Bioactive fractions from Allium humile alleviate the risk of high fat diet induced atherosclerosis in albino Wistar rats by inhibiting protein kinase C.

Atherosclerosis is a global concern that worsens with age, and plants that are effective medicinal herbs can give a viable alternative. PKC is a key factor in cardiovascular and other disorders; targeting it can reduce the risk of these diseases. We evaluated Allium humile for PKC inhibition and therapeutic efficacy against atherosclerosis. Soxhlet extraction was done to obtain extracts (hexane, ethyl acetate, methanol, ethanol and aqueous) and then tested for DPPH radical scavenging and PKC inhibitory activity. The methanolic extract was more active than the other extracts, so it was subjected to column chromatography, and seventeen fractions were obtained. Only 11, 12, and 15 showed good activity against PKC. Wistar rats were divided into six groups and each group received high fat diet for 30 days. Then the three potent fractions (10 mg/kg) were administered for 15 days along with high fat diet. Fraction II had the highest effectiveness (P < 0.0001) in decreasing lipid levels, lipid peroxidation, reducing IL-6 and TNF-α expression, and raising nitric oxide. This also demonstrated a decrease in PKC activity, as well as a decrease in the formation of the lipoidal layer in the aorta wall and rupture of the intima and media as validated by histological analysis. The two compounds, phytol acetate and cyanidin 3-(6″-o-malonyllaminaribioside) were characterised in fraction II by NMR and HRMS and cyanidin 3-(6″-o-malonyllaminaribioside) inhibited PKC more efficiently. Thus, Allium humile has strong anti-atherogenic activity as well as the ability to inhibit PKC both in vitro and in vivo.

Modern Computational Strategies for Designing Drugs to Curb Human Diseases: A Prospect.

Drug discovery is an exhaustive and time-consuming process involving numerous stages like target identification, validation, lead optimization, preclinical trials, clinical trials and finally postmarketing vigilance for drug safety. The application of computer-aided drug designing (CADD) is an indispensable approach for developing safe and effective drugs. Previous methods based on combinatorial chemistry (CC) and high throughput screening (HTS) consumed a lot of time as well as expenditure. CADD based approaches including pharmacophore modeling (PM), molecular docking (MD), inverse docking, chemical similarity (CS), quantitative structure-activity relationship (QSAR), virtual screening (VS) and molecular dynamics simulations have been quite productive in predicting the therapeutic outcome of candidate drugs/compounds besides saving precious time. CADD tools exploit structural and other information available regarding the target (enzyme/receptor) and the ligands to identify the compounds with the ability to treat diseases notably cancer, neurodegenerative disorders, malaria, Ebola, HIV-AIDS and many more. Computational approaches have led to the discovery of many drugs that have passed preclinical and clinical trials and become novel therapeutics in the treatment of a variety of diseases. Some notable examples of CADD derived novel drugs include dorzolamide, saquinavir, ritonavir, indinavir, captopril and tirofiban. CADD plays important role in predicting absorption, distribution, metabolism, excretion and toxicity (ADME/T) of candidate drugs. Overall, CADD represents an effective and much-needed strategy for designing therapeutically effective drugs to combat human diseases.

Efficacy of Aqueous and Methanolic Extracts of Rheum Spiciformis against Pathogenic Bacterial and Fungal Strains.

INTRODUCTION: Rheum spiciformis is a newly identified edible medicinal plant of genus Rheum. The plant is used to treat various diseases on traditional levels in Kashmir Valley, India. AIM: To evaluate the phytochemical screening, antibacterial and antifungal potential of aqueous and methanolic extracts of Rheum spiciformis, a traditionally used edible medicinal plant. MATERIALS AND METHODS: Methanolic and aqueous extracts of Rheum spiciformis were tested for their antimicrobial activities against six bacterial strains namely Bacillus subtilis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus vulgaris and Escherichia coli and four fungal strains Penicillium chrysogenum, Aspergillus fumigatus, Candida albicans and Saccharomyces cerevisiae. The susceptibility of microbial strains to the two extracts was determined using agar well diffusion method. Phytochemical screening was carried out by using various standard procedures. RESULTS: Methanolic extract showed potent antimicrobial activity as compared to aqueous extract at the concentrations of 10, 30, 50, 80 and 100mg/ml. The most susceptible bacterial strains were Staphylococcus aureus with zone of inhibition (25±0.10mm), Klebsiella pneumonia (23±0.25mm), Proteus vulgaris (22±0.10mm) at the concentration of 100mg/ml. Aqueous extracts at the higher concentration were found effective against Proteus vulgaris and Bacillus subtilis with zone of inhibition (17±0.24mm) and (17±0.10mm), respectively. Among fungal strains the most susceptible were Aspergillus fumigatus (21±0.10mm), Saccharomyces cerevisiae (20±0.20mm) and Penicillium Chrysogenum (17±0.15mm) at the concentration of 100mg/ml methanol extract. The zone of inhibition for aqueous extract against fungal strains ranged between 14±0.13mm to 16±0.19mm at the highest concentration of plant extract. Phytochemical analysis revealed the presence of various secondary metabolites like flavonoids, saponins, volatile oils, phenols, steroids, terpenoids and alkaloids. CONCLUSION: Our results indicate that this plant has enough potential to serve as an excellent candidate for obtaining antimicrobial compounds to combat bacterial and fungal infections.