Wahab Shadma, Khalid Mohammad, Alqarni Mohammed H, Elagib Mohamed Fadul A, Bahamdan Ghadah Khaled, Foudah Ahmed I, Aljarba Tariq M, Mohamed Mons S, Mohamed Nazik Salih, Arif Muhammad
Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia.
Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, Saudi Arabia.
J Clin Med. 2023 Mar 9;12(6):2152. doi: 10.3390/jcm12062152.
The 11 β- hydroxysteroid dehydrogenase 1 (11 β-HSD1) is hypothesized to play a role in the pathogenesis of type 2 diabetes and its related complications. Because high glucocorticoid levels are a risk factor for metabolic disorders, 11β-HSD1 might be a viable therapeutic target. In this investigation, docking experiments were performed on the main constituents of (SM) oleanolic acid, β-amyrin, and β-sitosterol to ascertain their affinity and binding interaction in the human 11β-hydroxysteroid dehydrogenase-1 enzyme's active region. The results of in vitro 11β HSD1 inhibitory assay demonstrated that the extract of had a significant ( < 0.05) decrease in the 11-HSD1% inhibition (63.97%) in comparison to STZ (31.79%). Additionally, a non-insulin-dependent diabetic mice model was used to examine the sub-acute anti-hyperlipidemic and anti-diabetic effects of SM fruits. Results revealed that, in comparison to the diabetic control group, SM fruit extract (SMFE) extract at doses of 200 and 400 mg/kg body weight considerably ( < 0.05 and < 0.01) lowered blood glucose levels at 21 and 28 days, as well as significantly decreased total cholesterol (TC) and triglycerides (TG) and enhanced the levels of high-density lipoprotein (HDL). After 120 and 180 s of receiving 200 and 400 mg/kg SMFE, respectively, disease control mice showed significantly poorer blood glucose tolerance ( < 0.05 and < 0.01). SMFE extract 200 ( < 0.05), SMFE extract 400 ( < 0.01), and Glibenclamide at a dosage of 5 mg/kg body weight all resulted in statistically significant weight increase ( < 0.01) when compared to the diabetic control group after 28 days of treatment. According to in silico, in vitro, and in vivo validation, SMFE is a prospective medication with anti-diabetic and hypoglycemic effects.
据推测,11β-羟基类固醇脱氢酶1(11β-HSD1)在2型糖尿病及其相关并发症的发病机制中起作用。由于高糖皮质激素水平是代谢紊乱的一个危险因素,11β-HSD1可能是一个可行的治疗靶点。在本研究中,对(SM)齐墩果酸、β-香树脂醇和β-谷甾醇的主要成分进行了对接实验,以确定它们在人11β-羟基类固醇脱氢酶-1酶活性区域的亲和力和结合相互作用。体外11β-HSD1抑制试验结果表明,与链脲佐菌素(31.79%)相比,(SM)提取物的11-HSD1%抑制率显著降低(<0.05)(63.97%)。此外,还使用非胰岛素依赖型糖尿病小鼠模型来研究SM果实的亚急性抗高血脂和抗糖尿病作用。结果显示,与糖尿病对照组相比,体重200和400mg/kg的SM果实提取物(SMFE)在第21天和28天显著降低血糖水平(<0.05和<0.01),同时显著降低总胆固醇(TC)和甘油三酯(TG)水平,并提高高密度脂蛋白(HDL)水平。分别给予200和400mg/kg SMFE 120和180秒后,疾病对照小鼠的血糖耐受性明显较差(<0.05和<0.01)。与糖尿病对照组相比,治疗28天后,200mg/kg的SMFE提取物(<0.05)、400mg/kg的SMFE提取物(<0.01)和5mg/kg体重的格列本脲均导致体重显著增加(<0.01)。根据计算机模拟、体外和体内验证,SMFE是一种具有抗糖尿病和降血糖作用的潜在药物。