Suaib Luqman

NFκB: a promising target for natural products in cancer chemoprevention

The transcription factor nuclear factor kappa B (NFκB) is found in nearly all animal cell types. It is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL and microbial antigens, and has been shown to regulate the expression of a number of genes including bcl‐2, bcl‐xl, cIAP, suvivin, TRAF, COX‐2, MMP‐9, iNOS and cell cycle‐regulatory components. Many carcinogens, inflammatory agents and tumor promoters have been shown to activate NFκB, and resulting tumors demonstrate misregulated NFκB. Incorrect regulation of NFκB has been linked to inflammatory and autoimmune diseases, septic shock, viral infection and improper immune development. Aberrant regulation of NFκB is involved in cancer development and progression as well as in drug resistance. Inhibitors of NFκB mediate effects potentially leading to antitumor responses or greater sensitivity to the action of antitumor agents. Tools have been developed for the rapid assessment of NFκB activity, so in concert with a better understanding of NFκB activation mechanisms, many agents capable of suppressing NFκB activation have been identified. The present article focuses on the functions of NFκB, its role in human cancer and the therapeutic potential and benefit of targeting NFκB by natural products in cancer chemoprevention. Copyright

Antimicrobial potential of Glycyrrhiza glabra roots.

The present study was aimed to investigate antimicrobial potential of Glycyrrhiza glabra roots. Antimycobacterial activity of Glycyrrhiza glabra was found at 500 microg/mL concentration. Bioactivity guided phytochemical analysis identified glabridin as potentially active against both Mycobacterium tuberculosis H(37)Ra and H(37)Rv strains at 29.16 microg/mL concentration. It exhibited antimicrobial activity against both Gram-positive and Gram-negative bacteria. Our results indicate potential use of licorice as antitubercular agent through systemic experiments and sophisticated anti-TB assay.

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.

Synthesis of chalcone derivatives on steroidal framework and their anticancer activities

Chalcone derivatives on estradiol framework have been synthesized. Some of the derivatives showed potent anticancer activity against some human cancer cell lines. Compounds 9 and 19 showed potent activity against MCF-7, a hormone dependent breast cancer cell line. Chalcone 7 was further modified to the corresponding indanone derivative (19) using the Nazarov reaction, which showed better activity than the parent compound against the MCF-7 breast cancer cell line. Active anticancer derivatives were also evaluated for osmotic hemolysis using the erythrocyte as a model system. It was observed that chalcone derivatives showing cytotoxicity against cancer cell lines did not affect the fragility of erythrocytes and hence may be considered as non-toxic to normal cells.

Natural antitubulin agents: Importance of 3,4,5-trimethoxyphenyl fragment

Microtubules are polar cytoskeletal filaments assembled from head-to-tail and comprised of lateral associations of α/β-tubulin heterodimers that play key role in various cellular processes. Because of their vital role in mitosis and various other cellular processes, microtubules have been attractive targets for several disease conditions and especially for cancer. Antitubulin is the most successful class of antimitotic agents in cancer chemotherapeutics. The target recognition of antimitotic agents as a ligand is not much explored so far. However, 3,4,5-trimethoxyphenyl fragment has been much highlighted and discussed in such type of interactions. In this review, some of the most important naturally occurring antimitotic agents and their interactions with microtubules are discussed with a special emphasis on the role of 3,4,5-trimethoxyphenyl unit. At last, some emerging naturally occurring antimitotic agents have also been tabulated.

Antitubercular potential of plants: a brief account of some important molecules.

Mycobacterium tuberculosis is the most lethal pathogen causing tuberculosis in human. After the discovery of antitubercular drugs pyrazinamide, rifampicin, isoniazid, streptomycin, and ethambutol (PRISE), the disease was controlled for a limited period. However, over the course of their usage, the pathogen acquired resistance and evolved into multi‐drug resistant, single‐drug resistant, and extensive drug resistant forms. A good number of plant secondary metabolites are reported to have antitubercular activity comparable to the existing antitubercular drugs or sometimes even better in potency. A well‐defined strategy is required to exploit these phytomolecules as antitubercular drugs. This review gives concise up‐to‐date information regarding the chemistry and pharmacology of plant‐based leads and some insight into their structure–activity relationship.

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.

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.