Explore the active ingredients and potential mechanisms of JianPi QingRe HuaYu Methods in the treatment of gastric inflammation-cancer transformation by network pharmacology and experimental validation.

BACKGROUND: JianPi QingRe HuaYu Methods (JQH) have been long used to treat chronic atrophic gastritis (CAG) and precancerous lesions of gastric cancer (PLGC). However, whether JQH can inhibit the transformation of gastritis to gastric cancer (GC) remains unclear. METHODS: Herein, we first retrieved the active ingredients and targets of JQH from the TCMSP database and the targets related to the gastric inflammation-cancer transformation from public databases. Differentially expressed genes (DEGs) related to gastric inflammation-cancer transformation were identified from the Gene Expression Omnibus (GEO) database. Then, we obtained the potential therapeutic targets of JQH in treating gastric inflammation-cancer transformation by intersecting drugs and disease targets. The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) analyses of the potential therapeutic targets were conducted using R software. Next, we conducted molecular docking and in vitro experiments to validate our results. RESULTS: We obtained 214 potential therapeutic targets of JQH by intersecting drugs and disease targets. We found that the potential mechanisms of JQH in treating gastric inflammation-cancer transformation might be related to JAK-STAT, Wnt, p53 and VEGF signaling pathways. The molecular docking indicated that quercetin, as the main active ingredient of JQH, might inhibit gastric inflammation-cancer transformation by binding with specific receptors. Our experimental results showed that quercetin inhibited cells proliferation (P < 0.001), promoted cell apoptosis (P < 0.001), reduced the secretion of pro-inflammatory cytokines (P < 0.001) and promoted the secretion of anti-inflammatory cytokines (P < 0.001) in MNNG-induced GES-1 cells. Furthermore, quercetin inhibited cells proliferation (P < 0.001) and reduced mRNA and protein level of markers of PLGC (P < 0.001) in CDCA-induced GES-1 cells. CONCLUSION: These results provide the material basis and regulatory mechanisms of JQH in treating gastric inflammation-cancer transformation.

Identification of berberine as a potential therapeutic strategy for kidney clear cell carcinoma and COVID-19 based on analysis of large-scale datasets.

Background: Regarding the global coronavirus disease 2019 (COVID)-19 pandemic, kidney clear cell carcinoma (KIRC) has acquired a higher infection probability and may induce fatal complications and death following COVID-19 infection. However, effective treatment strategies remain unavailable. Berberine exhibits significant antiviral and antitumour effects. Thus, this study aimed to provide a promising and reliable therapeutic strategy for clinical decision-making by exploring the therapeutic mechanism of berberine against KIRC/COVID-19. Methods: Based on large-scale data analysis, the target genes, clinical risk, and immune and pharmacological mechanisms of berberine against KIRC/COVID-19 were systematically investigated. Results: In total, 1,038 and 12,992 differentially expressed genes (DEGs) of COVID-19 and KIRC, respectively, were verified from Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively, and 489 berberine target genes were obtained from official websites. After intersecting, 26 genes were considered potential berberine therapeutic targets for KIRC/COVID-19. Berberine mechanism of action against KIRC/COVID-19 was revealed by protein-protein interaction, gene ontology, and Kyoto Encyclopedia of Genes and Genomes with terms including protein interaction, cell proliferation, viral carcinogenesis, and the PI3K/Akt signalling pathway. In COVID-19 patients, ACOX1, LRRK2, MMP8, SLC1A3, CPT1A, H2AC11, H4C8, and SLC1A3 were closely related to disease severity, and the general survival of KIRC patients was closely related to ACOX1, APP, CPT1A, PLK1, and TYMS. Additionally, the risk signature accurately and sensitively depicted the overall survival and patient survival status for KIRC. Numerous neutrophils were enriched in the immune system of COVID-19 patients, and the lives of KIRC patients were endangered due to significant immune cell infiltration. Molecular docking studies indicated that berberine binds strongly to target proteins. Conclusion: This study demonstrated berberine as a potential treatment option in pharmacological, immunological, and clinical practice. Moreover, its therapeutic effects may provide potential and reliable treatment options for patients with KIRC/COVID-19.

The different effects of Chinese Herb Solid Drink and lactulose on gut microbiota in rats with slow transit constipation induced by compound diphenoxylate.

Slow transit constipation (STC) has become an epidemic medical problem. There are several kinds of drugs for constipation; however, each drug has its limitations. The gut microbiota has a close relationship with STC. Lactulose is an effective drug for constipation because it is a kind of bulking laxative and microbioecologic, and it relieves the syndromes of STC. We found that the Chinese Herb Solid Drink (CHSD), which contains medicine food homologous materials such as psyllium husk, sweetalmond, semen sesami nigrum, and hemp seed, has a similar effect on relieving constipation as lactulose, although it has different effects on the gut microbiota. We investigated the mechanisms of CHSD in rats with STC, induced by diphenoxylate, via constipation index and enzyme linked immunosorbent assay (ELISA) analyses using serum and 16S rDNA amplicon and gas chromatography-mass spectroscopy (GC-MS). CHSD enhanced the relative abundance of some types of gut microbiota, such as Blautia, Ruminococcus, Roseburia, Coprococcus, Lachnospira, and Phascolarctobacterium, while lactulose enhanced the relative abundance of Blautia, Phascolarctobacterium, Eubacterium, and Akkernansia in diphenoxylate-induced STC rats. Both CHSD and lactulose enhanced the level of short-chain fatty acids in the faeces of rats; however, the composition of those were different between the two drugs. From the perspective of the gut neuroendocrine system, both CHSD and lactulose could elevate neurotransmitters, such as motilin (MTL) and substance P (SP), which promote intestinal peristalsis and reduce the expression of vasoactive intestinal peptide, which inhibits intestinal peristalsis in the serum of STC rats. CHSD could elevate gastrin expression, which also promoted intestinal peristalsis in serum, while lactulose did not have this effect. Our findings suggest that CHSD may be an effective and safe therapeutic choice for STC.

The Effect of Traditional Chinese Medicine Zhike-Houpu Herbal Pair on Depressive Behaviors and Hippocampal Serotonin 1A Receptors in Rats After Chronic Unpredictable Mild Stress.

OBJECTIVE: Zhike-Houpu herbal pair (ZKHPHP) is a well-known Chinese medicine to treat gastrointestinal motility dysfunction. Recently, many researchers have found that some of the compounds of ZKHPHP such as meranzin hydrate and magnolol have antidepressant effects. However, little is known about the antidepressant mechanism of ZKHPHP. Therefore, the main aim of the study is to evaluate the antidepressant-like effects of ZKHPHP and its possible mechanism of action on 5-hydroxytryptamine receptor 1A (HTR1A) in the hippocampus CA1 region in rats exposed to chronic unpredictable mild stress. METHODS: Male Sprague Dawley rats were randomly divided into the following six groups: normal, model, ZKHPHP (3 g/kg), ZKHPHP (10 g/kg), ZKHPHP (20 g/kg), and ZKHPHP (30 g/kg); n = 8 per group. We exposed the rats to chronic unpredictable mild stress and then assessed antidepressant-like effects of ZKHPHP by measuring weight change, observing the open-field test, and measuring sucrose water consumption. The antidepressant mechanism was examined by measuring the effect of ZKHPHP on HTR1A protein expression and HTR1A mRNA expression in the hippocampus CA1 region by using immunohistochemistry analysis, Western blotting, and real-time reverse transcription-polymerase chain reaction. RESULTS: ZKHPHP (10 or 20 g/kg) reduced the incidence of depressive-like behaviors and increased HTR1A protein and HTR1A mRNA expression in the hippocampus CA1 in rats displaying depressive behavior, whereas ZKHPHP (3 or 30 g/kg) had no obvious effect on the measured depression indicators. CONCLUSIONS: These data show that ZKHPHP has antidepressant-like effects based on a chronic unpredictable mild stress-induced depression model in rats. ZKHPHP may be attractive as an antidepressant because of its beneficial effects on depression and the absence of gastrointestinal dysregulation, which is a frequently observed unintended effect of many commonly used antidepressive medications.

Coffee intake and risk of pancreatic cancer: an updated meta-analysis of prospective studies.

INTRODUCTION: Inconsistent results on the relationship between coffee consumption and pancreatic cancer risk has been reported in both epidemiological studies and previous meta-analyses. This updated meta-analysis was conducted to assess the association of coffee intake with pancreatic cancer risk. EVIDENCE ACQUISITION: We evaluated the relationship of coffee ingestion and pancreatic cancer risk by performing a meta-analysis of prospective cohort studies and made an explicit document search in the PubMed database before November 2015. We also obtained prospective cohort studies of previous meta-analyses. A random-effects model was used for pooling overall relative risk. Twenty articles of coffee ingestion and pancreatic cancer were contained in our meta-analysis. EVIDENCE SYNTHESIS: The summary relative risk (RR) of pancreatic cancer and coffee intake of the highest compared with lowest category was 0.99 (95% CI=0.81-1.21), with statistically moderate heterogeneity (I2=47.9%, P=0.008). The heterogeneity reduced to I2=38.5% after excluding one study, and the RR was 1.06 (95% CI=0.94-1.20). The relationships of coffee intake and pancreatic risk did not modified by geographic areas, sex of participants, number of cases, follow-up years, and the number of adjusted confounders. CONCLUSIONS: Dose-response analysis indicated that every one-cup increase in coffee consumption was associated with an 1% increase in pancreatic cancer risk. No statistically significant publication biases existed. Coffee consumption may weakly increase the risk of pancreatic cancer.

Traditional Chinese medicine Zhiqiao-Houpu herb-pair induce bidirectional effects on gastric motility in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhiqiao-Houpu herb-pair (ZQHPHP), composed of Fructus Aurantii (Zhiqiao [ZQ] in Chinese) and Magnolia officinalis (Houpu [HP] in Chinese), is a traditional herbal formula that has been extensively used for treating gastrointestinal motor dysfunction. The aim of the study was to evaluate the effect and possible mechanism of ZQHPHP on gastric emptying (GE) and gastric antral smooth muscle contractility (GASMC). MATERIALS AND METHODS: This study includes four parts: (a) study of ZQHPHP's effect on GE; (b) study of ZQHPHP's effect on gastric antral smooth muscle contractility (GASMC); (c) comparing the effects of ZQHPHP, ZQ and HP on GASMC; (d) study of antagonists or agonists on ZQHPHP-induced GASMC. A test meal of Evans blue was adopted to estimate GE in rats. A polygraph was used to measure GASMC in rats. RESULTS: The in vivo experiments demonstrated that, at the doses of 10mg/kg bw and 20mg/kg bw, ZQHPHP could promote GE. While, at the higher dose of 30 mg/kg bw, ZQHPHP delayed the GE. From the in vitro experiments we found that ZQHPHP (3-10 µg/ml) concentration-dependently increased the mean amplitude of contractions in the antral circular strip compared to untreated controls. While, in the concentration of 30 µg/ml, ZQHPHP prohibited GASMC. Besides, atropine blocked the stimulatory effect of ZQHPHP on GASMC and norepinephrine partly prohibited the stimulatory effect of ZQHPHP on GASMC, whereas isoproterenol showed no effect. From the in vitro experiment, we also found that ZQ and HP used together can synergistically increase gut motor. CONCLUSIONS: The experiment indicated that ZQHPHP could induce bidirectional regulation on gastric motility. ZQ and HP used together can synergistically increase gut motor at a certain dosage. Lower dosage of ZQHPHP increases gastric motility, while higher dosage produces inhibition. In addition, the improvement of gastric motility by ZQHPHP is predominantly involved with muscarinic receptors and secondarily with alpha-receptors.