Yupingfeng San exhibits anticancer effect in hepatocellular carcinoma cells via the MAPK pathway revealed by HTS2 technology.

ETHNOPHARMACOLOGICAL RELEVANCE: Yupingfeng San (YPFS) is a classic rousing prescription in Chinese medicine, with widly clinical application and remarkably curative effect. It consists of three herbs named Astragalus mongholicus Bunge (Huangqi), Atractylodes rubra Dekker (Baizhu) and Saposhnikovia divaricata (Turcz.) Schischk. (Fangfeng), and has a variety of pharmacological activities including immune regulation, antioxidant, anti-tumor, regulation of cytokines, etc. AIM OF THE STUDY: It has been proved that YPFS exerts its anti-tumor effect through enhancing the systemic and local immune responses in tumor patients, moreover, it has the direct tumor-suppressing effect and can reduce the adverse reactions caused by radiotherapy and chemotherapy drugs. Therefore, in this study, we explored the potential anti-HCC mechanism of YPFS based on HTS2 technology and systems pharmacology, aiming to provide a scientific basis for the clinical application of YPFS and a new strategy for Chinese medicine research. MATERIALS AND METHODS: In this study, systems pharmacology plus high throughput sequencing-based high throughput screening (HTS2) technology, and experimental validation were used to investigate the therapeutic mechanisms and the chemical basis of YPFS in HCC treatment. Firstly, the potential therapeutic targets and signaling pathways of YPFS in the treatment of HCC were obtained through systems pharmacology. Subsequently, HTS2 technology combined with PPI network analysis were used to reveal potential therapeutic targets. Finally, the anti-HCC effects and underlying mechanisms of YPFS were further verified in vitro in human hepatocellular carcinoma cell lines. Moreover, the possible chemical basis was explored by drug target verification and molecular docking technology. RESULTS: In total, 183 active ingredients were predicted by YPFS screening and 49 anti-HCC targets were further identified. Most of these targets were enriched into the "MAPK pathway", and the expression of 37 genes was significantly changed after herb treatment. Among them, 5 key targets, including VEGFA, GRB2, JUN, PDGFRB and CDC42, were predicted by protein-protein interaction (PPI) network analysis. According to our results, YPFS inhibited the proliferation, induced the apoptosis and caused cell cycle arrest of HCC cells. In addition, YPFS significantly reduced P38 gene expression. Fangfeng, one of the three herbs in YPFS, significantly down-regulated the expression of more target genes than that of the other two herbs. Lastly, as revealed by molecular docking analysis, 4'-O-glucosyl-5-O-methylvisamminol, an active ingredient identified in Fangfeng, showed a high affinity for P38. CONCLUSION: Taken together, this study shows that YPFS possesses the activities of anti-proliferation and pro-apoptosis in treating HCC, which are achieved by inhibiting the MAPK signaling pathway. P38 is one of the critical targets of YPFS in treating HCC, which may be directly bound and inhibited by 4'-O-glucosyl-5-O-methylvisamminol, a compound derived from YPFS.

Luteolin Inhibited the Self-Renewal and Altered the Polarization of Primary Alveolar Macrophages.

Pure plant extract luteolin has been demonstrated to possess numerous biological and immunological effects. However, how luteolin affects mice alveolar macrophages' self-renewal and polarization closely related to inflammatory and immunomodulatory is still unknown. In our study, the transcriptomic analysis showed that several self-renewal-related pathways in luteolin-pretreated alveolar macrophages were inhibited compared to the granulocyte-macrophage colony-stimulating factor (GM-CSF)-treated group. Ki-67 staining and EdU assay indicated that luteolin inhibited GM-CSF-induced alveolar macrophage proliferation. Moreover, GM-CSF-induced expressions of c-Myc and KLF4 were significantly suppressed by luteolin at transcriptional and protein levels. Besides, we found that luteolin promoted M1 macrophage polarization induced by LPS plus IFN-γ. At the same time, it inhibited M2 macrophage polarization induced by IL-4 in both alveolar and bone marrow-derived macrophages by detecting macrophage polarization-related gene expressions at mRNA and protein levels. We found that luteolin inhibited self-renewal and altered the polarization of primary alveolar macrophages. Taken together, our data will aid in a better understanding of the immunomodulatory effects of luteolin on the primary alveolar macrophages.

A Meta-analysis of Xiaoyin Granules Combined with Acitretin Capsule in the Treatment of Psoriasis Vulgaris.

Background: Psoriasis is a chronic noncommunicable dermatological condition, and psoriasis vulgaris is the most common phenotype. Acitretin is the most widely used systemic retinoid in the treatment of psoriasis. This review evaluates the clinical therapeutic effects of Xiaoyin granule, a Chinese herbal medicine, combined with acitretin capsule in the treatment of psoriasis vulgaris. Methods: Six databases including PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Wan Fang, and China Biology Medicine disc (CBM) were searched for published studies on Xiaoyin granule and/or acitretin capsule in psoriasis vulgaris. The Cochrane Collaboration risk-of-bias instrument was used to assess the quality of the included RCTs. STATA 14.0 was used to conduct the statistical analysis. Results: Twenty-eight trials with 3281 patients were included in this meta-analysis. The results of this study show that the combined treatment of Xiaoyin granule and acitretin capsule could improve the total effective rate (TER) and cure rate (CR) when compared with acitretin capsule (TER: RR = 1.15, 95% CI (1.10, 1.21); CR: RR = 1.8, 95% CI (1.62, 2.00)) or Xiaoyin granule (TER: RR = 1.24, 95% CI (1.11, 1.39); CR: RR = 1.75, 95% CI (1.54, 1.98)) alone. The combined therapy could decrease the PASI score (mean difference = -1.45, 95% CI (-2.09, -0.80)) and inhibit inflammation (IL-10: mean difference = 1.16, 95% CI (0.94, 1.38); IL-17: mean difference = -2.06, 95% CI (-2.60, -1.51)) in psoriasis vulgaris patients. Conclusions: The combination of Xiaoyin granule and acitretin capsules could be a novel therapeutic strategy in the treatment of psoriasis vulgaris. However, the quality of trials in this study limited the conclusion, and more high-quality RCTs are needed for further evaluation.