The pathogenic mechanism of Parkinson’s disease (PD) remains to be elucidated; however, mitochondrial dysfunction at the level of complex I and oxidative stress is suggestively involved in the development of PD. In our previous work, salidroside (Sal), an active component extracted from the medicinal plant Rhodiola rosea L., might protect dopaminergic (DA) neurons through modulating ROS–NO-related pathway. However, the mechanism of Sal-induced neuroprotective effects against PD remains poorly understood. Therefore, we further investigated whether Sal plays neuroprotective effects by activating complex I via DJ-1/Nrf2-mediated antioxidant pathway. The results showed that Sal remarkably attenuated MPP⁺/MPTP-induced decline in cell viability, accompanied by decreases in reactive oxygen species (ROS), malondialdehyde (MDA), and 8-hydroxy-deoxyguanosine (8-OHdG) contents and increases in the superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), as well as glutathione (GSH) levels. Furthermore, Sal greatly improved the behavioral performance and prevented the severe reduction of TH-positive neuron numbers in the substantia nigra (SN). Moreover, in comparison with the MPP⁺/MPTP group, Sal increased the nuclear translocation of DJ-1 and Nrf2 and the mitochondrial translocation of DJ-1, accompanied by activating complex I. Furthermore, silencing of DJ-1/Nrf2 inhibited the increase of complex I activity and cell viability elicited by Sal. Together, these results support the neuroprotective effect of Sal against MPP⁺/MPTP-induced DA neurons damage.

Background. The neurotrophic pathway regulated by the brain‐derived neurotrophic factor (BDNF) plays a crucial role in the pathogenesis of poststroke depression (PSD). How the traditional Chinese medicine compound preparation Xingnao Jieyu (XNJY) decoction regulates the neurotrophic pathway to treat PSD is unclear. Objective. This study aimed to investigate the antidepressant effect of XNJY decoction on a rat model of PSD and the molecular mechanism intervening in the neurotrophic pathway. Methods. After a middle cerebral artery occlusion model was established, chronic unpredictable mild stress was applied for 21 days to prepare a PSD model. XNJY groups and a fluoxetine (Flu) group of rats were intragastrically administered with XNJY and Flu, respectively, for 21 consecutive days. Depressive‐like behaviors, including sucrose preference, open field test, and forced swimming test, were assessed. The survival and apoptosis of cortical and hippocampal neurons were evaluated by immunofluorescence assay and TUNEL staining. The contents of serotonin (5‐HT), norepinephrine (NE), and BDNF in the cortex and hippocampus were determined by ELISA. The protein levels of BDNF, p‐ERK/ERK, and p‐CREB/CREB in the cortical and hippocampal regions were tested by Western blot. Results. The depressive‐like behaviors markedly improved after XNJY and Flu treatment. XNJY and Flu promoted neuronal survival and protected cortical and hippocampal neurons from apoptosis. XNJY also increased the contents of 5‐HT, NE, and BDNF and recovered the protein levels of p‐ERK/ERK, p‐CREB/CREB, and BDNF in the cortical and hippocampal regions. Conclusion. These results indicated that the XNJY decoction exerts an obvious antidepressant effect, which may be due to the regulation of the BDNF/ERK/CREB signaling pathway.

Background. Poststroke depression (PSD) is a common neuropsychiatric disorder that affects the disability, mortality, functional recovery, and quality of daily life of patients. Xiaoyao Recipe (XYR) is often used to treat PSD and has achieved good clinical effects, but it lacks reliable evidence. Objective. This study aims to evaluate the effectiveness and safety of XYR on PSD through meta-analysis. Methods. A comprehensive literature search was carried out in multiple databases, including PubMed, the Cochrane Library, Chinese Biomedical Literature Service System, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and ClinicalTrials, from inception to July 1, 2021, to collect randomized controlled trials that applied XYR for patients with PSD. For a controlled trial, the search time limit was set from the time of the database’s establishment to July 2021. Two experienced researchers independently screened the literature according to the inclusion and exclusion criteria, extracted data, evaluated the quality of the literature, and used RevMan 5.3 software for meta-analysis. Results. A total of 12 studies were included in this study, involving 882 patients with PSD who were hospitalized or outpatients. The meta-analysis results showed that the total effective rate ( ) of the test group (XYR or XYR combined with antidepressants) after treatment was high; Hamilton’s Depression Scale score ( ), Scandinavian Stroke Scale score ( ), and Barthel index ( ) were improved; the incidence of adverse reactions ( ) was low; and the serum serotonin content ( ) was high. Conclusion. Compared with antidepressant drugs, XYR is more effective and safer in the treatment of PSD patients. However, more high-quality studies are needed to further support the above conclusions.

The neuroinflammatory pathway regulated by nuclear factor kappa-B (NF-κB) plays an important role in the occurrence, development, and prognosis of poststroke depression (PSD). The regulatory effect of the traditional Chinese medicine compound Xingnao Jieyu decoction (XNJY) on the NF-κB pathway of PSD is still unclear. This study aimed to observe the effect of XNJY on PSD and explore the molecular mechanism of its intervention in the NF-κB pathway. Middle cerebral artery occlusion (MCAO) and chronic unpredictable mild stress were used to establish a PSD rat model. Body mass measurement, behavioral testing, Nissl staining, ELISA, and Western blot were also performed. XNJY and fluoxetine hydrochloride (Flu) treatment of PSD model rats showed significant antidepressant effects. XNJY and Flu treatment could reduce cortical and hippocampal neuronal damage. XNJY reduced inflammation and restored the levels of IL-4, IL-10, and BDNF. In addition, XNJY showed a significant regulatory effect on the NF-κB pathway and the expression of synapse-related proteins PSD-95 and SYN. These results showed that XNJY could significantly reduce the depressive symptoms of PSD rats, and this reduction may be related to the regulation of the NF-κB signaling pathway to improve neuroinflammation and synaptic function.