Network Pharmacology and in vitro Experimental Verification on Intervention of Quercetin, Present in Chinese Medicine Yishen Qutong Granules, on Esophageal Cancer.

OBJECTIVE: To explore the potential mechanism of Yishen Qutong Granules (YSQTG) for the treatment of esophageal cancer using network pharmacology and experimental research. METHODS: The effective components and molecular mechanism of YSQTG in treating esophageal cancer were expounded based on network pharmacology and molecular docking. The key compound was identified by high-performance liquid chromatography and mass spectrometry (HPLC-MS) to verify the malignant phenotype of the key compounds in the treatment of esophageal cancer. Then, the interaction proteins of key compounds were screened by pull-down assay combined with mass spectrometry. RNA-seq was used to screen the differential genes in the treatment of esophageal cancer by key compounds, and the potential mechanism of key compounds on the main therapeutic targets was verified. RESULTS: Totally 76 effective compounds of YSQTG were found, as well as 309 related targets, and 102 drug and disease interaction targets. The drug-compound-target network of YSQTG was constructed, suggesting that quercetin, luteolin, wogonin, kaempferol and baicalein may be the most important compounds, while quercetin had higher degree value and degree centrality, which might be the key compound in YSQTG. The HPLC-MS results also showed the stable presence of quercetin in YSQTG. By establishing a protein interaction network, the main therapeutic targets of YSQTG in treating esophageal cancer were Jun proto-oncogene, interleukin-6, tumor necrosis factor, and RELA proto-oncogene. The results of cell function experiments in vitro showed that quercetin could inhibit proliferation, invasion, and clonal formation of esophageal carcinoma cells. Quercetin mainly affected the biological processes of esophageal cancer cells, such as proliferation, cell cycle, and cell metastasis. A total of 357 quercetin interacting proteins were screened, and 531 genes were significantly changed. Further pathway enrichment analysis showed that quercetin mainly affects the metabolic pathway, MAPK signaling pathway, and nuclear factor kappa B (NF- κ B) signaling pathway, etc. Quercetin, the key compound of YSQTG, had stronger binding activity by molecular docking. Pull-down assay confirmed that NF- κ B was a quercetin-specific interaction protein, and quercetin could significantly reduce the protein level of NF- κ B, the main therapeutic target. CONCLUSION: YSQTG can be multi-component, multi-target, multi-channel treatment of esophageal cancer, it is a potential drug for the treatment of esophageal cancer.

Effect of Oral Chinese Medicine Combined with Western Medicine on Cancer Pain: A Meta-Analysis.

OBJECTIVE: To assess the effect of oral Chinese medicine (OCM) combined with Western medicine (WM) on cancer pain. METHODS: PubMed, Embase, Cochrane Library, Clinical Trials Registry Platform, Chinese National Knowledge Infrastructure (CNKI), Wanfang and VIP databases were searched from their inception to September {dy2019}. Randomized controlled trials (RCTs) treating cancer pain by Chinese medicine (CM) combined with WM were included. The primary outcome were total pain relief rate and the quality of life (QOL), and the other outcomes were the average daily dosage of analgesics, the primary time of pain, the analgesic duration time, and adverse events. The methodological quality of RCTs was assessed in accordance with Cochrane 5.1.0 handbook of systematic reviews of interventions. Evidence level was assessed by the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. RESULTS: There were 1,087 patients in the 14 studies, with 544 in the experiment group and 543 in the control group. These studies were all conducted in China, and published between 2006 and {dy2019}. Compared with the WM, OCM combined with WM could significantly relieve the cancer pain [risk ratio (RR)=1.43, 95% confidence interval (CI): 1.32, 1.56), improve QOL (RR=8.57, 95% CI: 4.25, 12.89), decrease the primary time of pain (RR=-0.20, 95% CI: -0.24, -0.16], prolong the analgesic duration time (RR=3.47, 95% CI: 2.09, 4.85), reduce the dosage of analgesics (RR=-19.52, 95% CI: -36.32, -2.72), and reduce side events (RR=0.49, 95% CI: 0.37, 0.65). Evidence levels for total pain relief rate, primary time of pain and side events were low, evidence level for QOL, analgesic duration time and average daily dosage of analgesics were very low. CONCLUSIONS: Compared with the WM, OCM combined with WM could significantly relieve the cancer pain, improve the QOL, decrease the primary time of pain, prolong the analgesic duration time, reduce the dosage of analgesics and side events. The evidence levels were low or very low.

Molecular mechanism of HL-60 cell apoptosis induced by baicalin / 中国实验血液学杂志

This study was aimed to investigate the effect of baicalin on proliferation and apoptosis of HL-60 cells and its mechanism. Cell proliferation was assayed by using Cell Counting Kit-8. The morphological changes of HL-60 cells were examined by light microscopy and nucleolus morphological changes were observed by fluorescent microscopy after Hoechst 33342 staining. The early cell apoptosis was detected by using flow cytometry with Annexin V-FITC/PI double staining. The expression of caspase-3, caspase-9, Bcl-2 and Bax mRNA was detected by RT-PCR and Western blot assay was carried out to examine Bax, Bcl-2, caspase-8 and cleaved caspase-3 expression. The results showed that Baicalin inhibited the proliferation of HL-60 cells in a time- and concentration-dependent manner. HL-60 cells exhibited typical morphological features (for example, cell shrinkage, membrane blebbing and formation of apoptotic bodies). Cell apoptosis in early stage could be detected, the expression of caspase-3, caspase-9 and Bax mRNA was obviously up-regulated, while the Bcl-2 expression down-regulated, and accordingly Bcl-2/Bax ratio decreased. Such results were consistent with the expression of these proteins. In addition, the expression of cleaved caspase-8 protein was induced significantly after treated with baicalin. It is concluded that baicalin can significantly inhibit the proliferation of HL-60 cells and induce the apoptosis of HL-60 cells, which may occur through decreasing Bcl-2/Bax ratio by intrinsic pathway and through extrinsic pathway. It suggests that baicalin may be a promising drug for the therapy of acute myeloid leukemia.