Proprietary Medicines Containing Bupleurum chinense DC. (Chaihu) for Depression: Network Meta-Analysis and Network Pharmacology Prediction.

Background and Aims: The rapid development of society has resulted in great competitive pressures, leading to the increase in suicide rates as well as incidence and recurrence of depression in recent years. Proprietary Chinese medicines containing Bupleurum chinense DC. (Chaihu) are widely used in clinical practice. This study aimed at evaluating the efficacy and safety of oral proprietary Chinese medicines containing Chaihu for treating depression by network meta-analysis (NMA) and exploring the potential pharmacological mechanisms of the optimal drugs obtained based on NMA. Methods: This study searched for clinical randomized controlled trial studies (RCTs) about Chaihu-containing products alone or in combination with selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), and cyclic antidepressants (CAS) for depression in eight databases. The search deadline is from data inception to April 2021. For efficacy assessment, the clinical response rate, the Hamilton Depression Scale-17 (HAMD-17), and adverse reactions were calculated. The methodological quality of the included studies was assessed for risk of bias following the Cochrane Handbook for Systematic Reviews of Interventions, and the data were subjected to NMA via the Stata version 16.0 software. Subsequently, the optimal drug obtained from the NMA results, Danzhi Xiaoyao pill (DZXY), was used to conduct network pharmacology analysis. We searched databases to acquire bioactive and potential targets of DZXY and depression-related targets. The protein-protein interaction (PPI) network, component-target network, the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed by the STRING database, Cytoscape 3.9.0 software, and R version 4.1.2, respectively. Results: Thirty-seven RCTs, with a total of 3,263 patients, involving seven oral proprietary Chinese medicines containing Chaihu, were finally included. The results of the NMA demonstrated that the top four interventions with the best efficiency were Jiawei Xiaoyao + SSRI, DZXY + SNRI, Xiaoyao pill + SSRI, and Jieyu pill + SNRI; the top four interventions reducing HAMD score were DZXY + SNRI, Jiawei Xiaoyao, Jieyu pill, and Puyu pill + SNRI; the top four interventions with the least adverse effects were Jieyu pill, Anle pill + SSRI, DZXY + SNRI, and Puyu pill + SNRI. In the aspects above, DZXY + SNRI performed better than other treatments. After network meta-analysis, we conducted a network pharmacology-based strategy on the optimal drugs, DZXY, to provide the pharmacological basis for a conclusion. A total of 147 active compounds and 248 targets in DZXY were identified, of which 175 overlapping targets related to depression. Bioinformatics analysis revealed that MAPK3, JUN, MAPK14, MYC, MAPK1, etc. could become potential therapeutic targets. The MAPK signaling pathway might play an essential role in DZXY against depression. Conclusion: This is the very first systematic review and network meta-analysis evaluating different oral proprietary Chinese medicines containing Chaihu in depressive disorder. This study suggested that the combination of proprietary Chinese medicines containing Chaihu with antidepressants was generally better than antidepressant treatment. The incidence of adverse reactions with antidepressants alone was higher than that with proprietary Chinese medicines containing Chaihu alone or in combination with antidepressants. DZXY + SNRI showed significantly better results in efficacy, HAMD scores, and safety. The antidepressant effect of DZXY may be related to its regulation of neuroinflammation and apoptosis.

The study of neuroprotective effect of ferulic acid based on cell metabolomics.

Ferulic acid (FA), a naturally derived phenolic compound, has antioxidant and antidepressant-like effects. It is still a challenge to study its mechanism due to the complexity of the pathophysiology of depression. In this study, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to perform metabolomics studies based on biochemical changes in differentiated rat pheochromocytoma (PC12) cells treated with corticosterone-induced neurological damage after FA treatment. A total of 31 metabolites were identified as potential biomarkers for corticosterone-induced PC12 cells injury. Among them, 24 metabolites were regulated after FA treatment. Pathway analysis revealed that these metabolites were mainly involved in the amino acid metabolism, energy metabolism and glycerophospholipid metabolism. In addition, based on the results of metabolomics, three cell signaling pathways related to glutamate were discovered. To further study the interactions between FA and major targets in three signaling pathways, a molecular docking method was employed. The results showed that FA had the strongest binding power with protein kinase B (AKT). Furthermore, the result of mRNA changes analyzed by quantitative real time RT-PCR indicated that AKT and protein kinase A (PKA) in the signaling pathway were up regulated after treatment with FA compared with model group. This study shows that strategies based on cell metabolomics associated with molecular docking and molecular biology is a helpful tool to elucidate the neuroprotective mechanism of FA.

Betulinic acid increases radiosensitization of oral squamous cell carcinoma through inducing Sp1 sumoylation and PTEN expression.

Radiotherapy is one of the most effective non-surgical treatments for oral squamous cell carcinoma. However, radioresistance remains a major impediment to radiotherapy. Although BetA (Betulinic acid) can induce radiosensitization, the underlying mechanism and whether it could induce radiosensitization in oral squamous cell carcinoma are not fully understood. In this study, we showed that BetA increased radiosensitization in CAL-27 and Tca-83 cells. Radiation-triggered Sp1 overexpression was responsible for radioresistance of OSCC (oral squamous cell carcinoma) cells. Treatment with BetA downregulated Sp1 and upregulated PTEN through inducing Sp1 sumoylation and correspondingly increased radiosensitization. Moreover, Sumoylation of Sp1 upregulated PTEN protein expression by downregulating Sp1 as well as inhibiting Sp1 DNA binding activity, thereby leading to the activation of PTEN transcription. Our results suggested that BetA was able to enhance radiosensitization at least partially by downregulating Sp1 and upregulating PTEN through inducing Sp1 sumoylation. BetA is suggested to be a promising drug for increasing radiosensitization in oral squamous cell carcinoma radiotherapy.

Effect of primary percutaneous coronary intervention on serum collagen biomarkers following acute myocardial infarction.

OBJECTIVE: The aim of this study was to investigate the effect of primary percutaneous coronary intervention (PCI) on serum collagen biomarkers following acute myocardial infarction (AMI). METHODS AND RESULTS: Thirty-eight patients were enrolled into a primary PCI (n = 16) and a control (n = 22) group. The PCI group received successful PCI within 6 h of MI, whereas the control group received no PCI or thrombolytic therapy. Serum type I procollagen (PICP) and type III procollagen (PIIINP) were measured by enzyme-linked immunosorbent assay (ELISA). The baseline characteristics were similar between the PCI and control groups. There was no significant difference in left ventricular end-systolic, end-diastolic volume or ejection fraction between the two groups 30 min after MI (P > 0.05). A significant increase in PICP and PIIINP was noted in both groups 3 days after MI (P < 0.01). PICP and PIIINP in the PCI group declined overtime to the pre-PCI level, whereas they remained high in the control group. In the PCI group, the mean serum PICP and PIIINP on day 7, 14 and 30 was lower than in the control group (P < 0.01). CONCLUSIONS: AMI is associated with an increase in serum biomarkers of collagen synthesis. Early and successful PCI is associated with a reduction in serum collagen biomarkers.