High-Throughput Sequencing Reveals That Rotundine Inhibits Colorectal Cancer by Regulating Prognosis-Related Genes.

BACKGROUND: Rotundine is an herbal medicine with anti-cancer effects. However, little is known about the anti-cancer effect of rotundine on colorectal cancer. Therefore, our study aimed to investigate the specific molecular mechanism of rotundine inhibition of colorectal cancer. METHODS: MTT and cell scratch assay were performed to investigate the effects of rotundine on the viability, migration, and invasion ability of SW480 cells. Changes in cell apoptosis were analyzed by flow cytometry. DEGs were detected by high-throughput sequencing after the action of rotundine on SW480 cells, and the DEGs were subjected to function enrichment analysis. Bioinformatics analyses were performed to screen out prognosis-related DEGs of COAD. Followed by enrichment analysis of prognosis-related DEGs. Furthermore, prognostic models were constructed, including ROC analysis, risk curve analysis, PCA and t-SNE, Nomo analysis, and Kaplan-Meier prognostic analysis. RESULTS: In this study, we showed that rotundine concentrations of 50 µM, 100 µM, 150 µM, and 200 µM inhibited the proliferation, migration, and invasion of SW480 cells in a time- and concentration-dependent manner. Rotundine does not induce SW480 cell apoptosis. Compared to the control group, high-throughput results showed that there were 385 DEGs in the SW480 group. And DEGs were associated with the Hippo signaling pathway. In addition, 16 of the DEGs were significantly associated with poorer prognosis in COAD, with MEF2B, CCDC187, PSD2, RGS16, PLXDC1, HELB, ASIC3, PLCH2, IGF2BP3, CLHC1, DNHD1, SACS, H1-4, ANKRD36, and ZNF117 being highly expressed in COAD and ARV1 being lowly expressed. Prognosis-related DEGs were mainly enriched in cancer-related pathways and biological functions, such as inositol phosphate metabolism, enterobactin transmembrane transporter activity, and enterobactin transport. Prognostic modeling also showed that these 16 DEGs could be used as predictors of overall survival prognosis in COAD patients. CONCLUSIONS: Rotundine inhibits the development and progression of colorectal cancer by regulating the expression of these prognosis-related genes. Our findings could further provide new directions for the treatment of colorectal cancer.

Ethnobotany, phytochemistry and pharmacology of Stephania rotunda Lour.

ETHNOPHARMACOLOGICAL RELEVANCE: Stephania rotunda Lour. (Menispermaceae) is an important traditional medicinal plant that is grown in Southeast Asia. The stems, leaves, and tubers have been used in the Cambodian, Lao, Indian and Vietnamese folk medicine systems for years to treat a wide range of ailments, including asthma, headache, fever, and diarrhoea. AIM OF THE REVIEW: To provide an up-to-date, comprehensive overview and analysis of the ethnobotany, phytochemistry, and pharmacology of Stephania rotunda for its potential benefits in human health, as well as to assess the scientific evidence of traditional use and provide a basis for future research directions. MATERIAL AND METHODS: Peer-reviewed articles on Stephania rotunda were acquired via an electronic search of the major scientific databases (Pubmed, Google Scholar, and ScienceDirect). Data were collected from scientific journals, theses, and books. RESULTS: The traditional uses of Stephania rotunda were recorded in countries throughout Southeast Asia (Cambodia, Vietnam, Laos, and India). Different parts of Stephania rotunda were used in traditional medicine to treat about twenty health disorders. Phytochemical analyses identified forty alkaloids. The roots primarily contain l-tetrahydropalmatine (l-THP), whereas the tubers contain cepharanthine and xylopinine. Furthermore, the chemical composition differs from one region to another and according to the harvest period. The alkaloids exhibited approximately ten different pharmacological activities. The main pharmacological activities of Stephania rotunda alkaloids are antiplasmodial, anticancer, and immunomodulatory effects. Sinomenine, cepharanthine, and l-stepholidine are the most promising components and have been tested in humans. The pharmacokinetic parameters have been studied for seven compounds, including the three most promising compounds. The toxicity has been evaluated for liriodenine, roemerine, cycleanine, l-tetrahydropalmatine, and oxostephanine. CONCLUSION: Stephania rotunda is traditionally used for the treatment of a wide range of ailments. Pharmacological investigations have validated different uses of Stephania rotunda in folk medicine. The present review highlights the three most promising compounds of Stephania rotunda, which could constitute potential leads in various medicinal fields, including malaria and cancer.

Advancement of potent narcotic anaIgesics:combination of oxycodone / 中国药理学与毒理学杂志

Oxycodone,an opioid receptor agonist,is one of potent narcotic analgesics. Despite its potent analgesic effect,the tolerant and dependent liability of oxycodone as well as its inhibition on gas-trointestinal motility strongly restricts its clinical application. Since the end of the last century,antipyretic, opioid receptor agonist,opioid receptor antagonist and dopamine receptor antagonist have been used to in combination with oxycodone at different ratios as complex prescriptions,the aim of which is to enhance the effect of oxycodone,decrease the dosage of oxycodone,and prevent the adverse effect and the tendency for misuse. Here we reviewed the development of oxycodone compositions in the recent years,hoping to provide more data for its potential clinical application.