| Background and objectives:Diabetes is a metabolic disease characterized by hyperglycemia with a variety of severe complications,including diabetic nephropathy,diabetic retinopathy and diabetic foot ulcers.Diabetic foot is one of the serious complications of diabetes,where normal wound-healing processes are disrupted and stalled due to abnormalities in inflammation,angiogenesis,and extracellular matrix(ECM)remodeling.Chronic wound healing is the characteristic of diabetic foot ulcer.Studies have shown that Momordica Charantia L.Saponin(SMC)has a certain hypoglycemic effect and can promote the healing of general wounds.But the effect of SMC on diabetic wound healing is not clear.At the same time,the metabolic mechanism of SMC on type 2 diabetes mellitus(T2DM)and diabetic wound healing remains unclear.Therefore,this study investigated the effect of SMC on diabetic wound healing,and analyzed the mechanism of SMC efficacy based on metabonomics.Methods:1.SMC identification and content determination:Total saponins in SMC were determined by vanillin perchloric acid method;The total protein content in SMC was determined by Coomassie bright blue method;The total polysaccharides content in SMC was determined by phenol sulfate method.2.Hypoglycemic effect of SMC:type 2 diabetes mellitus model was induced by high-fat diet for 6 weeks and streptozotocin intraperitoneal injection for 4 days;The mice were divided into blank group,model group,positive medicine group,low-dose,medium-dose and high-dose(50 mg/kg,100 mg/kg,200 mg/kg)groups and administered continuously by gavage for four weeks.Fasting blood glucose was monitored weekly,insulin resistance and glucose tolerance were measured,and pancreatic morphology was observed.3.Lipid-lowering and anti-inflammatory effects of SMC:The levels of cholesterol(TC),ltriglyceride(TG),ow density lipoprotein(LDL-C),high density lipoprotein(HDL-C)and lipopolysaccharide(LPS)in serum of mice at the fourth week were determined.4.The MTT assay,scratch wound healing assay and transwell migration assay were carried out to assay SMC on the effects of human umbilical vein endothelial cells(HUVECs)in vitro.5.Promoting wound healing of SMC:External wound model was established by a 6mm perforator in diabetic mice,and the treatment was continued for 10 days.Images of wounds were obtained at days 0,3,7 and 10 post-wounding.HE tissue sections were used to observe the wound regeneration rate and scar width.Masson staining section was used to observe the density of collagen fiber.6.Untargeted metabolomics was used to analyze the level of metabolites in feces to evaluate the differences between different groups.Results:1.The content of saponin and protein in SMC was 65.96±0.62%and 5.37±0.12%respectively.2.The SMC could effectively decrease fasting blood glucose,blood lipid level and concentration of lipopolysaccharide(LPS)in serum.3.SMC promoted proliferation and migration of HUVECs incubated in high-glucose culture medium.4.SMC could dramatically facilitate wound healing,epidermal and dermal regeneration and collagen deposition.5.Metabolomic data revealed that SMC could regulate 112 biomarkers and affects glycine,serine and threonine metabolism,pyrimidine metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,citric acid cycle and vitamin B6 metabolism.Conclusion:1.Blood glucose in diabetic mice can be reduced and diabetic wound can be promoted healing by SMC.2.SMC can exert therapeutic effects by influencing metabolites,mainly including increased 4-pyridoxine and decreased guanidine acetic acid,shikimic acid,2-deoxyuridine,deoxycytidine,aspartic acid and malic acid. |
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