عنوان انگلیسی مقاله:
In silico and in vivo studies of Astragalus glycyphylloides saponin(s) with relevance to metabolic syndrome modulation
ترجمه فارسی عنوان مقاله:
در مطالعات سیلیکون و داخل بدن از گلیسفیلوئیدهای ساپونین آستراگال گلیسفیلوئیدها با ارتباط با مدولاسیون سندرم متابولیک
Sciencedirect - Elsevier - Food and Chemical Toxicology, 130 (2019) 317-325: doi:10:1016/j:fct:2019:05:032
Merilin Al Sharifa,∗, Vessela Vitchevab, Rumyana Simeonovab, Ilina Krastevac, Vasil Manovd, Petko Alova, Georgi Popovd, Aleksandar Shkondrovc, Ilza Pajevaa
Triterpenoids are well known modulators of metabolic syndrome. One of the suggested modes of action (MoAs)
involves peroxisome proliferator-activated receptor gamma (PPARγ) binding.
In this study we aimed to: (i) evaluate in silico potential metabolites and PPARγ-mediated MoA of the sapogenin
of the main saponin present in a purified saponins mixture (PSM) from Astragalus glycyphylloides; (ii)
estimate in silico and in vivo PSMs toxicity; and (iii) investigate in vivo antihyperglycaemic, hypolipidaemic,
antioxidant and hepatoprotective effects of PSM.
Metabolites and toxicity were predicted using Meteor and Derek Nexus expert systems (Lhasa Limited) and
PPARγ binding was investigated using the software MOE (CCG Inc.). PSMs acute oral toxicity was evaluated in
mice and the pharmacological effects were assessed in streptozotocin-induced diabetic spontaneously hypertensive
rats (SHRs). Liver histopathology was studied as well.
PPARγ weak partial agonism was predicted in silico for 24 probable/plausible Phase I metabolites which
docking poses were clustered in 12 different binding modes with characteristic protein-ligand interactions. PSMs
beneficial effects on the levels of blood glucose, triglycerides, and total cholesterol, on oxidative stress markers
and liver histology in diabetic SHRs were comparable to those of the PPARγ ligand pioglitazone. PSMs safety
profile was confirmed in silico and in vivo.
Keywords: Metabolic syndrome | Saponins | Metabolites | PPARγ | Pharmacophore-based docking | Diabetic spontaneously hypertensive rats