| Description: |
Berberine has neuroprotective, antidepressant, antineoplastic, and anti- fibrosis activities; it is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism, it may as a broad-spectrum anti-microbial medicine, a complementary therapeutic agent for HIV/AIDS; it also may be one of the targeted therapeutic agents that can restore barrier function in intestinal disease states.Berberine is used in histology for staining heparin in mast cells. As a natural dye, berberine has a colour index of 75160. |
| In vitro: |
| Mol Med Rep. 2014 Oct;10(4):1734-8. | | Berberine induces apoptosis and DNA damage in MG‑63 human osteosarcoma cells.[Pubmed: 25050485] | Berberine, an isoquinoline alkaloid extracted from the dry root of Coptidis Rhizoma, has been found to exhibit marked anticancer effects on a panel of established cancer cells. Among the human osteosarcoma lines treated, MG‑63 cells were found to be the most sensitive.
The present study investigated the potential genotoxic effect of berberine on MG‑63 human osteosarcoma cells.
METHODS AND RESULTS:
The effect of berberine on cell viability was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5‑diphenyltetrazolium bromide assay and cell apoptosis was analyzed by flow cytometry and a DNA ladder assay. γH2AX focus formation was used to detect DNA damage in MG-63 cells. Berberine induced a significant increase in apoptosis in MG-63 cells in a concentration- and time-dependent manner, as determined by DNA fragmentation analysis and flow cytometry. Furthermore, berberine induced significant concentration- and time-dependent increases in DNA damage compared with that in the negative control.
CONCLUSIONS:
In conclusion, these observations indicated that berberine induced apoptosis and DNA damage in MG‑63 cells. |
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| In vivo: |
| Biochem Biophys Res Commun. 2015 Mar 20;458(4):796-801. | | Berberine improves endothelial function by inhibiting endoplasmic reticulum stress in the carotid arteries of spontaneously hypertensive rats.[Pubmed: 25686503] | Activation of endoplasmic reticulum (ER) stress in endothelial cells leads to increased oxidative stress and often results in cell death, which has been implicated in hypertension.
The present study investigated the effects of berberine, a botanical alkaloid purified from Coptidis rhizoma, on ER stress in spontaneously hypertensive rats (SHRs) and the underling mechanism.
METHODS AND RESULTS:
Isolated carotid arteries from normotensive WKYs and SHRs were suspended in myograph for isometric force measurement. Protein phosphorylations and expressions were determined by Western blotting. Reactive oxygen species (ROS) level was measured by DHE staining. SHR carotid arteries exhibited exaggerated acetylcholine-triggered endothelium-dependent contractions (EDCs) and elevated ROS accumulation compared with WKY arteries. Moreover, Western blot analysis revealed the reduced AMPK phosphorylation, increased eIF2α phosphorylation, and elevated levels of ATF3, ATF6, XBP1 and COX-2 in SHR carotid arteries while these pathological alterations were reversed by 12 h-incubation with berberine. Furthermore, AMPK inhibitor compound C or dominant negative AMPK adenovirus inhibited the effects of berberine on above-mentioned marker proteins and EDCs. More importantly, ROS scavengers, tempol and tiron plus DETCA, or ER stress inhibitors, 4-PBA and TUCDA normalized the elevated levels of ROS and COX-2 expression, and attenuated EDCs in SHR arteries.
CONCLUSIONS:
Taken together, the present results suggest that berberine reduces EDCs likely through activating AMPK, thus inhibiting ER stress and subsequently scavenging ROS leading to COX-2 down-regulation in SHR carotid arteries. The present study thus provides additional insights into the vascular beneficial effects of berberine in hypertension. | | Diabetes. 2006 Aug;55(8):2256-64. | | Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states.[Pubmed: 16873688 ] | Berberine has been shown to have antidiabetic properties, although its mode of action is not known. Here, we have investigated the metabolic effects of berberine in two animal models of insulin resistance and in insulin-responsive cell lines.
METHODS AND RESULTS:
Berberine reduced body weight and caused a significant improvement in glucose tolerance without altering food intake in db/db mice. Similarly, berberine reduced body weight and plasma triglycerides and improved insulin action in high-fat-fed Wistar rats. Berberine downregulated the expression of genes involved in lipogenesis and upregulated those involved in energy expenditure in adipose tissue and muscle. Berberine treatment resulted in increased AMP-activated protein kinase (AMPK) activity in 3T3-L1 adipocytes and L6 myotubes, increased GLUT4 translocation in L6 cells in a phosphatidylinositol 3' kinase-independent manner, and reduced lipid accumulation in 3T3-L1 adipocytes.
CONCLUSIONS:
These findings suggest that berberine displays beneficial effects in the treatment of diabetes and obesity at least in part via stimulation of AMPK activity. | | Neurobiol Aging. 2012 Dec;33(12):2903-19. | | Berberine ameliorates β-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer's disease transgenic mouse model.[Pubmed: 22459600 ] | The accumulation of β-amyloid (Aβ) peptide derived from abnormal processing of amyloid precursor protein (APP) is a common pathological hallmark of Alzheimer's disease (AD) brains.
METHODS AND RESULTS:
In this study, we evaluated the therapeutic effect of berberine (BBR) extracted from Coptis chinensis Franch, a Chinese medicinal herb, on the neuropathology and cognitive impairment in TgCRND8 mice, a well established transgenic mouse model of AD. Two-month-old TgCRND8 mice received a low (25 mg/kg per day) or a high dose of BBR (100 mg/kg per day) by oral gavage until 6 months old. BBR treatment significantly ameliorated learning deficits, long-term spatial memory retention, as well as plaque load compared with vehicle control treatment. In addition, enzyme-linked immunosorbent assay (ELISA) measurement showed that there was a profound reduction in levels of detergent-soluble and -insoluble β-amyloid in brain homogenates of BBR-treated mice. Glycogen synthase kinase (GSK)3, a major kinase involved in APP and tau phosphorylation, was significantly inhibited by BBR treatment. We also found that BBR significantly decreased the levels of C-terminal fragments of APP and the hyperphosphorylation of APP and tau via the Akt/glycogen synthase kinase 3 signaling pathway in N2a mouse neuroblastoma cells stably expressing human Swedish mutant APP695 (N2a-SwedAPP).
CONCLUSIONS:
Our results suggest that BBR provides neuroprotective effects in TgCRND8 mice through regulating APP processing and that further investigation of the BBR for therapeutic use in treating AD is warranted. | | Front Pharmacol . 2021 Jun 17;12:632201. | | Berberine Sensitizes Human Hepatoma Cells to Regorafenib via Modulating Expression of Circular RNAs[Pubmed: 34220494] | | Regorafenib resistance is a key limiting factor in the treatment of advanced hepatocellular carcinoma (HCC). Increasing evidence has demonstrated that Berberine (BBR) can synergistically enhance the therapeutic effect of various chemotherapeutic agents. However, the contribution of BBR on regorafenib therapy remains unclear. The purpose of this study was to explore the combined treatment effect of berberine and regorafenib in HCC. We found that BBR enhanced the cytotoxicity of regorafenib in HCC cells. Compared with regorafenib alone, the combined treatment of BBR and regorafenib significantly inhibited the proliferation of HCC cells and induced cellular apoptosis. Meanwhile, the combined treatment group with BBR (10mg/kg/day) and regorafenib (5mg/kg/day) had a dramatic inhibitory effect on the growth of HCC xenograft tumors in nude mice. The increased apoptosis of xenograft tumors was seen in the combined treatment group. Moreover, a comprehensive circular RNA sequencing was performed to identify differentially expressed circRNAs in HCC cells after exposure to 100μM BBR and 5μM regorafenib. The volcano plot and scatter plot analyses revealed that there were 58 up-regulated and 19 down-regulated differentially expressed circRNAs between the combination treatment and control groups. Among them, the expression of hsa_circ_0032029 and hsa_circ_0008928 were up-regulated in HCC cells after treatment with 100μM BBR and 5μM regorafenib. Taken together, this study demonstrated that BBR enhanced the anti-HCC effect of regorafenib both in vitro and in vivo. The synergistic anti-tumor effect of BBR and regorafenib might be related to the up-regulation of hsa_circ_0032029 and hsa_circ_0008928 in HCC cells. |
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