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Objective. This study is designed to find out the molecular targets of effective Chinese medicine Ziyin Mingmu pills (ZMPs) in treating age-related macular degeneration (AMD) based on network pharmacology and experimental data. Methods. A comprehensive network pharmacology strategy that consists of three sequential modules (drug-disease target molecular docking, enrichment analysis, and external verification) was carried out to identify potential targets of ZMPs acting on AMD. Results. The active ingredients of ZMPs targeting 66 genes have effects on the process of AMD. GO and KEGG pathway enrichment analyses suggested that response to oxidative stress, regulation of angiogenesis, and lipid and atherosclerosis might serve as the most important signaling pathways in ZMPs for AMD treatment. Combined with the GSE29801 dataset for further analysis, two key genes, EGFR and VEGFA, were identified. Immune infiltration analysis showed that there was a strong association between EGFR and immune cell content. In addition, images were acquired following 24 h in the scratch experiment showed that ZMPs can reduce the percentage of wound healing distance. The Western blot assay found that ZMPs increased the expression of EGFR and decreased the expression of VEGFA. Conclusion. This study sheds light on some mechanisms of ZMP therapy for AMD, particularly the effect of ZMP on the oxidative stress in RPE and cell survival and angiogenesis in AMD. We propound ZMPs as a promising strategy to intervene in the process of AMD. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) is a critical reason for cancer chemotherapy failure. Babaodan (BBD) is a famous traditional Chinese patent medicine reported to have antigastric cancer activity. However, the roles and molecular mechanisms of the reversal of MDR of gastric cancer by BBD have not been well described until now. Therefore, the purpose of this study was to elucidate further the role of BBD in reversing the MDR of gastric cancer cells and its specific regulatory mechanism via in vitro experiments. To verify our results, MTT, Doxorubicin (DOX) staining, Rhodamin123 (Rho123) staining, DAPI staining, Annexin V-FITC, propidium iodide (PI), Cyto-ID, and western blot assays were performed. To determine whether BBD triggers apoptosis and autophagy through the PI3K/AKT/mTOR signaling, we also applied 3-methyladenine (3-MA), chloroquine (CQ), and 740Y-P (an activator of PI3K). The results showed that BBD reversed the MDR and induced apoptosis and autophagy of SGC7901/DDP cells. Pathway analyses suggested BBD inhibits PI3K/AKT/mTOR pathway activity and subsequent apoptosis-autophagy induction. Inhibition of autophagy with 3-MA and chloroquine (CQ) was performed to confirm that BBD promoted autophagy. PI3K agonist, 740Y-P, further verified BBD inhibition of PI3K/AKT/mTOR pathway activation. In conclusion, BBD may reverse the MDR of gastric cancer cells, induce apoptosis, and promote autophagy via inactivation of the PI3K/AKT/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Background. Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) often causes small intestinal ulcers in patients, but few effective drugs are currently available to manage such serious adverse events of NSAIDs. Li-Zhong decoction (LZD), a well-known traditional Chinese medicine (TCM) formula, is commonly prescribed for treatment of gastrointestinal diseases. The present study aimed to investigate the anti-ulcerogenic activity of LZD on indomethacin- (IND-) induced duodenal ulcer in rats. Mechanistic studies of action of LZD were focused on involvement of TLR-2/MyD88 signaling pathway. Methods. Fifty male Sprague-Dawley (SD) rats were randomly and evenly divided into five groups: normal control, ulcer control (IND, 25 mg/kg), IND + esomeprazole (ESO, 4.17 mg/kg), and IND + low and high doses of LZD (3.75 and 7.50 g/kg). Macroscopic and histopathological examinations were performed for evaluation of ulcer index (UI), curative index (CI), and microscopic score (MS). Levels of duodenal inflammatory biomarkers and cytoprotective mediators including interleukin-4 (IL-4), IL-10, tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) were measured by ELISA. Expression levels of TLR-2 and MyD88 mRNA were assessed by qRT-PCR. The expression and distribution of TLR-2 and MyD88 proteins were analyzed by western blot and immunohistochemistry, respectively. Results. Gross and microscopic examinations of the IND-treated rats revealed severe duodenal hemorrhagic necrosis, inflammatory infiltration, villus destruction, and crypt abscess, while LZD-treated rats manifested these pathological events to a markedly lesser degree. LZD significantly decreased UI and MS, increased CI, preserved the integrity of the villus and crypt, and normalized the tissue architecture of the duodenum of rats. The elevated TNF-α levels in the IND-treated rats were markedly diminished in the LZD-treated rats, while lower levels of IL-4, IL-10, and PGE2 observed in IND-treated rats were significantly increased in LZD-treated rats. Interestingly, improvement of immune function in duodenal mucosa by reduction of mRNA and protein expression levels of TLR-2 and MyD88 was also observed in rats treated with LZD. Consistently, immunohistochemical analyses revealed a lower co-localization of TLR-2 and MyD88 proteins in the duodenal mucosa of LZD-treated rats as compared to the IND-induced rats. Conclusions. Our data demonstrate that LZD protects the duodenal mucosa from IND-caused lesions, which is at least partially attributable to the interaction of its potential cytoprotective and anti-inflammatory mechanisms together with enhancement of the mucosal immunity through TLR-2/MyD88 signaling pathway. [ABSTRACT FROM AUTHOR]

Hypoxia-induced angiogenesis plays an important role in the development and metastasis of solid tumors and is highly regulated by HIF-1α/VEGF-A pathway. Therefore, inhibiting tumor angiogenesis via suppression of HIF-1α/VEGF-A signaling represents a promising strategy for anticancer treatment. As a traditional Chinese medicine formula, Pien Tze Huang (PZH) has long been used as a folk remedy for cancer in China and Southeast Asia. Previously, we reported that PZH inhibits colorectal cancer (CRC) growth both in vivo and in vitro. To elucidate the antitumor mechanisms of PZH, in the present study we used human umbilical vein endothelial cells (HUVEC) and colorectal carcinoma HCT-8 cells to evaluate the effects of PZH on hypoxia-induced angiogenesis and investigated the underlying molecular mechanisms. We found that PZH could inhibit hypoxia-induced migration and tube formation of HUVEC cells in a dose-dependent manner, although the low concentrations of PZH had no effect on HUVEC viability. Moreover, PZH inhibited hypoxia-induced activation of HIF-1α signaling and the expression of VEGF-A and/or VEGFR2 in both HCT-8 and HUVEC cells. Collectively, our findings suggest that PZH can inhibit hypoxia-induced tumor angiogenesis via suppression of HIF-1α/VEGF-A pathway. [ABSTRACT FROM AUTHOR]