Pro-apoptotic and cytotoxic effects of enriched fraction of Elytranthe parasitica (L.) Danser against HepG2 Hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC), the most common type of liver cancer accounts for more than one million deaths worldwide. Current treatment modality for HCC is marginally effective. Plants belonging to Mistletoe family (Loranthaceae) have been used in chemotherapy for many years. The present study was aimed at exploring the anti-proliferative, pro-oxidant and pro-apoptotic potential of stem of Elytranthe parasitica (L.) Danser (EP), a parasitic shrub belonging to Loranthaceae. METHODS: Elytranthe parasitica (L.) Danser, a climbing parasitic shrub was investigated for its cytotoxic activity against HepG2, a hepatocellular carcinoma cell line by Sulforhodamine B (SRB) assay. Further, pro-oxidant activity of EP extract/fractions was studied using copper phenanthroline assay. To understand the mechanism of cell death, the pro-apoptotic effects of Hep-G2 cells treated with EP extract/fractions were visualized by dual staining using acridine orange and ethidium bromide, a morphological marker of apoptosis. Phytochemical profiling of EP was explored by estimating the phenol, flavonoid and tannin content in its various fractions and extract. The occurrence of gallic acid, a principal polyphenol in EP extract and fractions was detected and further quantified using HPTLC (High Performance Thin Layer Chromatography) fingerprinting. RESULT: Active fraction of Elytranthe parasitica, EP.DEE exhibited potent cytotoxic activity in a dose dependent manner against HepG2 hepatocellular carcinoma cell line with an IC50 of 56.7 ± 7.8 µg/mL. Dual staining with acridine orange and ethidium bromide revealed that HepG2 cells treated with EP active fractions underwent cell death chiefly by apoptosis. Highest phenol, flavonoid and tannin content were observed in active fractions, EP.EA (Ethyl acetate fraction) and EP.DEE (Diethyl ether fraction). Gallic acid was identified and quantified in EP extract and active fractions, EP.DEE and EP.EA. CONCLUSION: Our findings indicate EP active fraction could be a promising contender in the treatment of hepatocellular carcinoma.

Nephroprotective potential of Graptophyllum pictum against renal injury induced by gentamicin.

OBJECTIVES: To evaluate the effect of Graptophyllum pictum on lipid peroxidation and tissue antioxidant enzymes in liver and kidney of gentamicin induced nephrotoxic rats. MATERIALS AND METHODS: Animals were grouped into 6: Group 1 received gum acacia, Group 2 received G. pictum ethanol extract (300 mg/kg), Group 3 received gentamicin, Groups 4, 5, 6 received gentamicin along with G. pictum at 300, 150, 75 mg/kg, respectively. Nephroprotective activity was evaluated by measuring thiobarbituric acid-reactive substances (TBARS), biochemical markers Glutathione (GSH), Glutathione-S Transferase(GST), Superoxide dismutase (SOD), Catalase (CAT), serum urea and creatinine levels. RESULTS: Results obtained showed that gentamicin induced nephrotoxic rats exhibited lower activities of biochemical markers and raised levels of TBARS, serum creatinine and urea. Remarkably, after treatment with G. pictum extract, anomalous levels of biochemical markers, lipid peroxidation and serum creatinine were returned to normal. CONCLUSION: The results propose that G. pictum has nephroprotective effects, and can be a promising natural source against gentamicin induced nephrotoxicity.

Identity-based High-performance thin Layer Chromatography Fingerprinting Profile and Tumor Inhibitory Potential of Anisochilus carnosus (L.f.) wall Against Ehrlich Ascites Carcinoma.

CONTEXT: Anisochilus carnosus (L.f.) wall belonging to the family Lamiaceae is a plant that is widely used in folk medicine for treating eczema, cold, cough, and fever. OBJECTIVE: In the present study, we explored the anticancer potential of A. carnosus leaves against Ehrlich ascites carcinoma (EAC) and estimated the quantity of luteolin present in various extracts and fractions of A. carnosus by high-performance thin layer chromatography (HPTLC) fingerprinting. MATERIALS AND METHODS: Various factors such as tumor volume, tumor cell viability, tumor weight, prolongation of lifespan, and hematological parameters were assessed. RESULT: We observed a significant lowering in tumor volume, tumor weight, and cell viability in EAC-induced mice following intervention with A. carnosus extracts. Also, there was a considerable prolongation of host lifespan and restoration of hematological parameters to almost normal levels with A. carnosus treatment. HPTLC fingerprinting of various extracts and fractions of A. carnosus along with luteolin as the reference standard revealed the occurrence of luteolin in all tested extracts and fractions of A. carnosus with the highest concentration being reported in the ethanol fraction. CONCLUSION: A. carnosus exhibits potent anti-tumor potential which can most likely be attributed to the occurrence of different phytochemicals such as phytosterols, terpenoids, and flavonoids in the plant. Further studies to isolate compounds from A. carnosus and understand the mechanism of anti-tumor activity would be worthwhile. SUMMARY: EAC induced mice that received A. carnosus treatment exhibited significant reduction in tumor volume, tumor weight and tumor cell viability. Their life span was considerably prolonged. We detected luteolin in A. carnosus aqueous and ethanol extract using HPTLC. Hence, anticancer activity of A. carnosus can be partly attributed to the presence of luteolin.

Cytotoxic potential of Anisochilus carnosus (L.f.) wall and estimation of luteolin content by HPLC.

BACKGROUND: Anisochilus carnosus (L.f.) wall (Lamiaceae), an annual herb which grows at high altitude is used extensively in folk medicine for the treatment of ailments such as gastric ulcer and skin diseases. The aim of our study was to evaluate the anticancer activity of different extracts of the leaves of A.carnosus. An attempt was also made to estimate the luteolin content in different extracts of Anisochilus carnosus by HPLC (High Performance Liquid Chromatography). METHODS: In the current study, we explored the cytotoxic potential of petroleum ether, ethanolic and aqueous extracts of A.carnosus against breast adenocarcinoma cell line (BT-549), by in vitro MTT and SRB assay. We also detected the luteolin content in different extracts (ethanolic and aqueous) of A.carnosus by using HPLC as a tool of analysis. RESULTS: The results demonstrate that petroleum ether and ethanolic extract of A.carnosus showed potent cytotoxic effect against BT-549 with an IC50 of 22.5 µg/ml (petroleum ether extract) and 87.24 µg/ml (ethanolic extract), by SRB assay, and 18.35 µg/ml (petroleum ether extract) and 58.64 µg/ml (ethanolic extract), by MTT assay. The aqueous extracts showed less cytotoxic effect with an IC50 of 211.26 µg/ml (by SRB assay) and 238.91 µg/ml (by MTT assay). HPLC results of luteolin content in various extracts using luteolin as the marker compound indicated the ethanol extract to contain the highest concentration of luteolin (0.372% w/w). The aqueous extract contained lower concentration of luteolin (0.282% w/w). CONCLUSION: Our findings demonstrate that petroleum ether and ethanolic extract of A.carnosus shows promising anticancer activity and has the potential to be developed into a therapeutic option for the treatment of cancer.

Synthesis, in vitro anticancer and antioxidant activity of thiadiazole substituted thiazolidin-4-ones.

A series of novel 5-alkyl/aryl thiadiazole substituted thiazolidin-4-ones were synthesized by a two-step process. In the first step, 5-alkyl/aryl substituted 2-aminothiadiazoles were synthesized, which on reaction with substituted aromatic aldehydes and thioglycolic acid in the presence of dicyclohexylcarbodiimide afforded thiazolidin- 4-ones. All the compounds were synthesized in fairly good yields and their structures were confirmed by spectral and physical data. The title compounds were screened for in vitro anti-proliferative activity on human breast adenocarcinoma cells (MCF-7) by MTT assay. Most of the derivatives showed an IC50 less than 150 µmol L⁻¹. Among the compounds tested, 2-(2-nitrophenyl)- 3-(5-methyl-1,3,4-thiadiazol-2-yl)-thiazolidin-4-one (3f), 2-(3-fluorophenyl)-3-(5-methyl-1,3,4-thiadiazol-2- -yl)-thiazolidin-4-one (3b), and 2-(4-chlorophenyl)-3- -(5-methyl-1,3,4-thiadiazol-2-yl)-thiazolidin-4-one (3c) were found to be the most active derivatives with IC50 values of 46.34, 66.84, and 60.71 µmol L⁻¹, respectively. Antioxidant studies of all the synthesized compounds were carried out by diphenylpicrylhydrazyl (DPPH) assay. Among the compounds tested, 2-phenyl-3-(5-styryl- -1,3,4-thiadiazol-2-yl)-thiazolidin-4-one (3s) elicited superior antioxidant activity with IC50 of 161.93 µmol L⁻¹.

Effect of ethanol extract of Sphaeranthus indicus on cisplatin-induced nephrotoxicity in rats.

Cisplatin is an anticancer drug extensively used against a variety of cancers. Cisplatin chemotherapy is found to manifest dose-dependent nephrotoxicity. Depletion of the renal antioxidant defence system has been suggested to be the main cause of cisplatin-induced nephrotoxicity. The purpose of this study is to investigate whether the ethanol extract of entire plant of Sphaeranthus indicus could reduce the intensity of toxicity in albino rats. Nephrotoxicity was assessed by determining the serum creatinine and urea levels and renal antioxidant status in rats after cisplatin administration (12 mg kg(-1) body weight, i.p.). The ethanol extract of S. indicus (150 and 300 mg kg(-1) body weight) was administered orally from the sixth day onwards for 10 days after cisplatin administration. The extract significantly reduced the elevated serum creatinine and urea levels. Renal antioxidant defence systems, such as superoxide dismutase, catalase, glutathione peroxidase activities and reduced glutathione level that are depleted by cisplatin therapy were restored to normal by treatment with the extract. Cisplatin-induced lipid peroxidation was also found to be markedly reduced by treatment with the extract. These results suggest that S. indicus has protective effect against cisplatin-induced nephrotoxicity, which may be attributed to its antioxidant potential.

Anti-inflammatory, Antipruritic and Mast Cell Stabilizing Activity of Aristolochia Indica.

OBJECTIVES: Aristolochia indica has been widely used in the traditional medicine for the treatment of a variety of diseases. In the present study different extracts of roots of A. indica were evaluated for their anti-inflammatory, antipruritic and mast cell stabilizing activity. MATERIALS AND METHODS: Anti-inflammatory activity was performed by compound 48/80 induced rat paw edema model and antipruritic activity by examining the incidence of scratching behavior. Mast cell stabilizing activity was performed by compound 48/80 and sheep serum induced mast cell degranulation methods. RESULTS: The ethanol extract (300 mg/kg) and petroleum ether extract (100 mg/kg) were found to inhibit mast cell degranulation significantly equivalent to that of standard drug ketotifen (69%) by compound 48/80 model. In sheep serum model the ethanol extracts (150 and 300 mg/kg) and petroleum ether extract (100 mg/kg) showed good mast cell stabilizing activity (66-67%). Ethanol extract at 150 mg/kg showed 70% reduction of rat paw oedema and also significantly reduced the scratching response. CONCLUSION: Results suggest A. indica has good mast cell stabilizing, anti-inflammatory and antipruritic activity.