Mechanistic Studies Of Pseudostellariae Polysaccharide And Curcumin In Activating Nrf2 To Alleviate Insulin Resistance

AimTo examine the effect of pseudostellaria heterophylla polysaccharide (PHP) on Nrf2 antioxidant system in streptozotocin-induced diabetes. Also,the effect of curcumin on Nrf2 antioxidant system in paraquat-induced insulin resistance.And to further explore the working mechanism underlying its attenuation on insulin resistance.MethodsMale C57BL/6J mice were used for induction of dibetes with a intraperitoneal injection of streptozotocin in the first part of this study. The random blood glucose levels were determined and 16.7 mmol was an established standard for the success of diabetic model. Mice were randomly divided into three groups that were the model control group,the streptozotocin(STZ) group and the STZ+PHP (PHP) group.The PHP group mice were fed with high fat diet containing PHP 500 mg/Kg for 7 days after the model succeeded. As soon as the glucose tolerance test showed its therapeutic efficacy, the serum samples, muscle and liver were collected. The content of malonaldchyde (MDA) indicated for lipid peroxidation was determined by TAB combined techniques. The protein content and phosphorylation levels for PKBSer473、P-AMPK, Nrf2、NQO-1、IκBα in muscle and liver tissue were examined by western blot.The second part of this study was continued by curcumin treatment of paraquat-induced insulin resistance in male C57BL/6J mice. Mice were randomly divided into three groups that were the model control group,the paraquat (PQ) group and the PQ+Curcumin (Cur) group. Glucose tolerance test was used to assure the model success. Then, the curcumin intervention group was continuously gavaged with curcumin for 7 days. The serum samples, muscle and liver were collected as soon as the glucose tolerance test showed its lowering blood glucose efficacy. Nucleus and mitochondria were extracted from muscle. The MDA content was determined by TAB combined techniques. And the protein abundance and phosphorylation levels in muscle tissue were examined by western blot.ResultsThe Nrf2 antioxidant system and glucose tolerance were significantly impaired in streptozotocin-induced diabetic model. Pseudostellaria heterophylla polysaccharide reduced the content of serum MDA in mice. Further study revealed that PHP apparently activated AMPK and PKBSer473 signalings in mice, enhanced the expression of the inflammation inhibiting protein IκBα. The Nrf2 system was activated in liver tissue, but not in muscle tissue.The Nrf2 antioxidant system and glucose tolerance were significantly impaired in paraquat-induced diabetic model. Curcumin significantly activated the Nrf2 system, promoted the Nrf2 translocation into nucleus, along with the enhanced expression of quinine oxidoreductasel (NQO-1). The lower serum MDA level was also consistent with this finding. Curcumin also increased IκBα content. In short, curcumin could alleviate oxidative stress and inflammation with the attenuation of PQ-caused impairment in PKBSer473 phosphorylation.ConclusionPseudostellaria heterophylla polysaccharide reduces the high blood glucose in streptozotocin-induced diabetes in male C57BL/6J mice. It may be related to the improvement in insulin signal transduction, the reduction of oxidative stress, the activation of Nrf2 signaling pathway and the inhibition of inflammatory signal.Similarly, curcumin treatment activates the Nrf2 antioxidant system andimproves the insulin signal transduction in paraquat-induced diabetic mice. It can also reduce oxidative stress and inflammation.This study shows that the attenuation of insulin resistance by curcumin and Pseudostellariae polysaccharide is attributed to its enhancing function of endogenous Nrf2 system and anti-inflammation efficacy.