临床传统医学和药理学(英文)2026,Vol.7Issue(2):88-100,13.DOI:10.1016/j.ctmp.2026.200289
Dillenia indica L.果实提取物对链脲佐菌素诱导的糖尿病相关血脂异常大鼠模型肝脏Cyp7a1基因表达的影响
Effects of Dillenia indica L.fruit extract on hepatic Cyp7a1 gene expression in a rat model of streptozotocin-induced diabetes-associated dyslipidemia
摘要
Abstract
Background:Dillenia indica fruit has long been documented to exert multiple health benefits,including antidiabetic and antidyslipidemic activities. Objective:To investigate whether modulation of hepatic Cyp7a1 gene expression mediates the antidiabetic and antidyslipidemic effects of an 80%methanolic extract of D.indica fruit(DiME). Methods:Phytochemical profiling of DiME was performed using qualitative assays and gas chromatography-tandem mass spectrometry(GC-MS/MS).Diabetes was induced in 48-hour-old rat pups via a single intraperi-toneal injection of streptozotocin(90 mg/kg).After 3 months,18 adult rats were confirmed as type 2 diabetes mellitus(T2DM)models using the oral glucose tolerance test(OGTT).Dyslipidemia was subsequently induced by feeding a high-cholesterol diet supplemented with 2%cholesterol and 1%cholic acid for 4 weeks.The rats were then randomly divided into four groups(n=6 per group)and received respective treatments for 28 con-secutive days.Blood samples were collected under halothane anesthesia.Therapeutic efficacy was evaluated by measuring fasting serum glucose(FSG),insulin,homeostatic model assessment(HOMA)indices(HOMA-B,HOMA-S,HOMA-IR),lipid profiles(total cholesterol(TC),triglyceride(TG),low-density lipoprotein(LDL)choles-terol,high-density lipoprotein(HDL)cholesterol),and liver enzymes(aspartate aminotransferase(AST),alanine aminotransferase(ALT)).Mechanistic studies included measurement of serum superoxide dismutase(SOD)activ-ity,pancreatic histopathological examination,semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR)analysis of hepatic Cyp7a1 gene expression,and in silico molecular docking. Results:DiME was rich in terpenoids,phenols,and fatty acids.In vivo,DiME treatment significantly reduced FSG(P<0.01)and markedly improved lipid profiles by decreasing serum TG,TC,and LDL cholesterol,while increas-ing HDL cholesterol(P<0.05).This was accompanied by a 93%elevation in serum insulin levels(P<0.001)and significant improvements in pancreatic β-cell function(HOMA-B)and insulin sensitivity(HOMA-S).Histo-logical analysis confirmed preservation of pancreatic islet integrity.DiME also ameliorated oxidative stress by increasing serum SOD activity and exerted hepatoprotective effects by reducing elevated serum AST and ALT levels.Mechanistically,DiME treatment induced an approximately 3-fold upregulation of hepatic Cyp7a1 gene expression. Conclusion:These findings indicate that DiME exerts its therapeutic effects via a dual mechanism by enhancing pancreatic insulin secretion and peripheral insulin sensitivity,and upregulating hepatic Cyp7a1 expression to promote cholesterol catabolism.关键词
Dillenia indica/血脂异常/胆固醇7α-羟化酶/2型糖尿病/气相色谱-串联质谱/分子对接Key words
Dillenia indica L./Dyslipidemia,Cyp7a1/Type 2 diabetes mellitus/GC-MS/MS,Molecular docking引用本文复制引用
Md Mahedi Hassan Tusher,Begum Rokeya,Md Asrafuzzaman,Md Hafizur Rahman,Sajib Halder,Nayem Sarker,Fatima Anjum Faruquee,Maliha Tabassum Rashid,Marzan Islam Lubaba,Abdullah Tayeb Fahim..Dillenia indica L.果实提取物对链脲佐菌素诱导的糖尿病相关血脂异常大鼠模型肝脏Cyp7a1基因表达的影响[J].临床传统医学和药理学(英文),2026,7(2):88-100,13.基金项目
This work was supported by the Ministry of Science and Technology[grant number #39.009.006.01.00.049.2013-14/MEDES-38/219] ()
In-ternational Program in the Chemical Sciences,Uppsala University[grant number ISPdrn2022/1:6]. ()