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Berberine and Its Study as an Antidiabetic Compound.

ABSTRACT: Diabetes mellitus (DM) is a metabolic disorder that causes hyperglycemia conditions and leads to various chronic complications that causes death. The prevalence of diabetes is predicted to continue to increase, and with the high toxicity levels of current diabetes drugs, the exploration of natural compounds as alternative diabetes treatment has been widely carried out, one of which is berberine. Berberine and several other alkaloid compounds, including some of its derivatives, have shown many bioactivities, such as neuraminidase and hepatoprotective activity. Berberine also exhibits antidiabetic activity. As an antidiabetic compound, berberine is known to reduce blood glucose levels, increase insulin secretion, and weaken glucose tolerance and insulin resistance by activating the AMPK pathway. Apart from being an antidiabetic compound, berberine also exhibits various other activities such as being anti-adipogenic, anti-hyperlipidemic, anti-inflammatory, and antioxidant. Many studies have been conducted on berberine, but its exact mechanism still needs to be clarified and requires further investigation. This review will discuss berberine and its mechanism as a natural compound with various activities, mainly as an antidiabetic.

SUBMITTER: Utami AR

PROVIDER: S-EPMC10376565 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Berberine and Its Study as an Antidiabetic Compound.

Utami Ayudiah Rizki AR Maksum Iman Permana IP Deawati Yusi Y

Biology 20230708 7

Diabetes mellitus (DM) is a metabolic disorder that causes hyperglycemia conditions and leads to various chronic complications that causes death. The prevalence of diabetes is predicted to continue to increase, and with the high toxicity levels of current diabetes drugs, the exploration of natural compounds as alternative diabetes treatment has been widely carried out, one of which is berberine. Berberine and several other alkaloid compounds, including some of its derivatives, have shown many bi ...[more]

PMID: 37508403

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Project description:The novel coronavirus disease, COVID-19, has grown into a global pandemic and a major public health threat since its breakout in December 2019. To date, no specific therapeutic drug or vaccine for treating COVID-19 and SARS has been FDA approved. Previous studies suggest that berberine, an isoquinoline alkaloid, has shown various biological activities that may help against COVID-19 and SARS, including antiviral, anti-allergy and inflammation, hepatoprotection against drug- and infection-induced liver injury, as well as reducing oxidative stress. In particular, berberine has a wide range of antiviral activities such as anti-influenza, anti-hepatitis C, anti-cytomegalovirus, and anti-alphavirus. As an ingredient recommended in guidelines issued by the China National Health Commission for COVID-19 to be combined with other therapy, berberine is a promising orally administered therapeutic candidate against SARS-CoV and SARS-CoV-2. The current study comprehensively evaluates the potential therapeutic mechanisms of berberine in preventing and treating COVID-19 and SARS using computational modeling, including target mining, gene ontology enrichment, pathway analyses, protein-protein interaction analysis, and in silico molecular docking. An orally available immunotherapeutic-berberine nanomedicine, named NIT-X, has been developed by our group and has shown significantly increased oral bioavailability of berberine, increased IFN-γ production by CD8+ T cells, and inhibition of mast cell histamine release in vivo, suggesting a protective immune response. We further validated the inhibition of replication of SARS-CoV-2 in lung epithelial cells line in vitro (Calu3 cells) by berberine. Moreover, the expression of targets including ACE2, TMPRSS2, IL-1α, IL-8, IL-6, and CCL-2 in SARS-CoV-2 infected Calu3 cells were significantly suppressed by NIT-X. By supporting protective immunity while inhibiting pro-inflammatory cytokines; inhibiting viral infection and replication; inducing apoptosis; and protecting against tissue damage, berberine is a promising candidate in preventing and treating COVID-19 and SARS. Given the high oral bioavailability and safety of berberine nanomedicine, the current study may lead to the development of berberine as an orally, active therapeutic against COVID-19 and SARS.

Project description:The present study was designed to evaluate the protective effect of sulphurenic acid (SA), a pure compound from Antrodia camphorata, on diabetes and hyperlipidemia in an animal model study and to clarify the underlying molecular mechanism. Diabetes was induced by daily 55 mg/kg intraperitoneal injections of streptozotocin (STZ) solution over five days. Diabetic mice were randomly divided into six groups and orally gavaged with SA (at three dosages) or glibenclamide (Glib), fenofibrate (Feno) or vehicle for 3 weeks. Our findings showed that STZ-induced diabetic mice had significantly increased fasting blood glucose, glycated hemoglobin (HbA1C), plasma triglyceride (TG), and total cholesterol (TC) levels (p < 0.001, p < 0.001, p < 0.001, and p < 0.05, respectively) but decreased blood insulin, adiponectin, and leptin levels compared to those of the control group (p < 0.001, p < 0.001, and p < 0.001, respectively). Administration of SA to STZ-induced diabetic mice may lower blood glucose but it increased the insulin levels with restoration of the size of the islets of Langerhans cells, implying that SA protected against STZ-induced diabetic states within the pancreas. At the molecular level, SA treatment exerts an increase in skeletal muscle expression levels of membrane glucose transporter 4 (GLUT4) and phospho-Akt to increase the membrane glucose uptake, but the mRNA levels of PEPCK and G6Pase are decreased to inhibit hepatic glucose production, thus leading to its hypoglycemic effect. Moreover, SA may cause hypolipidemic effects not only by enhancing hepatic expression levels of peroxisome proliferator-activated receptor α (PPARα) with increased fatty acid oxidation but also by reducing lipogenic fatty acid synthase (FAS) as well as reducing mRNA levels of sterol regulatory element binding protein (SREBP)1C and SREBP2 to lower blood TG and TC levels. Our findings demonstrated that SA displayed a protective effect against type 1 diabetes and a hyperlipidemic state in STZ-induced diabetic mice.

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Berberine and Its Study as an Antidiabetic Compound.

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Berberine and Its Study as an Antidiabetic Compound.

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