Identifying cancer-related molecular targets of Nandina domestica Thunb. by network pharmacology-based analysis in combination with chemical profiling and molecular docking studies.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruits of Nandina domestica Thunb. have served as folk medicines in Chinese and Japanese tradition for treatment of several tumors including pharynx tumor and tooth abscess for many years, yet its exact mechanism of action is not yet known. AIM OF THE STUDY: The study targets the identification of the main constituents of the fruits extracts and investigation of their mode of action in cancer therapy via pharmacology-based analysis and molecular docking. MATERIALS AND METHODS: The different extracts of N. domestica Thunb. were analyzed via UPLC-MS/MS for identification of their active constituents. STITCH, DAVID, KEGG and STRING database were utilized for construction of compound-target and compound-target-pathway networks using Cytoscape 3.2.1. Molecular docking analysis of the top hit compounds was performed against the identified top hit molecular targets in the constructed networks. In vitro-testing of Nandina domestica Thunb. against colorectal cancer cell lines was carried out and correlated to the chemical profile of the extract to identify important biomarkers. The ADME properties of the active compounds were also evaluated. RESULTS: 22 compounds were identified by UPLC-MS/MS analysis and were forwarded to network pharmacology-based analysis. Results showed the enrichment of 5 compounds and 4 molecular targets in the network namely; AKT1, CASP3, MAPK1 and TP53. The pathway analysis of the identified targets revealed that 15 cancer-related pathways were enriched including colorectal cancer, endometrial cancer and small-cell lung cancer. In-vitro testing of the extracts against colo-rectal cancer cell lines revealed the fractions enriched in the identified hit compounds were indeed the most active as revealed from the HCA-heat-map. ADME results showed that all compounds were drug-like candidates showing acceptable values according to Lipinski's rule. CONCLUSIONS: Network pharmacology analysis revealed that the compounds isoquercitrin, quercitrin, berberine, chlorogenic acid and caffeic acid showed strong synergistic interactions with the cancer-related targets and pathways. It could be concluded that N. domestica Thunb. constituents affect both apoptosis and Akt-signaling pathways during the stages of early and intermediate adenoma through interaction with the targets CASP3 and MAPK1 (ErC2) while during the stages of late adenoma and carcinoma, the compounds acts through the p53 and ErbB signaling pathways.

Diuretic activity of ethanolic extract of Panicum repens L. roots and rhizomes.

The diuretic activity of ethanolic extract of Panicum repens was investigated in rats. A single oral dose of 500 mg/kg of P. repens extract were given to rats, after 24 h, urine volume, its sodium and potassium concentrations were estimated. Treatment with P. repens extract caused a significant increase in tested parameters as compared to their corresponding controls, p < 0.05.

Anti-hyperlipidemic activity of an extract from roots and rhizomes of Panicum repens L. on high cholesterol diet-induced hyperlipidemia in rats.

The hypolipidemic effect of an ethanolic extract from the roots and rhizomes of Panicum repens L. was investigated in rats suffering from high-cholesterol, diet-induced hyperlipidemia, and the phytochemicals in the extract were analyzed. The extract was administered p.o. in doses of 250 mg/kg/day together with cholesterol at a dose of 100 mg/kg/day for 7 weeks. The high-cholesterol diet caused a significant increase in total lipids, total cholesterol (TC), total triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and the atherogenic index, whereas the level of high-density lipoprotein cholesterol (HDL-C) was significantly decreased. Administration of the P. repens extract (p<0.05) significantly reduced the rise of the serum levels of total lipids, TC, TG, and LDL-C, as well as the atherogenic index, whereas it significantly increased (p<0.05) the level of HDL-C. HPLC analysis of the phenolics and flavonoids in the extract revealed the presence of gallic acid, chlorogenic acid, chicoric acid, primulic acid, rutin, apigenin-7-glucoside, and quercetin. In conclusion, the P. repens extract was found to possess hypolipidemic activity in high-fat, diet-induced hyperlipidemic rats.

Antioxidant activity of Artocarpus heterophyllus Lam. (Jack Fruit) leaf extracts: remarkable attenuations of hyperglycemia and hyperlipidemia in streptozotocin-diabetic rats.

The present study examines the antioxidative, hypoglycemic, and hypolipidemic activities of Artocarpus heterophyllus (jack fruit) leaf extracts (JFEs). The 70% ethanol (JFEE), n-butanol (JFBE), water (JFWE), chloroform (JFCE), and ethyl acetate (JFEAE) extracts were obtained. Both JFEE and JFBE markedly scavenge diphenylpicrylhydrazyl radical and chelate Fe+2 in vitro. A compound was isolated from JFBE and identified using 1D and 2D 1H- and 13C-NMR. The administration of JFEE or JFBE to streptozotocin (STZ)-diabetic rats significantly reduced fasting blood glucose (FBG) from 200 to 56 and 79 mg%, respectively; elevated insulin from 10.8 to 19.5 and 15.1 µU/ml, respectively; decreased lipid peroxides from 7.3 to 5.4 and 5.9 nmol/ml, respectively; decreased %glycosylated hemoglobin A1C (%HbA1C) from 6.8 to 4.5 and 5.0%, respectively; and increased total protein content from 2.5 to 6.3 and 5.7 mg%, respectively. Triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), VLDL-C, and LDL/HDL ratio significantly declined by -37, -19, -23, -37, and -39%, respectively, in the case of JFEE; and by -31, -14, -17, -31, and -25%, respectively, in the case of JFBE; as compared to diabetic rats. HDL-C increased by +37% (JFEE) and by +11% (JFBE). Both JFEE and JFBE have shown appreciable results in decreasing FBG, lipid peroxides, %HbA1C, TC, LDL-C, and TG levels, and increasing insulin, HDL-C, and protein content. The spectrometric analysis confirmed that the flavonoid isolated from JFBE was isoquercitrin. We can conclude from this study that JFEE and JFBE exert hypoglycemic and hypolipidemic effects in STZ-diabetic rats through an antioxidative pathway that might be referred to their flavonoid contents.