Cocculus hirsutus: Molecular Docking to Identify Suitable Targets for Hepatocellular Carcinoma by In silico Technique.

BACKGROUND: Protein-ligand interaction plays a major role in identification of the possible mechanism by which a ligand can bind with the target and exerts the pharmacological action. OBJECTIVE: The aim is to identify the best candidate of Cocculus hirsutus which binds with the hepatocellular carcinoma (HCC) targets by docking studies. MATERIALS AND METHODS: The reported phytoconstituents such as coclaurine, hirsutine, cohirsine, cohirsinine, lirioresinol, cohirsitinine, haiderine, jamtinine, isotrilobine, shaheenine, jamtine, and cocsoline present in the plant, C. hirsutus were docked with the HCC targets such as Aurora kinase, c-Kit, fibroblast growth factor, nuclear factor kappa B (NF-kB), B-cell lymphoma-extra large, and vascular endothelial growth factor (VEGF) using in silico technique with the software Grid-Based Ligand Docking with Energies. RESULTS: Haiderine, shaheenine, and coclaurine had good interaction with Aurora kinase with the glide score and glide energy of - 7.632, -7.620, -7.464; and - 56.536, -55.203, -52,822, respectively. Coclaurine, lirioresinol, and haiderine possess good binding with c-Kit with the glide score and glide energy of - 8.572, -6.640, -6.478; and - 56.527, -57.138, -20,522, respectively. Lirioresinol, hirsutine, and coclaurine exhibit good binding with c-Kit with the glide score and glide energy of - 5.702, -5.694, -5.678; and - 48.666, -35.778, -41,673, respectively. Similarly, coclaurine, haiderine, and hisutine had good interaction with NF-kB. Haiderine, jamtinine, and coclaurine had good binding with VEGF receptors (VEGFR) and coclaurine, lirioresinol, and haiderine exhibit good bonding with VEGFR. CONCLUSION: Coclaurine, haiderine, and lirioresinol exibited good hydrogen bonding interactions and binding energy with the select targets. Hence, these compounds have to be taken up for experimental work against hepatocellular carcinoma. SUMMARY: Compounds of interest showed good interaction and binding with the selected targets. Hence these compounds has to be explored further to study their anticancer potentials. Abbreviations used: HCC: Hepatocellular Carcinoma, Bcl-xL: B-cell lymphoma-extra large, FGF: Fibroblast Growth Factor, VEGF: Vascular Endothelial Growth Factor, DLA: Dalton's Lymphoma Ascites.

Anticancer activity of cissampelos pareira against dalton's lymphoma ascites bearing mice.

BACKGROUND: Cissampelos pareira (Menispermaceae) is used in folk Indian system of alternative medicine, for its analgesic, antipyretic, diuretic, antilithic, and emmenagogue properties. OBJECTIVE: To evaluate Cissampelos pareira (C. pareira) for in vitro cytotoxicity and in vivo antitumor activity against Dalton's Lymphoma Ascites (DLA) cells in Swiss mice. MATERIALS AND METHODS: Cissampelos pareira was successively extracted using different solvents. In vitro cytotoxicity was assessed by the MTT assay. An in vivo study was carried out in methanol extract. Twenty-four hours after intraperitoneal inoculation of the DLA cells in mice, the methanol extract of C. pariera (MECP) was administered at 200 and 400 mg/kg body weight for 14 consecutive days. On day 14, six mice were sacrificed and the rest were kept alive for assessment of increase in life-span. The antitumor effect was assessed by evaluating the packed cell volume, viable tumor cell count, increase in body weight, and increase in life-span. The hematological and serum biochemical parameters and anti-oxidant properties were assessed by estimating the superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation. RESULTS: Methanol Extract of Cissampelos pariera (MECP) showed a potent cytotoxic activity, with an IC50 value of 95.5 µg/ml and a significant (P < 0.001) decrease in packed cell volume, viable cell count, and an increased lifespan (54 and 72%). The hematological and serum biochemical profiles were restored to normal levels in MECP-treated mice. The MECP-treated group significantly (P < 0.001) decreased SOD, lipid peroxidation, and CAT to normal. CONCLUSION: This study demonstrated that C. pariera exhibited significant in vitro and in vivo anti-tumor activities and that it was reasonably imputable to its increasing endogenous mechanism of antioxidant property.

Anticancer activity of Cocculus hirsutus against Dalton's lymphoma ascites (DLA) cells in mice.

CONTEXT: Cocculus hirsutus (L.) Diels (Menispermaceae) is used in Indian folk system of alternative medicine for rheumatism, eczema, diabetics, inflammation, and neuralgia. OBJECTIVE: To evaluate antitumor activities of C. hirsutus in vitro and in vivo. MATERIALS AND METHODS: C. hirsutus was successively extracted using hexane, petroleum ether, chloroform, ethyl acetate, methanol, and water. In vitro cytotoxicity was assessed by the MTT assay. Phytochemical analyses were conducted with methanol extract of C. hirsutus (MECH) and in vivo antitumor activity was carried out with MECH using Dalton's lymphoma ascites (DLA) mouse model. Antioxidant properties were assessed by estimating superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation. RESULTS AND DISCUSSION: Phytochemical studies indicated a high content of total alkaloid (165.6 mg/100 g), total phenolic (43.5 GAE mg/g), and total flavanoid (4.97 RE mg/g) in MECH. Anti-proliferative activity against the breast cancer cell line MCF-7 showed IC50 values of 221.5 ± 16.68, 255 ± 17.88, 213 ± 8.4, 147 ± 7.9, and 229 ± 8.02 µg/ml with hexane, petroleum ether, chloroform, ethyl acetate, methanol, and aqueous extracts, respectively. A significant (p < 0.01) decrease in packed cell volume, viable cell count, and increased lifespan (58 and 77%) was observed. Hematological and serum biochemical profiles were restored to normal levels in MECH-treated mice. MECH-treated group significantly (p < 0.001) decreased SOD, lipid peroxidation, and CAT towards normal. CONCLUSION: C. hirsutus exhibited significant in vitro and in vivo antitumor activities that are reasonably attributed to endogenous antioxidant mechanisms.

In vitro cytotoxic activity of menispermaceae plants against HeLa cell line.

BACKGROUND: Menispermaceae, a family of flowering plants, is a medium-sized family of 70 genera totaling 420 extant species, mostly of climbing plants. It has various medicinal properties, which are used in the Ayurvedic system of medicine. Plants belonging to this family are rich in alkaloids, especially bisbenzylisoquinoline type. The hypothesis of this study is that the bisbenzylisoquinoline alkaloids present in the selected plants may exhibit in vitro cytotoxic property. AIM: The present study is aimed at estimating the total alkaloidal content of methanolic extract of Cocculus hirsutus and Cissampelos pareira and evaluating the in vitro cytotoxic activity of both the extracts on the HeLa cell line. SETTINGS AND DESIGN: Methanolic extracts of both the plants in the concentrations of 500, 250, 125, 62.5, and 31.25 µg/ml were assessed for its cytotoxic activity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. MATERIALS AND METHODS: Total alkaloidal content was studied for both the plants using ultraviolet-visible spectroscopy method. Methanol extracts of both the plants were tested for its inhibitory effect on HeLa cell line. Cytotoxicity of the plant extracts was evaluated by MTT assay. Nonlinear regression graph was plotted between % cell inhibition and Log10 concentration, and IC50 was determined using GraphPad Prism software. RESULTS: Preliminary phytochemical studies confirm the presence of alkaloids in both the plants. The total alkaloids present in C. hirsutus and C. pareira were found to be 0.252%w/w and 0.1656%w/w respectively. The IC50 values of C. hirsutus and C. pareria were found to be 111 µg/ml and 129.3 µg/ml respectively. CONCLUSION: From this study, it is observed that C. hirsutus and C. pareira have in vitro cytotoxic activity against HeLa cell line.