Berberine: Potential preventive and therapeutic strategies for human colorectal cancer.

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.

Berberine alleviates neuroinflammation by downregulating NFκB/LCN2 pathway in sepsis-associated encephalopathy: network pharmacology, bioinformatics, and experimental validation.

BACKGROUND: Sepsis refers to a systemic inflammatory response caused by infection, involving multiple organs. Sepsis-associated encephalopathy (SAE), as one of the most common complications in patients with severe sepsis, refers to the diffuse brain dysfunction caused by sepsis without central nervous system infection. However, there is no clear diagnostic criteria and lack of specific diagnostic markers. METHODS: The main active ingredients of coptidis rhizoma(CR) were identified from TCMSP and SwissADME databases. SwissTargetPrediction and PharmMapper databases were used to obtain targets of CR. OMIM, DisGeNET and Genecards databases were used to explore targets of SAE. Limma differential analysis was used to identify the differential expressed genes(DEGs) in GSE167610 and GSE198861 datasets. WGCNA was used to identify feature module. GO and KEGG enrichment analysis were performed using Metascape, DAVID and STRING databases. The PPI network was constructed by STRING database and analyzed by Cytoscape software. AutoDock and PyMOL software were used for molecular docking and visualization. Cecal ligation and puncture(CLP) was used to construct a mouse model of SAE, and the core targets were verified in vivo experiments. RESULTS: 277 common targets were identified by taking the intersection of 4730 targets related to SAE and 509 targets of 9 main active ingredients of CR. 52 common DEGs were mined from GSE167610 and GSE198861 datasets. Among the 25,864 DEGs in GSE198861, LCN2 showed the most significant difference (logFC = 6.9). GO and KEGG enrichment analysis showed that these 52 DEGs were closely related to "inflammatory response" and "innate immunity". A network containing 38 genes was obtained by PPI analysis, among which LCN2 ranked the first in Degree value. Molecular docking results showed that berberine had a well binding affinity with LCN2. Animal experiments results showed that berberine could inhibit the high expression of LCN2,S100A9 and TGM2 induced by CLP in the hippocampus of mice, as well as the high expression of inflammatory factors (TNFα, IL-6 and IL-1ß). In addition, berberine might reduce inflammation and neuronal cell death by partially inhibiting NFκB/LCN2 pathway in the hippocampus of CLP models, thereby alleviating SAE. CONCLUSION: Overall, Berberine may exert anti-inflammatory effects through multi-ingredients, multi-targets and multi-pathways to partially rescue neuronal death and alleviate SAE.

Ameliorative effects of berberine and selenium against paracetamol-induced hepatic toxicity in rats.

Background: Paracetamol (PCM) overdosing induces hepatotoxicity, which can result in death if the dose is high enough and the patients are not given N-acetyl cysteine. Berberine (BBR) has a variety of biological proprieties including anti-inflammatory and antioxidant activities. Aim: Assessment of the potential effect of BBR and selenium when used alone or together on the PCM-induced acute hepatic toxicity in rats. Methods: This research involved 40 clinically healthy mature adult male albino rats, their weights ranged from 150 to 200 g and housed in standard conditions. Our study involved evaluating the potential effect of BBR and selenium when used alone or together on the PCM-induced acute hepatic toxicity via estimation of the liver function tests, determination of the antioxidant enzyme activities, lipid peroxidation markers, immune-modulatory effects, liver histopathological, and immunohistochemical studies. Results: Co-treatment of BBR (150 mg/kg BW) with selenium (5 mg/kg BW) showed significant improvement in the liver function parameters, the antioxidant enzyme activities, reduction in the nitric oxide (NO), lysozyme, malondialdehyde (MDA), TNF-α, and TGF-ß1 levels, and marked elevation in the IgM levels. Conclusion: Altogether, BBR, selenium, or both augment antioxidant activity and alleviate PCM-induced hepatic toxicity.

Berberine Effects in Pre-Fibrotic Stages of Non-Alcoholic Fatty Liver Disease-Clinical and Pre-Clinical Overview and Systematic Review of the Literature.

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.

Combination drug therapy by herbal nanomedicine prevent multidrug resistance protein 1: promote apoptosis in Lung Carcinoma.

Given the numerous adverse effects of lung cancer treatment, more research on non-toxic medications is urgently needed. Curcumin (CUR) and berberine (BBR) combat drug resistance by controlling the expression of multidrug resistant pump (MDR1). Fascinatingly, combining these medications increases the effectiveness of preventing lung cancer. Their low solubility and poor stability, however, restrict their therapeutic efficacy. Because of the improved bioavailability and increased encapsulation effectiveness of water-insoluble medicines, surfactant-based nanovesicles have recently received a great deal of attention. The current study sought to elucidate the Combination drug therapy by herbal nanomedicine prevent multidrug resistance protein 1: promote apoptosis in Lung Carcinoma. The impact of several tween (20, 60, and 80) types with varied hydrophobic tails on BBR/CUR-TNV was evaluated. Additionally, the MDR1 activity and apoptosis rate of the BBR/CUR-TNV combination therapy were assessed. The encapsulation effectiveness of TNV was affected by the type of tween. With the TNV made from tween 60, cholesterol, and PEG (47.5: 47.5:5), more encapsulation effectiveness was attained. By combining CUR with BBR, especially when given in TNV, apoptosis increased. Additionally, when CUR and BBR were administered in combination, they significantly reduced the risk of MDR1 development. The current work suggests that the delivery of berberine and curcumin as a combination medication therapy via tween-based nanovesicles may be a potential lung cancer treatment.

[Investigation of the effects and mechanisms of berberine on a mouse model of polycystic ovary syndrome: based on intestinal flora analysis].

Objective: To examine the impact of berberine on polycystic ovary syndrome (PCOS) in mice, and to investigate the effects of berberine on the intestinal flora and the intestinal flora on PCOS. Methods: A mouse model of PCOS was established by administering dehydroepiandrosterone in combination with high fat diet, and the mouse model was given a berberine treatment. The study consisted of a blank control group (C group), a PCOS model group (M group) and a berberine treatment group (T group). During the experiment, the mice were closely monitored through timed body weight measurements and estrous cycle monitoring; intraperitoneal glucose tolerance test and insulin tolerance test were done. Upon completion of the pharmacological intervention, the wet weights of liver, ovary and fat deposits of mice were assessed and subjected to HE staining to confirm the success of PCOS modeling and the efficacy of berberine. Additionally, fecal samples were analyzed for intestinal flora through 16S rRNA analysis. Results: The PCOS model was established successfully, berberine alleviated the disturbance of estrous cycle in mice, and significantly alleviated fat accumulation and metabolic abnormalities of glucose in mice. The cross-sectional area of fat pad cells in T group was (2 858±146) µm², which was significantly lower than that in M group [(9 518±347) µm²], and the difference was statistically significant (P<0.001). The blood glucose levels in T group were significantly lower than those in M group (P<0.05). The composition and structure of intestinal flora in mice of M group with PCOS (compared with C group) and in mice of T group after berberine intervention (compared with M group) were significantly altered. However, alpha diversity did not change significantly among three groups (P>0.05). Conclusion: Berberine could alleviate PCOS by intervening in the alterations of gut microbiota.

Berberine attenuates inflammation and oxidative stress and modulates lymphocyte E-NTPDase in acute hyperlipidemia.

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-1ß, 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.

Anti-inflammatory, antioxidant, and immunomodulatory effects of Berberis vulgaris and its constituent berberine, experimental and clinical, a review.

Berberis vulgaris (B. vulgaris or barberry) is a medicinal plant that has been used for various purposes in traditional medicine. Berberine is one of the main alkaloids isolated from B. vulgaris and other plants. Both B. vulgaris and berberine have shown anti-inflammatory, antioxidant, and immunomodulatory effects in different experimental models and clinical trials. This review aims to summarize the current evidence on the mechanisms and applications of B. vulgaris and berberine in modulating inflammation, oxidative stress, and immune responses. The literature search was performed using PubMed, Scopus, and Google Scholar databases until August 2023. The results indicated that B. vulgaris and berberine could inhibit the production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), interleukin 6 (IL-6), and interleukin-17 (IL-17), and enhance the expression of anti-inflammatory cytokines, such as interleukin 10 (IL-10) and transforming growth factor-ß (TGF-ß), in various cell types and tissues. B. vulgaris and berberine can also scavenge free radicals, increase antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and reduce lipid peroxidation and DNA damage. B. vulgaris and berberine have been reported to exert beneficial effects in several inflammatory, oxidative, and immune-related diseases, such as diabetes, obesity, cardiovascular diseases, neurodegenerative diseases, autoimmune diseases, allergic diseases, and infections. However, more studies are needed to elucidate the optimal doses, safety profiles, and potential interactions of B. vulgaris and berberine with other drugs or natural compounds.

Berberine prevents NAFLD and HCC by modulating metabolic disorders.

Non-alcoholic fatty liver disease (NAFLD) is a global metabolic disease with high prevalence in both adults and children. Importantly, NAFLD is becoming the main cause of hepatocellular carcinoma (HCC). Berberine (BBR), a naturally occurring plant component, has been demonstrated to have advantageous effects on a number of metabolic pathways as well as the ability to kill liver tumor cells by causing cell death and other routes. This permits us to speculate and make assumptions about the value of BBR in the prevention and defense against NAFLD and HCC by a global modulation of metabolic disorders. Herein, we briefly describe the etiology of NAFLD and NAFLD-related HCC, with a particular emphasis on analyzing the potential mechanisms of BBR in the treatment of NAFLD from aspects including increasing insulin sensitivity, controlling the intestinal milieu, and controlling lipid metabolism. We also elucidate the mechanism of BBR in the treatment of HCC. More significantly, we provided a list of clinical studies for BBR in NAFLD. Taking into account our conclusions and perspectives, we can make further progress in the treatment of BBR in NAFLD and NAFLD-related HCC.

Berberine: Pharmacological Features in Health, Disease and Aging.

BACKGROUND: Berberine is the main active compound of different herbs and is defined as an isoquinoline quaternary botanical alkaloid found in barks and roots of numerous plants. It exhibits a wide range of pharmacological effects, such as anti-obesity and antidiabetic effects. Berberine has antibacterial activity against a variety of microbiota, including many bacterial species, protozoa, plasmodia, fungi, and trypanosomes. OBJECTIVE: This review describes the role of berberine and its metabolic effects. It also discusses how it plays a role in glucose metabolism, fat metabolism, weight loss, how it modulates the gut microbiota, and what are its antimicrobial properties along with its potential side effects with maximal tolerable dosage. METHODS: Representative studies were considered and analyzed from different scientific databases, including PubMed and Web of Science, for the years 1982-2022. RESULTS: Literature analysis shows that berberine affects many biochemical and pharmacological pathways that theoretically yield a positive effect on health and disease. Berberine exhibits neuroprotective properties in various neurodegenerative and neuropsychological ailments. Despite its low bioavailability after oral administration, berberine is a promising tool for several disorders. A possible hypothesis would be the modulation of the gut microbiome. While the evidence concerning the aging process in humans is more limited, preliminary studies have shown positive effects in several models. CONCLUSION: Berberine could serve as a potential candidate for the treatment of several diseases. Previous literature has provided a basis for scientists to establish clinical trials in humans. However, for obesity, the evidence appears to be sufficient for hands-on use.

The therapeutic effects of berberine for gastrointestinal cancers.

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.

Exploring the molecular mechanism of berberine for treating diabetic nephropathy based on network pharmacology.

BACKGROUND AND PURPOSE: Diabetic nephropathy (DN) is a prevalent complication of diabetes mellitus characterized by hyperglycemia, hyperlipidemia, albuminuria and edema. Increasing evidence indicated that berberine (BBR) could alleviate the occurrence and development of DN. However, the molecular mechanism underlying the beneficial effects of BBR in the treatment of DN remains unclear. METHODS: The online public databases were chosen to screen the relevant targets of BBR and DN and the screened overlapped targets were analyzed by GO enrichment analysis, KEGG enrichment analysis and protein-protein interaction network analysis. The interaction between BBR and the key proteinwas verified by molecular docking and cellularthermalshiftassay. Additionally, the expression of key proteins and related indicators of DN were verified by immunofluorescence and western blot in vitro and in vivo. RESULTS: We successfully identified 92 overlapped targets of BBR and DN based on network pharmacology. Notably, VEGFR2 was identified to be the main target of BBR. Meanwhile, we found that BBR exhibited a high binding affinity to VEGFR2 protein, as confirmed by molecular docking and CETSA. This binding led to interfering with the PI3K/AKT/mTOR signaling pathway. In addition, we found that BBR could inhibit the abnormal proliferation of mesangial cells and reduce the expression of downstream pathway protein in vitro and in vivo. Finally, BBR was found to effectively lower the level of blood glucose and improve kidney function in mice, highlighting its potential as a therapeutic agent for the treatment of DN. CONCLUSION: Berberine interfered the PI3K/AKT/mTOR signaling pathway via targeting VEGFR2 protein, further led to the inhibition of abnormal proliferation of mesangial cells and ultimately resulted in improved renal function.

Role of berberine on angiogenesis and blood flow hemodynamics using zebrafish model.

Angiogenesis and hemodynamic instability created by the irregular blood vessels causes hypoperfusion and angiogenesis-mediated diseases. Therefore, therapies focusing on controlling angiogenesis will be a valuable approach to treat a broad spectrum of diseases. In this study, we explored the anti-angiogenic potential of berberine (BBR) and also analyzed blood flow hemodynamics using zebrafish embryos. Zebrafish embryos treated with BBR (0.01-0.75 mM) at various doses at 1 hour post-fertilization (hpf) developed a variety of phenotypic variations including aberrant blood vessels, tail bending, edema, and hemorrhage. Survival rates were much lower at higher dosages, and hatching rates were almost 99%, whereas control group appeared normal. Heart rate is an essential measure that has a strong association with hemodynamics. We used ImageJ software to study the heart rate of embryos treated with BBR, preceded by video processing. The resultant graph shows a significant decrease in heart rate of embryos treated with BBR in dose-dependent manner. Also, RBC staining using o-Dianisidine confirms the anti-angiogenic potential of BBR by indicating the decrease in the intersegmental vessels at 0.5 and 0.75 mM treated embryos. Further, the gene expression study determined that the transcripts (vegf, vegfr2, nrp1a, hif-1α, nos2a, nos2b, cox-2a, and cox-2b) measured were found to be downregulated by BBR at 0.5 mM concentration, from which we conclude that enos/vegf signaling could play an important role in modulating angiogenesis. Our data imply that BBR may be an effective compound for suppressing angiogenesis in vivo, which might be helpful in the treatment of vascular disorders like cancer and diabetic retinopathy in future.

Berberine ameliorates glucocorticoid-induced hyperglycemia: an in vitro and in vivo study.

Berberine (BBR), a bioactive compound isolated from Coptidis Rhizoma, possesses diverse pharmacological activities including anti-bacterial, anti-inflammatory, antitumor, hypolipidemic, and anti-diabetic. However, its role as an anti-diabetic agent in animal models of dexamethasone (Dex)-induced diabetes remains unknown. Studies have shown that natural compounds including aloe, caper, cinnamon, cocoa, green and black tea, and turmeric can be used for treating Type 2 diabetes mellitus (DM). Compared to conventional drugs, natural compounds have less side effects and are easily available. Herein, we studied the anti-diabetic effects of BBR in a mice model of Dex-induced diabetes. HepG2 cell line was used for glucose release and glycogen synthesis studies. Cell proliferation was measured by methylthiotetrazole (MTT) assay. For animal studies, mice were treated with Dex (2 mg/kg, i.m.) for 30 days and effect of BBR at the doses 100, 200, and 500 mg/kg (p.o.) was analyzed. Glucose, insulin, and pyruvate tests were performed for evaluating the development of the diabetic model. Echo MRI was performed to assess the fat mass. Further, to elucidate the mechanism of action of BBR, mRNA expression of genes regulating gluconeogenesis, glucose uptake, and glycolysis was analyzed. In vitro BBR had no impact on cell viability up to a concentration of 50 µM. Moreover, BBR suppressed the hepatic glucose release and improved glucose tolerance in HepG2 cells. In vivo, BBR improved glucose homeostasis in diabetic mice as evidenced by enhanced glucose clearance, increased glycolysis, elevated glucose uptake, and decreased gluconeogenesis. Further, Dex treatment increased the total fat mass in mice, which was ameliorated by BBR treatment. BBR improves glucose tolerance by increasing glucose clearance, inhibiting hepatic glucose release, and decreasing obesity. Thus, BBR may become a potential therapeutic agent for treating glucocorticoid-induced diabetes and obesity in the future.

The Effect of Berberine Supplementation on Glycemic Control and Inflammatory Biomarkers in Metabolic Disorders: An Umbrella Meta-analysis of Randomized Controlled Trials.

PURPOSE: Several meta-analyses reported berberine (BBR) supplementation improves glycemic parameters and inflammatory marker, but findings remain inconsistent. Therefore, this study was conducted. METHODS: We systematically searched PubMed, Embase, Web of Science, Scopus, and Google Scholar to identify the relevant meta-analyses up to April 2023. FINDINGS: BBR supplementation was effective in reducing fasting blood glucose (FBG) (ESWMD: -0.77; 95% CI: -0.90 to -0.63, and ESSMD: -0.65; 95% CI: -0.83 to -0.47), hemoglobin A1C (HbA1C) (ESWMD: -0.57; 95% CI: -0.68 to -0.46), homeostasis model assessment for insulin resistance (HOMA-IR) (ESWMD: -1.04; 95% CI: -1.66 to -0.42, and ESSMD: -0.71; 95% CI: -0.97 to -0.46), insulin (ESWMD: -1.00; 95% CI: -1.70 to -0.30, and ESSMD: -0.63; 95% CI: -0.94 to -0.32), interleukin (IL)-6 (ESSMD: -1.23; 95% CI: -1.61 to -0.85), tumor necrosis factor-α (TNF-α) (ESSMD: -1.04; 95% CI: -1.28 to -0.79), and C-reactive protein (CRP) (ESWMD: -0.62; 95% CI: -0.74 to -0.50, and ESSMD: -1.70; 95% CI: -2.21 to -1.19). IMPLICATIONS: The finding of our umbrella showed that the supplementation of BBR could be effective in improving glycemic parameters and inflammatory marker in adults.

The pharmacological effects of Berberine and its therapeutic potential in different diseases: Role of the phosphatidylinositol 3-kinase/AKT signaling pathway.

The phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway plays a central role in cell growth and survival and is disturbed in various pathologies. The PI3K is a kinase that generates phosphatidylinositol-3,4,5-trisphosphate (PI (3-5) P3), as a second messenger responsible for the translocation of AKT to the plasma membrane and its activation. However, due to the crucial role of the PI3K/AKT pathway in regulation of cell survival processes, it has been introduced as a main therapeutic target for natural compounds during the progression of different pathologies. Berberine, a plant-derived isoquinone alkaloid, is known because of its anti-inflammatory, antioxidant, antidiabetic, and antitumor properties. The effect of this natural compound on cell survival processes has been shown to be mediated by modulation of the intracellular pathways. However, the effects of this natural compound on the PI3K/AKT pathway in various pathologies have not been reviewed so far. Therefore, this paper aims to review the PI3K/AKT-mediated effects of Berberine in different types of cancer, diabetes, cardiovascular, and central nervous system diseases.

The role of berberine in polycystic ovary syndrome - a summary of knowledge.

Polycystic ovary syndrome (PCOS) is a widely prevalent condition that affects approximately 5-10% of women of reproductive age. Although first described in the 18th century, a detailed account of the disease was not provided until Stein and Leventhal's 1935 report. Due to the varied symptomatology of PCOS, treatment must be tailored and often involves using multiple drugs for optimal pharmacotherapy. Berberine, an alkaloid with a longstanding history of use, has gained popularity as a potential treatment option for PCOS. Previous studies have demonstrated that berberine can improve hormonal imbalances by reducing testosterone and FAI, increasing SHBG, and mitigating the clinical symptoms of androgen excess, including hirsutism and acne. Moreover, berberine enhances the therapeutic effects of other drugs commonly used in PCOS, such as metformin and oral contraceptive pills. It is generally well-tolerated with a favourable safety profile. However, further research is warranted to establish conclusive evidence regarding berberine's mechanistic underpinnings, therapeutic potential, and long-term safety as a PCOS treatment modality.

Berberine exerts antidepressant effects in vivo and in vitro through the PI3K/AKT/CREB/BDNF signaling pathway.

BACKGROUND: Depression, a global neuropsychiatric disorder, brings a serious burden to patients and society as its incidence continues to rise. Berberine is one of the main compounds of a variety of Chinese herbal medicines and has been shown to have multiple pharmacological effects. However, whether berberine can exert antidepressant effects in vivo and in vitro and its related mechanisms remain to be explored. METHODS: The chronic restraint stress (CRS) method and corticosterone (CORT) were applied to simulate depression-like behavior in vivo and neuronal apoptosis in vitro, respectively. The antidepressant effects of berberine were evaluated by behavioral tests and changes in the content of monoamine neurotransmitters. Inflammatory cytokines were detected and immunofluorescence staining was used to observe the expression levels of apoptosis-related proteins. RT-qPCR and Western blot were used to examine the mRNA and protein expression (or phosphorylation) levels of biomarkers of the PI3K/AKT/CREB/BDNF signaling pathways. RESULTS: Behavioral tests and levels of neurotransmitters proved that berberine could effectively ameliorate depression-like symptoms in CRS mice. Meanwhile, the results of ELISA and immunofluorescence staining showed that berberine could alleviate inflammatory status and reduce cell apoptosis in vivo and in vitro. Moreover, the changes of the PI3K/AKT/CREB/BDNF signaling pathway induced by CRS or CORT in mouse hippocampus or HT-22 cells were significantly reversed by berberine. CONCLUSION: Our current study suggested that berberine could exert antidepressant effects in vitro and in vivo, which may be associated with the PI3K/AKT/CREB/BDNF signaling pathway.

Synergistic Inhibitory Effect of Berberine and Low-Temperature Plasma on Non-Small-Cell Lung Cancer Cells via PI3K-AKT-Driven Signaling Axis.

Low-temperature plasma (LTP) is an emerging biomedical technique that has been proposed as a potential approach for cancer therapy. Meanwhile, berberine (BER), an active ingredient extracted from various medical herbs, such as Coptischinesis, has been proven antitumor effects in a broad spectrum of cancer cells. In this study, we seek to develop a novel dual cancer therapeutic method by integrating pre-administration of BER and LTP exposure and evaluating its comprehensive antitumor effect on the human non-small-cell lung cancer (NSCLC) cell lines (A549 and H1299) in vitro. Cell viability, cell cycle, cell apoptosis, and intracellular and extracellular ROS were investigated. The results showed that cotreatment of BER and LTP significantly decreased the cell viability, arrested the cell cycle in the S phase, promoted cell apoptosis, and increased intracellular and extracellular ROS. Additionally, RNA Sequencing (RNA-Seq) technology was used to explore potential mechanisms. The differentially expressed genes among different treatment groups of NSCLC cells were analyzed and were mainly enriched in the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Moreover, cotreatment of BER and LTP notably depressed the total protein expression level of PI3K and AKT with immunoblotting. In conclusion, BER and LTP have a synergistic inhibitory effect on NSCLC cells via the PI3K-AKT signaling pathway, which could provide a promising strategy for supplementary therapy in the anti-NSCLC battle.

Identification of Autophagy-Related Targets of Berberine against Non-Small Cell Lung Cancer and Their Correlation with Immune Cell Infiltration By Combining Network Pharmacology, Molecular Docking, and Experimental Verification.

OBJECTIVE: Non-small cell lung cancer (NSCLC) is the most common lung cancer type with high incidence. This study aimed to reveal the anti-NSCLC mechanisms of berberine and identify novel therapeutic targets. METHODS: Berberine-related targets were acquired from SuperPred, SwissTargetPrediction, and GeneCards. NSCLC-re-lated targets were collected from GeneCards and DisGeNET. Differentially expressed genes (DEGs) were identified GEO database, UCSC Xena, and limma. GO and KEGG analyses were performed using clusterProfiler. Autophagy-related genes and transcriptional factors were collected from HADb and KnockTF, respectively. STRING and Cytoscape were used for PPI network analysis. Immune cell infiltration in NSCLC was assessed using CIBERSORT, and its correlation with autophagy-related targets was evaluated. Molecular docking was conducted using PyMOL and AutoDock. qRT-PCR and CCK-8 assay was used for in vitro verification. RESULTS: Thirty intersecting targets of berberine-related targets, NSCLC-related targets, and DEGs were obtained. GO and KEGG analyses revealed that the intersecting targets were mainly implicated in oxidative stress, focal adhesion, and cell-substrate junction, as well as AGE-RAGE, relaxin, FoxO, and estrogen signaling pathways. Significantly, CAPN1, IKBKB, and SIRT2 were identified as the foremost autophagy-related targets, and 21 corresponding transcriptional factors were obtained. PPI network analysis showed that CAPN1, IKBKB, and SIRT2 interacted with 50 other genes. Fifty immune cell types, such as B cells naive, T cells CD8, T cells CD4 naive, T cells follicular helper, and monocytes, were implicated in NSCLC pathogenesis, and CAPN1, IKBKB, and SIRT2 were related to immune cells. Molecular docking revealed the favorable binding activity of berberine with CAPN1, IKBKB, and SIRT2. In vitro assays showed lower CAPN1, IKBKB, and SIRT2 expression in NSCLC cells than that in normal cells. Notably, berberine inhibited the viability and elevated CAPN1, IKBKB, and SIRT2 expression in NSCLC cells. CONCLUSIONS: Berberine might treat NSCLC mainly by targeting CAPN1, IKBKB, and SIRT2.