Computational simulations of identified marine-derived natural bioactive compounds as potential inhibitors of oral cancer.

Oral squamous cell carcinoma is characterized by the upregulation of RAC-alpha serine/threonine-protein kinase (Akt1) and RAC-beta serine/threonine-protein kinase (Akt2). In this work, Akt1 and Akt2 were inhibited using a cocktail of 20 marine algae chemicals. From the PyRx Virtual Screening Tool, dieckol, 6,6'-bieckol, siphonaxanthin and sargachromanol E were chosen as the best four compounds for Akt1 based on the scoring. Similarly, dieckol, 6,6'-bieckol, dioxinodehydroeckol and caulerpenyne were chosen as Akt2 inhibitors. Additionally, the results of the Lipinski rule of five indicated that some of the selected compounds, such as dieckol, 6,6'-bieckol and siphonaxanthin, violated some Lipinski rules, but they demonstrated excellent binding in terms of scoring. Thus, this study demonstrates that the identified lead compounds may act against Akt1 and Akt2 in oral cancer.

Systemic effect of arecoline on the gastrointestinal system in oral submucous fibrosis affected wistar rats.

Background: The intestine plays an important role in the digestion and absorption of ingested food and the elimination of undigested food, microbes, and microbial products. The functional reliability of the intestinal mucosal epithelial cells depends on the organised regulation of the epithelial cells, mucus layer, the intercellular tight junction, host innate and acquired immune response. The mucus layer of the gastrointestinal tract is the first line of innate host defense, essentially because of the secretory products of intestinal cells. Aim: Present study was conducted to evaluate the effect of arecoline on the gastrointestinal system due to systemic absorption of the drug during the induction period of oral submucous fibrosis (OSMF) in Wistar rats. Methods: Oral submucous fibrosis was induced by submucosal injection of arecoline in the buccal mucosa. Arecoline hydrochloride at a dosage of 10 mg/kg was injected into the submucosa of right buccal mucosa in experimental animals over a period of 3 months on every alternate day. After which, right buccal mucosa, gastrointestinal tract organs like stomach, large intestine, small intestine and liver were dissected, subjected to histopathological evaluation of the healthy and experimental Wistar rats were subjected to histopathological evaluation. Results: On histological evaluation, OSMF was seen to affect Wistar rats showed significant changes in oral mucosa, decrease number of goblet cells in the small intestine as well in the large intestine and deranged hepatocytes. These marked changes indicated a definite effect on the gastro intestinal system by arecoline. Conclusion: The study has highlighted the effect of arecoline due to systemic absorption during the induction process of OSMF in Wistar rats.

Thiolated polymer nanocarrier reinforced with glycyrrhetinic acid for targeted delivery of 5-fluorouracil in hepatocellular carcinoma.

The present work investigates the targeting efficacy of a novel thiolated polymer-based nanocomposite reinforced with glycyrrhetinic acid (GA) and loaded with 5-fluorouracil in hepatocellular carcinoma (HCC). The thiolated polymers were synthesized by EDAC-mediated conjugation reactions and lyophilization. The nanoparticles were prepared by solvent diffusion and high-pressure homogenization method. The prepared nanocomposite was characterized by Fourier transform infrared (FTIR) radiation, x-ray diffraction (XRD), dynamic light scattering (DLS), scanning electron microscopy (SEM) and atomic force microscopy (AFM) techniques. Pharmacological evaluation of the formulation was carried out on a rat model of diethylnitrosamine (DEN), and carbon tetrachloride (CCl4)-induced HCC and MTT assay was carried out with HEP-G2 cell line. In silico studies were conducted to investigate the probable mechanistic pathway of the nanocomposite. FTIR and XRD analysis indicated the successful thiolation of the polymers and confirmed the formation of the nanocomposite without any incompatibilities. DLS, SEM/EDX and AFM characterization confirmed that the nanoparticles were within the nano-size range. MTT assay implied the cytotoxic nature of the nanocomposite against hepatic carcinoma cells. The in vivo study revealed that serum SGOT, SGPT, ALP, GGT and total bilirubin levels were significantly reduced, in comparison with disease control and the result was confirmed by histopathology studies. The results of the HPLC analysis of liver homogenate confirmed the liver targeting ability of the nanocomposite. In silico studies exhibited significant binding affinity of GA and thiolated Eudragit towards liver homolog receptor-1 (LRH-1) suggesting that the developed nanocomposite could be a potential material for the treatment of HCC.

Toxicological evaluation of Sargassum Wightii greville derived fucoidan in wistar rats: Haematological, biochemical and histopathological evidences.

OBJECTIVE: The present study aimed to investigate the acute and subacute toxicity profile of fucoidan obtained from Sargassum wightii Greville, a brown marine algae in order to assess its safety. METHODS: Fucoidan was isolated from Sargassum wightii Greviile and subjected to FTIR analysis to confirm the functional groups. In acute toxicity study, a single dose of fucoidan (2000 mg/kg) was orally administered to three female rats as per OECD guideline 423. OECD guidelines 407 was adopted for subacute toxicity study. Fucoidan was orally administered to male and female rats at doses of 100, 200 and 400 mg/kg. Hematological, biochemical and histopathological analyses were carried out. RESULTS: FTIR analysis confirmed the presence of major functional groups. The animals did not show any remarkable toxic signs or mortality in acute toxicity study at single oral administration of fucoidan at the dose of 2000 mg/kg bodyweight. In subacute toxicity, no statistically significant difference in body weight, relative weight of vital organs, food and water intake compared to the control group was observed. Serum glucose and cholesterol showed a statistically significant reduction at all the doses when compared to normal control and the reduction was in a dose dependent manner. There were no other changes observed in biochemical or haematological parameters. Histopathological analysis showed no significant toxic signs at organ levels in treated groups when compared to normal control. CONCLUSIONS: Based on the results obtained from acute and subacute toxicity study, fucoidan is considered to be safe in the models tested, which encourages its long term administration for medicinal uses. This study supports the application of fucoidan as a traditional medicine.

Phytochemical Screening and Toxicological Evaluation of Sargassum wightii Greville in Wistar Rats.

OBJECTIVES: The present study was conducted to identify the phytoconstituents present in different extracts of Sargassum wightii and to assess the toxicity of its ethanol extract. MATERIALS AND METHODS: Successive solvent extraction and total ethanol extraction of S. wightii were performed and preliminary phytochemical screening was carried out. The acute toxicity of ethanol extract of S. wightii (ESW) was studied. The subchronic toxicity of ESW was tested with doses of 100, 200, and 400 mg/kg. The animals were observed for changes in body weight and food and water intake. At the end of the study, the relative weights of vital organs were noted, followed by histopathological examinations. Various hematological and biochemical estimations were also carried out. RESULTS: Phytochemical screening of S. wightii revealed the presence of alkaloids, carbohydrates, glycosides, phenolic compounds, and tannins. ESW did not induce any mortality or pre-terminal death in the acute toxicity study. There were no significant differences in body weight, relative weight of vital organs (except the brain), or food or water intake compared to the control group. The histopathological examination showed normal architecture, suggesting absence of pathological lesions. Hematological and biochemical parameters were also comparable to those of the control group except for reductions in glucose and cholesterol levels, which are postulated to be beneficial. CONCLUSION: The presence of various phytoconstituents in S. wightii is evidence that it could be a potential source for treating different ailments. No significant toxic effects were observed after treatment with ESW. Thus, it is proposed to be safe and can be recommended for long-term treatment.

Antihyperglycemic and neuroprotective effects of Wattakaka volubilis (L. f. ) Stapf root against streptozotocin induced diabetes

ABSTRACT Murva is an important drug in Ayurveda. Wattakaka volubilis is used as one of the botanical sources of Murva. The aim of this study is to evaluate the effect of the alcohol extract of W. volubilis root in streptoztocin (STZ) induced diabetes and diabetic neuropathy. Diabetes mellitus (DM) was induced by the administration of STZ (45 mg/kg, i.p). DM was induced within 72 h. Diabetic animals were treated with glimepiride (0.5 mg/kg) and ethyl alcohol extract 100 and 200 mg/kg for 21 d. After determining the changes in fasting serum glucose and lipid profile, animals were further treated for a period of 15 d to determine the protective effect of extract against diabetic neuropathy. All the alcohol extract treated animals, showed a significant decrease in serum glucose level (P<0.001), and overall decrease in the severity of diabetic neuropathy. Alcohol extract of W. volubilis root showed antihyperglycemic activity and beneficial protection against diabetic neuropathy and hence can be a promising agent for treatment and prevention of diabetic neuropathy.

Studies on anti-hyperglycemic effect of Euphorbia antiquorum L. root in diabetic rats.

BACKGROUND/AIM: To determine the anti-hyperglycemic effect of Euphorbia antiquorum L. root. MATERIALS AND METHODS: The study evaluates the anti-hyperglycemic effect of E. antiquorum root in streptozotocin-nicotinamide-induced Type 2 diabetes mellitus and fructose-induced insulin resistance models. Alcohol and aqueous extracts of E. antiquorum root were administered at doses 200 and 400 mg/kg p.o. Serum levels of glucose, total cholesterol, triglycerides, glycosylated hemoglobin (GHb), and hepatic levels of malondialdehyde, glutathione, and glycogen were estimated. RESULTS: Treatment with the alcohol and aqueous extracts of E. antiquorum roots resulted in significant (P < 0.001) lowering of serum blood glucose and GHb levels in both the models. Flavonoids, phenolic compounds, and glycosides were detected in the preliminary phytochemical screening. CONCLUSION: Root of E. antiquorum showed promising anti-hyperglycemic effect which may be due to the presence of important phytochemicals.

In vitro antioxidant and anticancer activity studies on drosera indica L. (Droseraceae).

PURPOSE: The aim of present in vitro studies was performed to examine the antioxidant and anticancer activities of ethanol and aqueous extracts of Drosera indica L. METHODS: Different concentrations (5 - 640mcg/ml) of the ethanol (EEDI) and aqueous (AEDI) extracts of D.indica L were used in various antioxidant assay methods such as hydroxyl radicals, DPPH, super oxide radical scavenging activity, chelating ability of ferrous ion, nitric oxide radical inhibition, ABTS and reducing power. Ascorbic acid (AA) was used as the standard antioxidant for the free radical scavenging assays. Dalton's Ascitic Lymphoma (DAL) and Ehrlich Ascitic Carcinoma (EAC) cell lines were used as the in vitro cancer models for the tryphan blue dye and LDH leakage assays, where 5 to 250mcg /ml of both EEDI and AEDI were tested. RESULTS: EEDI showed antioxidant activities with the minimum IC50 values of 34.8±0.43 mcg/ml in scavenging of hydroxyl radical and moreover AEDI showed minimum IC50 values of 94.51±0.84 mcg/ml in Fe(2+)chelating assay. EEDI on the reducing power assay and ABTS showed higher IC50 than standard AA. IC50 values of AEDI on Fe(2+) chelating assay and super oxide radical assay was lesser than IC50 value of AA. Both extracts at 250mcg/ml dose showed remarkable increase in the percentage of dead cancer cells (90% by EEDI and 86% by AEDI in DAL model and 89% by EEDI and 80% by AEDI in EAC model). CONCLUSION: It is concluded from this study that D.indica L exhibited excellent antioxidant activity against the different in vitro antioxidant models and anticancer activity against the two different cell lines tested.

Effect of Smilax zeylanica roots and rhizomes in paracetamol induced hepatotoxicity.

CONTEXT: Smilax zeylanica L.(Smilacaceae) is a climbing shrub with woody prickly stems. OBJECTIVE: This study evaluated the hepatoprotective effect of S. zeylanica against paracetamol induced hepatotoxicity in Wistar rats. MATERIALS AND METHODS: The protective effects of the methanol extract (200 and 400 mg/kg) of root and rhizome of S. zeylanica were studied on paracetamol induced (1 g/kg) hepatic damage in Wistar rats by estimating the serum levels of AST, ALT, alkaline phosphatase (ALP), total proteins, total bilirubin and albumin. Sections of liver were observed for histopathological changes in liver architecture. RESULTS: Rats were protected from the hepatotoxic action of paracetamol as evidenced by the significant reduction in the elevated serum levels of ALT (P<0.001), AST (P< 0.01, P< 0.001), ALP (P<0.05, P< 0.001), total bilirubin (P< 0.05) and an increased level of total protein (P< 0.05) and albumin (P< 0.05, P<0.01) with a significant reduction in liver weight (P<0.001), when compared with the paracetamol control. Silymarin (100 mg/kg) was used as the standard. DISCUSSION AND CONCLUSION: The biochemical observations were supplemented by the histopathological studies on the liver sections of different groups. The methanol extract of S. zeylanica was found to alter the damage caused to hepatocytes by paracetamol and prevent the leakage of vital serum markers, which confirmed the hepatoprotective effect of this plant.

Protective effects of Capparis sepiaria root extracts against acetaminophen-induced hepatotoxicity in Wistar rats.

Capparis sepiaria L. known as Himsra is an important drug in Ayurveda. In this study extracts of the root of C. sepiaria were evaluated for their hepatoprotective potential on acetaminophen-induced hepatotoxicity in albino Wistar rats. The extent of hepatoprotection was evaluated by estimating the serum levels of hepatic transaminases (SGPT and SGOT), alkaline phosphatase (ALP), total protein (TP), and bilirubin (total and direct). Aqueous and ethanol extracts of C. sepiaria significantly reduced the increased liver weight as well as serum levels of SGPT, SGOT, ALP, and bilirubin, and normalized the reduced serum protein levels in the treated rats. These observations were supported by the results of histopathology studies as well. The extracts were also subjected to preliminary organic analysis and chromatographic studies including HPTLC finger print studies. The results indicate that the roots of C. sepiaria show significant hepatoprotective effect on acetaminophen-induced hepatotoxicity, thus substantiating its use as a potential hepatoprotective drug.