Anti-diabetic Activity of Brucine in Streptozotocin-Induced Rats: In Silico, In Vitro, and In Vivo Studies

被引:23
作者
Khan, Naimat Ullah [1 ]
Qazi, Neelum Gul [1 ]
Khan, Arif-ullah [1 ]
Ali, Fawad [2 ]
ul Hassan, Syed Shams [3 ,4 ]
Bungau, Simona [5 ]
机构
[1] Riphah Int Univ, Riphah Inst Pharmaceut Sci, Islamabad 44000, Pakistan
[2] Kohat Univ Sci & Technol, Dept Pharm, Kohat 2600, Pakistan
[3] Shanghai Jiao Tong Univ, Sch Pharm, Shanghai Key Lab Mol Engn Chiral Drugs, Shanghai 200240, Peoples R China
[4] Shanghai Jiao Tong Univ, Sch Pharm, Dept Nat Prod Chem, Shanghai 200240, Peoples R China
[5] Univ Oradea, Fac Med & Pharm, Dept Pharm, Oradea 410028, Romania
关键词
PATHWAY; MECHANISM;
D O I
10.1021/acsomega.2c04977
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Diabetes mellitus (DM) is a complex and multiple group of disorders, and understanding the molecular mechanisms is a key role in identifying various markers involved in the diagnosis of the disease. Brucine is derived from the seeds of Strychnos nux-vomica L. (Loganiaceae), which has been used in traditional medicine to cure a variety of ailments, such as chronic rheumatism, nervous system diseases, dyspepsia, gonorrhea, anemia, and bronchitis, and has analgesic, anti-inflammatory, anti-oxidant, anti-snake venom, and anti-diabetic properties. The anti-diabetic potential of brucine was studied utilizing in vitro, in silico, in vivo, and molecular methods, including streptozotocin-induced diabetic rat models, alpha-glucosidase and alpha-amylase inhibitory assays, and via Auto-DocVina software. Brucine exhibits binding affinities of -5.0 to -10.1 Kcal/mol against chosen protein targets, according to an in silico investigation. In vitro studies revealed that brucine inhibited the enzymes alpha-amylase and alpha-glucosidase, and brucine (20 mg/kg) reduced blood glucose levels, oral glucose tolerance overload, body weight, glycosylated hemoglobin levels, total cholesterol, triglycerides, low-density lipoprotein, alanine transaminase, aspartate aminotransferase, total bilirubin, and alkaline phosphatase and elevated high-density lipoprotein levels in in vivo studies. The brucine binding energy against certain protein targets ranges from -5.0 to -10.1 Kcal/mol. It has anti-diabetic, anti-hyperlipidemic, hepatoprotective, anti-oxidant, and anti-inflammatory properties, which are mediated via inhibition of alpha-glucosidase and alpha-amylase.
引用
收藏
页码:46358 / 46370
页数:13
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