EVALUATION OF ANTICANCER ACTIVITY OF CUCUMIS CALLOSUS AGAINST EHRLICH'S ASCITES CARCINOMA BEARING MICE

Objective: Our previous research isolated Cucurbitacin B (CuB) and ebenone leucopentaacetate (ELP) from methanolic fruit extract of Cucumis callosus (MFCC). The fruits of C. callosus (Rottl.) Cogn. (Family: Cucurbitaceae) plant have been traditionally used for antioxidant, anti-inflammatory, and antidiabetic actions. The objective of this research was to evaluate in vitro and in vivo anticancer effect of MFCC on Ehrlich Ascites Carcinoma (EAC) cell lines.Methods: In vitro anticancer assay of MFCC and standard drug, 5-fluorouracil (5-FU) was evaluated using Trypan blue and 3-(4, 5-dimethylthiazol-yl)-2, 5-diphenyl tetrazolium bromide methods. In vivo anticancer activity of MFCC and 5-FU was also performed after 24h of EAC cells (2×106cells/ mouse) inoculation based on toxicity study for 9 consecutive days. The activity of the extract was assessed by the study of tumor volume, tumor weight, viable and non-viable cell count, hematological parameters, and biochemical estimations.Results: The MFCC showed the direct antitumor effect on EAC cells in a dose-dependent manner with an IG50 value of 0.61 mg/ml. Furthermore, MFCC (350 mg/kg) exhibited significant (p<0.01) decrease in tumor volume, tumor weight, and viable cell count of EAC-treated mice. Hematological profile, biochemical estimation assay significantly (p<0.01) reverted to normal level in MFCC, and 5-FU treated mice.Conclusion: The anticancer activity of fruits of C callosus is may be either due to the presence of CuB or/and ELP as phytoconstituent and the activity is comparable to standard drug 5-FU

ISOLATION OF CUCURBITACIN-B FROM CUCUMIS CALLOSUS AND ITS HYPOGLYCEMIC EFFECT IN ISOLATED RAT ENTEROCYTES

Objective: The pericarp of fruits of Cucumis callous (Rottl.) Cogn. (Cucurbitaceae) is traditionally used for curing diabetes, epilepsy, and diarrhea. It has an active compound include Cucurbitacin-B (CuB), which acts as a potent inducer of CYP450 of rat enterocytes. This study was conducted with the aim of elaborating and reconciling our previous finding on the glucose-lowering effect of Cucumis callosus (Rottl.) Cogn. fruits.Methods: In vivo hypoglycemic potential for methanolic pericarp extracts from C callosus (MPCC, 350 mg/kg b.w. p. o), methanolic seed extract of C callosus (MSCC, 250 mg/kg b.w. p. o) and CuB (80 µg/kg b.w. p. o) were studied in streptozotocin (STZ, 55 mg/kg b.w. i. p) induced diabetic rats. Metformin (25 mg/kg b.w. p. o) served as reference drug. Ex vivo model of intestinal tissue preparation of Swiss albino rats named Single Pass Intestinal Perfusion (SPIP) technique was performed for ex vivo hypoglycemic study. The glucose levels in the serosal fluid were determined by commercially available glucose oxidase kit and compared with the standard drug metformin (0.1 mg/kg).Results: In vivo results showed that administration of MPCC (350 mg/kg b.w. p. o) and Cucurbitacin-B (80 µg/kg b.w. p. o) produced the hypoglycemic effect. The MPCC (1.4 mg/kg) and CuB (0.4 µg/kg) produced hypoglycemic effect in ex vivo technique. These effects are due to induction of 0.53 mµmoles of CYP450 proteins with maximum absorption at 454 mµ in rat enterocytes.Conclusion: The present investigation gave evidence that bitter pericarp of C callosus fruit has a hypoglycemic effect due to the presence of Cucurbitacin B as phytoconstituent but seeds did not have such effects

IN VITRO HYPOGLYCEMIC AND ANTIMICROBIAL ACTIVITY OF CUCUMIS CALLOSUS (ROTTL.) COGN. FRUIT

ABSTRACTObjective: This research investigated in vitro hypoglycemic and antimicrobial activity of methanolic fruit extract of Cucumis callosus (MECC) (Rottl.)cogn.Methods: The in vitro antidiabetic ability of MECC was evaluated by inhibition studies of the digestive enzymes including α-amylase and α-glycosidase.The antimicrobial activity of extract was further evaluated against 21 laboratory strains belongs to 8 bacterial species and 4 fungal species using cupplateagardiffusion assayand agardilution assay.Results: Our assay result suggested that the MECC exhibited dose-dependent increase in percentage inhibitory activity on α-glycosidase(IC50 405.37 µg/ml) and α-amylase enzymes (IC721.55 µg/ml). The results of antimicrobial activity also showed that the extract inhibited the growthof 13 strains of 7 bacterial species and all fungal species.50 Conclusion: The observed inhibitions of α-amylase and α-glycosidase and inhibition of some microbial species suggested that the MECC may be usefulin the management of diabetes mellitus and treatment of some infectious diseases.Keywords: Cucumis callosus, Diabetes, α-amylase, α-glycosidase, Antimicrobial

Formulation and Evaluation of Tacrolimus Transdermal Gel

The present investigation is concerned with formulation and evaluation of Transdermal gels of Tacrolimus, anti-psoriasis drug, to circumvent the first pass effect and to improve its bioavailability with reduction in dosing frequency and dose related side effects. Twelve formulations were developed with varying concentrations of polymers like Carbopol 934P, HPMCK4M and Sodium CMC. The gels were tested for clarity, Homogeneity, Spreadability, Extrudability, Viscosity, surface pH, drug Content uniformity, in-vitro drug diffusion study and ex-vivo permeation study using rat abdominal skin. FTIR studies showed no evidence on interactions between drug, polymers and excipients. The best in-vitro drug release profile was achieved with the formulation F4 containing 0.5 mg of exhibited 6 hr drug release i.e. 98.68 % with desired therapeutic concentration which contains the drug and Carbopol 934p in the ratio of 1:2. The surface pH, drug content and viscosity of the formulation F4 was found to be 6.27, 101.3% and 3, 10,000cps respectively. The drug permeation from formulation F4 was slow and steady and 0.89gm of tacrolimus could permeate through the rat abdominal skin membrane with a flux of 0.071 gm hr-1 cm-2. The in-vitro release kinetics studies reveal that all formulations fit well with zero order kinetics followed by non-Fickian diffusion mechanism. Keywords: Transdermal gel, Viscosity, In-vitro drug release, In-vitro drug release kinetics study, Ex-vivo permeation stud

Insilico and Invitro anthelmintic properties of phytocompounds in Rostellularia quinquangularis (J. Koenig ex Roxb.) Nees

The present study aimed to evaluate the anthelmintic activity of various extracts of Rostellularia quinquangularis (R. quinquangularis) against adult Indian earthworms (Pheretima posthuma). Petroleum ether extract (PERQ), ethyl acetate extract (RQEA), and ethanol extract (RQEE) of R. quinquangularis were tested at different concentrations (10, 20, 50, and 100 mg/mL), along with the positive control (albendazole) and negative control (normal saline). Anthelmintic activity was assessed based on the duration of paralysis and mortality. The RQEE extract showed significant anthelmintic activity, with the highest activity observed at a concentration of 100 mg/mL, exhibiting paralysis time of 1.62 min and death times of 19.9 min, compared to the standard albendazole. Further, HR LC-MS analysis of the RQEE extract revealed the presence of various phytoconstituents based on m/z signals. Molecular docking analysis using AutoDock Vina indicated that Columbianetin, Dunnione, Cryptochlorogenic acid, Gaylussacin, Luvangetin, and Albendazole showed docking scores of -8.1, -7.9, -7.4, -7.3, -7.2, and -6.8 Kcal/mol, respectively. These results suggest that R. quinquangularis possesses potent anthelmintic activity, supporting its traditional use in medicinal practices.

Utilizing Andrographis paniculata leaves and roots by effective usage of the bioactive andrographolide and its nanodelivery: investigation of antikindling and antioxidant activities through in silico and in vivo studies

To valorise the bioactive constituents abundant in leaves and other parts of medicinal plants with the objective to minimize the plant-based wastes, this study was undertaken. The main bioactive constituent of Andrographis paniculata, an Asian medicinal plant, is andrographolide (AG, a diterpenoid), which has shown promising results in the treatment of neurodegenerative illnesses. Continuous electrical activity in the brain is a hallmark of the abnormal neurological conditions such as epilepsy (EY). This can lead to neurological sequelae. In this study, we used GSE28674 as a microarray expression profiling dataset to identify DEGs associated with andrographolide and those with fold changes >1 and p-value <0.05 GEO2R. We obtained eight DEG datasets (two up and six down). There was marked enrichment under various Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Ontology (GO) terms for these DEGs (DUSP10, FN1, AR, PRKCE, CA12, RBP4, GABRG2, and GABRA2). Synaptic vesicles and plasma membranes were the predominant sites of DEG expression. AG acts as an antiepileptic agent by upregulating GABA levels. The low bioavailability of AG is a significant limitation of its application. To control these limitations, andrographolide nanoparticles (AGNPs) were prepared and their neuroprotective effect against pentylenetetrazol (PTZ)-induced kindling epilepsy was investigated using network pharmacology (NP) and docking studies to evaluate the antiepileptic multi-target mechanisms of AG. Andrographolide is associated with eight targets in the treatment of epilepsy. Nicotine addiction, GABAergic synapse, and morphine addiction were mainly related to epilepsy, according to KEGG pathway enrichment analysis (p < 0.05). A docking study showed that andrographolide interacted with the key targets. AG regulates epilepsy and exerts its therapeutic effects by stimulating GABA production. Rats received 80 mg/kg body weight of AG and AGNP, phenytoin and PTZ (30 mg/kg i.p. injection on alternate days), brain MDA, SOD, GSH, GABAand histological changes of hippocampus and cortex were observed. PTZ injected rats showed significantly (***p < 0.001) increased kindling behavior, increased MDA, decreased GSH, SOD, GABA activities, compared with normal rats, while treatment AGNPs significantly reduced kindling score and reversed oxidative damage. Finally, we conclude that the leaves and roots of A. Paniculata can be effectively utilized for its major bioactive constituent, andrographolide as a potent anti-epileptic agent. Furthermore, the findings of novel nanotherapeutic approach claim that nano-andrographolide can be successfully in the management of kindling seizures and neurodegenerative disorders

One-pot multicomponent diastereoselective synthesis of novel dihydro-1<i>H</i>-furo[2,3-<i>c</i>]pyrazoles

<p>An efficient method was developed for the diastereoselective synthesis of novel fused dihydro-1<i>H</i>-furo[2,3-<i>c</i>]pyrazole by a one-pot, four-component reaction of β-keto ester, hydrazine, aromatic aldehyde, and pyridinium ylide in the presence of triethylamine under microwave irradiation in solvent-free conditions in good yields. The merits of this cascade Knoevenagel condensation/Michael addition/cyclization sequence include its high atom economy, good yields, and efficiency of producing three new bonds (two C–C and one C–O) and two stereocenters in a single operation.</p

Computational exploration of Zika virus RNA-dependent RNA polymerase inhibitors: a promising antiviral drug discovery approach

The emergence of the Zika virus, which belongs to the Flaviviridae family, became a significant worldwide health issue due to its link with severe neurological complications. The RNA-dependent RNA polymerase (RdRp) of the Zika virus plays a significant part in the replication of the virus and is considered a promising candidate for antiviral drug identification. In this study, we employed computer-based drug discovery approaches to identify potential natural compounds that could act as inhibitors against the RdRp protein of the Zika virus. A comprehensive virtual screening strategy was implemented using the MTiOpenScreen webserver to identify natural compounds from the NP-Lib database. Four natural compounds having the ZINC ID – ZINC000253499147, ZINC000299817665, ZINC000044404209, and ZINC000253388535 were selected based on the binding score revealed during virtual screening. Molecular docking simulations of these selected compounds and reference compounds were performed to assess the binding affinities and the molecular bonds formed during the docking. Additionally, molecular dynamics (MD) simulations, endpoint free binding energy calculation and principal component analysis (PCA) were performed to evaluate the stability and dynamics of the protein-ligand complexes. These compounds exhibited favourable binding energies and formed stable interactions within the active site of the RdRp protein. Moreover, the molecular dynamics simulations revealed the robustness of the protein-ligand complexes, suggesting the potential for sustained inhibition. These findings provide valuable insights for the design and development of novel therapeutic interventions against Zika virus infection. Further experimental validation and optimization of the identified compounds are warranted to advance their potential translation into effective antiviral drugs. Communicated by Ramaswamy H. Sarma</p