Suchita Srivastava

Experimental Assessment of Moringa oleifera Leaf and Fruit for Its Antistress, Antioxidant, and Scavenging Potential Using In Vitro and In Vivo Assays

We have investigated effect of Moringa oleifera leaf and fruit extracts on markers of oxidative stress, its toxicity evaluation, and correlation with antioxidant properties using in vitro and in vitro assays. The aqueous extract of leaf was able to increase the GSH and reduce MDA level in a concentration-dependent manner. The ethanolic extract of fruit showed highest phenolic content, strong reducing power and free radical scavenging capacity. The antioxidant capacity of ethanolic extract of both fruit and leaf was higher in the in vitro assay compared to aqueous extract which showed higher potential in vivo. Safety evaluation studies showed no toxicity of the extracts up to a dose of 100 mg/kg body weight. Our results support the potent antioxidant activity of aqueous and ethanolic extract of Moringa oleifera which adds one more positive attribute to its known pharmacological importance.

Gallic acid-based indanone derivatives as anticancer agents.

Gallic acid-based indanone derivatives have been synthesised. Some of the indanones showed very good anticancer activity in MTT assay. Compounds 10, 11, 12 and 14 possessed potent anticancer activity against various human cancer cell lines. The most potent indanone (10, IC(50)=2.2 microM), against MCF-7, that is, hormone-dependent breast cancer cell line, showed no toxicity to human erythrocytes even at higher concentrations (100 microg/ml, 258 microM). While, indanones 11, 12 and 14 showed toxicities to erythrocytes at higher concentrations.

Antifungal activity of Glycyrrhiza glabra extracts and its active constituent glabridin.

Glabridin, an active constituent of Glycyrrhiza glabra roots, was found to be active against both yeast and filamentous fungi. Glabridin also showed resistance modifying activity against drug resistant mutants of Candida albicans at a minimum inhibitory concentration of 31.25–250 µg/mL. Although the compound was reported earlier to be active against Candida albicans, but this is the first report of its activity against drug resistant mutants. Copyright

Antiproliferative and antioxidant activities of Juglans regia fruit extracts

Context: Cancer chemopreventive action of walnut [Juglans regia L. (Juglandaceae)] has been explored. Objective: This study evaluated antiproliferative and antioxidant activities of walnut. Materials and methods: Various fractions of walnut extract have been screened for antiproliferative activity against human cancer cell lines using the MTT assay. All these fractions have also been evaluated for total phenolic content, antioxidant activity, and reducing power capacity. Results and discussion: Chloroform and ethyl acetate fractions exhibited a high level of antiproliferation against HepG-2, liver cancer cell line (IC50 = 9 and 15 µg/mL, respectively). Conclusion: Exhibiting high phenolic content, antioxidant activity, and potent antiproliferative activity, walnut may act as a cancer chemopreventive agent.

A promising anticancer and antimalarial component from the leaves of Bidens pilosa.

Bidens pilosa is used in folk medicine for various applications due to the presence of polyacetylenes, flavonoids, terpenoids, phenylpropanoids and others. Bioactivity-guided fractionation of different extracts of B. pilosa leaf showed potential in vitro anticancer and antimalarial activity and led to the identification of a potential marker compound, phenyl-1,3,5-heptatriyne. Erythrocyte osmotic fragility experiments revealed the various extracts as well as the marker components toxicity profiles on normal blood cells.

α-(-)-bisabolol reduces pro-inflammatory cytokine production and ameliorates skin inflammation.

α-(-)-bisabolol is a natural monocyclic sesquiterpene present in the essential oil has generated considerable interest in the chemical and pharmaceutical industries and currently in use in various formulations, mainly in cosmetics. This study was undertaken to evaluate its therapeutic profile against skin inflammation using in-vitro, in-vivo and in-silico assays. Lipopolysachharide (LPS) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced production of proinflammatory cytokines (TNF-α and IL-6) in macrophage cells as well as in TPA-induced skin inflammation in mice was significantly inhibited by α-(-)-bisabolol. TPA-induced ear thickness, ear weight and lipid peroxidation and histopathological damage in the ear tissue were also significantly inhibited by topical application of α-(-)-bisabolol in a dose dependent manner. In-vitro and in-vivo toxicity profiles indicate that it is safe for topical application on skin. Molecular docking study also revealed its strong binding affinity to the active site of the pro-inflammatory proteins. These findings suggested that α-(-)-bisabolol may be a useful therapeutic candidate for the treatment of skin inflammation.

Glycyrrhetinic acid and its analogs: a new class of antifilarial agents.

Although a number of chemicals have been isolated from Glycyrrhiza glabra, only a few have been evaluated for their biological significance. As part of our drug discovery program for antifilarial agents from Indian medicinal plants, the roots of G. glabra were chemically investigated, which resulted in the isolation and characterization of an antifilarial agent, glycyrrhetinic acid (GA, 1a) effective against microfilariae (mf) in vitro (LC100: 12.5 μM; IC50: 1.20 μM), but was inactive against adult worms. Further, GA (1a) was converted into six analogs (2a-7a) and their antifilarial potential was evaluated by studying in vitro motility and MTT reduction assays employing mf and adult worms of Brugia malayi. The results showed that out of six GA analogs, the benzyl amide analog (6a) killed adults and mf at 25 and 50 μM concentration, respectively, and inhibited 49% MTT reduction potential of the adult parasites. The IC50 values were found to be 8.8 and 2.2 μM for adults and mf, respectively. The SI of the compound was >60. On the other hand the octylamide analog (7a) required much higher concentration to adversely affect the parasites. Finally, both active amide analogs (6a and 7a) were in vivo evaluated using B. malayi-jird model, which showed that analog 6a possesses promising macrofilaricidal activity at 100mg/kg, s.c. ×5 days and around 40% of the treated animals showed calcified masses of worm fragments in peritoneal cavity of the animals. To the best of our knowledge this is the first ever report on the antifilarial potential of GA analogs. Further work on optimization of the antifilarial lead is under progress.

QSAR Guided Semi-synthesis and In-Vitro Validation of Anticancer Activity in Ursolic Acid Derivatives

As a part of our anticancer drug discovery programme, QSAR models were developed for the prediction of anticancer activities of ursolic acid derivatives against the human hepatocellular carcinoma HepG2, breast carcinoma MDA-MB-231 and the human ductal breast epithelial T47D cancer cell lines followed by wet lab semi-synthesis of virtually active derivatives, their in-vitro biological evaluation and apoptosis. The development of QSAR models was carried out by forward stepwise multiple linear regression method using a leave-one-out approach. Virtually active derivatives were semi synthesized, spectroscopically characterized and then in-vitro tested against human cancer cell lines. Active derivatives were checked via DNA fragmentation assay. The results exhibited regression coefficients (r(2)) and the cross-validation regression coefficients (rCV(2)) for the human HepG2, MDA-MB-231 and T47D cancer cell lines as .95 and .90; .92 and .87; .89 and .83 respectively showing the prediction accuracy of the models against biological activities. Computational molecular modeling is a valid modern approach, widely used in the identification of potential drug leads. The most active virtual derivatives of UA were semi- synthesized and their in-vitro and ex-vivo evaluation showed similar results with the predicted one, validating our QSAR models. Out of several active derivatives, the three UA2, UA7 and UA10 were potentially active against the above human cancer cell lines. These findings may be of immense importance in the anticancer drug development of an inexpensive and widely available natural product, ursolic acid.

Protective effect of medicinal plant extracts on biomarkers of oxidative stress in erythrocytes

Plants are universally recognized as a vital part of the world’s natural heritage and up to 80% of the population rely on plants for their primary healthcare. Varieties of medicinal plants are recognized as a source of natural antioxidants that can protect from oxidative stress, thus playing an important role in chemoprevention of diseases. In the present investigation, 22 extracts from different parts of eight medicinal plants (Punica granatum Linn. (Punicaceae), Caesalpinia bonducella Flem. (Fabaceae), Hibiscus subdariffa Linn. [(Malvaceae), Moringa oleifera Lam. (Moringaceae), Garcinia indica Linn. (Clusiaceae), Emblica officinalis Gaertn. (Euphorbiaceae), Momordica charantia Linn. (Cucurbitaceae), and Matricaria chamomilla Linn. (Asteraceae)] were screened for their protection against oxidative stress in erythrocytes induced by hydrogen peroxide (2 mM) and tert-butyl hydroperoxide (0.01 mM). The effect was also compared with known antioxidants and flavonoids. Subjecting erythrocytes to oxidative stress by incubation with hydrogen peroxide and tert-butyl hydroperoxide caused a significant alteration in reduced glutathione (GSH) and malondialdehyde (MDA) concentration compared to the control. Our results show that medicinal plant extracts protect erythrocytes from hydrogen peroxide and tert-butyl hydroperoxide induced oxidative stress; known antioxidant (vitamin C, E, and β-carotene) and flavonoid (quercetin) also showed a similar protective effect. Our observations may, in part, suggest the use of the spent/waste parts of medicinal plants. This could be an economically viable source of natural and potent antioxidants effective against complications arising from oxidative stress. The results may also improve the ethanopharmacological knowledge of medicinal plants.

Rapid and Sensitive HPLC Method for the Determination of Polyphenols in Various Lichen Species of Himalayan Origin

Abstract A reversed‐phase high performance liquid chromatograph (HPLC) with photodiode array detection method was developed to determine bioactive polyphenolic substances, methyl β‐orcinolcarboxylate (MBO) and ethyl haematommate (EH) in thalli of various lichen species. The MBO and EH were separated by RP‐HPLC (C18 column, 150 mm×4.6 mm, 5 µm) using isocratic elution systems of acetonitrile:water (0.1% acetic acid). Base line separation of the compounds was obtained in less than 20 min. The method was validated for linearity, repeatability, limits of detection (LOD), and limits of quantification (LOQ). Repeatability (inter‐ and intra‐day, n=6) showed less than 1.5% relative standard deviation (RSD). The LOD and LOQ were found to be 5.97 and 15.51 ng for MBO and 42.63 and 69.03 ng for EH, respectively. The validated HPLC method was employed to quantify MBO and EH in eleven lichen species, used in folklore/traditional systems of medicine collected from the Himalayan region of India.