed using machine learning, with Morgan fingerprints serving as molecular descriptors. Compounds from the database were input into Random Forest, XGBoost, CatBoost, and LightGBM machine learning models to train the OB 7prediction model and evaluate its performance. Subsequently, berberine and atenolol were modified using Chemdraw software with ten different substituents for mono-substitution, and chlorine atoms for a full range of double substitutions. The modified molecular structures were converted into the same format as the training set for OB prediction. The predicted OB values of the modified structures of berberine and atenolol were compared. An OB database of 386 drugs was obtained. It was found that smaller molecular weight and a higher number of rotatable bonds (ten or less) could potentially lead to higher OB. The four machine learning models were evaluated using MSE, R2 score, MAE, and MFE as metrics, with Random Forest performing the best. The models' predictions for the test set were particularly accurate when OB ranged from 30% to 90%. After mono-substitution and double substitution of berberine and atenolol, the OB of both drugs was significantly improved. This study found that some ADME properties of molecules do not have an absolute impact on OB. The database played a decisive role in the process of the machine learning OB prediction model, and the performance of the model was evaluated based on predictions within a range of strong generalization ability. In most cases, mono-substitution and double substitution were beneficial for enhancing the OB of berberine and atenolol. In summary, this study successfully constructed a machine learning regression prediction model that can accurately predict drug OB, which can guide drug design to achieve higher OB to some extent. [ABSTRACT FROM AUTHOR]

Pressure ulcer (PU) is a worldwide problem that is difficult to address because of the related inflammatory response, local hypoxia, and repeated ischaemia/reperfusion, causing great suffering and financial burden to patients. Traditional Chinese medicine turtle plate powder can treat skin trauma, but its composition is complex and inconvenient to use. Here, we combined cholesterol myristate (S8) with berberine (BBR), with anti‐inflammatory and antibacterial effects, as a drug and used hydroxypropyl methylcellulose and polyvinylpyrrolidone K30 as carriers to construct a novel film‐forming polymeric solution (S8 + BBR FFPS), comprehensively study its reparative effect on PU and explore the potential mechanism in rat PU models. The results showed that S8 + BBR FFPS inhibits excessive inflammatory response, promotes re‐epithelialization, and promotes hair follicle growth during the healing process of PU, which may be related to the activation of the Wnt/β‐catenin signalling pathway by S8 + BBR FFPS to mediate hair follicle stem cell proliferation and maintain skin homeostasis. Therefore, S8 + BBR FFPS may be a potential candidate for the treatment of chronic skin injury, and its association with the Wnt/β‐catenin signalling pathway may provide new ideas to guide the design of biomaterial‐based wound dressings for chronic wound repair. [ABSTRACT FROM AUTHOR]

Oleogel is a viscoelastic, spreadable and semi‐solid structure, which is used as a fat substitute and a controller the release of bioactive compounds. The aim of this study was to develop low fat dairy dessert enriched with berberine with applying oleogel system as delivery system and fat replacer. The oleogel prepared with an emulsion‐templated methods based on soluble interaction of whey protein concentrate (WPC), WPC‐basil seed gum (BSG), and WPC‐xanthan gum (XG). In the first step, berberine release kinetic in in‐vitro gastrointestinal environment was studied. The results showed that the mouth environment had the highest release rate of berberine. Cooperation of hydrocolloids in oleogel increase stability of structure in stomach condition in compared with WPC oleogel. The suitable model to fit the oleogels contain beberine was the Korsmeyer‐Papas that was the highest R2 (.98). According to release results of berberine from oleogel network, the oleogel 0.6BSG:WPC was chosen and applied in formulation of dairy dessert at different levels (0%, 25%, 50%, 75% and 100% of oleogel) instead of cream. The dessert contained uncoated berberine had the unacceptable bitterness in comparison with samples containing coated berberine with oleogel. The overall acceptance decreased with increment of oleogel due to increasing of bitter taste. Appling berberine (therapeutic compound) and oleogel (fat‐substitute) to achieve marketable consumer products showed positive effects on trend of the study, especially at low level of substitution. [ABSTRACT FROM AUTHOR]

[Display omitted] Berberine (Ber), an isoquinoline alkaloid, is a potential drug therapy for ulcerative colitis (UC) because of its anti-inflammatory activity, high biological safety, and few side effects. Nevertheless, its clinical application is hindered by its limited water solubility and low bioavailability. Currently, compared to synthetic nanocarriers, exosomes as carriers possess advantages such as low toxicity, high stability, and high specificity. Human placental mesenchymal stem cell-derived exosomes (HplMSC-Exos) have emerged as a promising drug delivery system, offering intrinsic anti-inflammatory and antioxidant activities. Therefore, we engineered MSC-Exos loaded with Ber (Exos-Ber) to enhance the solubility and bioavailability of Ber and for colon targeting, revealing a novel approach for treating UC with natural compounds. Structurally and functionally, Exos-Ber closely resembled unmodified Exos. Both in vitro and in vivo investigations confirmed the antioxidant and anti-inflammatory properties of Exos-Ber. Notably, Exos-Ber exhibited reparative effects on injured epithelial cells and reduced cellular apoptosis. Furthermore, Exos-Ber concurrently demonstrated anti-inflammatory and antioxidant activities, contributing to the mitigation of UC, possibly through its modulation of the MAPK signaling pathway. Overall, our findings demonstrate the potential of Exos-Ber as a promising therapeutic option for alleviating UC, highlighting its capacity to enhance the clinical applicability of Ber. [ABSTRACT FROM AUTHOR]

Erythrocytes are impressive tools for drug delivery, especially to macrophages. Therefore, berberine was loaded into erythrocytes using both hypotonic pre-swelling and endocytosis methods to target macrophages. Physicochemical and kinetic parameters of the resulting carrier cells, such as drug loading/release kinetics, osmotic fragility, and hematological indices, were determined. Drug loading was optimized for the study using Taguchi experimental design and lab experiments. Loaded erythrocytes were targeted to macrophages using ZnCl2 and bis-sulfosuccinimidyl-suberate, and targeting was evaluated using flow cytometry and Wright–Giemsa staining. Differentiated macrophages were stimulated with lipopolysaccharide, and the inflammatory profiles of macrophages were evaluated using ELISA, western blotting, and real-time PCR. Findings indicated that the endocytosis method is preferred due to its low impact on the erythrocyte's structural integrity. Maximum loading achieved (1386.68 ± 22.43 μg/ml) at 1500 μg/ml berberine treatment at 37 °C for 2 h. Berberine successfully inhibited NF-κB translation in macrophages, and inflammatory response markers such as IL-1β, IL-8, IL-23, and TNF-α were decreased by approximately ninefold, sixfold, twofold, eightfold, and twofold, respectively, compared to the LPS-treated macrophages. It was concluded that berberine-loaded erythrocytes can effectively target macrophages and modulate the inflammatory response. [ABSTRACT FROM AUTHOR]

The treatment of osteosarcoma, as the most destructive bone cancer, is allied with many challenges. One of the new tissue engineering approaches is the use of a local drug delivery system implanted after surgery. This system can be a scaffold mimicking the natural tissue extracellular matrix, loaded with drugs. Therefore, the purpose of this study was to construct different berberine-loaded nano-hydroxyapatite/gelatin scaffolds, and to investigate their effects on osteosarcoma cancer cells. The scaffolds after fabrication were analyzed for physicochemical properties using XRD, EDS, FTIR, and FE-SEM. The drug loading and release, and the biocompatibility (MTT and LDH) were also evaluated. Moreover, apoptosis, viability, colony formation, and scratch tests were conducted on cancer cells. The scaffolds exhibited a porosity of 66.64% with pore sizes of 10–70 micrometers. The results showed that the released berberine had a cytotoxic effect on cancer cells (cell death of ∼38–80% based on LDH, and cell proliferation <56% and <21% in terms of early and late exposure based on MTT). The apoptosis results revealed a remarkable increase in the percentage of apoptotic MG63 cells after treatment with berberine-loaded scaffolds in a dose-dependent manner. All scaffolds with berberine were able to significantly prevent colony formation and cell migration (only 9.7–15.7% closure). [ABSTRACT FROM AUTHOR]

Simple Summary: An excessive carbohydrate content in diets can have a negative effect on fish growth. In this study, the effects of berberine supplementation in high-carbohydrate diets on the growth performance, glucose metabolism, bile acid synthesis, liver transcriptome, and intestinal flora of Nile tilapia were investigated. Conclusion: An appropriate amount of berberine can stimulate the synthesis of bile acids by changing the structure of the intestinal flora of tilapia, thus promoting glycolysis and inhibiting gluconeogenesis, then regulating the blood glucose, which is beneficial to the growth of tilapia. This provides the data to improve carbohydrate utilization in tilapia and support the development of high-carbohydrate diets in aquaculture. Berberine is an alkaloid used to treat diabetes. This experiment aimed to investigate the effects of berberine supplementation in high-carbohydrate diets on the growth performance, glucose metabolism, bile acid synthesis, liver transcriptome, and intestinal flora of Nile tilapia. The six dietary groups were the C group with 29% carbohydrate, the H group with 44% carbohydrate, and the HB1-HB4 groups supplemented with 25, 50, 75, and 100 mg/kg of berberine in group H. The results of the 8-week trial showed that compared to group C, the abundance of Bacteroidetes was increased in group HB2 (p < 0.05). The cholesterol-7α-hydroxylase (CYP7A1) and sterol-27-hydroxylase (CYP27A1) activities were decreased and the expression of FXR was increased in group HB4 (p < 0.05). The pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase (PEPCK) activities was decreased in group HB4 (p < 0.05). The liver transcriptome suggests that berberine affects carbohydrate metabolic pathways and primary bile acid synthesis pathways. In summary, berberine affects the glucose metabolism in tilapia by altering the intestinal flora structure, enriching differentially expressed genes (DEGs) in the bile acid pathway to stimulate bile acid production so that it promotes glycolysis and inhibits gluconeogenesis. Therefore, 100 mg/kg of berberine supplementation in high-carbohydrate diets is beneficial to tilapia. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is the predominant cause of chronic liver conditions, and its progression is marked by evolution to non-alcoholic steatosis, steatohepatitis, cirrhosis related to non-alcoholic steatohepatitis, and the potential occurrence of hepatocellular carcinoma. In our systematic review, we searched two databases, Medline (via Pubmed Central) and Scopus, from inception to 5 February 2024, and included 73 types of research (nine clinical studies and 64 pre-clinical studies) from 2854 published papers. Our extensive research highlights the impact of Berberine on NAFLD pathophysiology mechanisms, such as Adenosine Monophosphate-Activated Protein Kinase (AMPK), gut dysbiosis, peroxisome proliferator-activated receptor (PPAR), Sirtuins, and inflammasome. Studies involving human subjects showed a measurable reduction of liver fat in addition to improved profiles of serum lipids and hepatic enzymes. While current drugs for NAFLD treatment are either scarce or still in development or launch phases, Berberine presents a promising profile. However, improvements in its formulation are necessary to enhance the bioavailability of this natural substance. [ABSTRACT FROM AUTHOR]

In the present investigation, we employed the hydrothermal approach for crafting mesoporous KIT-6 scaffolds and the post-impregnation technique for incorporating the drug. The concentration of berberine within the mesoporous channels of KIT-6 was assessed through UV–visible spectrophotometer. The results showed that the drug molecules were well integrated into the structure of KIT-6, displaying the material’s 3D cubic mesoporous shape and its notable specific surface area of 1376 m2/g. The in vitro drug release profile was investigated in phosphate-buffered saline (pH = 6.8), and the findings point to the possibility of controlling the drug release quantity by loading the drug into the carrier. Using Vero cell lines, the toxicity of the drug-free and drug-loaded samples was examined and it was concluded that by adding berberine to the mesoporous matrix, the drug’s toxicity was dramatically lowered. [ABSTRACT FROM AUTHOR]

Rumen microbial urease inhibitors have been proposed for regulating nitrogen emission and improving nitrogen utilization efficiency in ruminant livestock industry. However, studies on plant-derived natural inhibitors of rumen microbial urease are limited. Urease accessory protein UreG, plays a crucial role in facilitating urease maturation, is a new target for design of urease inhibitor. The objective of this study was to select the potential effective inhibitor of rumen microbial urease from major protoberberine alkaloids in Rhizoma Coptidis by targeting UreG. Our results showed that berberine chloride and epiberberine exerted superior inhibition potential than other alkaloids based on GTPase activity study of UreG. Berberine chloride inhibition of UreG was mixed type, while inhibition kinetics type of epiberberine was uncompetitive. Furthermore, epiberberine was found to be more effective than berberine chloride in inhibiting the combination of nickel towards UreG and inducing changes in the second structure of UreG. Molecular modeling provided the rational structural basis for the higher inhibition potential of epiberberine, amino acid residues in G1 motif and G3 motif of UreG formed interactions with D ring of berberine chloride, while interacted with A ring and D ring of epiberberine. We further demonstrated the efficacy of epiberberine in the ruminal microbial fermentation with low ammonia release and urea degradation. In conclusion, our study clearly indicates that epiberberine is a promising candidate as a safe and effective inhibitor of rumen microbial urease and provides an optimal strategy and suitable feed additive for regulating nitrogen excretion in ruminants in the future. Key points: • Epiberberine is the most effective inhibitor of rumen urease from Rhizoma Coptidis. • Urease accessory protein UreG is an effective target for design of urease inhibitor. • Epiberberine may be used as natural feed additive to reducing NH3 release in ruminants. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by pathophysiological deposits of extracellular amyloid beta (Aβ) peptides and intracellular neurofibrillary tangles of tau. The central role of Aβ in AD pathology is well-established, with its increased deposition attributed mainly to its decreased cerebral clearance. Here, it is noteworthy that apolipoprotein E (ApoE), the most significant risk factor for AD, has been shown to play an isoform-specific role in clearing Aβ deposits (ApoE2 > ApoE3 > ApoE4), owing mainly to its lipidation status. In addition to the pathophysiological Aβ deposits, AD is also characterized by abnormal glucose metabolism, which is a distinct event preceding Aβ deposition. The present study established, for the first time, a possible link between these two major AD etiologies, with glucose metabolism directly influencing ApoE lipidation and its secretion by astrocytes expressing human ApoE4. Specifically, glucose dose-dependently activated liver X receptor (LXR), leading to elevated ABCA1 and ABCG1 protein levels and enhanced ApoE lipidation. Moreover, co-treatment with a glycolytic inhibitor significantly inhibited this LXR activation and subsequent ApoE lipidation, further supporting a central role of glucose metabolism in LXR activation leading to enhanced ApoE lipidation, which may help against AD through potential Aβ clearance. Therefore, we hypothesized that pharmacological agents that can target cellular energy metabolism, specifically aerobic glycolysis, may hold significant therapeutic potential against AD. In this context, the present study also led to the discovery of novel, small-molecule stimulants of astrocytic glucose metabolism, leading to significantly enhanced lipidation status of ApoE4 in astrocytic cells. Three such newly discovered compounds (lonidamine, phenformin, and berberine), owing to their promising cellular effect on the glycolysis-ApoE nexus, warrant further investigation in suitable in vivo models of AD. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease is a global health concern and reducing plasma LDL-C levels is a major goal in cardiovascular prevention. Our study aimed to evaluate the effectiveness of a nutraceutical formulation including leucoselect® phytosome®, red yeast rice, policosanol and folic acid on LDL-c levels in patients at low cardiovascular risk with dyslipidemia. Materials and Methods: We prospectively enrolled all consecutive patients with dyslipidemia at low cardiovascular risk who were unresponsive to diet and physical activity. Clinical assessments and laboratory analyses, encompassing lipid profile, hepatic function, and CPK levels, were performed at baseline prior to initiating treatment and repeated at the 12-week mark following administration of the study nutraceutical. Results: Sixty (60) consecutive patients (mean age 48.02 ± 10.1 years; 60% male) were included. At the 12-week follow-up, a statistically significant reduction in Total Cholesterol (13.1%) and LDL-c serum level (20.4%) was observed. Hepatic and muscular function remain stable over the time. The adherence to therapy was 99% and the persistence was maximum. Conclusions: The nutraceutical formulation including leucoselect® phytosome® red yeast rice, policosanol and folic acid significantly reduced the LDL-c plasma levels, consistent with previous research showing that the bioactive component in red yeast rice—lovastatin—is effective in addressing problems with lipid metabolism. Importantly, it was safe and well-tolerated among patients with dyslipidemia in a real-world setting. [ABSTRACT FROM AUTHOR]

Mesoporous titanium nanoparticles (MTN) have always been a concern and are considered to have great potential for overcoming antibiotic-resistant bacteria. In our study, MTN modified with functionalized UV-responsive ethylene imine polymer (PEI) was synthesized. The characterization of all products was performed by different analyses, including SEM, TEM, FT-IR, TGA, XRD, XPS, and N2 adsorption-desorption isotherms. The typical antibacterial drug berberine hydrochloride (BH) was encapsulated in MTN-PEI. The process exhibited a high drug loading capacity (22.71 ± 1.12%) and encapsulation rate (46.56 ± 0.52%) due to its high specific surface area of 238.43 m2/g. Moreover, UV-controlled drug release was achieved by utilizing the photocatalytic performance of MTN. The antibacterial effect of BH@MTN-PEI was investigated, which showed that it could be controlled to release BH and achieve a corresponding antibacterial effect by UV illumination for different lengths of time, with bacterial lethality reaching 37.76% after only 8 min of irradiation. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the nanoparticles have also been studied. The MIC of BH@MTN-PEI was confirmed as 1 mg/mL against Escherichia coli (E. coli), at which the growth of bacteria was completely inhibited during 24 h and the concentration of 5 mg/mL for BH@MTN-PEI was regarded as MBC against E. coli. Although this proof-of-concept study is far from a real-life application, it provides a possible route to the discovery and application of antimicrobial drugs. [ABSTRACT FROM AUTHOR]

In this paper, berberine hydrochloride-loaded liposomes-in-gel were designed and developed to investigate their antioxidant properties and therapeutic effects on the eczema model of the mouse. Berberine hydrochloride-liposomes (BBH-L) as the nanoparticles were prepared by the thin-film hydration method and then dispersed BBH-L evenly in the gel matrix to prepare the berberine hydrochloride liposomes-gel (BBH-L-Gel) by the natural swelling method. Their antioxidant capacity was investigated by the free radical scavenging ability on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and H2O2 and the inhibition of lipid peroxides malondialdehyde (MDA). An eczema model was established, and the efficacy of the eczema treatment was preliminarily evaluated using ear swelling, the spleen index, and pathological sections as indicators. The results indicate that the entrapment efficiency of BBH-L prepared by the thin-film hydration method was 78.56% ± 0.7%, with a particle size of 155.4 ± 9.3 nm. For BBH-L-Gel, the viscosity and pH were 18.16 ± 6.34 m Pas and 7.32 ± 0.08, respectively. The cumulative release in the unit area of the in vitro transdermal study was 85.01 ± 4.53 μg/cm2. BBH-L-Gel had a good scavenging capacity on DPPH and H2O2, and it could effectively inhibit the production of hepatic lipid peroxides MDA in the concentration range of 0.4–2.0 mg/mL. The topical application of BBH-L-Gel could effectively alleviate eczema symptoms and reduce oxidative stress injury in mice. This study demonstrates that BBH-L-Gel has good skin permeability, excellent sustained release, and antioxidant capabilities. They can effectively alleviate the itching, inflammation, and allergic symptoms caused by eczema, providing a new strategy for clinical applications in eczema treatment. [ABSTRACT FROM AUTHOR]

In recent years, an increasing interest in phytotherapy has been observed. Parallel to the research on the total extracts of plant material, numerous studies on the activity of single molecules derived from plants are being conducted to address their mechanisms of action and determine active doses and eventual interactions. Despite this phenomenon, the isolation of individual compounds is a bottleneck due to its difficulty and cost. This work presents the results of a careful optimization of magnoflorine and berberine (isoquinoline alkaloids) recovery from a commonly distributed shrub, Berberis vulgaris, growing in Poland and Georgia, using CPC. Both compounds are known for their numerous medicinal properties, which makes the isolation methodology an important area of research. Additionally, CPC has the ability to isolate high-quality compounds in large quantities, which makes it an effective and easy-to-commercialize method. For a successful separation, the biphasic solvent system composed of hexane, butanol, ethanol, and water in a ratio (3:12:4:16 v/v/v/v) was used in the ascending mode, together with the flow rate of 8 mL/min and rotation speed of 1600 rpm. The method was selective for both compounds, and it delivered good results for both root and stem extracts from the plant. The qualitative composition of alkaloids in the studied extracts determined by HPLC-ESI-QTOF-MS/MS confirmed the presence of berberine, magnoflorine, jatrorhizine, and palmatine alkaloids from the group of isoquinolines. The isolates, magnoflorine and berberine, were subjected to the Helicobacter pylori growth inhibition assay and urease inhibition test to assess whether, next to the previously proved anticancer properties, these compounds are characterized by H. pylori inhibition. MGN was found to exhibit inhibitory potential against urease (IC50 = 25 mg/L). [ABSTRACT FROM AUTHOR]

This document is a correction notice for a paper on the potential bioactive compound bromelain. The authors have identified errors in one section of the paper and provide revised references. The corrected table includes therapeutic studies of bromelain based on experimental studies. The document also includes a compilation of various scientific studies and articles related to the use of bromelain for various medical purposes. The studies explore the potential benefits of bromelain in treating conditions such as cancer, inflammation, thrombosis, and pain. The document provides a comprehensive overview of the scientific research on bromelain and its potential applications in medicine. [Extracted from the article]

Hyperlipidemia is a common clinically encountered health condition worldwide that promotes the development and progression of cardiovascular diseases, including atherosclerosis. Berberine (BBR) is a natural product with acknowledged anti‐inflammatory, antioxidant, and metabolic effects. This study evaluated the effect of BBR on lipid alterations, oxidative stress, and inflammatory response in rats with acute hyperlipidemia induced by poloxamer‐407 (P‐407). Rats were pretreated with BBR (25 and 50 mg/kg) for 14 days and acute hyperlipidemia was induced by a single dose of P‐407 (500 mg/kg). BBR ameliorated hypercholesterolemia, hypertriglyceridemia, and plasma lipoproteins in P‐407‐adminsitered rats. Plasma lipoprotein lipase (LPL) activity was decreased, and hepatic 3‐hydroxy‐3‐methylglutaryl CoA (HMG‐CoA) reductase activity was enhanced in hyperlipidemic rats. The expression of low‐density lipoprotein receptor (LDL‐R) and ATP‐binding cassette transporter 1 (ABCA1) was downregulated in hyperlipidemic rats. BBR enhanced LPL activity, upregulated LDL‐R, and ABCA1, and suppressed HMG‐CoA reductase in P‐407‐administered rats. Pretreatment with BBR ameliorated lipid peroxidation, nitric oxide (NO), pro‐inflammatory mediators (interleukin [IL]‐6, IL‐1β, tumor necrosis factor [TNF]‐α, interferon‐γ, IL‐4 and IL‐18) and enhanced antioxidants. In addition, BBR suppressed lymphocyte ecto‐nucleoside triphosphate diphosphohydrolase (E‐NTPDase) and ecto‐adenosine deaminase (E‐ADA) as well as NO and TNF‐α release by macrophages isolated from normal and hyperlipidemic rats. In silico investigations revealed the binding affinity of BBR toward LPL, HMG‐CoA reductase, LDL‐R, PSK9, ABCA1, and E‐NTPDase. In conclusion, BBR effectively prevented acute hyperlipidemia and its associated inflammatory responses by modulating LPL, cholesterolgenesis, cytokine release, and lymphocyte E‐NTPDase and E‐ADA. Therefore, BBR is an effective and safe natural compound that might be employed as an adjuvant against hyperlipidemia and its associated inflammation. [ABSTRACT FROM AUTHOR]

Cancer is one of the most serious human health issues. Drug therapy is the major common way to treat cancer. There is a growing interest in using natural compounds to overcome drug resistance, adverse reactions, and target specificity of certain types of drugs that may affect several targets with fewer side effects and be beneficial against various types of cancer. In this regard, the use of herbal medicines alone or in combination with the main anticancer drugs is commonly available. Berberine (BBR), a nature‐driven phytochemical component, is a well‐known nutraceutical due to its wide variety of pharmacological activities, including antioxidant, anti‐inflammatory, antibacterial, antifungal, antiparasitic, antidiabetic, antihypertensive, and hypolipidemic. In addition, BBR exerts anticancer activities. In present article, we summarized the information available on the therapeutic effects of BBR and its mechanisms on five types of the most prevalent gastrointestinal cancers, including esophageal, gastric, colorectal, hepatocarcinoma, and pancreatic cancers. [ABSTRACT FROM AUTHOR]

Actively treadmilling FtsZ acts as the pivotal scaffold for bacterial cell divisome components, providing them with a circumferential ride along the site of future division. FtsZ from slow-growing Helicobacter pylori (HpFtsZ), a class I carcinogen that thrives abundantly in the acidic environment, is poorly understood. We studied HpFtsZ as a function of pH, cations and time and compared it with well-studied Escherichia coli FtsZ (EcFtsZ). HpFtsZ shows pH-dependent GTPase activity, which is inhibited under acidic conditions. Mg+2 ions play an indispensable role in its GTPase activity; however, higher Mg+2 levels negatively affect its activity. As compared to EcFtsZ, HpFtsZ exhibits lower and slower nucleotide hydrolysing activity. Molecular dynamics simulation studies of FtsZ reveal that GTP binding induces a rewiring of the hydrogen bond network, which results in reduction of the binding cleft volume leading to the spontaneous release of GTP. The GTPase activity is linked to the extent of reduction in the binding cleft volume, which is also supported by the binding free energy analysis. Evidently, HpFtsZ is a pH-sensitive GTPase with low efficiency that may reflect on the overall slow growth rate of H. pylori. [ABSTRACT FROM AUTHOR]

Implementing combination medication through crystal engineering technology receives increasing attention from researchers due to improvements in the clinical treatment effects as well as the physicochemical properties of the drug. Berberine (BER) is commonly used to treat gastroenteritis and bacterial diarrhea, with the problems of poor solubility and low oral bioavailability. Recently, it is found that gallic acid (GA) also has anti‐inflammatory and anti‐bacterial activities. Therefore, if the above‐mentioned two ingredients can be combined, it is possible to enhance the therapeutic effects and physicochemical properties of BER. Inspired by this, 8‐hydroxy‐7,8‐dihydroberberine (8H‐HBER) in this study is employed to react with gallic acid to yield BER gallate dihydrate (2BER‐2GA‐2 W). Furthermore, dissolution experiments demonstrate that the maximum apparent solubility (MAS) of 2BER‐2GA‐2 W in dilute hydrochloric acid solution medium (pH 1.2) has increased by 7 times compared to the commercial form of BER, because of avoiding the common‐ion effect. Moreover, 2BER‐2GA‐2 W has also obviously enhanced stability relative to the commercial form of BER. In addition, 2BER‐2GA‐2 W has a better inhibitory effect on Staphylococcus aureus (S. aureus) relative to the commercial form of BER. Hence, 2BER‐2GA‐2 W will be a promising solid‐state form of BER for its further development. [ABSTRACT FROM AUTHOR]

Human glioblastoma is probably the most malignant and aggressive among cerebral tumors, of which it represents approximately 80% of the reported cases, with an overall survival rate that is quite low. Current therapies include surgery, chemotherapy, and radiotherapy, with associated consistent side effects and low efficacy. The hardness in reaching the site of action, and overcoming the blood–brain barrier, is a major limitation of pharmacological treatments. In this paper, we report the synthesis and characterization of ZIF-90 (ZIF, Zeolitic Imidazolate Framework) nanoparticles as putative carriers of anticancer drugs to the brain. In particular, we successfully evaluated the biocompatibility of these nanoparticles, their stability in body fluids, and their ability to uptake in U251 human glioblastoma cell lines. Furthermore, we managed to synthesize ZIF-90 particles loaded with berberine, an alkaloid reported as a possible effective adjuvant in the treatment of glioblastoma. These findings could suggest ZIF-90 as a possible new strategy for brain cancer therapy and to study the physiological processes present in the central nervous system. [ABSTRACT FROM AUTHOR]

The emergence of multidrug resistance in bacterial infections has limited the use of antibiotics. Helping the action of antibiotics is one of the needs of the day. Today, the biosynthesis of nanoparticles (NPs) is considered due to its safety and cost-effectiveness. In this study, we investigated the effect of biosynthesized silver nanoparticles (AgNPs) by Berberine plant extract against standard strains of multidrug-resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa. Utilized UV–Vis, FTIR, FESEM/EDX, XRD, DLS, and Zeta potential techniques to confirm the biosynthesis of NPs. Then, disk diffusion agar (DDA) and minimum inhibitory concentration (MIC) tests were performed using common classes of standard antibiotics and AgNPs on the mentioned bacteria. The synergistic action between AgNPs and antibiotics was evaluated by the checkerboard method. First, we obtained the confirmation results of the biosynthesis of AgNPs. According to the DDA test, both standard bacterial strains were sensitive to NPs and had an inhibition zone. Also, the MIC values showed that AgNPs inhibit the growth of bacteria at lower concentrations than antibiotics. On the other hand, the results obtained from checkerboard monitoring showed that AgNPs, in combination with conventional antibiotics, have a synergistic effect. The advantage of this study was comparing the antibacterial effect of AgNPs alone and mixed with antibiotics. The antibacterial sensitivity tests indicated that the desired bacterial strains could not grow even in low concentrations of AgNPs. This property can be applied in future programs to solve the drug resistance of microorganisms in bacterial diseases. [ABSTRACT FROM AUTHOR]

Peony seed oil (PSO) is an edible oil with high nutritional value. In this study, a stable oil-in-water microemulsion (Blank-ME) was prepared using PSO as the oil phase, and RH 60-CO 40-Span 80-PEG 200 (RCSP) as surfactants and co-surfactants. The physicochemical properties and stability of Blank-ME samples with different water mass fractions and RCSP/PSO ratios were studied. The average particle size and polydispersity index (PDI) decreased as the water mass fraction increased, and the PDIs of the samples containing PSO were all lower than 0.3. The visual appearance, average particle size, and PDI indicated that Blank-ME samples had good environmental stability when they were centrifuged at 10,000 r/min for 30 minutes, stored at 55 °C for 12 hours, and stored at 4 °C for 10 days. The Blank-ME could effectively encapsulate berberine hydrochloride (BH), and a BH-ME was prepared. The average particle sizes of all BH-ME samples were less than 35.00 nm, and increased as the BH concentration was increased from 0.05 to 1.0 mg/g. The system prepared with a BH concentration of 1.0 mg/g had good structural stability under different storage temperatures (4 °C, 25 °C, and 37 °C). BH and Blank-ME showed good synergy effects (32.87%) of the DPPH• scavenging capacity after 24 hours of reaction. The antitumor and antibacterial activities also exhibited possible synergism between BH and Blank-ME. These findings are positive for the application of MEs and BH in pharmaceutical, food, and other industries. [ABSTRACT FROM AUTHOR]

Monoclonal antibody Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors reduce total cholesterol (TC), low density lipoproteins (LDL), high density lipoproteins (HDL), and triglycerides (TG). We assessed the ability of berberine, a natural PCSK9 inhibitor, to reduce lipid concentrations either alone or combined with other nutraceuticals. We searched PubMed, Scopus and EMBASE from inception to September 30th, 2022 for randomized controlled trials (RCTs) assessing 8-18 wk of berberine therapy on. A total of 41 RCTs with 4,838 patients met our inclusion criteria. Berberine containing products significantly reduced TC (MD −17.42 mg/dL [95%CI: −22.91 to −11.93]), LDL (MD −14.98 mg/dL [95%CI: −20.67 to −9.28]), and TG (MD −18.67 mg/dL [95%CI: −25.82 to −11.51]) while raising HDL (MD 1.97 mg/dL [95%CI: 1.16 to 2.78]) versus control (I2 > 72% for all analyses). Products with berberine alone had less robust effects on TC (MD −12.08 mg/dL [95%CI: −21.79 to −2.37]), LDL (MD −9.26 mg/dL [95%CI: −20.31 to 1.78]), and HDL (MD 1.38 mg/dL [95%CI: −1.27 to 4.03]) but TG effects were similar (MD −17.40 mg/dL [95%CI: −32.57 to −2.23]). Berberine along with red yeast rice reduced TC (MD −19.62 mg/dL [95%CI: −28.56 to −10.68]) and LDL (MD −18.79 mg/dL [95%CI: −28.03 to −9.54]) as did combination therapy with Silybum maranium for TC (MD −31.81 mg/dL [95%CI: −59.88 to −3.73]) and LDL (MD −30.82 mg/dL [95%CI: −56.48 to −5.16]). Berberine, alone or with other nutraceuticals, can provide a modest positive impact on lipid concentrations. [ABSTRACT FROM AUTHOR]

Anthracycline antibiotics, namely, doxorubicin (DOX) and daunorubicin, are among the most widely used anticancer therapies, yet are notoriously associated with severe myocardial damage due to oxidative stress and mitochondrial damage. Studies have indicated the strong pharmacological properties of Berberine (Brb) alkaloid, predominantly mediated via mitochondrial functions and nuclear networks. Despite the recent emphasis on Brb in clinical cardioprotective studies, pharmaceutical limitations hamper its clinical use. A nanoformulation for Brb was developed (mMic), incorporating a cationic lipid, oleylamine (OA), into the TPGS-mixed corona of PEGylated-phosphatidylethanolamine (PEG-PE) micelles. Cationic TPGS/PEG-PE mMic with superior Brb loading and stability markedly enhanced both intracellular and mitochondria-tropic Brb activities in cardiovascular muscle cells. Sub-lethal doses of Brb via cationic OA/TPGS mMic, as a DOX co-treatment, resulted in significant mitochondrial apoptosis suppression. In combination with an intense DOX challenge (up to ~50 µM), mitochondria-protective Brb-OA/TPGS mMic showed a significant 24 h recovery of cell viability (p ≤ 0.05–0.01). Mechanistically, the significant relative reduction in apoptotic caspase-9 and elevation of antiapoptotic Bcl-2 seem to mediate the cardioprotective role of Brb-OA/TPGS mMic against DOX. Our report aims to demonstrate the great potential of cationic OA/TPGS-mMic to selectively enhance the protective mitohormetic effect of Brb to mitigate DOX cardiotoxicity. [ABSTRACT FROM AUTHOR]

Berberine is a natural isoquinoline alkaloid with low toxicity, which exists in a wide variety of medicinal plants. Berberine has been demonstrated to exhibit potent prevention of indomethacin-induced gastric injury (GI) but the related mechanism remains unclear. In the present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied for the first time to investigate the alteration of serum metabolites in the protection of berberine against indomethacin-induced gastric injury in rats. Subsequently, bioinformatics was utilized to analyze the potential metabolic pathway of the anti-GI effect of berberine. The pharmacodynamic data indicated that berberine could ameliorate gastric pathological damage, inhibit the level of proinflammatory factors in serum, and increase the level of antioxidant factors in serum. The LC-MS-based metabolomics analysis conducted in this study demonstrated the presence of 57 differential metabolites in the serum of rats with induced GI caused by indomethacin, which was associated with 29 metabolic pathways. Moreover, the study revealed that berberine showed a significant impact on the differential metabolites, with 45 differential metabolites being reported between the model group and the group treated with berberine. The differential metabolites were associated with 24 metabolic pathways, and berberine administration regulated 14 of the 57 differential metabolites, affecting 14 of the 29 metabolic pathways. The primary metabolic pathways affected were glutathione metabolism and arachidonic acid metabolism. Based on the results, it can be concluded that berberine has a gastroprotective effect on the GI. This study is particularly significant since it is the first to elucidate the mechanism of berberine's action on GI. The results suggest that berberine's action may be related to energy metabolism, oxidative stress, and inflammation regulation. These findings may pave the way for the development of new therapeutic interventions for the prevention and management of NSAID-induced GI disorders. [ABSTRACT FROM AUTHOR]

The prevalence and incidence of obesity and the comorbidities linked to it are increasing worldwide. Current therapies for obesity and associated pathologies have proven to cause a broad number of adverse effects, and often, they are overpriced or not affordable for all patients. Among the alternatives currently available, natural bioactive compounds stand out. These are frequently contained in pharmaceutical presentations, nutraceutical products, supplements, or functional foods. The clinical evidence for these molecules is increasingly solid, among which epigallocatechin-3-gallate, ellagic acid, resveratrol, berberine, anthocyanins, probiotics, carotenoids, curcumin, silymarin, hydroxy citric acid, and α-lipoic acid stand out. The molecular mechanisms and signaling pathways of these molecules have been shown to interact with the endocrine, nervous, and gastroenteric systems. They can regulate the expression of multiple genes and proteins involved in starvation–satiety processes, activate the brown adipose tissue, decrease lipogenesis and inflammation, increase lipolysis, and improve insulin sensitivity. This review provides a comprehensive view of nature-based therapeutic options to address the increasing prevalence of obesity. It offers a valuable perspective for future research and subsequent clinical practice, addressing everything from the molecular, genetic, and physiological bases to the clinical study of bioactive compounds. [ABSTRACT FROM AUTHOR]

Objectives: Despite significant advancements in modern medicine, effective hepatoprotective medication with minimal side effects is still lacking. In this context. Tinospora cordifolia, an Indian Ayurvedic liana, has attracted much attention. Key findings: Traditionally, T. cordifolia has been found to be effective in the treatment of jaundice; according to the literature, T. cordifolia is a hepatoprotective agent, and the CCl4 model is the most frequently used to evaluate its potential. Its hepatoprotective effects might be attributed to alkaloids (berberine, palmatine, and jatrorrhizine) and sinapic acid. Berberine decreases inflammation by inhibiting the proinflammatory cascade triggered by TNF-α and reduces nitrosative stress by inhibiting iNOS. T. cordifolia also exhibits anticancer, anti-inflammatory, antimicrobial, antioxidant, and other activities; it is safe at concentrations up to 2000 mg/kg. Its biological action can be attributed to polyphenols, alkaloids, steroids, terpenoids, and glycosides. T. cordifolia has also been found to be an active ingredient in several polyherbal formulations used to treat chemical-mediated hepatotoxicity. Conclusion: T. cordifolia's hepatoprotective effects are mediated by the inhibition of lipid peroxidation, the management of oxidative stress, and other factors. T. cordifolia can be used to manage liver disorders and as a hepatoprotective supplement in the food industry. The bioprospecting of its alkaloids can lead to the development of novel formulations against hepatic ailments. [ABSTRACT FROM AUTHOR]