ObjectiveTo observe the effects of the water extracts of Trichosanthis Radix-Polygonati Rhizoma at different ratios on glucose and lipid metabolism in KKAy mice with spontaneous type 2 diabetes and explore the mechanism of the extract in alleviating insulin resistance based on phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/forkhead box O1 （FoxO1） signaling pathway. MethodThe 8-week-old C57BL/6J male mice were taken as the normal control group， and KKAy male mice of the same age were randomly assigned into a model group， a metformin group， Trichosanthis Radix-Polygonati Rhizoma groups at the ratios of 1∶1 （Trichosanthis Radix 30 g， Polygonati Rhizoma 30 g）， 1∶3 （Trichosanthis Radix 15 g， Polygonati Rhizoma 45 g）， and 1∶5 （Trichosanthis Radix 10 g， Polygonati Rhizoma 50 g） according to blood glucose level and body weight， with 6 mice in each group. The administration lasted for 8 weeks， and the body weight （BW） and fasting blood glucose （FBG） of mice were recorded at the same time points of the 2nd， 4th， 6th， and 8th weeks， respectively. Oral glucose tolerance test （OGTT） was performed at the 7th week. After drug administration， the serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， and fasting insulin （FINS） were measured， and homeostasis model assessment-insulin resistance （HOMA-IR） index was calculated. The liver tissue samples were stained with hematylin-eosin （HE） and periodic acid-Schiff （PAS） for observation of the fat distribution and glycogen content. The protein levels of PI3K， Akt， p-Akt， FoxO1， and p-FoxO1 in the liver were determined by Western blot. ResultCompared with the normal group， the model group showed increased food intake， FBG， glucose tolerance， FINS， HOMA-IR， TC， TG， and LDL-C （P<0.01）， and down-regulated protein levels of PI3K， Akt， phosphorylaison （p）-Akt， FoxO1， and p-FoxO1 in the liver （P<0.01）. Compared with the model group， Trichosanthis Radix-Polygonati Rhizoma lowered FBG and HOMA-IR （P<0.05， P<0.01）. In particular， the combination at the ratio of 1∶3 showed the best performance （P<0.01） comparable to metformin. Furthermore， Trichosanthis Radix-Polygonati Rhizoma at different ratios lowered blood glucose at different time points of OGTT （P<0.05） and TC and LDL-C （P<0.01）. Additionally， the combination at the ratio of 1∶3 reduced TG （P<0.01）. The liver of mice in the drug administration groups showed regular morphology， with few lipid droplets and rich glycogen. Western blot showed that Trichosanthis Radix-Polygonati Rhizoma up-regulated the protein levels of PI3K and p-Akt， down-regulated the protein level of FoxO1， and up-regulated the protein level of p-FoxO1 （P<0.05）. ConclusionTrichosanthis Radix-Polygonati Rhizoma， especially at the ratio of 1∶3， lowered the FBG， TC， LDL-C， and HOMA-IR index， promoted liver glycogen synthesis， and reduced steatosis in KKAy mice， which may be related to the regulation of PI3K/Akt/FoxO1 signaling pathway in the liver.

Diabetic nephropathy （DN） is a chronic microvascular complication in diabetic patients and the main cause of end-stage renal disease （ESRD）. Studies have shown that nuclear factor kappa-B （NF-κB） signaling pathway is involved in the pathological process of DN by activating pathological mechanisms such as inflammation， oxidative stress， fibrosis， apoptosis， autophagy， and pyroptosis. Therefore， blocking the transduction of NF-κB signaling pathway can help prevent and treat DN. Currently， western medical treatment involves strategies such as lowering blood sugar， blood pressure， and lipids， as well as using endothelin receptor antagonists， mineralocorticoid receptor antagonists， aldosterone synthase inhibitors， and other drugs， but they still cannot block the pathological process of DN. Traditional Chinese medicine （TCM） offers a simpler and more cost-effective approach that addresses both the symptoms and underlying causes of DN. Recent research has shown promising results in managing DN with TCM， and NF-κB， as a key factor， plays an important role in the prevention and treatment of DN. This article summarized the research results of TCM based on the NF-κB signaling pathway for the treatment of DN in the past five years. It described a variety of TCM extracts， such as polysaccharides， terpenes， phenols， flavonoids， saponins， and alkaloids， as well as TCM compound prescriptions such as Huaiqihuang granules， Astragalus mongholicus Bunge and Panax notoginseng formula， and Danzhi Jiangtang capsules， which regulated the NF-κB signaling pathway and its upstream and downstream factors to block the pathological process of DN. This inhibition aims to prevent renal pathological damage caused by DN and slow down the deterioration of renal function. The article aims to provide new ideas and references for the research and development of drugs for the prevention and treatment of DN.