Coptis chinensis is an ancient Chinese herb treating diabetes in China for thousands of years. However, its underlying mechanism remains poorly understood. Here, we report the effects of its main active component, berberine (BBR), on stimulating insulin secretion. In mice with hyperglycemia induced by a high-fat diet, BBR significantly increases insulin secretion and reduced blood glucose levels. However, in mice with hyperglycemia induced by global or pancreatic islet β-cell-specific Kcnh6 knockout, BBR does not exert beneficial effects. BBR directly binds KCNH6 potassium channels, significantly accelerates channel closure, and subsequently reduces KCNH6 currents. Consequently, blocking KCNH6 currents prolongs high glucose-dependent cell membrane depolarization and increases insulin secretion. Finally, to assess the effect of BBR on insulin secretion in humans, a randomized, double-blind, placebo-controlled, two-period crossover, single-dose, phase 1 clinical trial (NCT03972215) including 15 healthy men receiving a 160-min hyperglycemic clamp experiment is performed. The pre-specified primary outcomes are assessment of the differences of serum insulin and C-peptide levels between BBR and placebo treatment groups during the hyperglycemic clamp study. BBR significantly promotes insulin secretion under hyperglycemic state comparing with placebo treatment, while does not affect basal insulin secretion in humans. All subjects tolerate BBR well, and we observe no side effects in the 14-day follow up period. In this study, we identify BBR as a glucose-dependent insulin secretagogue for treating diabetes without causing hypoglycemia that targets KCNH6 channels.

/pdf/berberine-is-an-insulin-secretagogue-targeting-the-kcnh6-546kbo2sd1.pdf

Berberine is an insulin secretagogue targeting the KCNH6 potassium channel.

Japanese encephalitis virus (JEV), a member of the Flavivirus genus, is an important pathogen that causes human and animal infectious diseases in Asia. So far, no effective antiviral agents are available to treat JEV infection. Here, we found that LDLR is a host factor required for JEV entry. Berbamine significantly decreases the level of LDLR at the plasma membrane by inducing the secretion of LDLR via extracellular vesicles (EVs), thereby inhibiting JEV infection. Mechanistically, berbamine blocks TRPMLs (Ca2+ permeable non-selective cation channels in endosomes and lysosomes) to compromise the endolysosomal trafficking of LDLR. This leads to the increased secretion of LDLR via EVs and the concomitant decrease in its level at the plasma membrane, thereby rendering cells resistant to JEV infection. Berbamine also protects mice from the lethal challenge of JEV. In summary, these results indicate that berbamine is an effective anti-JEV agent by preventing JEV entry.

https://www.tandfonline.com/doi/pdf/10.1080/22221751.2021.1941276

Berbamine inhibits Japanese encephalitis virus (JEV) infection by compromising TPRMLs-mediated endolysosomal trafficking of low-density lipoprotein receptor (LDLR).

Background and purpose The multikinase inhibitor sorafenib is a first-line drug for advanced hepatocellular carcinoma. The response to sorafenib varies among hepatocellular carcinoma patients and many of the responders suffer from reduced sensitivity after long-term treatment. This study aims to explore a novel strategy to potentiate or maximize the anti-hepatocellular carcinoma effects of sorafenib. Experimental approach We used hepatocellular carcinoma cell lines, western blotting, various antagonists, siRNA and tumour xenografts mouse model to determine the anti- hepatocellular carcinoma effects of sorafenib in combination with berbamine or other Na+ /K+ -ATPase ligands. Key results Berbamine and the cardiotonic steroid, ouabain, synergize with sorafenib to inhibit hepatocellular carcinoma cells growth. Mechanistically, berbamine induces Src phosphorylation in Na+ /K+ -ATPase-dependent manner, leading to the activation of p38MAPK and EGFR-ERK pathways. The Na+ /K+ -ATPase ligand ouabain also induces Src, EGFR, type I insulin-like growth factor receptor, ERK1/2 and p38MAPK phosphorylation in hepatocellular carcinoma cells. Treatment of hepatocellular carcinoma cells with Src or EGFR inhibitor inhibits the induction of ERK1/2 phosphorylation by berbamine. Moreover, sorafenib inhibits the induction of Src, p38MAPK, EGFR and ERK1/2 phosphorylation by berbamine and ouabain. Importantly, combination of sorafenib with berbamine or ouabain synergistically inhibits both sorafenib-naive and sorafenib-resistant hepatocellular carcinoma cells growth. Co-treatment of hepatocellular carcinoma cells with berbamine and sorafenib significantly induces cell death and significantly inhibits hepatocellular carcinoma xenografts growth in vivo. Conclusion and implications Berbamine or other Na+ /K+ -ATPase ligands have a potential for improving sorafenib responsiveness in hepatocellular carcinoma. Targeting Na+ /K+ -ATPase represents a novel strategy to potentiate the anti- hepatocellular carcinoma effects of sorafenib.

Targeting Na+ /K+ -ATPase by berbamine and ouabain synergizes with sorafenib to inhibit hepatocellular carcinoma.

Inhibition of intracellular Ca2+ mobilization and potassium channels activation are involved in the vasorelaxation induced by 7-hydroxycoumarin

Long-term antibiotic use induces drug resistance in bacteria. This has given rise to the challenge of refractory infections, which have become a global health threat. Berberine (BBR) and tannic acid (TA) from plants exhibit promising antibacterial activities and may overcome antibiotic resistance. However, poor solubility and/or low penetration capability have limited their application. Carrier-free co-assembled nanocomposites composed entirely of BBR and TA exhibit improved or new properties and produce improved efficacy. Herein, we demonstrated that an ordered nanostructure could be spontaneously co-assembled by the solvent evaporation method using the two natural products. These co-assembled berberine–tannic acid nanoparticles (BBR-TA NPs) exhibited the best antibacterial effect compared with the corresponding physical mixture, pristine BBR, and some first-line antibiotics (benzylpenicillin potassium-BP and ciprofloxacin-Cip) against Staphylococcus aureus (S. aureus) and multidrug-resistant Staphylococcus aureus (MRSA). Even if the concentration of BBR-TA NPs was as low as 15.63 μg/mL, the antibacterial rate against S. aureus and MRSA was more than 80%. In addition to the synergistic effect of the two compounds, the antibacterial mechanism underlying the nanostructures was that they strongly adhered to the surface of the bacterial cell wall, thereby inducing cell membrane damage and intracellular ATP leakage. Furthermore, the in vivo wound healing effect of BBR-TA NPs was verified using an MRSA wound infection mouse model. The BBR-TA NPs achieved the best efficacy compared with BP and Cip. Moreover, cytotoxic and histopathological evaluations of mice revealed that the nanodrug had good biological safety. This facile and green co-assembly strategy for preparing nanoparticles provides a feasible reference for the clinical treatment of bacterial infection. 

/pdf/fabrication-of-co-assembly-from-berberine-and-tannic-acid-38n18r78.pdf

Fabrication of Co-Assembly from Berberine and Tannic Acid for Multidrug-Resistant Bacteria Infection Treatment

A potent antiarrhythmic drug N-methyl berbamine extends the action potential through inhibiting both calcium and potassium currents.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Ling Yan

Author Tools

Chat about Author

Papers

A potent antiarrhythmic drug N-methyl berbamine extends the action potential through inhibiting both calcium and potassium currents.