Mechanism of baixiangdan capsules on anti-neuroinflammation: combining dry and wet experiments.

Neuroinflammation plays an important role in the pathogenesis of neurological disorders, and despite intensive research, treatment of neuroinflammation remains limited. BaiXiangDan capsule (BXD) is widely used in clinical practice. However, systematic studies on the direct role and mechanisms of BXD in neuroinflammation are still lacking. We systematically evaluated the potential pharmacological mechanisms of BXD on neuroinflammation using network pharmacological analysis combined with experimental validation. Multiple databases are used to mine potential targets for bioactive ingredients, drug targets and neuroinflammation. GO and KEGG pathway analysis was also performed. Interactions between active ingredients and pivotal targets were confirmed by molecular docking. An experimental model of neuroinflammation was used to evaluate possible therapeutic mechanisms for BXD. Network pharmacological analysis revealed that Chrysoeriol, Kaempferol and Luteolin in BXD exerted their anti-neuroinflammatory effects mainly by acting on targets such as NCOA2, PIK3CA and PTGS2. Molecular docking results showed that their average affinity was less than -5 kcal/mol, with an average affinity of -8.286 kcal/mol. Pathways in cancer was found to be a potentially important pathway, with involvement of PI3K/AKT signaling pathways. In addition, in vivo experiments showed that BXD treatment ameliorated neural damage and reduced neuronal cell death. Western blotting, RT-qPCR and ELISA analysis showed that BXD inhibited not only the expression of IL-1ß, TNF-α and NO, but also NF-κB, MMP9 and PI3K/AKT signaling pathways. This study applied network pharmacology and in vivo experiments to explore the possible mechanisms of BXD against neuroinflammation, providing insight into the treatment of neuroinflammation.

Baixiangdan capsule and Shuyu capsule regulate anger-out and anger-in, respectively: GB1-mediated GABA can regulate 5-HT levels in multiple brain regions.

The identity of the mechanism by which the Baixiangdan capsule (BXD) and the Shuyu capsule (SY) control anger-out (AO) and anger-in (AI) in rodents is unclear. The current study clarified the intervention role of BXD and SY on AO and AI male rats. We further explored the differences between BXD and SY in the treatment of AO and AI rats. Social isolation combined with the resident-intruder paradigm was used to establish the anger-out and AI rats models. On this basis, GABA content in the dorsal raphe nucleus (DRN) and serotonin (5-HT) contents in these brain regions were detected using ELISA after various time courses (0, 1, 3, 5, and 7 days) treated with BXD and SY. Co-expression of 5-HT and GB1 in the DRN was detected. GB1-specific agonist baclofen and GB1-specific inhibitor CGP35348 were injected into the DRN. Changes in 5-HT levels in these brain regions were then detected. After treatment, rats in the BXD group exhibited lower aggressive behavior scores, longer latencies of aggression, lower total distances in the open field test, and a higher sucrose preference coefficient. Meanwhile, rats in the SY group exhibited higher aggressive behavior scores, shorter latencies of aggression, higher total distances in the open field test, and higher sucrose preference coefficients. With increasing medication duration, 5-HT levels in these brain regions were increased gradually, whereas GABA levels in the DRN were decreased gradually, and all recovered to normal levels by the 7th day. A large number of 5-HT-positive cells could be found in the immunofluorescence section in the DRN containing GABABR1 (GB1)-positive cells, indicating that 5-HT neurons in the DRN co-expressed with GB1. Furthermore, after the drug intervention, the 5-HT level in the DRN was elevated to a normal level, and the GB1 level in the DRN was decreased to a normal level. After the microinjection of baclofen into the DRN, the 5-HT contents in these brain regions were decreased. By contrast, the 5-HT contents were increased after injection with CGP35348. BXD and SY could effectively improve the abnormal behavior changes of AO and AI rats, and the optimal duration of action was 7 days. The improvement way is as follows: Decreased abnormal increase of GABA and GB1 in the DRN further mediated synaptic inhibition and increased 5-HT level in the DRN, leading to increased 5-HT levels in the PFC, hypothalamus, and hippocampus. Therefore, GB1-mediated GABA in the DRN could regulate 5-HT levels in these brain regions, which may be one of the ways by which BXD and SY treat AO and AI, respectively.

Effects of Baixiangdan capsule on learning and memory in PMS rat model with liver-qi invasion syndrome / 中国药理学通报

Aim To explore the effects of Baixiangdan capsule on learning and memory in PMS rat model with liver-qi invasion syndrome. Methods Liver-qi inva-sion rat model was prepared using foot-shock and noise stimulation, and then the model was treated with drugs, finally all the group of rats were evaluated using open-field test. We also detected learning and memory function of PMS liver-qi invasion rats model using Y-maze, new-object recognition and Morris water maze test. Results Compared with the normal group, the total distance increased significantly, number of crosses into the central area and duration of movement in the central area decreased significantly in model group. The total distance decreased significantly, number of crosses into the central area and duration of movement in the central area increased significantly in Baixiang-dan treatment group compared to the model group, and the total distance decreased significantly in fluoxetine treatment group compared to the model group. Com-pared with the normal group, DI decreased significant-ly in model group, and DI increased significantly in Baixiangdan treatment group. During place navigation training, the model group’ s escape latency was obvi-ously delayed on 2nd, 4th day. Compared with the model group, Baixiangdan and fluoxetine treatment group’ s escape latency was obviously reduced. During spatial probe test, compared with the normal group, the escape latency was obviously delayed, and the number of crossing platforms was significantly reduced in the model group. Compared with the model group, the number of crossing platforms significantly increased in Baixiangdan treatment group. Conclusion PMS liver-qi invasion rat model presents learning and memo-ry damage, which could be improved by Baixiangdan capsules, and the treatment effect may be superior to that of fluoxetine.

Effect of Baixiangdan Capsule on expression and behavior and sex hormone of rhesus monkey with premenstrual syndrome and liver-qi invasion / 中成药

AIM: To study the effect of Baixiangdan Capsule (Radix paeoniae alba and Rhizoma cyperi) on expression and behavior and sex hormone of rhesus monkey with premenstrual syndrome (PMS) and liver-qi invasion. METHODS: Twenty-four young rhesus monkeys in high rank and in the ovalatory menstrual cycle were isolated and squeezed 7 h a day for 5 d by specifically designed isolating-cage. At the same time Baixiangdan Capsule orally administed was compared with the control group of Jingqianping Granule. The expression and behavior changes of rhesus monkeys were observed and evaluated by The Measure Table of Emotion Evaluation of Female Experiment Macaque. And the levels of prolactin (PRL),estradiol (E2) and progesterone (P) in serum were investigated by radioimmunoassay. RESULTS: The scores of anxiety factors of the model monkeys were higher than the normal and the serum E2,and P levels decreased and PRL level increased significantly in the control group. As compared with the model group,Baixiangdan Capsule reduced the enhancing anxiety factor scores and also could increase the lower E2 and P levels in serum obviously and decrease PRL level. CONCLUSION: The above findings suggest that Baixiangdan Capsule has good regulative effects and makes it to the normal state on the abnormal expression and behavior and serum sex hormones of rhesus monkey with PMS and liver-qi invasion.

Determination of paeoniflorin,paeonol and ?-cyperone in Baixiangdan Capsule by HPLC / 中成药

AIM: To establish the analytical methods for determing paeoniflorin,paeonol and ?-cyperone in Baixiangdan Capsule(extract of Radix Paeoniae alba,extract of paeonol,volatile oil of Rhizoma Cyperi). METHODS: The contents of paeoniflorin,paeonol and ?-cyperone in the capsule were determined by HPLC respectively. RESULTS: The linear range of paeoniflorin was within 0.6125.508 ?g(r=(0.999 3)) and the average recovery was 98.16%(RSD=1.18%,n=5).The linear range of paeonol was 0.150 4 ?g-1.353 6 ?g(r=(0.999 8)) and the average recovery was 98.16%(RSD=1.52%,n=5).The linear range of ?-cyperone was(0.271)-2.439 ?g(r=(0.999 9)) and the average recovery was 98.02%(RSD=1.58%,n=5). CONCLUSION: The method is reliable,accurate,feasible and reproducible and can be applied to the quality control of Baixiangdan Capsule.