Bioinformatics and Molecular Biology Unit, Department of Biochemistry, Federal University of Technology Akure, Akure, Ondo State, P.M.B 704, Nigeria.
Bioinformatics and Molecular Biology Unit, Department of Biochemistry, Federal University of Technology Akure, Akure, Ondo State, P.M.B 704, Nigeria; Phytomedicine and Toxicology Unit, Department of Biochemistry, Federal University of Technology Akure, Akure, Ondo State, P.M.B 704, Nigeria.
J Ethnopharmacol. 2020 Nov 15;262:113130. doi: 10.1016/j.jep.2020.113130. Epub 2020 Jul 28.
Endoplasmic reticulum (ER) stress plays a role in the pathogenesis of diabetes mellitus, contributing to pancreatic dysfunction and insulin resistance. Ameliorating ER stress may be a viable therapeutic approach in the proper management of diabetes mellitus. Cymbopogon citratus (C.citratus) has been used in traditional medicine in the management of diabetes mellitus. Although well known for its anti-diabetic effect, the mechanism underlying this effect remains unclear.
This study was designed to investigate the effect of C. citratus methanolic leaves extract on ER stress induced by streptozotocin (STZ) in wistar rats.
STZ (60 mg/kg) was used to induce ER stress in the pancreas of rats. The rats were administered C. citratus methanolic leaves extract via gastric gavage at doses 100, 200 and 400 mg/kg for two weeks while metformin (100 mg/kg) was used as positive control. Fasting blood glucose (FBG), expression of ER-stress related genes (GRP78, CHOP, ATF4, TRB3, PERK, IRE1), antioxidant (Nrf2 and AhR) and pro-inflammatory (TNF-α) genes were determined. Possible compounds responsible for this effect were also predicted through molecular docking.
Induction of ER stress using STZ significantly increased FBG while administration of C. citratus methanolic extract restored it to normal control level (p < 0.05). Significant down-regulation of ER stress genes was observed upon treatment of ER stress induced rats with C. citratus methanolic extract when compared to ER-stress untreated rats. Significant up-regulation (p < 0.05) of genes coding for Nrf2 and AhR was also noticed upon treatment of ER stress induced rats with C. citratus methanolic extract. Molecular docking suggests that apigenin targets GRP78 with binding affinity of -9.3 kcal/mol while kaempferol and quercetin target Keap1 with binding affinity of -9.5 kcal/mol and may be responsible for this ameliorative effect on ER stress.
These observations suggest that C. citratus mitigate ER stress induced by STZ via its down-regulative effect on GRP78 and up-regulative effect on NRF2 signaling.
内质网（ER）应激在糖尿病的发病机制中起作用，导致胰腺功能障碍和胰岛素抵抗。减轻 ER 应激可能是糖尿病适当治疗的可行方法。香茅（C.citratus）已在传统医学中用于糖尿病的治疗。尽管它以其抗糖尿病作用而闻名，但这种作用的机制尚不清楚。
本研究旨在研究香茅甲醇叶提取物对链脲佐菌素（STZ）诱导的 Wistar 大鼠 ER 应激的影响。
使用 STZ（60mg/kg）诱导大鼠胰腺 ER 应激。将大鼠通过胃内灌胃给予香茅甲醇叶提取物，剂量分别为 100、200 和 400mg/kg，共两周，而二甲双胍（100mg/kg）用作阳性对照。测定空腹血糖（FBG）、ER 应激相关基因（GRP78、CHOP、ATF4、TRB3、PERK、IRE1）、抗氧化（Nrf2 和 AhR）和促炎（TNF-α）基因的表达。还通过分子对接预测了负责这种作用的可能化合物。
使用 STZ 诱导 ER 应激显著增加了 FBG，而给予香茅甲醇提取物可将其恢复至正常对照水平（p<0.05）。与未用 ER 应激处理的大鼠相比，用香茅甲醇提取物处理 ER 应激诱导的大鼠可显著下调 ER 应激基因。还观察到用香茅甲醇提取物处理 ER 应激诱导的大鼠可显著上调（p<0.05）编码 Nrf2 和 AhR 的基因。分子对接表明，芹菜素以-9.3kcal/mol 的结合亲和力靶向 GRP78，而山奈酚和槲皮素以-9.5kcal/mol 的结合亲和力靶向 Keap1，这可能是其对 ER 应激具有改善作用的原因。
这些观察结果表明，香茅通过下调 GRP78 和上调 NRF2 信号来减轻 STZ 诱导的 ER 应激。
