Cymbopogon citratus (DC.) Stapf mitigates ER-stress induced by streptozotocin in rats via down-regulation of GRP78 and up-regulation of Nrf2 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: This study was designed to investigate the effect of C. citratus methanolic leaves extract on ER stress induced by streptozotocin (STZ) in wistar rats. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Mobola plum seed methanolic extracts exhibit mixed type inhibition of angiotensin Ⅰ-converting enzyme in vitro

Objective:To explore the possible inhibitory potentials and mechanism by Mobola plum (Parinari curatellifolia) seeds crude methanol (CE) and flavonoid-rich (FE) extracts on angiotensin-1-converting enzyme (ACE I).Methods:The sensitivity and kinetic model of inhibition of CE and FE on ACE I using N-[3-(2-furyl)-acryloyl]-Phe-Gly-Gly as enzyme substrate for ACE I was evaluated by Michealis Menten approach.The inhibition mechanism was explored from LineweaverBurk model and IC50 was determined from Cheng-Prusoff empirical analysis.Results:The IC50 of CE and FE were 13.54 and 39.38 μg/mL,respectively.Both extracts exhibited mixed type inhibition with the inhibitory constant (Ki) of CE was between 0.38 and 0.37 μg/mL while that of FE showed a two-fold increase (1.62 μg/mL and 0.28 μg/mL).FE on ACE I demonstrated positive cooperativity with a Hill's coefficient of 1.89.Conclusions:The study reveals the superior ACE I inhibitory potential of CE over FE and suggest that mixed inhibition pattern of the enzyme might be the underlying mechanism of antihypertensive activity.

In vitro antioxidant activity and effect of Parkia biglobosa bark extract on mitochondrial redox status.

Aqueous-methanolic extract of Parkia biglobosa bark (PBB) was screened for its polyphenolic constituents, in vitro antioxidant activity, and effect on mitochondria redox status. The in vitro antioxidant activity was assessed by using the scavenging abilities and the reducing powers of 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) diammonium salt radical cation against Fe(3+). Subsequently, the ability of PBB to inhibit lipid peroxidation induced by FeSO(4) (10 µm) and its metal-chelating potential were investigated. The effects of the extract on basal reactive oxygen species (ROS) generation and on the mitochondrial membrane potential (ΔΨm) in isolated mitochondria were determined by using 2', 7'-dichlorodihydrofluorescin (DCFH) oxidation and safranin fluorescence, respectively. PBB mitigated the Fe(II)-induced lipid peroxidation in rat tissues and showed dose-dependent scavenging of DPPH (IC(50): 98.33 ± 10.0 µg/mL) and ABTS. (trolox equivalent antioxidant concentration, TEAC value = 0.05), with considerable ferric-reducing and moderate metal-chelating abilities. PBB caused slight decreases in both the liver and the brain mitochondria potentials and resulted in a significant decrease (p < 0.001) in DCFH oxidation. Screening for polyphenolics using high-performance liquid chromatography coupled to a diode array detector (HPLC-DAD) revealed the presence of caffeic acid, gallic acid, catechin, epigalocatechin, rutin, and quercetin. These results demonstrate for the first time the considerable in vitro antioxidant activity and favorable effect of PBB on mitochondria redox status and provide justification for the use of the plant in ethnomedicine.