Abstract
BackgroundDanshensu 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.MethodsIn 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.ResultsDanshensu 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.ConclusionsThe neuroprotective effects of Danshensu on rotenone-induced PD are attributed to the anti-oxidative properties by activating PI3K/AKT/Nrf2 pathway and increasing Nrf2-induced expression of HO-1, GCLC, and GCLM, at least in part.
Highlights
Danshensu is an active constituent in the extracts of Danshen which is a traditional Chinese medical herb
When exposed to rotenone for 24 h, a significant decrease of cell viability was observed with 10 nM and more significant toxicity was seen in 200 nM and 400 nM (Fig. 1b)
In line with the results of in vitro, Danshensu resulted in the increase of GSH content followed by the decrease of MDA level. These results suggested that the neuroprotective effects of Danshensu against rotenone toxicity are attributed to the anti-oxidative properties
Summary
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. Wang et al BMC Complementary Medicine and Therapies (2020) 20:20 peroxidase, catalase and a reduction of glutathione (GSH) has been observed in PD patients [7]. It has been reported that GSH level is reduced and GSSG level is elevated in the substantia nigra of PD patients. The altered GSH/GSSG ratio in the substantia nigra of PD indicates that oxidative stress plays a key role in the pathogenesis of nigral cell death in PD [8]. Control and regulation of oxidative stress may be a promising therapeutic approach for the PD patients
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