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The risk of ulcerative colitis (UC) is increasing worldwide with limited success using classical drugs, which has underscored the development of novel agents. Recently, carrier-free molecular assembly has been proven to be an effective drug delivery system, but it has yet to be examined for UC drug development using phytochemicals. Based on traditional Chinese medicine compatibility and potential medicinal uses, a pair of natural compounds, berberine (BBR) and magnolol (MAG), were found to self-assemble into nanostructures in aqueous solutions. Spectral analysis revealed that the assembly mechanisms of BBR and MAG were mediated through charge interactions and π-π stacking. Pharmacokinetic studies and animal imaging showed that BBR-MAG self-assembly (BM) effectively promoted the oral bioavailability and biodistribution of BBR in the colon. BM exhibited superior effects in regulating inflammatory factors, maintaining colon barrier integrity, and regulating gut microbiota in a dextran sulfate sodium salt-induced colitis mouse model. Additionally, no apparent signs of toxicity were observed, suggesting that BM has a favorable safety profile. This study presents a new strategy for UC management and highlights the cooperative effects of combined phytochemicals. [ABSTRACT FROM AUTHOR]

Antioxidant-rich supplementation plays an essential role in the function of mammals’ central nervous system. However, no research has documented the effect of berberine (BER) supplementation on the cerebrocerebellar function of prepubertal rats. The present study was designed to investigate the impact of BER supplementation on neurochemical and behavioural changes in prepubertal male rats. Five groups (90 ± 5 g, n = 7 each) of experimental rats were orally treated with corn oil or different doses of BER (25, 50, 100, and 200 mg/kg bw) from the 28th at 68 post-natal days. On the 69 days of life, animals underwent behavioural assessment in the open field, hanging wire, and negative geotaxis tests. The result revealed that BER administration improved locomotive and motor behaviour by increasing distance travelled, line crossings, average speed, time mobile, and absolute turn angle in open field test and decrease in time to re-orient on an incline plane, a decrease in immobility time relative to the untreated control. Furthermore, BER supplementation increased (p < 0.05) antioxidant enzyme activities such as SOD, CAT, GPx, GSH, and TSH and prevented increases (p < 0.05) in oxidative and inflammatory levels as indicated by decreases in RONS, LPO, XO, carbonyl protein, NO, MPO, and TNF-α compared to the untreated control. BER-treated animals a lessened number of dark-stained Nissl cells compared to the untreated control rats. Our findings revealed that BER minimised neuronal degeneration and lesions, improved animal behaviour, and suppressed oxidative and inflammatory mediators, which may probably occur through its agonistic effect on PPAR-α, PPAR-δ, and PPAR-γ – essential proteins known to resolve inflammation and modulate redox signalling towards antioxidant function. [ABSTRACT FROM AUTHOR]

Introduction and purpose : Type 2 diabetes is currently a serious problem worldwide. Each year, the number of individuals with carbohydrate metabolism disorders is increasing. This is due to an unhealthy lifestyle, lack of physical activity, and a diet rich in highly processed foods. Currently, the treatment of type 2 diabetes is based on the use of oral antidiabetic medications, with the first choice often being a derivative of biguanides, such as metformin. Berberine has been used in China for many years as a hypoglycemic agent, and its efficacy is compared to metformin preparations. This paper focuses on the benefits of using berberine in patients with prediabetes or type 2 diabetes and compares the effects of berberine preparations to classical medications used in diabetes treatment. Material and methods : The literaue was reviewed in PubMed and Google Scholar scientific database in 2013-2023 using the following keywords : berberine, diabetes mellitus type 2, hyperlipidemia, hyperglicemia. Conclusions : The studies included in this manuscript have shown that berberine is a promising agent for adjunctive treatment in type 2 diabetes. It exhibits a range of positive effects such as lowering blood glucose levels, improving lipid profile, with no serious adverse effects reported. However, further research is needed to confirm these findings and develop an effective treatment plan. [ABSTRACT FROM AUTHOR]

Simple Summary: Yaks are economically important food animals in the plateau regions of China, but bacterial diarrheal diseases frequently occur, with limited effective treatments. In this study, we investigated the effects of Lactobacillus salivarius and berberine on diarrheal yak calves. Our results showed that yaks treated with Lactobacillus salivarius and berberine had higher weight growth rates and lower diarrhea scores. Serum analysis indicated that these treatments increased the levels of T-AOC, SOD, GSH-Px, and IL-10 while reducing MDA, TNF-α, IL-1β, and IL-6. Microbiota sequencing identified significant changes in two phyla and twenty-seven genera, including beneficial genera, such as Faecalibaculum and Parvibacter, and harmful genera, like Marvinbryantia and Lachnospiraceae UCG-001. These findings provide novel insights for developing new therapies to combat ruminant diarrhea. Yaks are important food animals in China; however, bacterial diarrheal diseases frequently occur on the plateau, with limited effective therapies. The objective of this research was to evaluate the effectiveness of Lactobacillus salivarius (LS) and berberine in alleviating diarrhea in yak calves. For this purpose, eighteen healthy yak calves were divided into control (JC), infected (JM), and treatment (JT) groups. Yaks in the JT group were treated with 2 × 1010 CFU/calf L. salivarius and 20 mg/kg berberine, and yaks in the JM and JT groups were induced with multi-drug-resistant Escherichia coli. The results showed that the weight growth rate in the JM group was significantly lower than that in the JC and JT groups. The diarrhea score in the JM group was significantly higher than that in both the JC and JT groups. Additionally, the contents of T-AOC, SOD, GSH-Px, and IL-10 were significantly lower in the JM group than those in the JC and JT groups, while MDA, TNF-α, IL-1β, and IL-6 were significantly higher in the JM group. Microbiota sequencing identified two phyla and twenty-seven genera as significant among the yak groups. Notably, probiotic genera such as Faecalibaculum and Parvibacter were observed, alongside harmful genera, including Marvinbryantia and Lachnospiraceae UCG-001. Our findings indicate that treatment with L. salivarius and berberine significantly reduced diarrhea incidence, improved growth performance, and positively modulated intestinal microbiota, which could provide novel insights for developing new therapies for ruminant diarrhea. [ABSTRACT FROM AUTHOR]

Bovine mastitis caused by infectious pathogens, mainly Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), constitutes a major destructive challenge for the dairy industry and public health. Berberine chloride (BER) and Cyperus rotundus possess a broad spectrum of anti-inflammatory, antioxidant, antibacterial, and antiproliferative activities; however, their bioavailability is low. This research aimed first to prepare an ethanolic extract of Cyperus rotundus rhizomes (CRE) followed by screening its phytochemical contents, then synthesis of BER and CRE loaded chitosan nanoparticles (NPs) (BER/CH-NPs and CRE/CH-NPs), afterward, the analysis of their loading efficiency in addition to the morphological and physicochemical characterization of the formulated NPs employing Scanning Electron Microscopy (SEM), Zeta Potential (ZP), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) assessments compared to their crude forms to evaluate the enhancement of bioavailability and stability. Isolation of bacterial strains from the milk of mastitic cows, used for induction of mammary gland (MG) inflammation in female albino rats, and a preliminary investigation of the prophylactic oral doses of the prepared NPs against S. aureus-induced mastitis in female rats. The minimal inhibitory concentration (MIC) of BER/CH-NPs and CRE/CH-NPs is 1 mg/kg b.w. BER/CH-NPs and CRE/CH-NPs alone or in combination show significant (P ≤ 0.05) DPPH radical scavenging activity (69.2, 88.5, and 98.2%, respectively) in vitro. Oral administration of BER/CH-NPs and CRE/CH-NPs to mastitis rats significantly (P ≤ 0.05) attenuated TNF-α (22.1, 28.6 pg/ml), IL-6 (33.4, 42.9 pg/ml), IL-18 (21.7, 34.7 pg/ml), IL-4 (432.9, 421.6 pg/ml), and MPO (87.1, 89.3 pg/ml) compared to mastitis group alongside the improvement of MG histopathological findings without any side effect on renal and hepatic functions. Despite promising results with BER and CRE nanoparticles, the study is limited by small-scale trials, a focus on acute administration, and partially explored nanoparticle-biological interactions, with no economic or scalability assessments. Future research should address these limitations by expanding trial scopes, exploring interactions further, extending study durations, and assessing economic and practical scalability. Field trials and regulatory compliance are also necessary to ensure practical application and safety in the dairy industry. In conclusion, the in vitro and in vivo results proved the antioxidant and anti-inflammatory efficacy of BER/CH-NPs and CRE/CH-NPs in low doses with minimal damage to the liver and kidney functions, supposing their promising uses in mastitis treatment. [ABSTRACT FROM AUTHOR]

Melanoma is a cutaneum carcinoma caused by the malignant transformation of melanocytes. This study aimed to predict potential targets of berberine in melanoma treatment and its mechanism of action through a network pharmacological analysis. The GeneCards databases and SwissTargetPrediction yielded five overlapped targets, including RAC1, CDK4, KIT, and CHEK2. The components-targets network diagram indicated that berberine interacted with the targets. The molecular docking showed that berberine exhibited a high binding affinity with all five targets and bound to them through hydrogen bonding and hydrophobicity. Furthermore, gene ontology enrichment analysis revealed that these targets were primarily involved in the hepatocyte growth factor receptor signaling pathway, followed by positive regulation of microtubule polymerization. The PI3K-Akt, Rap1, and Ras signaling pathways were the most significant influences in the Kyoto Encyclopedia of Genes and Genome analysis. This study predicted that berberine may be involved in the hepatocyte growth factor receptor signaling pathway and the PI3K-Akt signaling pathway in melanoma through MET, RAC1, CDK4, KIT, and CHEK2 through network pharmacological methods. [ABSTRACT FROM AUTHOR]

Berberine is an isoquinolone alkaloid present in a wide variety of plants. Other than Type 2 diabetes and hypertension it is also found to have an effect in lowering blood cholesterol levels. However, because of its poor oral bioavailability and substantial first pass hepatic metabolism it is consumed in higher dosage leading to side effects. To reduce dosage and avoid adverse effects, transdermal delivery is investigated using transethosomal gel as a carrier. Transethosomes are ethanolic nanocarriers that are specifically designed for the dermal or transdermal delivery route as it has enhanced permeation of the vesicles. In our study we have successfully investigated the potential use of berberine loaded transethosomal gel (BBR-TE) as a carrier for transdermal delivery. Three-level three-factorial Box Behnken Design was used to optimize BBR-TE (Opt-BBR-TE). The optimized formulation was further evaluated and found to have a particle size of 165.70 nm with entrapment efficiency of 79.60±4.07%. The in vitro drug release study suggested the non-Fickian transport mechanism. The ex vivo skin permeation was found to be 94.35±3.64% when compared to berberine conventional formulation. Berberine has also shown promising antioxidant activity when compared to the standard solution and was entrapped inside TE vesicles in non-crystalline form. The Opt-BBR-TE was converted into gel form. Various parameters of the gel such as pH, Drug Content, Spreadability and extrudability were found to have promising results. Present study data revealed that the developed transethosomal gel formulation was found to be a potentially useful drug carrier for transdermal delivery of berberine. [ABSTRACT FROM AUTHOR]

Given the increasing aging population and the rising prevalence of musculoskeletal diseases due to obesity and injury, urgent research is needed to formulate new treatment alternatives, as current options remain inadequate. Viruses can exacerbate arthritis and worsen symptoms in patients with pre-existing osteoarthritis. Over the past decade, the chikungunya virus (CHIKV) has emerged as a significant public health concern, especially in Asia and South America. Exploring natural products, such as berberine, has shown promise due to its anticatabolic, antioxidative, and anti-inflammatory effects. However, berberine's low stability and bioavailability limit its efficacy. We hypothesized that encapsulating berberine into a proniosome gel, known for its ease of preparation and stability, could enhance its bioavailability and efficacy when applied topically, potentially treating CHIKV infection. Our investigation focused on how varying berberine loads and selected excipients in the proniosome gel influenced its physical properties, stability, and skin permeability. We also examined the biological half-life of berberine in plasma upon topical administration in mice to assess the potential for controlled and sustained drug release. Additionally, we analyzed the antioxidant stress activity and cell viability of HaCaT keratinocytes and developed a lipopolysaccharide-stimulated cell culture model to evaluate anti-inflammatory effects using pro-inflammatory cytokines. Overall, the research aims to transform the treatment landscape for arthritis by leveraging berberine's therapeutic potential. [ABSTRACT FROM AUTHOR]

Berberine (BBR), as a natural isoquinoline alkaloid, has demonstrated various pharmacological activities, and is widely applied in the treatment of diseases. The quantitative analysis of BBR is important for pharmacological studies and clinical applications. In this work, utilizing the specific interaction between BBR and triplex DNA, a sensitive and selective fluorescent detecting method was established with DNA-templated silver nanoclusters (DNA-AgNCs). After binding with the triplex structure in the template of DNA-AgNCs, BBR quenched the fluorescence of DNA-AgNCs and formed BBR-triplex complex with yellow–green fluorescence. The ratiometric fluorescence signal showed a linear relationship with BBR concentration in a range from 10 nM to 1000 nM, with a detection limit of 10 nM. Our method exhibited excellent sensitivity and selectivity, and was further applied in BBR detection in real samples. [ABSTRACT FROM AUTHOR]

This study compared the capacity of two different models of HIIT [high‐(HC) and low‐(LC) compression], with or without the use of berberine (BBR), on NOD‐like receptor pyrin domain‐containing protein‐3 (NLRP3), H19, interleukin (IL)‐1β, high‐sensitivity C‐reactive protein (hs‐CRP), and insulin resistance markers. Fifty‐four middle‐aged men with overweight or obesity and prediabetes [fasting blood glucose (FBG) 110–180 mg/dL] were randomly and equally assigned to the HC, LC, HC + BBR, LC + BBR, BBR, and non‐exercising control (CON) groups. The HC (2:1 work‐to‐rest) and LC (1:1 work‐to‐rest) home‐based training programs included 2–4 sets of 8 exercises at 80%–95% HRmax, twice a week for 8 weeks. Participants in the berberine groups received approximately 1000 mg daily. All exercise interventions led to a significant reduction in hs‐CRP, IL‐1β, insulin, FBG, and insulin resistance index (HOMA‐IR) versus CON. Notably, there was a significant reduction in FBG and HOMA‐IR with the BBR group compared to the baseline. Both NLRP3 and H19 experienced a significant drop only with LC in comparison to the baseline. While both exercise protocols were beneficial overall, LC uniquely exhibited more anti‐inflammatory effects, as indicated by reductions in H19 and NLRP3. However, the addition of berberine to the exercise programs did not demonstrate additional benefits. [ABSTRACT FROM AUTHOR]

Small intestine damage caused by diclofenac is called diclofenac enteropathy. Berberine (BBR), a class of isoquinoline alkaloids derived from Berberis vulgaris and Phellodendron amurense, is widely used in intestinal diseases. The present study evaluated the protective effect of BBR on the intestinal mucosal mechanical barrier in diclofenac enteropathy and its possible action mechanism. The in vitro animal experiment revealed that BBR downregulated the expression of long non-coding RNA H19 (lncRNA H19) in the small intestine and exosomes. In the co-culture experiment involving exosomes and intestinal epithelial cell-6 (IEC-6) cells, the results of qRT-PCR, western blotting, and immunofluorescence assays demonstrated that the elevated expression of lncRNA H19 in the small intestine, conveyed via exosomes derived from the diclofenac group, suppressed the expression levels of autophagy-associated protein 5 (Atg 5) and light chain 3 (LC 3), as well as and the tight junction (TJ) proteins zonula occludens-1 (ZO-1), claudin-1, and occluding, relative to the control group. BBR treatment attenuated exosomal lncRNA H19 levels, upregulated the expression of Atg5 and LC3 expression, enhanced TJ protein expression, and increased the light chain 3 (LC3)-II/LC3-I ratio. These findings significantly elucidated that BBR promoted the restoration of autophagy in IECs by inhibiting exosomal lncRNA H19, thereby mitigating the impairment of the intestinal mucosal mechanical barrier function in diclofenac enteropathy. The process involving exosomal lncRNA H19 regulating autophagy, thereby affecting the intestinal mucosal mechanical barrier, offers a novel perspective for the application of BBR in the treatment of diclofenac enteropathy. [ABSTRACT FROM AUTHOR]

The rising incidence of colorectal cancer (CRC) and gastric cancer (GC) worldwide, coupled with the limited effectiveness of current chemotherapeutic agents, has prioritized the search for new therapeutic options. Natural substances, which often exhibit cytostatic properties, hold significant promise in this area. This review evaluates the anticancer properties of three natural alkaloids—berberine, sanguinarine, and chelerythrine—against CRC and GC. In vivo and in vitro studies have demonstrated that these substances can reduce tumor volume and inhibit the epithelial–mesenchymal transition (EMT) of tumors. At the molecular level, these alkaloids disrupt key signaling pathways in cancer cells, including mTOR, MAPK, EGFR, PI3K/AKT, and NF-κB. Additionally, they exhibit immunomodulatory effects, leading to the induction of programmed cell death through both apoptosis and autophagy. Notably, these substances have shown synergistic effects when combined with classical cytostatic agents such as cyclophosphamide, 5-fluorouracil, cetuximab, and erlotinib. Furthermore, berberine has demonstrated the ability to restore sensitivity in individuals originally resistant to cisplatin GC. Given these findings, natural compounds emerge as a promising option in the chemotherapy of malignant gastrointestinal tumors, particularly in cases with limited treatment options. However, more research is necessary to fully understand their therapeutic potential. [ABSTRACT FROM AUTHOR]

Sulphated glycosaminoglycans (GAGs) such as heparin are a major component of mast cell granules and form the matrix within which biogenic mediators are stored. Since GAGs released from mast cells also play an important role in helminth expulsion, understanding GAG storage can offer new insights into mast cell function. Sodium butyrate (NaBu), a short-chain fatty acid, causes ultrastructural changes within the granules of human mast cells (HMC-1) and increases their histamine content. Therefore, we hypothesized that NaBu treatment would also modify the storage of polysaccharides such as GAGs. NaBu (1 mM) significantly increased GAG content and granularity in a time- and concentration-dependent manner without affecting cell viability and metabolic activity. NaBu increased the expression of enzymes associated with heparin biosynthesis (GLCE, NDST1, NDST2, HS6ST1, and GALT1) in a time-dependent manner. A cholesteryl butyrate emulsion (CholButE) increased heparin content after 24 and 48 h and modestly altered the expression of genes involved in heparin biosynthesis. Similar to NaBu, CholButE reduced cell proliferation without significantly altering viability or metabolic activity. These data show that butyrate increases the synthesis and storage of heparin in human mast cells, perhaps by altering their metabolic pathways. [ABSTRACT FROM AUTHOR]

Context: Diabetes mellitus (DM) is a metabolic disorder disease that causes hyperglycemia conditions and associated with various chronic complications leading to mortality. Due to high toxicity of conventional diabetic drugs, the exploration of natural compounds as alternative diabetes treatments has been widely carried out. Previous in silico studies have highlighted berberine, a natural compound, as a promising alternative in antidiabetic therapy, potentially acting through various pathways, including the inhibition of the FOXO1 transcription factor in the gluconeogenesis pathway. However, the specific mechanism by which berberine interacts with FOXO1 remains unclear, and research in this area is relatively limited. Therefore, this study aims to determine the stability of berberine structure with FOXO1 based on RMSD, RMSF, binding energy, and trajectory analysis to determine the potential of berberine to inhibit the gluconeogenesis pathway. This research was conducted by in silico method with molecular docking using AutoDock4.2 and molecular dynamics study using Amber20, then visualized by VMD. Methods: Docking between ligand and FOXO1 receptor was carried out with Autodock4.2. For molecular dynamics simulations, the force fields of DNA.OL15, protein.ff14SB, gaff2, and tip3p were used. [ABSTRACT FROM AUTHOR]

Background: Global cerebral ischemia (GCI) is characterized by the hindrance of blood flow to the brain due to obstruction in the carotid arteries. In this study, the neuroprotective effects of berberine chloride (BBR) and cinnamaldehyde (CA) against GCI in male Wistar rats were investigated, and their efficacy was compared. Methods: Twenty‐four rats were randomly assigned to four groups: Sham, GCI, GCI + BBR, and GCI + CA. 100 mg/kg of BBR and CA were administered five minutes and six hours after inducing GCI by occluding two common carotids for 20 minutes. Results: The findings showed that both compounds mitigated GCI‐induced damage to the hippocampus and its subfields, and CA demonstrated better neuroprotective efficacy than BBR. These results was also supported by behavioural tests, which revealed better memory function in GCI + CA compared to GCI + BBR. Conclusion: The study showed the neuroprotective impact of CA and BBR against GCI, and CA emerged as a more effective therapeutic agent against GCI‐induced damage. Further research is necessary to uncover the specific mechanisms behind these differences. [ABSTRACT FROM AUTHOR]

The purpose of this study was to demonstrate the regulatory effect of berberine (BBR) on the intestinal microbiota and related epigenetics during the inhibition of colon cancer cell growth in vitro and in vivo. We used a nude mouse xenograft model with HT29 colon cancer cells to establish and divide into a model group and BBR group. The mice were treated for four weeks, and HT29 cells in the BBR group were cultured for 48 h. Cetuximab and the DNA transmethylase (DNMT) inhibitor 5-AZA-dC were added to HT29 cells. Tumour volume and weight were measured by hematoxylin–eosin (HE) staining for histopathological observation. Mouse faeces were collected, and the gut microbiota was analysed with 16S rDNA amplicons. The levels of cytokines in the supernatant of HT29 cells were measured by ELISA. A CCK-8 kit was used to examine the proliferation of HT29 cells, and RT‒PCR was used to measure the levels of c-Myc, DNMT1, DNMT3A, and DNMT3B. We found that BBR reduced the growth of colon cancer cells to a certain extent in vitro and in vivo, although the difference was not statistically significant compared with that in the model group. BBR significantly mediated the abundance, composition and metabolic functions of the intestinal microbial flora in mice with colon cancer. The effect of BBR on inflammatory cytokines, including IL-6, FGF, and PDGF, was not obvious, but BBR significantly downregulated IL-10 levels (P < 0.05) and reduced c-Myc, DNMT1, and DNMT3B levels (P < 0.05). Inhibiting DNMTs with 5-AZA-dC significantly suppressed the proliferation of HT29 cells, which was consistent with the effect of BBR. The inhibitory effect of berberine on colon cancer is related not only to the intestinal microbiota and its metabolic functions but also to the regulation of DNMTs. [ABSTRACT FROM AUTHOR]

Cyclophosphamide (CYP) is widely used to treat various types of cancer. In addition to the therapeutic properties of this drug, unfortunately, its side effects are still not fully understood. This study investigated the protective effect of curcumin (CURC) and berberine (BER) on CYP‐induced cardiac damage. Thirty‐six male rats were equally divided into the control, dimethyl sulfoxide (DMSO), CYP, CYP + CURC, CYP + BER and CYP + BER + CURC groups. Troponin‐I, Creatine kinase‐myocardial band (CK‐MB), total cholesterol, triglyceride levels in serum samples, and reactive oxygen species (ROS), poly(ADP‐ribose) polymerase‐1 (PARP‐1), and transient receptor potential melastatin 2 (TRPM2) channel levels in heart tissue were measured using an enzyme‐linked immunoassay (ELISA) kit. In addition, histopathological examination and immunohistochemical investigation of the TRPM2 channel, fibroblast specific protein‐1 (FSP1), transforming growth factor‐beta‐ 1 (TGF‐β1) and α‐smooth muscle actin (α‐SMA) expressions were determined in heart tissue. The CYP group's troponin‐I, total cholesterol, triglyceride, CK‐MB, ROS, PARP‐1 and TRPM2 channel levels were higher than in the other groups in the ELISA measurements (p < 0.05). In contrast, these parameters in the group treated with CURC and BER together with CYP were lower than in the CYP group (p < 0.05). Additionally, CUR and BER reduced CYP‐induced pathological damage, TRPM2, FSP1, TGF‐β1 and α‐SMA expressions. The data showed that CYP administration can cause cardiac damage by increasing the TRPM2 channel, TGF‐β1, FSP1 and α‐SMA expression levels. Therefore, we concluded that CURC and BER administration following CYP application may be used as therapeutic agents to prevent CYP‐induced cardiac damage. [ABSTRACT FROM AUTHOR]

Lung cancer is the second most prevalent cancer and ranks first in cancer‐related death worldwide. Due to the resistance development to conventional cancer therapy strategies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, various natural products and their extracts have been revealed as alternatives. Berberine (BBR), which is present in the stem, root, and bark of various trees, could exert anticancer activities by regulating tumor cell proliferation, apoptosis, autophagy, metastasis, angiogenesis, and immune responses via modulating several signaling pathways within the tumor microenvironment. Due to its poor water solubility, poor pharmacokinetics/bioavailability profile, and extensive p‐glycoprotein‐dependent efflux, BBR application in (pre) clinical studies is restricted. To overcome these limitations, BBR can be encapsulated in nanoparticle (NP)‐based drug delivery systems, as monotherapy or combinational therapy, and improve BBR therapeutic efficacy. Nanoformulations also facilitate the selective delivery of BBR into lung cancer cells. In addition to the anticancer activities of BBR, especially in lung cancer, here we reviewed the BBR nanoformulations, including polymeric NPs, metal‐based NPs, carbon nanostructures, and others, in the treatment of lung cancer. [ABSTRACT FROM AUTHOR]

Obesity and Type 2 diabetes are prevalent metabolic dysfunctions that present significant health challenges worldwide. Available cures for these ailments have constraints with accompanying unwanted effects that persistently exist. Compounds originated from plants have recently been introduced as hopeful remedies to treat metabolic disorders because of their diverse pharmacological activities. This detailed observation gives an introduction into the treatment capacity of plant‐derived compounds regarding metabolic syndromes while analyzing various groups alongside their performance in this field despite unique mechanisms designed by nature itself. Interestingly, this study provides some examples including curcumin, resveratrol, quercetin, berberine, epigallocatechin gallate (EGCG), and capsaicin, which highlights potential therapeutic impacts for future testing. However, current clinical trials inspecting human studies investigating efficacies concerning metabolism challenge present limitations. Finally, the review weighs up bad reactions possibly inflicted after administering plant‐originated materials though suggestive insights will be provided later. Above all, it outlines the chance to identify novel therapies encapsulated within natural substances based upon recent developments could hold significant promise toward managing misplaced metabolisms globally. [ABSTRACT FROM AUTHOR]

Global cerebral ischemia (GCI) results in damage to the neurons and leads to cognitive impairments. Berberine (BBR) is known for its neuroprotective qualities. This study aimed to investigate the effects of BBR on memory, Blood–brain barrier (BBB) permeability, biochemical factors, and neuronal structure. Sixty‐three adult male Wistar rats were divided randomly into Sham (21), GCI (21), and GCI + BBR (21) groups. The GCI + BBR group received 50 mg/kg of BBR for 7 days before and 6 h after 20 min of GCI induction. After 24 h, assessments included hippocampal neuronal structure, catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GPX) levels, memory performance, and BBB permeability. The GCI + BBR group reduced volume loss in the CA1 and its sublayers (oriens, pyramidal, and radiatum) compared to the GCI group (p < 0.0001, p < 0.001, p < 0.01 and p < 0.001, respectively). Additionally, the GCI + BBR group showed higher pyramidal neuron density (p < 0.0001) and number (p < 0.0001) compared to the GCI group. BBR also decreased MDA levels (p < 0.0001) and increased CAT activity (p < 0.0001) in the GCI + BBR group compared to the GCI group, with GPX and SOD activity approaching Sham levels (p < 0.0001, both). BBR demonstrated significant improvements in short and long‐term memory compared to the GCI group (p < 0.01, p < 0.0001, respectively). Furthermore, BBB permeability in the GCI + BBR group was significantly reduced compared to the GCI group (p < 0.0001). These findings demonstrated BBR's potential to protect the neurons in the CA1 and BBB structures, enhance antioxidant activity, and alleviate GCI‐induced memory impairments. [ABSTRACT FROM AUTHOR]

White adipose tissue accumulation and inflammation contribute to obesity by inducing insulin resistance. Herein, we aimed to screen the synergistic components of the herbal pair Coptidis Rhizoma‐Glycyrrhizae Radix et Rhizoma for the treatment of insulin resistance and explore the potential synergistic mechanisms. Enzyme‐linked immunosorbent assay and quantitative PCR were used to detect expression levels of inflammatory genes in vitro and in vivo. Western blotting and immunohistochemistry were performed to detect protein levels of the insulin signaling pathway and macrophage markers. The effects on obesity‐induced insulin resistance were verified using a diet‐induced obesity (DIO) mouse model. Interactions between macrophage and adipocyte were assessed using a cellular supernatant transfer assay. Berberine (BBR) and isoliquiritigenin (ISL) alleviated mRNA levels and secretion of inflammatory genes in vitro and in vivo. Furthermore, BBR acted synergistically with ISL to ameliorate obesity and dyslipidemia in DIO mice. Meanwhile, the combination treatment significantly improved glucose intolerance and insulin resistance and decreased M1‐macrophage accumulation and infiltration in the adipose tissue. Mechanistically, co‐treatment with BBR and ISL upregulated the protein expression of the IRS1‐PI3K‐Akt insulin signaling pathway, enhanced glucose uptake in adipocyte, and suppressed the interaction between macrophage and adipocyte. BBR and ISL were identified as the synergistic components of the herbal pair Coptidis Rhizoma‐Glycyrrhizae Radix et Rhizoma for treating insulin resistance. The synergistic combination of BBR with ISL can be a promising and effective strategy for improving obesity‐induced adipose inflammation and insulin resistance. [ABSTRACT FROM AUTHOR]

The present study, as one part of a larger project that aimed to investigate the effects of dietary berberine (BBR) on fish growth and glucose regulation, mainly focused on whether miRNAs involve in BBR's modulation of glucose metabolism in fish. Blunt snout bream Megalobrama amblycephala (average weight of 20.36 ± 1.44 g) were exposed to the control diet (NCD, 30% carbohydrate), the high-carbohydrate diet (HCD, 43% carbohydrate) and the berberine diet (HCB, HCD supplemented with 50 mg/kg BBR). After 10 weeks' feeding trial, intraperitoneal injection of glucose was conducted, and then, the plasma and liver were sampled at 0 h, 1 h, 2 h, 6 h, and 12 h. The results showed the plasma glucose levels in all groups rose sharply and peaked at 1 h after glucose injection. Unlike the NCD and HCB groups, the plasma glucose in the HCD group did not decrease after 1 h, while remained high level until at 2 h. The NCD group significantly increased liver glycogen content at times 0–2 h compared to the other two groups and then liver glycogen decreased sharply until at times 6–12 h. To investigate the role of BBR that may cause the changes in plasma glucose and liver glycogen, miRNA high-throughput sequencing was performed on three groups of liver tissues at 2 h time point. Eventually, 20 and 12 differentially expressed miRNAs (DEMs) were obtained in HCD vs NCD and HCB vs HCD, respectively. Through function analyzing, we found that HCD may affect liver metabolism under glucose loading through the NF-κB pathway; and miRNAs regulated by BBR mainly play roles in adipocyte lipolysis, niacin and nicotinamide metabolism, and amino acid transmembrane transport. In the functional exploration of newly discovered novel:Chr12_18892, we found its target gene, adenylate cyclase 3 (adcy3), was widely involved in lipid decomposition, amino acid metabolism, and other pathways. Furthermore, a targeting relationship of novel:Chr12_18892 and adcy3 was confirmed by double luciferase assay. Thus, BBR may promote novel:Chr12_18892 to regulate the expression of adcy3 and participate in glucose metabolism. [ABSTRACT FROM AUTHOR]

Background and Objective: Periodontitis is intimately associated with the development of various systemic diseases, among which type 2 diabetes mellitus (T2DM) has a bidirectional relationship with the pathogenesis of periodontitis. The objective of the present work was to investigate the role of berberine (BBR) in periodontitis with T2DM and related mechanisms. Methods: The mRNA expression of macrophage polarization‐related factors in the microenvironment of periodontal inflammation was detected using real‐time quantitative PCR (RT‐qPCR). The experimental periodontitis model was constructed in wild‐type (WT) and T2DM (db/db) mice, which were administered BBR after 7 days of modeling. Alveolar bone loss (ABL) in each group of mice was measured utilizing micro‐computed tomography images. RT‐qPCR was performed to analyze the levels of macrophage polarization‐related factors in mouse gingiva. Lastly, using western blotting and RT‐qPCR, the signaling pathway of BBR affecting macrophage polarization in the microenvironment of periodontitis was explored. Results: BBR inhibited M1 polarization and stimulated M2 polarization in the periodontitis microenvironment. BBR decreased ABL in the WT and T2DM periodontitis models. And BBR reduced the production of proinflammatory cytokines and increased anti‐inflammatory cytokine expression in the gingiva of WT and T2DM model mice. Ultimately, BBR mediates its anti‐inflammatory effects on periodontitis through inhibition of the NF‐κB pathway. Conclusions: BBR had a therapeutic effect on T2DM‐associated periodontitis via inhibiting the NF‐κB pathway to affect macrophage polarization, which may have implications for the new pharmacological treatment of T2DM‐associated periodontitis. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH), for which there are currently no effective preventive or treatment methods, has a very high fatality rate. Statins, such as atorvastatin (ATV), are the first‐line drugs for regulating blood lipids and treating hyperlipidemia‐related cardiovascular diseases. However, ATV‐associated ICH has been reported, although its incidence is rare. In this study, we aimed to investigate the protective action and mechanisms of berberine (BBR) against ATV‐induced brain hemorrhage. We established an ICH model in zebrafish induced by ATV (2 μM) and demonstrated the effects of BBR (10, 50, and 100 μM) on ICH via protecting the vascular network using hemocyte staining and three transgenic zebrafish. BBR was found to reduce brain inflammation and locomotion injury in ICH‐zebrafish. Mechanism research showed that ATV increased the levels of VE‐cadherin and occludin proteins but disturbed their localization at the cell membrane by abnormal phosphorylation, which decreased the number of intercellular junctions between vascular endothelial cells (VECs), disrupting the integrity of vascular walls. BBR reversed the effects of ATV by promoting autophagic degradation of phosphorylated VE‐cadherin and occludin in ATV‐induced VECs examined by co‐immunoprecipitation (co‐IP). These findings provide crucial insights into understanding the BBR mechanisms involved in the maintenance of vascular integrity and in mitigating adverse reactions to ATV. This study investigated the effect of berberine on atorvastatin‐induced cerebral hemorrhage in zebrafish. Our results indicate that BBR enhances the survival rate of zebrafish with brain hemorrhage, reduces hemorrhage and inflammation, and improves the locomotion function of ICH‐zebrafish by stabilizing vascular integrity. In vitro experiments using HUVEC cells show that BBR counteracts the adverse effects of ATV on endothelial cell connections by promoting the autophagic degradation of intracellularly phosphorylated connexins. These findings suggest the potential of BBR as a treatment for hemorrhagic stroke. [ABSTRACT FROM AUTHOR]

Viral infections and associated illnesses account for approximately 3.5 million global fatalities and public health problems. Medicinal plants, with their wide therapeutic range and minimal side effects, have gained limelight particularly in response to growing concerns about drug resistance and sluggish development of antiviral drugs. This study computationally assessed 11 chemical compounds from Berberis lycium along with two antiviral drugs to inhibit SARS CoV 2 (coronavirus disease 2019 [COVID-19]) RNA-dependent RNA polymerase (RdRP), influenza virus RdRP, and two crucial dengue virus (DENV) enzymes (NS2B/NS3 protease and NS5 polymerase). Berberine and oxyberberine passed all pharmacokinetics analysis filters including Lipinski rule, blood-brain barrier permeant, and cytochrome suppression and demonstrated drug-likeness, bioavailability, and a non-toxic profile. Docking of phytochemicals from B lycium returned promising results with selected viral proteins, ie, DENV NS2BNS3 (punjabine –10.9 kcal/mol), DENV NS5 (punjabine –10.4 kcal/mol), COVID-19 RdRP (oxyacanthine –9.5 kcal/mol), and influenza RdRP (punjabine –10.4 kcal/mol). The optimal pharmacokinetics of berberine exhibited good binding energies with NS2BNS3 (–8.0 kcal/mol), NS5 (–8.3 kcal/mol), COVID RdRP (–7.7 kcal/mol), and influenza RdRP (–8.3 kcal/mol), while molecular dynamics simulation of a 50-ns time scale by GROMACS software package provided insights into the flexibility and stability of the complexes. A hidden treasure trove for antiviral research, berberine, berbamine, berbamunine, oxyberberine, oxyacanthine, baluchistanamine, and sindamine has showed encouraging findings as possible lead compounds. Pharmacological analyses provide credence for the proposed study; nevertheless, as the antiviral mechanisms of action of these phytochemicals are not well understood, additional research and clinical trials are required to demonstrate both their efficacy and toxicity through in vitro and in vivo studies. [ABSTRACT FROM AUTHOR]

Background: The prevention of obesity represents a major health and socio-economic challenge. Nutraceuticals are regularly highlighted for their beneficial effects in preventing the metabolic disturbances associated with obesity. However, few studies have described the combined action of nutraceutical mixtures combining polyphenols with alkaloids. Objective: The aim of this study was to evaluate the effects of long-term dietary supplementation with a mixture of Berberine, Citrus and Apple extracts (BCA) in the primary prevention of obesity and its metabolic and vascular complications in the obese Zucker rat, a spontaneous model of genetic obesity and insulin resistance. Methods: Sixteen 8-week-old obese Zucker male rats were randomly divided into two groups: all rats received oral gavage daily either with water, untreated obese (U-ObZ) or BCA (BCA-ObZ) mixture for thirteen weeks. Morphological and metabolic parameters were measured along the study. Cumulative concentration-response curves to insulin, acetylcholine and phenylephrine were determined on isolated thoracic aorta. Colon permeability measurements were performed using the Ussing chamber technique. Fecal samples collected at the beginning and the end of the protocol were used as a template for amplification of the V3-V4 region of the 16S rDNA genes. Results: BCA supplementation reduced weight gain (p<0.05) and food intake (p<0.05) in the BCA-ObZ group rats compared to the U-ObZ group rats. It also improved glucose tolerance (p<0.001) and decreased fasting insulin and Homeostasis model assessment index (p<0.05). Through ex vivo experiments, the BCA mixture enhanced significantly aortic insulin relaxation (p<0.01), reduced α1-adrenoceptor-mediated vasoconstriction (p<0.01), and decreased distal colon permeability. Moreover, short-chain fatty acid producers such as Bacteroides, Blautia, and Akkermansia were found to be increased by the BCA mixture supplementation. Conclusion: The results showed that a 13-week-supplementation with BCA mixture prevented weight gain and improved glucose metabolism in obese Zucker rats. We also demonstrated that BCA supplementation improved vascular function, colonic barrier permeability and gut microbiota profile. [ABSTRACT FROM AUTHOR]

Objective To explore the effect and mechanism of berberine combined with curcumin on atherosclerosis (AS) by mediating M1 macrophages polarization. Methods M1-type macrophages were obtained from mouse mononuclear macrophages (RAW264.7) induced by lipopolysaccharide (LPS, 100 ng/mL) and interferon (IFN)-γ (20 ng/mL). A cell model was established. The cells were divided into a control group, model group, berberine group, curcumin group and berberine plus curcumin group. Concentrations of berberine and curcumin were detected by CCK-8 assay. The expression levels of M1-type macrophage markers iNOS, TNF-α, CXCL9 and p-STAT6/STAT6 in macrophage supernatant were detected by ELISA. Levels of iNOS, TNF-α and CXCL9 mRNA were detected by RT-PCR. Levels of iNOS, STAT6 and p-STAT6 proteins in each group were detected by Western blot. After down-regulation of STAT6 level by siRNA technology, expression of p-STAT6 protein was detected by Western blot. Expression levels of iNOS, TNF-α, CXCL9 and p-STAT6 were detected by ELISA. Results In the polarization of M1 macrophages induced by LPS and IFN-γ, berberine (25 μmol/L) and curcumin (20 μmol/L) were the best concentrations as compared with other drug concentration groups, and neither alone nor combined use could significantly inhibit the viability of RAW264.7 cells (P < 0.05). As compared with the normal group, iNOS, TNF-α and CXCL9 mRNA and protein levels were increased in the model group, while P-STAT6/STAT6 levels were decreased, with statistical differences (P < 0.05). As compared with the model group, iNOS, TNF-α and CXCL9 mRNA and protein levels in the berberine group, curcumin group, and berberine plus curcumin group were decreased, while P-STAT6 /STAT6 levels were increased, and the changes were more obvious in berberine plus curcumin group, with statistical difference (P < 0.05). After transfection of STAT6 siRNA in M1 macrophages in the berberine plus curcumin group, P-STAT6 levels were down-regulated, while expressions of iNOS, TNF-α and CXCL9 were up-regulated, with statistical differences (P < 0.05). Conclusions Both berberine and curcumin can inhibit the activity of M1-type macrophages and reduce inflammatory response. The action of berberine combined with curcumin is more advantageous than that of either drug alone, which may be the main mechanism of action through activation of STAT6. [ABSTRACT FROM AUTHOR]

This article explores the effects of the Yizhi Qingxin formula (YQF) extract on cognitive impairment in aged rats. The study found that oral treatment with YQF extract improved spatial learning and memory abilities in aged rats. The extract also had positive effects on histopathological and morphological characteristics in the rats. Additionally, the YQF extract activated the brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) pathway, which is involved in cognitive impairment. However, it is important to note that this article has been retracted, so further research is needed to confirm these findings. [Extracted from the article]

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]

Gymnema sylvestre (GS) and berberine (BBR) are natural products that have demonstrated therapeutic potential for the management of obesity and its comorbidities, as effective and safe alternatives to synthetic drugs. Although their anti-obesogenic and antidiabetic properties have been widely studied, comparative research on their impact on the gene expression of adipokines, such as resistin (Res), omentin (Ome), visfatin (Vis) and apelin (Ap), has not been reported. Methodology: We performed a comparative study in 50 adult Mexican patients with obesity treated with GS or BBR for 3 months. The baseline and final biochemical parameters, body composition, blood pressure, gene expression of Res, Ome, Vis, and Ap, and safety parameters were evaluated. Results: BBR significantly decreased (p < 0.05) body weight, blood pressure and Vis and Ap gene expression and increased Ome, while GS decreased fasting glucose and Res gene expression (p < 0.05). A comparative analysis of the final measurements revealed a lower gene expression of Ap and Vis (p < 0.05) in patients treated with BBR than in those treated with GS. The most frequent adverse effects in both groups were gastrointestinal symptoms, which attenuated during the first month of treatment. Conclusion: In patients with obesity, BBR has a better effect on body composition, blood pressure, and the gene expression of adipokines related to metabolic risk, while GS has a better effect on fasting glucose and adipokines related to insulin resistance, with minimal side effects. [ABSTRACT FROM AUTHOR]

This study mainly investigated the effects of berberine (BBR) on the bile acid metabolism in gut-liver axis and the microbial community in large intestine of weaned piglets challenged with enterotoxigenic Escherichia coli (ETEC) by microbiome and metabolome analyses. Sixty-four piglets were randomly assigned to four groups including Control group, BBR group, ETEC group, and BBR + ETEC group. Dietary BBR supplementation upregulated the colonic mRNA expression of Occludin, Claudin-5, trefoil factor 3 (TFF3), and interleukin (IL)-10, and downregulated colonic IL-1β and IL-8 mRNA expression in piglets challenged with ETEC K88 (p < 0.05). The hepatic non-targeted metabolome results showed that dietary BBR supplementation enriched the metabolic pathways of primary bile acid biosynthesis, tricarboxylic acid cycle, and taurine metabolism. The hepatic targeted metabolome analyses showed that BBR treatment increased the hepatic concentrations of taurocholic acid (TCA) and taurochenodeoxycholic acid (TDCA), but decreased the hepatic cholic acid (CA) concentration (p < 0.05). Further intestinal targeted metabolome analyses indicated that the deoxycholic acid (DCA), hyocholic acid (HCA), 7-ketodeoxycholic acid (7-KDCA), and the unconjugated bile acid concentrations in ileal mucosa was decreased by dietary BBR treatment (p < 0.05). Additionally, BBR treatment significantly upregulated the hepatic holesterol 7 α-hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1) mRNA expression, and upregulated the ileal mRNA expression of farnesoid X receptor (FXR) and apical sodium-dependent bile acid transporter (ASBT) as well as the colonic mRNA expression of FXR, fibroblast growth factor19 (FGF19), takeda G protein-coupled receptor 5 (TGR5) and organic solute transporters beta (OST-β) in piglets (p < 0.05). Moreover, the microbiome analysis showed that BBR significantly altered the composition and diversity of colonic and cecal microbiota community, with the abundances of Firmicutes (phylum), and Lactobacillus and Megasphaera (genus) significantly increased in the large intestine of piglets (p < 0.05). Spearman correlation analysis showed that the relative abundances of Megasphaera (genus) were positively correlated with Claudin-5, Occludin, TFF3, and hepatic TCDCA concentration, but negatively correlated with hepatic CA and glycocholic acid (GCA) concentration (p < 0.05). Moreover, the relative abundances of Firmicute (phylum) and Lactobacillus (genus) were positively correlated with hepatic TCDCA concentration (p < 0.05). Collectively, dietary BBR supplementation could regulate the gut microbiota and bile acid metabolism through modulation of gut-liver axis, and attenuate the decreased intestinal tight junction expression caused by ETEC, which might help maintain intestinal homeostasis in weaned piglets. [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]

Research is increasingly revealing that inflammation significantly contributes to various diseases, particularly inflammatory bowel disease (IBD). IBD is a major medical challenge due to its chronic nature, affecting at least one in a thousand individuals in many Western countries, with rising incidence in developing nations. Historically, indigenous people have used natural products to treat ailments, including IBD. Ethnobotanically guided studies have shown that plant-derived extracts and compounds effectively modulate immune responses and reduce inflammation. Similarly, helminths and their products offer unique mechanisms to modulate host immunity and alleviate inflammatory responses. This review explored the pharmaceutical potential of Aboriginal remedial plants and helminths for treating IBD, emphasizing recent advances in discovering anti-inflammatory small-molecule drug leads. The literature from Scopus, MEDLINE Ovid, PubMed, Google Scholar, and Web of Science was retrieved using keywords such as natural product, small molecule, cytokines, remedial plants, and helminths. This review identified 55 important Aboriginal medicinal plants and 9 helminth species that have been studied for their anti-inflammatory properties using animal models and in vitro cell assays. For example, curcumin, berberine, and triptolide, which have been isolated from plants; and the excretory-secretory products and their protein, which have been collected from helminths, have demonstrated anti-inflammatory activity with lower toxicity and fewer side effects. High-throughput screening, molecular docking, artificial intelligence, and machine learning have been engaged in compound identification, while clustered regularly interspaced short palindromic repeats (CRISPR) gene editing and RNA sequencing have been employed to understand molecular interactions and regulations. While there is potential for pharmaceutical application of Aboriginal medicinal plants and gastrointestinal parasites in treating IBD, there is an urgent need to qualify these plant and helminth therapies through reproducible clinical and mechanistic studies. [ABSTRACT FROM AUTHOR]

With the rising prevalence of diabetes and its association with cognitive impairment, interest in the use of dietary alkaloids and other natural products has grown significantly. Understanding how these compounds manage diabetic cognitive dysfunction (DCD) is crucial. This comprehensive review explores the etiology of DCD and the effects of alkaloids in foods and dietary supplements that have been investigated as DCD therapies. Data on how dietary alkaloids like berberine, trigonelline, caffeine, capsaicin, 1‐deoxynojirimycin, nuciferine, neferine, aegeline, tetramethylpyrazine, piperine, and others regulate cognition in diabetic disorders were collected from PubMed, Research Gate, Web of Science, Science Direct, and other relevant databases. Dietary alkaloids could improve memory in behavioral models and modulate the mechanisms underlying the cognitive benefits of these compounds, including their effects on glucose metabolism, gut microbiota, vasculopathy, neuroinflammation, and oxidative stress. Evidence suggests that dietary alkaloids hold promise for improving cognition in diabetic patients and could open exciting avenues for future research in diabetes management. [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]

This study aimed to assess the prophylactic effects of Berberine on experimentally induced lung sepsis and examine its effects on selected cytokines, genes, and protein expression besides the histopathological evaluation. Berberine significantly reduced the wet/dry lung ratio, the broncho-alveolar lavage fluid (BALF) protein, cells, neutrophils percentage, and cytokines levels. In addition, pretreatment with Berberine decreased the myeloperoxidase (MPO) and malondialdehyde (MDA) levels and decreased gene expression of nuclear factor kappa B (NF-κB), monocyte chemoattractant protein-1 (MCP-1), and the intracellular adhesion molecule 1 (ICAM-1) by RT-qPCR analysis, revealing Berberine’s antioxidant and anti-inflammatory mode of action. Western blot analysis revealed increased peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in the Berberine pretreated group compared to the cecal ligation and puncture (CLP) group, in which the histopathological examination evidenced this improvement. In conclusion, Berberine improved lung sepsis via its PPAR-γ mediated antioxidant and anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

Evolving antibiotic resistance of bacteria is a prevailing global challenge in health care and requires the development of safe and efficient alternatives to classic antibiotics. Photodynamic Inactivation (PDI) has proven to be a promising alternative for treatment of a broad range of microorganisms. Photodynamic Inactivation uses photoactive molecules that generate reactive oxygen species (ROS) upon illumination and in the presence of oxygen, which immediately kill pathogenic target organisms. Relevant photoactive properties are provided by berberine. Originally extracted from Barberry (Berberis vulgaris), it is a natural compound widely used in Traditional Chinese Medicine for its antimicrobial and anti-inflammatory effects. With this study, we demonstrated the potential of berberine chloride hydrate (Ber) as a photosensitizer for PDI of important human pathogens, Gram(+) Staphylococcus capitis subsp. capitis, Gram(+) Staphylococcus aureus, and Gram(−) Escherichia coli. In vitro experiments on planktonic and biofilm cultures were conducted focusing on Ber activated with visible light in the blue wavelength range. The number of planktonic S. capitis cells was reduced by 7 log10 steps using 100 µM Ber (5 min incubation, illumination with 435 nm LED array, radiant exposure 25 J/cm2). For an antibacterial effect of 4 log10 steps, static S. capitis biofilms required 1 mM Ber, a drug-to-light interval of 60 min, and illumination with 100 J/cm2. Almost all planktonic cells of Staphylococcus aureus could be photokilled using 100 µM Ber (drug-to-light interval of 30 min, radiant exposure 25 J/cm2). Biofilms of S. aureus could be phototreated (3 log10 steps inactivation) when using 1 mM Ber incubated for 5 min and photoactivated with 100 J/cm2. The study is highlighted by the proof that PDI treatment using Ber showed an antibacterial effect on Gram(−) E. coli. Planktonic cells could be reduced by 3 log10 steps with 100 µM Ber (5 min incubation, 435 nm, 25 J/cm2). With 5 mM ethylenediamine tetraacetic acid disodium salt dihydrate (Na2EDTA) or 1.2% polyaspartic acid (PASA) in addition, a relative inactivation of 4 log10 steps and 7 log10 steps, respectively, was detectable. Furthermore, we showed that an antibacterial effect of 3.4 log10 towards E. coli biofilms was given when using 1 mM Ber (5 min incubation, 435 nm, 100 J/cm2). These results underscore the significance of PDI-treatment with Ber as a natural compound in combination with blue light as valuable antimicrobial application. [ABSTRACT FROM AUTHOR]

Sensorineural hearing loss (SNHL) is mainly caused by injury or loss of hair cells (HCs) and associated spiral ganglion neurons (SGNs) in the inner ear. At present, there is still no effective treatment for SNHL in clinic. Recently, advances in organoid bring a promising prospect for research and treatment of SNHL. Meanwhile, three‐dimensional (3D) printing provides a tremendous opportunity to construct versatile organoids for tissue engineering and regenerative medicine. In this study, gelatin (Gel), sodium alginate (SA), and polyvinyl alcohol (PVA) were used to fabricate biomimetic scaffold through 3D printing. The organ of Corti derived from neonatal mice inner ear was seeded on the PVA/Gel/SA scaffold to construct organ of Corti organoid. Then, the organ of Corti organoid was used to study the potential protective effects of berberine sulfate on neomycin‐juried auditory HCs and SGNs. The results showed that the PVA/Gel/SA biomimetic 3D scaffolds had good cytocompatibilities and mechanical properties. The constructed organoid could maintain organ of Corti activity well in vitro. In addition, the injury intervention results showed that berberine sulfate could significantly inhibit neomycin‐induced HC and SGN damage. This study suggests that the fabricated organoid is highly biomimetic to the organ of Corti, which may provide an effective model for drug development, cell and gene therapy for SNHL. [ABSTRACT FROM AUTHOR]

Background: Metabolic imbalance is the common basis of many diseases. As natural isoquinoline alkaloid, berberine (BBR) has shown great promise in regulating glucose and lipids metabolism and treating metabolic disorders. However, the related mechanism still lacks systematic research. Aim: To discuss the role of BBR in the whole body's systemic metabolic regulation and further explore its therapeutic potential and targets. Method: Based on animal and cell experiments, the mechanism of BBR regulating systemic metabolic processes is reviewed. Potential metabolism-related targets were summarized using Therapeutic Target Database (TTD), DrugBank, GeneCards, and cutting-edge literature. Molecular modeling was applied to explore BBR binding to the potential targets. Results: BBR regulates the whole-body metabolic response including digestive, circulatory, immune, endocrine, and motor systems through adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), sirtuin (SIRT)1/forkhead box O (FOXO)1/sterol regulatory element-binding protein (SREBP)2, nuclear factor erythroid 2-related factor (Nrf) 2/heme oxygenase (HO)-1, and other signaling pathways. Through these reactions, BBR exerts hypoglycemic, lipidregulating, anti-inflammatory, anti-oxidation, and immune regulation. Molecular docking results showed that BBR could regulate metabolism targeting FOXO3, Nrf2, NAD(P)H quinone oxidoreductase 1 (NQO1), glutathione peroxidase (Gpx) 4 and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Evaluating the target clinical effects, we found that BBR has the therapeutic potential of anti-aging, anti-cancer, relieving kidney disease, regulating the nervous system, and alleviating other chronic diseases. Conclusion: This review elucidates the interaction between potential targets and small molecular metabolites by exploring the mechanism of BBR regulating metabolism. That will help pharmacologists to identify new promising metabolites interacting with these targets. [ABSTRACT FROM AUTHOR]

Liyan Sun,1 Jinshuai Lan,1,2 Zhe Li,1,2 Ruifeng Zeng,1,2 Yi Shen,1 Tong Zhang,1,2 Yue Ding1– 3 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3National Innovation Platform for Medical Industry-Education Integration, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaCorrespondence: Yue Ding; Tong Zhang, Email dingyue-2001@hotmail.com; zhangtongshutcm@hotmail.comAbstract: Berberine (BBR), recognized as an oncotherapeutic phytochemical, exhibits its anti-cancer properties via multiple molecular pathways. However, its clinical application is hindered by suboptimal tumor accumulation, rapid systemic elimination, and diminished bioactive concentration owing to extensive metabolic degradation. To circumvent these limitations, the strategic employment of nanocarriers and other drugs in combination with BBR is emerging as a focus to potentiate its anti-cancer efficacy. This review introduced the expansive spectrum of BBR’s anti-cancer activities, BBR and other drugs co-loaded nanocarriers for anti-cancer treatments, and evaluated the synergistic augmentation of these amalgamated modalities. The aim is to provide an overview of BBR for cancer treatment based on nano-delivery. Berberine (BBR), recognized as an oncotherapeutic phytochemical, exhibits its anti-cancer properties via multiple molecular pathways. However, its clinical application is hindered by suboptimal tumor accumulation, rapid systemic elimination, and diminished bioactive concentration owing to extensive metabolic degradation. To circumvent these limitations, the strategic employment of nanocarriers and other drugs in combination with BBR is emerging as a focus to potentiate its anti-cancer efficacy. Nano-delivery systems increase drug concentration at the tumor site by improving pharmacological activity and tissue distribution, enhancing drug bioavailability. Organic nanocarriers have advantages for berberine delivery including biocompatibility, encapsulation, and controlled release of the drug. While the advantages of inorganic nanocarriers for berberine delivery mainly lie in their efficient loading ability of the drug and their slow release ability of the drug. This review introduced the expansive spectrum of BBR’s anti-cancer activities, BBR and other drugs co-loaded nanocarriers for anti-cancer treatments, and evaluated the synergistic augmentation of these amalgamated modalities. The aim is to provide an overview of BBR for cancer treatment based on nano-delivery.Keywords: berberine, anti-cancer, nano drug delivery system, combination therapy

Abstract Bovine mastitis caused by infectious pathogens, mainly Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), constitutes a major destructive challenge for the dairy industry and public health. Berberine chloride (BER) and Cyperus rotundus possess a broad spectrum of anti-inflammatory, antioxidant, antibacterial, and antiproliferative activities; however, their bioavailability is low. This research aimed first to prepare an ethanolic extract of Cyperus rotundus rhizomes (CRE) followed by screening its phytochemical contents, then synthesis of BER and CRE loaded chitosan nanoparticles (NPs) (BER/CH-NPs and CRE/CH-NPs), afterward, the analysis of their loading efficiency in addition to the morphological and physicochemical characterization of the formulated NPs employing Scanning Electron Microscopy (SEM), Zeta Potential (ZP), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) assessments compared to their crude forms to evaluate the enhancement of bioavailability and stability. Isolation of bacterial strains from the milk of mastitic cows, used for induction of mammary gland (MG) inflammation in female albino rats, and a preliminary investigation of the prophylactic oral doses of the prepared NPs against S. aureus-induced mastitis in female rats. The minimal inhibitory concentration (MIC) of BER/CH-NPs and CRE/CH-NPs is 1 mg/kg b.w. BER/CH-NPs and CRE/CH-NPs alone or in combination show significant (P ≤ 0.05) DPPH radical scavenging activity (69.2, 88.5, and 98.2%, respectively) in vitro. Oral administration of BER/CH-NPs and CRE/CH-NPs to mastitis rats significantly (P ≤ 0.05) attenuated TNF-α (22.1, 28.6 pg/ml), IL-6 (33.4, 42.9 pg/ml), IL-18 (21.7, 34.7 pg/ml), IL-4 (432.9, 421.6 pg/ml), and MPO (87.1, 89.3 pg/ml) compared to mastitis group alongside the improvement of MG histopathological findings without any side effect on renal and hepatic functions. Despite promising results with BER and CRE nanoparticles, the study is limited by small-scale trials, a focus on acute administration, and partially explored nanoparticle-biological interactions, with no economic or scalability assessments. Future research should address these limitations by expanding trial scopes, exploring interactions further, extending study durations, and assessing economic and practical scalability. Field trials and regulatory compliance are also necessary to ensure practical application and safety in the dairy industry. In conclusion, the in vitro and in vivo results proved the antioxidant and anti-inflammatory efficacy of BER/CH-NPs and CRE/CH-NPs in low doses with minimal damage to the liver and kidney functions, supposing their promising uses in mastitis treatment.

Indah Purwaningsih,1,2 Iman Permana Maksum,1 Dadan Sumiarsa,1 Sriwidodo Sriwidodo3 1Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Padjadjaran, Sumedang, 45363, Indonesia; 2Department of Medical Laboratory Technology, Poltekkes Kemenkes Pontianak, Pontianak, 78124, Indonesia; 3Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, IndonesiaCorrespondence: Indah Purwaningsih; Iman Permana Maksum, Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Padjadjaran, Sumedang, 45363, Indonesia, Tel +6281345719669 ; +6282240839482, Email indah20013@mail.unpad.ac.id; iman.permana@unpad.ac.idPurpose: This study aimed to isolate and characterize palmatine from Fibraurea tinctoria Lour stems, quantify its content, and determine its antioxidant and antidiabetic activities.Patients and Methods: Palmatine was isolated from the methanol extract of Fibraurea tinctoria Lour stems by silica gel column chromatography. Structural elucidation of the isolated compounds was performed using spectral data analysis and comparison with the literature. High-Performance Liquid Chromatography (HPLC) was used to quantitatively determine palmatine in the crude methanol extract and fractions. The DPPH and non-enzymatic SOD mimic methods were used to assess the antioxidant activity of the methanol extract, fractions, and isolated compounds. The antidiabetic activity was evaluated in silico by the molecular docking method of alpha-glucosidase and DPP-IV enzymes. Palmatine was used as a test ligand and was compared with berberine and its native ligand or standard compounds.Results: The isolated compound was identified as palmatine. Quantification of palmatine compound by HPLC showed that palmatine was found in the extract and all fractions. In the in vitro antioxidant activity test using the DPPH method, fraction 4 showed the highest activity, with an IC50 value of 91 ppm. In contrast, using the non-enzymatic SOD mimic method, the methanol extract, fraction 5, and isolated compound (palmatine) exhibited very strong antioxidant activity, with IC50 values of 18, 20, and 28 ppm, respectively. The in silico antidiabetic activity of palmatine is thought to have the potential to inhibit these two enzymes.Conclusion: These results showed that Fibraurea tinctoria Lour stems have potential as an antioxidant and antidiabetic agent. Further research on phytochemical and pharmacological is required to validate the use of this plant species for the treatment of various diseases, especially diabetes mellitus.Keywords: Fibraurea tinctoria Lour, berberine, palmatine, antioxidant, antidiabetic

Jilei Li,1,&ast; Wenchao Dan,2,&ast; Chenchen Zhang,3 Nian Liu,3 Yichong Wang,1 Jixiang Liu,3 Shengsheng Zhang1 1Digestive Disease Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China; 2Department of Dermatology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China; 3Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengsheng Zhang, Digestive Disease Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, Tel +8613801088329, Email zhangshengsheng@bjzhongyi.comPurpose: This study aimed to delineate the molecular processes underlying the therapeutic effects of berberine on UC by employing network pharmacology tactics, molecular docking, and dynamic simulations supported by empirical validations both in vivo and in vitro.Patients and Methods: We systematically screened potential targets and relevant pathways affected by berberine for UC treatment from comprehensive databases, including GeneCards, DisGeNET, and GEO. Molecular docking and simulation protocols were used to assess the interaction stability between berberine and its principal targets. The predictions were validated using both a DSS-induced UC mouse model and a lipopolysaccharide (LPS)-stimulated NCM460 cellular inflammation model.Results: Network pharmacology analysis revealed the regulatory effect of the TLR4/NF-κB/HIF-1α pathway in the ameliorative action of berberine in UC. Docking and simulation studies predicted the high-affinity interactions of berberine with pivotal targets: TLR4, NF-κB, HIF-1α, and the HIF inhibitor KC7F2. Moreover, in vivo analyses demonstrated that berberine attenuates clinical severity, as reflected by decreased disease activity index (DAI) scores, reduced weight loss, and mitigated intestinal inflammation in DSS-challenged mice. These outcomes include suppression of the proinflammatory cytokines IL-6 and TNF-α and downregulation of TLR4/NF-κB/HIF-1α mRNA and protein levels. Correspondingly, in vitro findings indicate that berberine decreases cellular inflammatory injury and suppresses TLR4/NF-κB/HIF-1α signaling, with notable effectiveness similar to that of the HIF-1α inhibitor KC7F2.Conclusion: Through network pharmacology analysis and experimental substantiation, this study confirmed that berberine enhances UC treatment outcomes by inhibiting the TLR4/NF-κB/HIF-1α axis, thereby mitigating inflammatory reactions and improving colonic pathology. Keywords: berberine, ulcerative colitis, TLR4/NF-κB/HIF-1α, network pharmacology, molecular docking, experimental validation, inhibitor

BACKGROUND: Berberine has the potential to induce osteogenic differentiation of various mesenchymal stem cells under normal conditions and special conditions such as high glucose, infection and inflammation. It is a natural small molecule drug that can induce bone formation in seed cells instead of growth factors, and has great application prospect in bone tissue engineering. OBJECTIVE: To review and summarize the research progress in the osteogenic mechanism and efficacy of berberine, especially its osteogenic potential under high glucose, infection and inflammation conditions, and its biological safety, so as to provide theoretical basis for its development and application in bone tissue engineering. METHODS: PubMed, WanFang, and CNKI were searched for relevant literature using the keywords of “berberine, bone defects, bone repair, bone regeneration, osteoinductive, osteoporosis, osteoblast, osteoclast, bone tissue engineering, bone, high glucose, diabetes, inflam*, infect*” in English and Chinese, respectively. A total of 105 literatures were selected for review. RESULTS AND CONCLUSION: Berberine can be used to treat multiple diseases including bone diseases, and it has the ability to promote bone regeneration. This article systematically reviews the mechanism of berberine on bone regeneration and in vivo and in vitro studies. Studies have shown that it can play a role in bone repair by promoting osteogenesis, inhibiting osteoclast formation and activity, and preventing osteoporosis. It shows excellent osteogenic differentiation potential mainly via Wnt/β-catenin, PI3K/AKT, EGFR/MEK/p38MAPK, cAMP/PKA/CREB, ERK and other signaling pathways. Berberine can also relieve the inhibition of osteogenic differentiation caused by high glucose, infection and inflammation, which provides more possibilities for the treatment of bone defects in patients with diabetes or infection and inflammation in the bone defect site. Berberine also has the advantages of low toxicity, low price, easy access (currently it can be synthesized), which is a relatively ideal bone induction potential drug. In recent years, the application of berberine in the treatment of bone defect tends to be localized, mainly through the combination with bone tissue engineering technology to improve bioavailability, and has shown good bone repair effect and excellent biological safety in animal experiments. In addition, preclinical experiments have shown splendid bone regeneration potential in the conditions of diabetes, local infection and inflammation. In the future, more studies are needed to fully reveal the osteogenic mechanism and biological safety of berberine, and seek the most suitable controlled release loading system to make artificial bone replacement materials with good mechanical strength, efficacy and biological safety. [ABSTRACT FROM AUTHOR]

Context: Berberine (BBR) can regulate enteric glial cells (eGcs) and the gut vascular barrier (GVB). Objective: to explore whether BBR regulates GVB permeability via the s100B pathway. Materials and methods: GVB hyperpermeability in c57Bl/6J mice was induced by burns or s100B enema. BBR (25 or 50 mg/kg/d, 3 d) was gavaged preburn. s100B monoclonal antibody (s100Bmab) was i.v. injected postburn. Mouse intestinal microvascular endothelial cells (MiMecs) were treated with s100B, s100B plus BBR, or Z-ietD-FMK. GVB permeability was assayed by Fitc-dextran, s100B by elisa, caspase-8, β-catenin, occludin and PV-1 by immunoblot. Results: Burns elevated s100B in serum and in colonic mucosa to a peak (147.00 ± 4.95 ng/ml and 160.30 ± 8.50 ng/mg, respectively) at 36 h postburn, but BBR decreased burns-induced s100B in serum (126.20 ± 6.30 or 90.60 ± 3.78 ng/ml) and in mucosa (125.80 ± 12.40 or 91.20 ± 8.54 ng/mg). Burns raised GVB permeability (serum Fitc-dextran 111.40 ± 8.56 pg/ml) at 48 h postburn, but BBR reduced GVB permeability (serum Fitc-dextran 89.20 ± 6.98 or 68.60 ± 5.50 ng/ml). s100B enema (1 μM) aggravated burns-raised GVB permeability (142.80 ± 8.07 pg/ml) and PV-1, but the effect of s100B was antagonized by BBR. Z-ietD-FMK (5 μM) increased s100B-induced permeability to Fitc-dextran (205.80 ± 9.70 to 263.80 ± 11.04 aUs) while reducing β-catenin in MiMecs. BBR (5 μM) reduced s100B-induced permeability (104.20 ± 9.65 aUs) and increased caspase-8, β-catenin and occludin. Discussion and conclusion: BBR decreases burns-induced GVB hyperpermeability via modulating s100B/ caspase-8/β-catenin pathway and may involve eGcs. [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]

Purpose: Venous leg ulcers (VLUs) are prevalent chronic wounds with limited treatment options. This study aimed to investigate the potential of berberine to enhance endothelial progenitor cell (EPC) function in VLU healing. Methods: Histopathological changes and inflammatory cytokine levels in a deep venous thrombosis (DVT) mouse model were assessed using HE staining and ELISA assays. A luciferase reporter assay was employed to identify the miR-21-3p and RRAGB targeting relationship. EPC proliferation, migration, and tube formation were evaluated through CCK-8, Transwell, and tubule formation assays, while the mTOR pathway and autophagy-related proteins were analyzed by immunofluorescence staining and western blotting. Results: Berberine significantly improved EPC functions, such as proliferation, migration, and tube formation in vitro, and enhanced in vivo EPC-mediated wound healing in a DVT mouse model. Furthermore, miR-21-3p was downregulated in EPCs from VLU patients, and its overexpression improved model EPC functions. Mechanistically, RRAGB, which regulates the mTOR pathway, was identified as a potential miR-21-3p target in EPCs. Overexpression of RRAGB inhibited autophagic activity and impaired EPC function. Conclusion: Berberine shows promise in ameliorating EPC function and promoting wound healing in VLUs. The regulation of the miR-21-3p/RRAGB axis by berberine could offer a promising therapeutic approach for managing VLUs.

Abstract 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

Abstract 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.