Modified Si-Miao-San ameliorates pancreatic B cell dysfunction by inhibition of reactive oxygen species-associated inflammation through AMP-kinase activation / 中国天然药物

AIM@#To observe the effect of modified Si-Miao-San (mSMS) on advanced glycation end products (AGEs)-induced pancreatic B cell dysfunction, as well as examining the underlying mechanisms.@*METHOD@#Pancreatic B cells (INS-1) were stimulated with advanced glycation end products (AGEs, 200 μg·mL(-1)) for 24 h to produce dysfunction in pancreatic B cells and the effects of mSMS observed on insulin secretion, NF-κB (p65) phosphorylation, reactive oxygen species (ROS) production, mitochondria membrane potential (Δψm), cell apoptosis, phosphorylation of AMP-kinase (AMPK), and caspase 3 activity.@*RESULTS@#The AGEs challenge resulted in increased basal insulin secretion, but decreased insulin secretion in response to high glucose, whereas this situation was reversed by mSMS treatment. AGEs stimulation induced NF-κB (p65) phosphorylation and reactive oxygen species (ROS) production, as well as Δψm collapse and cell apoptosis. mSMS inhibited ROS production and inhibited NF-κB activation by attenuating p65 phosphorylation. Meanwhile, AGEs-induced Δψm collapse and cell apoptosis were also reversed by mSMS treatment. Compound C, an inhibitor of AMP-Kinase (AMPK), abolished the beneficial effects of mSMS on the regulation of B cell function, indicating the involvement of AMPK.@*CONCLUSION@#mSMS ameliorated AGEs-induced B cell dysfunction by suppressing ROS-associated inflammation, and this action was related to its beneficial regulation of AMPK activity.

Modified Si-Miao-San inhibits inflammation and promotes glucose disposal in adipocytes through regulation of AMP-kinase / 中国天然药物

Modified Si-Miao-San (mSMS) is composed of Rhizoma Coptidis, Cortex Phellodendri, Rhizoma Coptidis Semen Coicis and Atractylodes Rhizome. The prescription is used for the management of diabetes and insulin resistance in the clinic. This study aims to investigate its regulation of glucose disposal in adipocytes. Differentiated 3T3-L1 adipocytes were stimulated with conditioned medium derived from activated macrophages to induce insulin resistance and observed the effects of Mac-CM on insulin-mediated glucose uptake along the insulin receptor substrate-1/PI3K/Akt signaling pathway. Moreover, its regulation of AMPK phosphorylation was also investigated. mSMS enhanced AMPK phosphorylation and promoted basal glucose uptake in adipocytes; mSMS inhibited NF-κB activation by reducing P65 phosphorylation and improved insulin-stimulated IRS-1 tyrosine and Akt phosphorylation, leading to the restoration of insulin-mediated glucose uptake when cells were exposed to inflammatory stimulation. These beneficial effects were diminished in the presence of the AMPK inhibitor compound C. mSMS positively regulated AMPK activity, and this action contributed to improving insulin PI3K signaling by the beneficial regulation of IRS-1 function through inhibition of inflammation in adipocytes.