The protective effect of natural compounds against rotenone‐induced neurotoxicity

Abstract

Rotenone is a widely used organic pesticide; its serious side effect for off-target species is neurotoxicity. The primary mechanism of rotenone toxicity is inhibition of the mitochondrial complex I. Oxidative stress, apoptosis, and reduction of autophagy are key outcomes of the inhibition of complex I. Numerous in vitro and in vivo studies have shown antioxidant, anti-apoptotic, and autophagy enhancement of a variety of natural compounds (NCs). In this manuscript, we reviewed several NCs, which have protective effects against rotenone-induced neurotoxicity.

A review on the protective effects of naringenin against natural and chemical toxic agents

“…Rotenone is an organic pesticide and a known neurotoxin, which has been widely used in experimental models of Parkinson's disease (PD) (Yarmohammadi, Wallace Hayes, Najafi, & Karimi, 2020). During the PD progression, a marked decline in dopamine and biosynthetic enzymes such as tyrosine hydroxylase (TH) has been shown to lead to the death of dopaminergic (DAergic) neurons in the substantia nigra and cause motor dysfunction.…”

The role of ferroptosis in organ toxicity

“…20 ROS levels are controlled by enzymatic and non-enzymatic antioxidants, including glutathione (GSH), superoxide dismutase (SOD), and glutathione peroxidase 4 (GPX4). 20,21 An imbalance between ROS generation and its detoxification can lead to DNA damage and the peroxidation of proteins and lipids. 21 Lipid peroxides (LPOs) are an important class of ROS that exert their toxic effects through altering membrane properties and producing DNA-protein crosslinks.…”

“…19 The overproduction of ROS potentially contributes to cellular oxidative injury. 20 ROS levels are controlled by enzymatic and non-enzymatic antioxidants, including glutathione (GSH), superoxide dismutase (SOD), and glutathione peroxidase 4 (GPX4). 20,21 An imbalance between ROS generation and its detoxification can lead to DNA damage and the peroxidation of proteins and lipids.…”

Targeting Mitochondria by Plant Secondary Metabolites: A Promising Strategy in Combating Parkinson’s Disease

“…Boswellic acids, a group of pentacyclic triterpenes, from the genus Boswellia, have been shown to reduce rotenone-induced mitochondrial malfunction by inhibiting the interleukin (IL)-6/signal transducer and activator of transcription-3 (STAT3)/NF-κB signaling pathways [92]. Tormentic acid is a triterpene found in medicinal plants, including Rosa rugosa and Potentilla chinensis that significantly suppressed ROS's intracellular aggregation and Bax/Bcl-2 ratio induced by MPP + in SH-SY5Y cells.…”

“…In vitro: SH-SY5Y cells ↑VDAC1, ↓cytosolic cytochrome c, ↑ PINK1/parkin-mediated mitophagy [91] Tormentic acid Triterpene In vitro: SH-SY5Y cells ↓ROS, ↓Bax/Bcl-2 ratio through stimulation of the PI3K/Akt/GSK-3β signaling pathway [93] Boswellic acids Pentacyclic triterpene In vivo: Rats ↓Rotenone-induced mitochondrial malfunction by inhibiting the IL-6/STAT3/NF-κB signaling pathways [92] Ginsenosides-Rg…”