Dharmender Rathee

Mechanism of Action of Flavonoids as Anti-inflammatory Agents: A Review

Flavonoids are polyphenolic compounds that occur ubiquitously in plants having a variety of biological effects both in vitro and in vivo. They have been found to have antimicrobial, antiviral, anti-ulcerogenic, cytotoxic, anti-neoplastic, mutagenic, antioxidant, antihepatotoxic, antihypertensive, hypolipidemic, antiplatelet and anti-inflammatory activities. Flavonoids also have biochemical effects, which inhibit a number of enzymes such as aldose reductase, xanthine oxidase, phosphodiesterase, Ca(+2)-ATPase, lipoxygenase, cycloxygenase, etc. They also have a regulatory role on different hormones like estrogens, androgens and thyroid hormone. They have been found to have anti-inflammatory activity in both proliferative and exudative phases of inflammation. Several mechanisms of action have been proposed to explain anti-inflammatory action of flavonoids. The aim of the present review is to give an overview of the mechanism of action of potential anti-inflammatory flavonoids.

Mushrooms as therapeutic agents

Mushrooms have been known for their nutritional and culinary values and used as medicines and tonics by humans for ages. In modern terms, they can be considered as functional foods which can provide health benefits beyond the traditional nutrients. There are monographs that cover the medicinal and healing properties of some individual traditional mushrooms. There has been a recent upsurge of interest in mushrooms not only as a health food which is rich in protein but also as a source of biologically active compounds of medicinal value which include complementary medicine/dietary supplements for anticancer, antiviral, hepatoprotective, immunopotentiating and hypocholesterolemic agents. However the mechanisms of the various health benefits of mushrooms to humans still require intensive investigation, especially given the emergence of new evidence of their health benefits. In the present paper the medicinal potential of mushrooms is being discussed.

In vitro anticancer activity of stachydrine isolated from Capparis decidua on prostate cancer cell lines

In this article we report our work on the isolation, characterisation and evaluation of in vitro anticancer activity of stachydrine on solid tumour cells. The in vitro activity was assessed by MTT assay and propidium iodide (PI) staining. Further, an attempt was also made to check the effect of stachydrine on the invasion and metastasis of cancer cells by inhibiting the expression of chemokine receptors (CXCR3 and CXCR4). The influence of stachydrine on the gene expression of CXCR3 and CXCR4 at mRNA and protein levels was examined. Studies revealed a dose dependent decrease in expression of mRNA, and protein levels were observed in stachydrine-treated human prostate cancer cells (PC-3 and LNcaP) as detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The data therefore provides direct evidence for the role of stachydrine as a potent anti-metastatic agent, which can markedly inhibit the malignancy and invasive capacity of malignant cancer cells.

In-vitro cytotoxic activity of β-Sitosterol triacontenate isolated from Capparis decidua(Forsk.) Edgew

OBJECTIVE To study the isolation and characterization of the constituent responsible for the cytotoxic activity of the ethanolic extract of stem of Capparis decidua (C. decidua). METHODS The preliminary cytotoxic effect of isolated compound (β-Sitosterol triacontenate) was investigated by MTT assay on A549 solid tumor cells. RESULTS IC(50) value of the β-Sitosterol triacontenate was found to be 1 μM. The cytotoxic activity increased in a dose dependent manner in case of β-Sitosterol triacontenate. CONCLUSIONS The data therefore provide direct evidence for the role of β-Sitosterol triacontenate as a potent antimetastatic agent, which can markedly inhibit the metastatic and invasive capacity of malignant cells.

Prediction of MMP-9 inhibitory activity of N-hydroxy-α-phenylsulfonylacetamide derivatives by pharmacophore based modeling and 3-D QSAR studies

Abstract Matrix metalloproteinase-9 (MMP-9), also known as gelatinase B, is a MMP that is strongly associated with multiple cellular processes including proliferation, angiogenesis, and metastasis. Various studies have shown that N-hydroxy-&agr;-phenylsulfonylacetamide (HPSAs) derivatives are promising and selective for the MMP-9 inhibition. In the present study, we have selected and reported 80 HPSAs derivatives as inhibitors of MMP-9 and performed structure-based 3-dimensional quantitative structure–activity relationship (3D-QSAR) studies to elucidate the important structural elements responsible for binding affinity. Developed pharmacophore models; QSAR model I contains 2 hydrogen-bond acceptors (A), 2 hydrogen-bond donors (D), and 1 aromatic ring (R) and QSAR model II contains 3 hydrogen-bond acceptors (A), 1 positive ionic (P), and 1 aromatic ring (R). The statistical results of QSAR models (I and II) such as good correlation coefficient (0.61 for I and 0.63 for II), good predictive power (0.84 and 0.77 for I and II, respectively) with low standard deviation (SD\0.3 for both) strongly suggest that the developed models are virtuous for the future prediction of MMP-9 inhibitory activity of HPSAs derivatives. The geometry and features of pharmacophore were expected to be useful for further design and development of selective MMP-9 inhibitors.

Targeting matrix metalloproteinases with novel diazepine substituted cinnamic acid derivatives: design, synthesis, in vitro and in silico studies

Lung cancer is the notable cause of cancer associated deaths worldwide. Recent studies revealed that the expression of matrix metalloproteinases (MMPs) is extremely high in lung tumors compared with non-malignant lung tissue. MMPs (-2 and -9) play an important part in tumor development and angiogenesis, which suggests that creating potent MMP-2 and -9 inhibitors, should be an important goal in lung cancer therapy. In the present study, an effort has been made to develop new anti-metastatic and anti-invasive agents, wherein a series of novel diazepine substituted cinnamic acid derivatives were designed, synthesized and assayed for their inhibitory activities on MMP-2 and MMP-9. These derivatives were prepared via microwave assisted reaction of tert-butyl (3-cinnamamidopropyl)carbamate derivatives mixed with 2,3-dibromopropanoic acid and potassium carbonate was added to obtain 4-(tert-butoxycarbonyl)-1-cinnamoyl-1,4-diazepane-2-carboxylic acid derivatives. The newly synthesized compounds were characterized by IR, NMR and mass spectroscopy. All the tested compounds showed good to excellent cytotoxic potential against A549 human lung cancer cells. The active compounds displaying good activity were further examined for the inhibitory activity against MMPs (-2 and -9). In addition, the structure and anticancer activity relationship were further supported by in silico docking studies of the active compounds against MMP-2 and MMP-9.

Antimicrobial Activity of Oleiyl Glucoside Isolated from the Traditional Medicinal Plant, Capparis decidua

Ethnopharmacological relevance: In the traditional system of medicine, the plant Capparis decidua is well known for curing a variety of ailments such as toothache, cough, asthma, intermittent fever, rheumatism and inflammation. Aim of the study: The aim of the current study was to isolate and characterize the constituent responsible for the antimicrobial activity of the ethanolic extract of C decidua. Materials and methods: The isolated compound was extracted from ethanolic extract & characterized by spectroscopic methods. The antimicrobial activity of isolated compound was carried out against gram positive strains (S aureus, M luteus, B subtilus) and gram negative ones (P aeruginosa, E coli), and Fungi like C albicans and A niger by the cup-plate assay method and minimum inhibitory concentrations (MICs). Results: The active principle Oleiyl glucoside (n-octadec-9-enyl- � -D- glucopyranoside) was isolated from the ethanolic extract. The MIC values of the compound against gram positive bacteria were 62.5� g/ml, 62.5 � g/ml, 125� g/ml and against gram negative ones 31.25� g/ml, 250� g/ml. The compound was found to be active against C albicans 250 � g/ml only.