Berberine hydrochloride

The herb of Coptis chinensis Franch.

Berberine has shown to be effective in inhibiting cell proliferation and promoting apoptosis in various cancerous cells; MAPK and Wnt/β-catenin pathways affected by Berberine. IC50 value: Target: Anticancer agent The plant-based alkaloid berberine has potential therapeutic applications for breast cancer, although a better understanding of the genes and cellular pathways regulated by this compound is needed to define the mechanism of its action in cancer treatment. In this review, the molecular targets of berberine in various cancers, particularly breast cancer, are discussed. Berberine was shown to be effective in inhibiting cell proliferation and promoting apoptosis in various cancerous cells. Some signaling pathways affected by berberine, including the MAP (mitogen-activated protein) kinase and Wnt/β-catenin pathways, are critical for reducing cellular migration and sensitivity to various growth factors [1]. Treatment with BBR(Berberine) in rats on the atherogenic diet reduced plasma total cholesterol and nonHDL cholesterol levels by 29%-33% and 31%-41%, respectively, with no significant differences being observed among the three doses [2]. Berberine induced both apoptotic and autophagic death of HepG2 cells, which was associated with a significant activation of AMPK and an increased expression of the inactive form of acetyl-CoA carboxylase (ACC) [3]. Berberine did not show major effects on viability of HEK-293 embryonic kidney and HCT116 colon carcinoma cells and was not toxic in concentrations up to 20 μM. Berberine inhibited β-catenin transcriptional activity and attenuated anchorage-independent growth. As a result of berberine treatment, cellular levels of active β-catenin were reduced concomitant with an increase in the expression of E-cadherin [4].

References:
[1]. Jabbarzadeh Kaboli P, et al. Targets and mechanisms of berberine, a natural drug with potential to treat cancer with special focus on breast cancer. Eur J Pharmacol. 2014 Jun 26. pii: S0014-2999(14)00467-1. [2]. Wang Y, et al. Berberine decreases cholesterol levels in rats through multiple mechanisms, including inhibition of cholesterol absorption. Metabolism. 2014 Jun 4. pii: S0026-0495(14)00162-0. [3]. Yu R, et al. Berberine-induced apoptotic and autophagic death of HepG2 cells requires AMPK activation. Cancer Cell Int. 2014 Jun 11;14:49. [4]. Albring KF, et al. Berberine acts as a natural inhibitor of Wnt/β-catenin signaling--identification of more active 13-arylalkyl derivatives. Biofactors. 2013 Nov-Dec;39(6):652-62.

Berberine hydrochloride prevents postsurgery intestinal adhesion and inflammation in rats.[Pubmed:24676878]

J Pharmacol Exp Ther. 2014 Jun;349(3):417-26.

Intestinal adhesion, characterized by connection of the loops of the intestine with other abdominal organs by fibrous tissue bands, remains an inevitable event of abdominal operations and can cause a number of complications. Berberine hydrochloride (berberine), a natural plant alkaloid derived from Chinese herbal medicine, is characterized by diverse pharmacological effects, such as anticancer and lower elevated blood glucose. This study is designed to investigate the effects of berberine on adhesion and inflammation after abdominal surgeries and the underlying molecular mechanisms. Adhesion severity grades and collagen deposition were assessed 14 days after surgery. We evaluated the levels of intercellular adhesion molecule-1 (ICAM-1) and inflammatory cytokines interleukin-1beta (IL-1beta), IL-6, transforming growth factor beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), and examined transforming growth factor-activated kinase 1 (TAK1)/c-Jun N-terminal kinase (JNK) and TAK1/nuclear factor kappaB (NF-kappaB) signaling. The surgery group experienced the most severe adhesions, and berberine strikingly reduced the density and severity of adhesion. Results showed significant lower expression of IL-1beta, IL-6, TGF-beta, TNF-alpha, and ICAM-1, in berberine groups compared with the operation group. Activities of phosphorylated JNK and phosphorylated NF-kappaB were inhibited in the berberine groups compared with the surgery group. Our novel findings identified Berberine hydrochloride as a promising strategy to prevent adhesion by downregulating ICAM-1 and reduce inflammation by inhibiting the TAK1/JNK and TAK1/NF-kappaB signaling after abdominal surgery, which brought out a good therapeutic approach for the development of clinical application for postoperative abdominal adhesion and inflammation.

Berberine hydrochloride: anticancer activity and nanoparticulate delivery system.[Pubmed:21931477]

Int J Nanomedicine. 2011;6:1773-7.

BACKGROUND: Berberine hydrochloride is a conventional component in Chinese medicine, and is characterized by a diversity of pharmacological effects. However, due to its hydrophobic properties, along with poor stability and bioavailability, the application of Berberine hydrochloride was hampered for a long time. In recent years, the pharmaceutical preparation of Berberine hydrochloride has improved to achieve good prospects for clinical application, especially for novel nanoparticulate delivery systems. Moreover, anticancer activity and novel mechanisms have been explored, the chance of regulating glucose and lipid metabolism in cancer cells showing more potential than ever. Therefore, it is expected that appropriate pharmaceutical procedures could be applied to the enormous potential for anticancer efficacy, to give some new insights into anticancer drug preparation in Chinese medicine. METHODS AND RESULTS: We accessed conventional databases, such as PubMed, Scope, and Web of Science, using "Berberine hydrochloride", "anti-cancer mechanism", and "nanoparticulate delivery system" as search words, then summarized the progress in research, illustrating the need to explore reprogramming of cancer cell metabolism using nanoparticulate drug delivery systems. CONCLUSION: With increasing research on regulation of cancer cell metabolism by Berberine hydrochloride and troubleshooting of issues concerning nanoparticulate delivery preparation, Berberine hydrochloride is likely to become a natural component of the nanoparticulate delivery systems used for cancer therapy. Meanwhile, the known mechanisms of Berberine hydrochloride, such as decreased multidrug resistance and enhanced sensitivity of chemotherapeutic drugs, along with improvement in patient quality of life, could also provide new insights into cancer cell metabolism and nanoparticulate delivery preparation.

Berberine hydrochloride attenuates lipopolysaccharide-induced endometritis in mice by suppressing activation of NF-kappaB signal pathway.[Pubmed:25479718]

Int Immunopharmacol. 2015 Jan;24(1):128-32.

Endometritis is a common disease in animal production and influences breeding all over the world. Berberine is one of the main alkaloids isolated from Rhizoma coptidis. Previous reports showed that berberine has anti-inflammatory potential. However, there have been a limited number of published reports on the anti-inflammatory effect of Berberine hydrochloride on LPS-induced endometritis. The purpose of the present study was to investigate the effects of Berberine hydrochloride on LPS-induced mouse endometritis. Berberine hydrochloride was administered intraperitoneally at 1h before and 12h after LPS induction. Then, a biopsy was performed, and uterine myeloperoxidase (MPO) and nitric oxide (NO) concentrations were determined. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) levels in the uterus homogenate were measured by ELISA. The extent of IkappaB-alpha and P65 phosphorylation was detected by Western blot. The results showed that Berberine hydrochloride significantly attenuated neutrophil infiltration, suppressed myeloperoxidase activity and decreased NO, TNF-alphaand IL-1betaproduction. Furthermore, Berberine hydrochloride inhibited the phosphorylation of the NF-kappaB p65 subunit and the degradation of its inhibitor, IkappaBalpha. These findings suggest that Berberine hydrochloride exerts potent anti-inflammatory effects on LPS-induced mouse endometritis and might be a potential therapeutic agent for endometritis.

Berberine chloride is an alkaloid isolated from the Chinese herbal medicine Huanglian, as an antibiotic. Berberine chloride induces reactive oxygen species (ROS) generation and inhibits DNA topoisomerase. Antineoplastic properties.

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