Mexican tea (Dysphania ambrosioides (L.) Mosyakin & Clemants) seeds attenuate tourniquet-induced hind limb ischemia-reperfusion injury by modulating ROS and NLRP3 inflammasome pathways

• Published in: Journal of functional foods 2023-09, Vol.108, p.105712, Article 105712
• Main Authors: Annaz, Hassan, Abdelaal, Shimaa, Mandour, Dalia A., Mahdi, Ismail, Mahmoud, Mona F., Sobeh, Mansour
• Format: Article
• Language: English
• Subjects: Apoptosis; Dysphania ambrosioides; Gastrocnemius muscle; HLIRI; Inflammation; Oxidative stress
• ISSN: 1756-4646; 2214-9414
• DOI: 10.1016/j.jff.2023.105712

[Display omitted] •D. ambrosioides aqueous extract is rich in 60 secondary metabolites, mainly phenolic acids, and flavonoids.•Pretreatment of rats with D. ambrosioides extract ameliorated structural defects of both the left kidney and left gastrocnemius muscle.•The extract decreased serum markers of both muscle and kidney damages.•D. ambrosioides extract attenuated oxidative stress by modulation of the Nrf2/HO-1 signaling pathway.•D. ambrosioides extract attenuated NLRP3 inflammasome by reducing key inflammatory cytokines, IL-1β and TNF-α.•The extract also inhibited the apoptotic cell death of muscle fibers by attenuating the proapoptotic caspase-3 enzyme levels. The main pathophysiological mechanisms of hind limb ischemia-reperfusion injury (HLIRI) are increased oxidative stress and inflammation. The present study was designed to characterize the phytocontents of Dysphania ambrosioides (DA) seeds extract via LC-MS/MS and investigate its effect on left hindlimb IR injury and the underlying mechanisms. Thirty adult rats (n = 6 per group) were divided into five groups: Control group; HLIRI group, HLIRI + DA (100 mg/kg) group, HLIRI + DA (200 mg/kg) group, and HLIRI + cilostazol (30 mg/kg) group. HE staining’s of the left gastrocnemius muscle and left kidney, renal function, and both total and muscle creatine kinases were measured in serum. Oxidative stress markers (MDA, SOD, Nrf2 and HO-1), inflammatory markers (NLRP3, IL-1β and TNF-α) and caspase-3 as an apoptotic marker were measured in left gastrocnemius muscle. We found that DA extract contains 60 metabolites and its pretreatment prevented left kidney and left gastrocnemius muscle damage and decreased oxidative stress markers, inflammatory markers, and caspase-3 levels, compared with the control group. Moreover, the effect of the extract was dose-dependent and better than that of the reference drug, cilostazol. This study suggested that D. ambrosioides seeds have a protective effect on HLIRI, which may be related to the antioxidant, anti-inflammatory and antiapoptotic mechanisms.