Neuroprotective effects of Danshensu on rotenone-induced Parkinson’s disease models in vitro and in vivo

Abstract

Background: Danshensu is an active constituent in the extracts of Danshen which is a traditional Chinese medical herb. Rotenone inhibits complex I of the mitochondrial electron transport chain in dopaminergic neurons leading to glutathione (GSH) level reduction and oxidative stress. The aim of this study is to investigate neuroprotective effects of Danshensu on rotenone-induced Parkinson's disease (PD) in vitro and in vivo. Methods: In vitro, SH-SY5Y human neuroblastoma cell line was pretreated with Danshensu and challenged with rotenone. Then the reactive oxygen species (ROS) production was assayed. In vivo, male C57BL/6 mice were intragastrically administered with Danshensu (15, 30, or 60 mg/kg), followed by oral administration with rotenone at a dose of 30 mg/kg. Pole and rotarod tests were carried out at 28 d to observe the effects of Danshensu on PD. Results: Danshensu repressed ROS generation and therefore attenuated the rotenone-induced injury in SH-SY5Y cells. Danshensu improved motor dysfunction induced by rotenone, accompanied with reducing MDA content and increasing GSH level in striatum. Danshensu increased the number of TH positive neurons, the expression of TH and the dopamine contents. The expressions of p-PI3K, p-AKT, Nrf2, hemeoxygenase (HO-1), glutathione cysteine ligase regulatory subunit (GCLC), glutathione cysteine ligase modulatory subunit (GCLM) were significantly increased and the expression of Keap1 was decreased in Danshensu groups. Conclusions: The neuroprotective effects of Danshensu on rotenone-induced PD are attributed to the antioxidative properties by activating PI3K/AKT/Nrf2 pathway and increasing Nrf2-induced expression of HO-1, GCLC, and GCLM, at least in part.

Forced exercise activates the NrF2 pathway in the striatum and ameliorates motor and behavioral manifestations of Parkinson's disease in rotenone-treated rats

“…von Wrangel et al, (24) reported that rotenone-treated rats showed signi cant impairment in Rotarod and signi cant decline in tyrosine hydroxylase in the striatum. Similarly, (25), in their study reported that rotenone treatment in rats caused signi cant Rota-rod test impairment, and reduction in tyrosine hydroxylase. Cannon et al (26) reported signi cant decreased locomotion, gait impairment and 50% loss in tyrosine hydroxylase activity in rotenone-treated rats (27).…”

“…Whether rotenone increases or decreases the expression of NrF2 and Nqo1 is a matter of debate. Many studies (25). found that rotenone in in-vivo and in vitro studies downregulated the expression of these genes and enhanced apoptosis of the neurons of the nigrostriatum which was reversed by administration of danshensu herbal extract.…”

α‐Lipoic acid alleviates ferroptosis in the MPP+‐induced PC12 cells via activating the PI3K/Akt/Nrf2 pathway

“…Similarly, the PI3K/Akt pathway is implicated in α‐LA's effects on inhibiting neuronal apoptosis (Ma et al, 2016). Moreover, the PI3K/Akt/Nrf2 pathway activation shows a close relationship with the neuroprotective effects on PD (de Oliveira et al, 2016; Wang et al, 2020). Consistently, we verified that blocking the PI3K/Akt/Nrf2 pathway dramatically weakened the protective effect of α‐LA on MPP + ‐induced cell viability decrease and ferroptosis in PC12 cells.…”

Forced exercise activates the NrF2 pathway in the striatum and ameliorates motor and behavioral manifestations of Parkinson's disease in rotenone-treated rats

“…Whether rotenone increases or decreases the expression of Nrf2 and NQO1 is a matter of debate. Many studies [36] found that rotenone in in-vivo and in-vitro studies downregulated the expression of these genes and enhanced apoptosis of the neurons in the nigrostriatal tissue which was reversed by administration of danshensu herbal extract. Similarly, Cui et al [37] found decreased expression of NRF2 and NQO1 proteins measured by western blotting in rotenone treated rats which were corrected with pretreatment with curcumin.…”