Antioxidant and Anti-Inflammatory Activities of Berberine in the Treatment of Diabetes Mellitus

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.