Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus

Abstract

Oxidative stress and inflammation are proved to be critical for the pathogenesis of diabetes mellitus. Berberine (BBR) is a natural compound isolated from plants such as Coptis chinensis and Hydrastis canadensis and with multiple pharmacological activities. Recent studies showed that BBR had antioxidant and anti-inflammatory activities, which contributed in part to its efficacy against diabetes mellitus. In this review, we summarized the antioxidant and anti-inflammatory activities of BBR as well as their molecular basis. The antioxidant and anti-inflammatory activities of BBR were noted with changes in oxidative stress markers, antioxidant enzymes, and proinflammatory cytokines after BBR administration in diabetic animals. BBR inhibited oxidative stress and inflammation in a variety of tissues including liver, adipose tissue, kidney and pancreas. Mechanisms of the antioxidant and anti-inflammatory activities of BBR were complex, which involved multiple cellular kinases and signaling pathways, such as AMP-activated protein kinase (AMPK), mitogen-activated protein kinases (MAPKs), nuclear factor erythroid-2-related factor-2 (Nrf2) pathway, and nuclear factor- κ B (NF- κ B) pathway. Detailed mechanisms and pathways for the antioxidant and anti-inflammatory activities of BBR still need further investigation. Clarification of these issues could help to understand the pharmacology of BBR in the treatment of diabetes mellitus and promote the development of antidiabetic natural products.

Figure 1

Schematic illustration of the molecular mechanisms and pathways of BBR in reducing oxidative stress and inflammation. (1) BBR could inhibit oxidative stress by upregulation of SOD, UCP2 and downregulation of NADPH oxidase expression, which was possible to be mediated by the SIRT1/FOXO or AMPK pathway. (2) BBR administration induced the activation of the Nrf2 pathway, which was crucial for the antioxidant and anti-inflammatory activities of BBR. The effect of BBR on Nrf2 relied on the activation of AMPK, PI3K/Akt, and P38 pathways. (3) BBR could suppress inflammation by blocking the MAPK pathways in an AMPK-dependent manner, inhibiting the classic NF-κB signaling pathway; inhibiting the Rho GTPase pathway, which was proved to play a role in NF-κB regulation, and attenuating the transcription activity of AP-1, which was possible to be mediated by PPARγ activation. The black lines/boxes and red lines/boxes indicate pathways and molecules involved in the antioxidant or anti-inflammatory activity of BBR, respectively. Red boxes with black frame indicate pathways and molecules responsible for both antioxidant and anti-inflammatory activities of BBR. The symbols of “?” indicate possible mechanisms and pathways that need to be further verified. There was a vicious cycle between oxidative stress and inflammation, which was possibly able to be terminated by BBR administration.