Bishan Datt Gupta

Anti‐inflammatory activity of oleanolic acid in rats and mice

Abstract— Oleanolic acid displayed anti‐inflammatory activity in carrageenan and dextran‐induced oedema in rats. It elicited marked anti‐arthritic action in adjuvant‐induced polyarthritis in rats and mice and in formaldehyde‐induced arthritis in rats. Oleanolic acid checked the inflammation‐induced increased serum transaminase levels. It reduced exudate volume and inhibited leucocyte infiltration in carrageenan‐induced pleurisy in rats. It is devoid of any analgesic, antipyretic or ulcerogenic action. Oleanolic acid did not affect the parturition time in pregnant rats or castor oil‐induced diarrhoea in rats. Oral LD50 was found to be greater than 2 g kg−1 in mice and rats.

Anti-inflammatory and anti-arthritic activities of silymarin acting through inhibition of 5-lipoxygenase.

Silymarin, a mixture of flavonolignans, comprised mainly of three isomers, silybin, silydianin and silychristin isolated from the fruits of Silybum marianum, is currently in therapeutic use as a hepatoprotective agent. Silymarin on evaluation exhibited significant antiinflammatory and antiarthritic activities in the papaya latex induced model of inflammation and mycobacterial adjuvant induced arthritis in rats. Results of the study indicate its action through inhibition of 5-lipoxygenase for antiinflammatory and antiarthritic activities.

Evaluation of the Antimicrobial, Antioxidant, and Anti-Inflammatory Activities of Hydroxychavicol for Its Potential Use as an Oral Care Agent

ABSTRACT Hydroxychavicol isolated from the chloroform extraction of aqueous extract of Piper betle leaves showed inhibitory activity against oral cavity pathogens. It exhibited an inhibitory effect on all of the oral cavity pathogens tested (MICs of 62.5 to 500 μg/ml) with a minimal bactericidal concentration that was twofold greater than the inhibitory concentration. Hydroxychavicol exhibited concentration-dependent killing of Streptococcus mutans ATCC 25175 up to 4× MIC and also prevented the formation of water-insoluble glucan. Interestingly, hydroxychavicol exhibited an extended postantibiotic effect of 6 to 7 h and prevented the emergence of mutants of S. mutans ATCC 25175 and Actinomyces viscosus ATCC 15987 at 2× MIC. Furthermore, it also inhibited the growth of biofilms generated by S. mutans and A. viscosus and reduced the preformed biofilms by these bacteria. Increased uptake of propidium iodide by hydroxychavicol-treated cells of S. mutans and A. viscosus indicated that hydroxychavicol probably works through the disruption of the permeability barrier of microbial membrane structures. Hydroxychavicol also exhibited potent antioxidant and anti-inflammatory activities. This was evident from its concentration-dependent inhibition of lipid peroxidation and significant suppression of tumor necrosis factor alpha expression in human neutrophils. Its efficacy against adherent cells of S. mutans in water-insoluble glucan in the presence of sucrose suggests that hydroxychavicol would be a useful compound for the development of antibacterial agents against oral pathogens and that it has great potential for use in mouthwash for preventing and treating oral infections.

Immunomodulatory activity of biopolymeric fraction BOS 2000 from Boswellia serrata

Oral administration of BOS 2000 (1–10 mg/kg) elicited a dose related increase in the delayed hypersensitivity reaction (early 24 h and delayed 48 h) in mice. It also stimulated the IgM and IgG titre expressed in the form of plaques (PFC) and complement fixing antibody titre. The concentration of cytokines (IL‐4, IFN‐γ and TNF‐α) in serum with respect to T cell interactions, i.e. (CD4/CD8) and the proliferation of lymphocytes were significantly increased at 10 mg/kg compared with the control. The results in these studies demonstrated the immunostimulatory effect of BOS 2000 in a dose‐dependent manner with respect to the macrophage activation possibly expressing the phagocytosis and nitrite production by the enhancement of TNF‐α and IFN‐γ production as a mode of action. Copyright

A unique immuno-stimulant steroidal sapogenin acid from the roots of Asparagus racemosus

A new steroidal sapogenin molecule 1 having unique characteristics, 21-nor and unusual C19 carboxylic acid has been isolated from the roots of Asparagus racemosus. On the basis of chemical evidence, extensive spectroscopic analysis including two dimensional (2D) NMR and X-ray studies of single crystal, the structure of 1 was determined as (1S,2R,3S,8S,9S,10S,13S,14S,16S,17R,22R,25R)-21-nor-18β,27α-dimethyl-1β,2β,3β-trihydroxy-25-spirost-4-en-19β-oic acid. 1 crystallizes in monoclinic space group P2₁ with a=9.295(2), b=11.238(2), c=11.376(2) Å; β=91.993(4)°, Z=2, D(cal)=1.344 Mg/m³. The structure was solved by direct methods and refined by full-matrix least-squares procedure to a final R-value of 0.0561 for 4064 observed reflections. 1 was tested against the type of immune responses generated during treatment in normal and immune-suppressed animals and detailed biological activity evaluation suggests it to be a potent immunostimulator.

Chemoprevention with Aqueous Extract of Butea monosperma Flowers Results in Normalization of Nuclear Morphometry and Inhibition of a Proliferation Marker in Liver Tumors

Butea monosperma (Lam.) (family: Fabaceae) popularly known as ‘Palas’ or ‘fire of forest’ has been used traditionally as a hepatoprotective agent. This study evaluated the hepatoprotective and antitumorigenic properties of the aqueous extract and butanol fractions of B. monosperma flowers in animal models. Dried flowers of B. monosperma were extracted with water and fractionated further using n‐butanol. The hepatoprotective activity of the aqueous extract was initially confirmed in a carbon tetrachloride‐induced liver damage model of rats. Oral administration of the aqueous extract produced a strong hepatoprotective effect similar to silymarin and normalized the serum levels of ALT, AST, bilirubin and triglyceride in rats. However, it did not affect the levels of glutathione and malondialdehyde which are oxidative stress markers in liver. Intraperitoneal administration of the aqueous extract in the X15‐myc oncomice not only maintained liver architecture and nuclear morphometry but also down‐regulated the serum VEGF levels. Immunohistochemical staining of liver sections with anti‐Ribosomal protein S27a antibody showed post‐treatment abolition of this proliferation marker from the tumor tissue. The butanol fractions, however, did not show antitumorigenic activity. Thus, the aqueous extract of B. monosperma flowers is not only hepatoprotective but also antitumorigenic by preserving the nuclear morphometry of the liver. Copyright

Osthol and curcumin as inhibitors of human Pgp and multidrug efflux pumps of Staphylococcus aureus: reversing the resistance against frontline antibacterial drugs

The in-house IIIM natural product repository of 302 small molecules was screened for their ability to inhibit P-glycoprotein (Pgp) in Pgp-overexpressing human adenocarcinoma LS-180 cells. The screening has identified 13 natural products displaying significant Pgp-inhibition activity, which include praeruptorin B, curcumin, imperatorin, osthol, 5,7-diacetoxy-8-(3-methyl-2-butenyl)-coumarin, 5,7-dihydroxy-8-(3-methyl-2-butenyl) coumarin, pongamol, phellopterin, tangeretin, 3-(2-methyl but-3-en-2-yl) xanthyletin, 7-demethyl osthol, allorottlerin and tetrahydroangeolide. These natural products were then screened for their effects on bacterial efflux pump inhibition activity against NorA (Staphylococcus aureus), MdeA (S. aureus Mupr-1), TetK (S. aureus SA-K2192), and MsrA (S. aureus SA-K2191) efflux pumps. Curcumin and osthol showed significant inhibition of the S. aureus NorA efflux pump with 8- and 4-fold reductions in the MIC of ciprofloxacin at 25 μM. The molecular docking studies of curcumin and osthol with the human Pgp and S. aureus NorA efflux pump identified plausible binding modes and binding sites for these natural products.

Synthesis and biologic activities of some novel heterocyclic chalcone derivatives

We synthesized 36 chalcone-like (E)-3-(substitutedphenyl)-1-hetrylprop-2-en-1-ones by condensing 2-acetylfuran/2-acetylpyrrole with substituted benzaldehydes under basic conditions. Of the 36 molecules synthesized, 10 are new to the literature. Bio-evaluation studies of these molecules revealed that compounds 5, 9, 15, 25, and 29 were potent NorA efflux pump inhibitors against Staphylococcus aureus by reducing MIC of ciprofloxacin fourfold, while compounds 11, 21, 25, and 26 showed promising anticancer activity in all four tested cancer cell lines (HL-60, MOLT-4, PC-3, and HeLa). Compound 25 emerged as a very good potentiator of ciprofloxacin against multidrug resistant S. aureus and also showed promising anticancer activity. The present communication describes syntheses, bio-evaluation, and structure-related activity of the (E)-3-(substitutedphenyl)-1-hetrylprop-2-en-1-ones.

A New Glycoside, 3-o-Demethylcolchicine-3-o-α-d-Glucopyranoside, from Gloriosa Superba Seeds

Abstract A new colchicine glycoside, 3-O-demethylcolchicine-3-O-α-D-glucopyranoside, has been isolated from Gloriosa superba seeds. The assigned structure has been corroborated by spectroscopic data and enzymatic hydrolysis.

Induction of Apoptosis in Human Promyelocytic Leukemia HL60 Cells by an Extract From Erythrina suberosa Stem Bark

In this study, the apoptosis-inducing effect of an alcoholic extract from Erythrina suberosa stem bark (ESB) was investigated using human promyelocytic leukemia HL60 cells. Cell viability was estimated by MTT assay. We found that the ESB inhibited cell proliferation in a dose- and time-dependent manner. A series of well-documented morphological changes, such as cell shrinkage, condensation of nuclear chromatin, and nuclear fragmentation, were observed by fluorescence microscopy. The gold standard scanning electron micrographs showed apoptotic bodies and formation of blebs. Cell cycle analysis showed a significant increase in Sub G0 population of cells above 50 μg/ml. ESB treatment resulted in a dose-dependent increase in annexin V positive cells. Increase in intracellular ROS production up to sixfold was detected in ESB-treated HL60 cells by DCFH-DA assay. Dissipation of mitochondrial membrane potential of intact cells accompanied by increase in cytosolic cytochrome c was observed, which was followed by activation of caspase-9 and -3 but not caspase-8. DNA fragmentation analysis revealed typical ladders as early as 18 h indicative of caspase-3 role in the apoptotic pathway. The overall results suggest that ESB induces mitochondria-mediated intrinsic apoptotic pathway in HL60 cells and might have therapeutic value against human leukemia.