1.Effect of Ferroptosis on Diabetes Mellitus and Its Complications and Intervention of Chinese Medicine: A Review
Qinyuan ZHANG ; Zhisheng JIN ; Xiaoxue JIANG ; Yanxu CHEN ; Boling ZHANG ; Yaoqin FU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):280-288
Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia caused by absolute or relative insufficiency of insulin secretion. As the disease progresses, patients begin to suffer from diabetic nephropathy, diabetic cardiomyopathy, non-alcoholic fatty liver disease or other complications, which increase the burden on the patients. Moreover, the number of patients is increasing, which brings a heavy burden to the society. Ferroptosis is a new type of programmed cell death which has attracted wide attention in recent years. It refers to the cell death caused by the excessive accumulation of lipid peroxide under the overload of iron ions. Studies have discovered that ferroptosis exists in diabetes mellitus and its complications. Inhibiting ferroptosis can greatly slow down the occurrence and progression of diabetes mellitus and its complications. Chinese medicine, the unique medical treasure in China, acts in a multi-pathway, multi-target manner and is praised for the cheap price, low toxicity, and mild side effects. It has been widely used in the treatment of diabetes mellitus and its complications and has demonstrated definite therapeutic effects, bringing the good news for the majority of patients. The regulation of ferroptosis by Chinese medicine may be a new direction for the treatment of diabetes mellitus and its complications in the future. This paper briefly describes the mechanism of ferroptosis, explores the relationship of ferroptosis with diabetes mellitus and its complications, summarizes the research status of Chinese medicine interventions, and puts forward suggestions, aiming to provide a reference for further research on the treatment of diabetes mellitus and its complications with Chinese medicine.
2.Mechanism of Hedysari Radix Polysaccharide on Diabetic Nephropathy in db/db Mice Based on JAK2/STAT3 Signaling Pathway
Yanxu CHEN ; Zhisheng JIN ; Xiaoxue JIANG ; Boling ZHANG ; Yaoqin FU ; Caiyun JIN ; Qinyuan ZHANG ; Changqing XU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(13):65-71
ObjectiveTo observe the effect of Hedysari Radix polysaccharide (HRP) on the Janus kinase 2 (JAK2)/signal transducer and activator of transcription protein 3 (STAT3) signaling pathway in diabetic nephropathy db/db mice. MethodFifty db/db mice were randomly divided into model group, irbesartan group (irbesartan suspension, 22.75 mg·kg-1), and high-, medium-, and low-dose HRP groups (HRP suspension, 200, 100, 50 mg·kg-1) according to the body weight, with 10 mice in each group. Another 10 C57BL/6 mice were assigned to the normal group. The mice were treated with corresponding drugs by gavage, while those in the normal group and the model group received distilled water at 5 mL·kg-1. The mice in the six groups were administered once a day by gavage for 12 consecutive weeks. The uric acid (UA), triglycerides (TG), and total cholesterol (TC) were detected. Periodic acid-Schiff (PAS) staining and Masson staining were used to observe the pathological changes in kidney tissues. Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were used to detect the protein and mRNA expression levels of JAK2, STAT3, suppressor of cytokine signaling 3 (SOCS3), and tumor necrosis factor-α (TNF-α) in the kidney. ResultAfter 12 weeks of treatment, compared with the normal group, the model group showed significant pathological ultrastructural changes in kidney tissues and increased UA, TG, and TC levels (P<0.01). Compared with the model group, the high- and medium-dose HRP groups and the irbesartan group showed improvement in pathological ultrastructure of kidney tissues and reduced UA, TG, and TC levels (P<0.05, P<0.01). Compared with the normal group, the model group showed a decrease in SOCS3 protein and mRNA expression levels and an increase in JAK2, STAT3, and TNF-α protein and mRNA expression levels (P<0.01). Compared with the model group, the high- and medium-dose HRP groups and the irbesartan group showed an increase in SOCS3 protein and mRNA expression levels and a decrease in JAK2, STAT3, and TNF-α protein and mRNA expression levels (P<0.05, P<0.01). ConclusionHRP can alleviate renal damage in diabetic nephropathy to a certain extent, and its mechanism may be related to the inhibition of the activation of the JAK2/STAT3 signaling pathway.
3.Mechanism of miRNA-related Signaling Pathway Against Diabetic Nephropathy and Intervention of Traditional Chinese Medicine: A Review
Xiaoxue JIANG ; Zhisheng JIN ; Caiyun JIN ; Yanxu CHEN ; Boling ZHANG ; Yaoqin FU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(4):228-235
Diabetic nephropathy (DN), as one of the common chronic microvascular complications of diabetes, has become the main cause of renal failure in end-stage renal disease in China, increasing the risks of renal dialysis and kidney transplantation in diabetes patients. It is the leading cause of death in people with diabetes. The latest research on DN has focused on the gene level. microRNAs (miRNAs) are a family of endogenous accessible short-chain non-coding RNA molecules. By acting on a particular target, they activate or inhibit its mediated signaling pathways and related molecules, playing an important role in the occurrence and development of DN. They have become microeconomic factors for the prevention and treatment of DN. Traditional Chinese medicine (TCM) has a long history in the diagnosis and treatment of DN and has unique advantages such as significant curative effect and few side effects. A large number of studies have proved that TCM can target miRNA to affect multiple signaling pathways, participate in the regulation of inflammatory response, pyroptosis, mesenchymal transdifferentiation, and other pathological changes, and delay the further development of DN. Therefore, this study discusses the biogenesis mechanism of miRNA and its action mechanism in disease-related signaling pathways based on TCM diagnosis and treatment approaches from the perspective of miRNA, and summarizes the effect of TCM targeting miRNA on the disease-related signaling pathways and on DN. Thus, this study is expected to provide a theoretical reference for exploring the progress of TCM intervention in DN from the perspective of genes.
4.Mechanism of Hedysarum Polysaccharide in Diabetic Nephropathy in db/db Mice Based on Wnt/β-catenin Signal Pathway
Yanxu CHEN ; Caiyun JIN ; Zhisheng JIN ; Xiaoxue JIANG ; Boling ZHANG ; Yaoqin FU ; Liu HE
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(21):74-80
ObjectiveTo observe the effect of Hedysarum polysaccharides (HPS) on the Wnt/β-catenin signal pathway in db/db mice with diabetic nephropathy. MethodFifty db/db mice were randomly divided into model group, irbesartan group, and high, middle, and low-dose HPS experimental groups according to their body mass, with 10 mice in each group, and another 10 C57BL/6 mice were selected as a normal group. The normal group and the model group were given 5 mL·kg-1·d-1 distilled water, the irbesartan group was given 22.75 mg·kg-1·d-1 irbesartan suspension, and the high, middle, and low-dose HPS experimental groups were given 200, 100, and 50 mg·kg-1·d-1 HPS suspensions, respectively. The mice in the 6 groups were given intragastric administration once a day for 12 weeks. The general state, blood glucose (GLU), 24 h urine protein (UTP), blood creatinine (SCr), and urea nitrogen (BUN) of mice in each group were determined. The pathological changes in the kidney tissue were observed by hematoxylin-eosin staining (HE). The protein and mRNA expression levels of Wnt1, β-catenin, glycogen synthesis kinase-3β (GSK-3β), and phosphorylated GSK-3β (p-GSK-3β) in the kidney were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultAfter treatment for 12 weeks, as compared with the normal group, the general state of mice in the model group was worse and the pathological ultrastructural lesions of kidney tissues were obvious. The levels of GLU, 24 h UTP, SCr, and BUN in the model group increased (P<0.01). As compared with the model group, the general state and renal pathological ultrastructure of mice in the high and middle-dose HPS groups were improved to some extent, and the levels of SCr, BUN, and 24 h UTP in the high and middle-dose HPS groups decreased (P<0.05,P<0.01). As compared with the normal group, the expression levels of Wnt1, β-catenin, GSK-3β, and p-GSK-3β protein and mRNA in the model group were higher (P<0.01), while the expression levels of Wnt1, β-catenin, GSK-3β, and p-GSK-3β protein and mRNA in the high and middle-dose HPS groups were lower than those in the model group (P<0.05,P<0.01). ConclusionHPS can alleviate the renal injury of diabetic nephropathy to some extent, and its mechanism may be related to the inhibition of the activation of the Wnt/β-catenin signal pathway.