School of Pharmacy and Life Sciences

Reduced oxygen tension combined with high glucose concentration leads to chronic wounds in diabetic patients. Delayed wound healing is due in part to impaired angiogenesis as a result of reduced endothelial cell migration. Topical applications, in the form of sterile lyophilised wafers hold promise for the treatment of chronic diabetic wounds. In this study wafers containing silymarin were prepared using xanthan gum and sterilised with 25 and 40 kGy gamma radiation. The rheological properties of xanthan gels, before and after lyophilisation, were measured and it was concluded that an increased dose of gamma rays (40 kGy) increased the viscosity coefficient and yield stress of silymarin wafers. HPLC analysis indicated that 89-90% of silymarin was retained in the wafers after irradiation. Dermal microvascular cell migration studies in the presence of high glucose and reduced oxygen tension levels, using novel radial migration and wound healing assays developed 'in house', were also undertaken. Silymarin, when formulated as a lyophilised wafer, successfully retained its ability to overcome the high glucose induced reduction in endothelial cell migration.

Cardioprotective activity of alcoholic extract of Saraca indica (SI) bark was investigated against cyclophosphamide induced cardiotoxicity. Cardiotoxicity was induced in Wistar rats by administering cyclophosphamide (200 mg/kg, i.p.) single injection on first day of experimental period. Saraca indica (200 and 400 mg/kg, p.o.) was administered immediately after administration of cyclophosphamide on first day and daily for 10 days. The general observations and mortality were measured. Cyclophosphamide administration significantly (p < 0.05) increased lipid peroxidation (LPO) and decreased the levels of antioxidant markers such as reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). Cyclophosphamide elevated the levels of biomarker enzymes like creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB), lactate dehydrogenase (LDH), aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP). Further, the cyclophosphamide treated rats showed changes in electrocardiogram (ECG) along with increased levels of cholesterol and triglycerides. Treatment with Saraca indica significantly (p < 0.05) reversed the status of cardiac biomarkers, ECG, oxidative enzymes and lipid profile in cyclophosphamide induced cardiotoxicity. Potential cardioprotective effect of Saraca indica was supported by histopathological examination that reduced severity of cellular damage of the myocardium. The biochemical, ECG and histopathology reports support the cardioprotective effect of Saraca indica which could be attributed to antioxidant activity.

Aim: This study was designed to evaluate the effect of β-asarone on diethylnitrosamine (DEN) induced and phenobarbital-promoted hepatocellular carcinoma in rats. Materials and Methods: The experiments were carried out with two models, i.e., tumor initiation and promotion model. The effect of β-asarone was evaluated by the estimation of food and water consumption, body and liver weights, liver function indicators such as aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total and direct bilirubin, cancer indicators such as alpha-fetoprotein, DNA, RNA, and total liver protein content, and histopathological studies. Results: The results showed that the levels of liver function indicators were brought down to near normal level by β-asarone. Similarly, cancer indicators were also brought down to near normal level by β-asarone. A comparative histopathological study of liver, treated with β-asarone exhibited normal architecture, which was found to be disrupted in DEN-treated rats. Conclusion: The results indicate that the β-asarone has significant hepatoprotective effect and may potentially possess an anticancer activity.

Objective: This study aims to evaluate the role of Lycopersicon esculentum in diethylnitrosamine (DEN)-induced and phenobarbital (PB)-promoted hepatocellular carcinoma. Materials and Methods: The hepatocarcinogenesis was induced in male Wistar albino rats by DEN (single injection, 200 mg/kg, i.p.); 2 weeks later, 0.05% w/v of PB was administered through drinking water for 16 weeks. The treatment group rats received a similar dosage as above along with enzymatic extract of L. esculentum (250 mg/kg body weight p.o.) at 3 rd week onward. The carcinogenesis was evaluated by estimating biochemical markers such as alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and bilirubin, DNA and RNA levels, liver protein, and cancer biomarkers as alpha-fetoprotein (AFP). Results: Treatment with enzymatic extract of L. esculentum significantly reduced DEN/PB-mediated elevation of ALT, AST, ALP, and bilirubin levels. A significant decrease in the levels of DNA, RNA, and AFP and increase in liver protein were observed when L. esculentum-treated rats were compared with DEN/PB-treated rats. Conclusion: The present study suggests that L. esculentum possesses chemopreventive activity against DEN-induced and PB-promoted liver cancer.

Background Metabolic dysregulation is one of the hallmarks of tumor cell proliferation. Evidence indicates the potential role of the 5′adenosine monophosphate-activated protein kinase (AMPK) and protein kinase B/Akt signaling pathway in regulating cell proliferation, survival, and apoptosis. The present study explores the effect of metformin HCl and the combination of α- and β-asarone on the proliferation of HepG2 cells in the presence of high glucose levels simulating the diabetic-hepatocellular carcinoma (HCC) condition. Results The metformin and asarone reduced HepG2 cell viability in a dose-dependent manner and induced morphological changes as indicated by methyl thiazolyl tetrazolium (MTT) assay. The metformin and asarone arrested the cells at the G0/G1 phase, upregulated the expression of AMPK, and downregulated Akt expression in high glucose conditions as identified by the flow cytometry technique. Further, the upregulated AMPK led to a decrease in the expression of phosphoen...

Background Efficacy of Anthracycline derivative Doxorubicin (Dox) has been proven in several malignancies such as breast cancer, Hodgkin and non-Hodgkin lymphoma, acute leukemia, lung, thyroid and ovarian cancer. However its clinical usefulness is restricted due to its cardiotoxicity and nephrotoxicity. Rosa centifolia belongs to family Rosaceae and in Ayurveda it is claimed for use in renal disorders. The main phyto-constituents of the plant are terpenoids, glycosides, flavonoids, tannins, phenolic compounds, pro-antroocyanides, pectin and riboflavin. Objective To investigate the ameliorative role of ethanolic extract of petals of R. centifolia in doxorubicin induced nephrotoxicity in rats. Materials and methods Nephrotoxicity was produced by administration of doxorubicin (2.5 mg/kg b.w., i.p. alternate day) in six equal injections for two weeks to achieve a cumulative concentration of 15 mg/kg. Low (LERC - 100 mg/kg p.o.) and high (HERC - 200 mg/kg p.o.) dosees of ethanolic extract of petals of R. centifolia was administered as a pretreatment prior to doxorubicin administration. The general parameters such as body weight, food and water intake were measured throughout the study period. Serum biomarkers such as blood urea nitrogen (BUN), serum creatinine and albumin were measured before treatment and at the end of the experiments. Anti-oxidant enzymes such as glutathione (GSH), melonldehyde (MDA), catalase (CAT) and superoxide dismutase (SOD) were monitored after the last dose. Nephrotoxicity was assessed through histopathological analysis. Results The repeated administration of doxorubicin produces several morphological changes including reduction in the body weight as well as decreased food and water consumption. Serum biomarkers such as BUN, serum creatinine were increased and albumin concentration was decreased. The GSH, SOD and CAT concentrations were decreased, whereas MDA concentration was increased. Deteriorating changes in the histological architecture of kidney tissue were observed. In the LERC and HERC pretreated groups following changes were observed in dose dependent manner: increase in body weight, food and water intake (p < 0.05 and p < 0.01), decrease in the BUN (p < 0.05 and p < 0.01) and serum creatinine (p < 0.05 and p < 0.05) concentrations respectively. The significant increase in the albumin (p < 0.01) concentration was observed only in HERC. The pretreatment with LERC and HERC increased the antioxidant enzymes concentrations i.e. GSH (p < 0.01 and p < 0.01), SOD (p < 0.01 and p < 0.01), CAT (p < 0.05 and p < 0.01) and decreased the MDA concentration (p < 0.05 and p < 0.01) respectively. Histopathological studies showed that the pretreatment with low and high doses of ethanolic extract of petals of Rosa centifolia LERC and HERC groups minimized the tubular damage and reduced the inflammation as compared to doxorubicin treated group. Conclusion The biochemical and histopathological data from the present study clearly support the nephroprotective effect of ethanolic extract of petals of R. centifolia, which might be credited to its anti-oxidant property.

Dietary fern Diplazium esculentum (Retz.) Sw. (Athyriaceae family) has a wide range of biological properties, including that against diabetes mellitus. The current work was conducted to perform an in silico docking study of bioactive phytoconstituents from D. esculentum against a mutated protein of diabetes mellitus. Out of 16 reported phytoconstituents, five were identified and chosen based on meeting the Lipinski rule of 5. The drug-likeness score and side effects for the selected compounds were predicted using Molsoft L.L.C and ADVERPred databases. The pharmacokinetics and toxicological properties of the chosen phytoconstituents were predicted using the PreADMET online server tool. Further, a docking study was performed using the AutoDock tool and Vina to predict the binding affinity of the selected phytoconstituents with the mutated protein from the protein data bank. Pterosin B scored the highest drug-likeness score (0.58) in comparison to beta-ocimene, showing a negative score (− 1.63). Molecular docking experiments revealed that the ligands bind to the active site of the targeted protein and have good binding energy values. Ptaquiloside showed the highest binding affinity (− 7.2 kcal/mol) with the targeted protein, whereas beta-ocimene (− 5.0 kcal/mol) showed the least. Our findings indicated that screened phytochemicals in D. esculentum could be a potential therapeutic option against diabetes mellitus and need to be further investigated and confirmed with detailed in-vitro and in-vivo studies. Graphical abstract