Objective Patients with hypertension have a risk of depression. Morinda officinalis oligosaccharides (MOOs) have anti-depressant properties. In this study, we aimed to determine whether MOOs can improve the symptoms of depression in individuals with hypertension. Methods Dahl salt-sensitive rats fed with a high-salt diet were stimulated by chronic unpredictable mild stress to mimic hypertension with depression. Primary astrocytes and neurons were isolated from these rats. Astrocytes underwent LPS stimulation to simulate the inflammatory astrocytes during depression. MOOs were administrated at 0.1 mg/g/day in vivo and 1.25, 2.5, and 5 mg/mL in vitro. Mitophagy was inhibited using 5 mM 3-methyladenine (3-MA). Astrocyte-mediated neurotoxicity was detected by co-culturing astrocytes and neurons. Results MOOs decreased systolic pressure, diastolic pressure, and mean arterial pressure, thereby improving depression-like behavior, including behavioral despair, lack of enthusiasm, and loss of pleasure during hypertension with depression. Furthermore, MOOs inhibited inflammation, astrocytic dysfunction, and mitochondrial damage in the brain. Then, MOOs promoted autophagosome and lysosome enriched in mitochondria in LPS-stimulated astrocytes. MOOs suppressed mitochondrial damage and the release of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β in astrocytes undergoing LPS stimulation. Importantly, MOOs rescued the impaired neurons co-cultured with astrocytes. The effects of MOOs on LPS-stimulated astrocytes were reversed by 3-MA. Finally, MOOs upregulated LPS-downregulated Mfn2 expression in astrocytes. Mfn2 inhibition partly reversed the effects of MOOs on hypertension with depression. Intriguingly, Mfn2 suppression activated PI3K/Akt/mTOR pathway during MOOs treatment. Conclusions Astrocytes develop neuroinflammation in response to mitochondrial damage during hypertension with depression. MOOs upregulated Mfn2 expression to activate the PI3K/Akt/mTOR pathway-mediated mitophagy, thereby removing impaired mitochondria in astrocytes. Highlights MOOs have anti-hypertensive and anti-depressive properties. MOOs inhibit inflammation and injury in astrocytes during hypertension with depression. MOOs induce mitophagy activation in inflammatory astrocytes with mitochondrial damage. MOOs upregulate Mfn2 expression in astrocytes. Mfn2 activates mitophagy to resist mitochondrial damage in astrocytes.

Background and objective: With the exact clinical efficacy, Buyang Huanwu decoction (BHD) is a classical prescription for the treatment of ischemic stroke (IS). Here, we aimed to investigate the pharmacological mechanisms of BHD in treating IS using systems biology approaches.Methods: The bioactive components and potential targets of BHD were screened by TCMSP, BATMAN-TCM, ETCM, and SymMap databases. Besides, compounds that failed to find the targets from the above databases were predicted through STITCH, SWISS, and SEA. Moreover, six databases were searched to mine targets of IS. The intersection targets were obtained, and analyzed by GO and KEGG enrichment. Furthermore, BHD-IS PPI network, compound-compound target-IS network and pathway of drug-compound target-IS network were constructed by Cytoscape 3.6.0. Finally, AutoDock was used for molecular docking verification.Results：A total of 253 putative targets were obtained from 60 active compounds in BHD. Among them, 62 targets were related to IS. PPI network showed that the top ten key targets were IL6, TNF, VEGFA, and AKT1, etc. The enrichment analysis demonstrated candidate BHD targets were more frequently involved TNF, PI3K-Akt, and NF-kappa B signaling pathway. Network topology analysis showed that Radix Astragali was the main herb in BHD, and the key components were quercetin, beta-Sitosterol, kaempferol, and stigmasterol, etc. The results of molecular docking showed the active components in BHD had a good binding ability with the key targets.Conclusions: This study firstly adopted the methods of network pharmacology and molecular docking to reveal the relationships among herbs in BHD, the putative targets and IS-related pathways.

Background: Synaptic damage and glutamate excitotoxicity have been implicated in the pathogenesis of vascular dementia (VD). Clathrin, RAB5B and N-methyl-d-aspartic acid receptor 1 (NMDAR1) proteins play a vital role in endocytosis of synaptic vesicles in neurons and glutamate over accumulation. Previous researches have been confirmed that Shenzhi Jiannao (SZJN) formula has an anti-apoptotic and neuroprotective effect in VD, but the underlying mechanisms are still unclear. In this study, we aimed to explore the effect of SZJN formula on cognitive impairment and glutamate excitotoxicity via clathrin-mediated endocytosis (CME) in vivo and in vitro. Methods: Both common carotid arteries were permanent occluded (2‐vessel occlusion, 2VO) in male Sprague Dawley (SD) rats to model VD. One day after operation, the rats began daily treatment with SZJN formula for two weeks. The neuroprotective effects of SZJN formula was subsequently assessed by the novel object recognition test, Morris water maze, hematoxylin-eosin (HE) staining and Nissl staining. Glutamate cytotoxicity was assessed by detecting cell viability and cell death of PC12 cells. Immunohistochemistry, immunofluorescence, Western blot, and quantitative real‐time PCR were used to detect the expression levels of clathrin, RAB5B, and NMDAR1.Results: Administration of SZJN formula effectively improved short-term memory and spatial memory. SZJN treatment significantly reduced hippocampal neuronal loss, and recovered the arrangement and morphology of neurons and Nissl bodies. Moreover, SZJN formula promoted the proliferation of PC12 cells and inhibited glutamate-induced cell death. The down-regulation of clathrin and RAB5B, as well as the upregulation of NMDAR1 in the brain induced by 2VO or glutamate was also notably reversed by SZJN formula at both the protein and mRNA levels, which may contribute to SZJN formula induced improved neurological function. Conclusions: Taken together, our findings provide evidence that the neuroprotective effects of SZJN formula in experimental VD maybe mediated through promoting the expression of clathirn-mediated endocytosis and reducing NMDARs‐associated glutamate excitotoxicity. SZJN formula serves as a promising alternative therapy and may be a useful herbal medicine for preventing progression of VD.

IntroductionInsomnia was widely distributed among the population, and it was a risk factor for many diseases. To evaluate the condition of usage of drugs in Chinese hospital of Longgang, Shenzhen, we carried this cross-sectional research. We extracted the information of drug usage, symptoms of patients by R software (version 4.0.2) from Hospital Information System (HIS). The research was registered in Chinese Clinical Trial Registry, ChiCTR2000040703.MethodsA retrospective, cross-sectional study was conducted in Shenzhen Hospital of Beijing University of Chinese Medicine (Long Gang). Insomnia patients from Jan 1, 2016 to Nov 10, 2020 were included to cross-sectional study. We analyzed the basic information, the condition of drug usage and the relation of symptoms and drug usage by R software (version 4.0.2).ResultsTotally 9439 patients were included in the study. The average age of these patients was 45.81years (SD 13.97 years). Anxiety, dreaminess, dizzy, palpitation, headache, thirsty, weakness, chest distress, annoyance, abdominal distension, bad moods, difficulty falling asleep and bitter taste were core symptoms of insomnia. Totally 14256 times (67.65%) patients received drug prescription and more than one insomnia drug was administered in 8355 patients. The 10 most used drugs ranged from more to less were Estazolam (29.99%), Zaoren Anshen Capsule (15.50%), Oryzanol (14.82%), Diazepam (14.51%), Flupentixol and Melitracen (14.30%), Alprazolam (8.12%), Zolpidem Tartrate (5.29%), Vitamin B6 (4.76%), Sertraline (4.03%), Clonazepam (2.97%). ConclusionThe drug usage for insomnia in the Chinese medicine hospital in Long gang, Shenzhen were mainly included benzodiazepines, nonbenzodiazepines, Chinese patent medicines, anti-anxiety and anti-depression drugs, Oryzanol and Vitamin B6. The usage of Oryzanol and Vitamin B6 should be abused in Chinese medicine hospital, and the usage of Chinese medicine should be more rigorously evaluated. The nonbenzodiazepines should be promoted and broader understood in Chinese medicine hospital in Longgang, Shenzhen.