IR@IIIM - Indian Institute of Integrative Medicine (CSIR)
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Comparative studies and identification of camptothecin produced by an endophyte at shake flask and bioreactor
No full textThe fungus showing homology with Nodulisporium by 28S ribosomal gene sequencing, which has been discovered as an endophyte on medicinal plant Nothapodytes foetida, was found to produce 45 and 5.5 mg of camptothecin (CPT)per gram of mycelia at bioreactor and at shake flask, respectively, which was further quantified and characterised by various spectroscopic analyses
Immune modulation and apoptosis induction: Two sides of antitumoural activity of a standardised herbal formulation of Withania somnifera
No full textDeregulated apoptosis and suppressed tumour reactive immunity render tumour cells to grow amok in the host body. Traditionally used botanicals may offer potential anticancer
chemo-immunotherapeutic leads.We report in this study a chemically standardised herbal formulation (WSF) of Withania somnifera possessing anticancer and Th1 immune up-regulatory activities. WSF produced cytotoxicity in a panel of human cancer cell lines in vitro.The molecular mechanism of cell cytotoxicity, IC50 48 h �20 lg/ml, was investigated in HL-60, where it induced apoptosis by activating both intrinsic and extrinsic signalling pathways.
It induced early generation of reactive nitrogen and oxygen species (RNOS), thus producing oxidative stress mediated mitochondrial membrane potential (MMP) loss leading to
the release of cytochrome c, the translocation of Bax to mitochondria and apoptosis-inducing factor to the nuclei. These events paralleled the activation of caspase-9, -3 and PARP cleavage. WSF also activated caspase-8 through enhanced expression of TNF-R1 and DR-4, suggesting also the involvement of extrinsic pathway of apoptosis. WSF at 150 mg/kg, i.p., inhibited >50% tumour growth in the mouse tumour models. In tumour-bearing mice,WSF inhibited the expression of pStat-3, with a selective stimulation of Th1 immunity as evidenced by enhanced secretion of IFN-c and IL-2. In parallel, it enhanced the proliferation of CD4+/CD8+ and NK cells along with an increased expression of CD40/CD40L/CD80. In addition, WSF also enhanced T cell activation in camptothecin treated tumour-bearing mice. WSF being safe when given orally up to 1500 mg/kg to rats for 6 months may be found useful in the management of malignancy by targeting at multiple pathways
Regio-selective acylation of biologically important iridoid glycosides by Candida antarctica lipase
No full textLipase catalyzed regio-selective acylation of five iridoid glycosides viz., picroside I&II, catalpol, agnuside and negundoside in the presence of various acyl donors such as vinyl acetate and p-nitrophenyl alkanoates was studied. The regio-selectivity of enzymatic acylation and yieldswere found to vary amongst different substrates. Monoacylated products were isolated with all the substrates under scrutiny indicating high regio-selective nature of such transformations. A series of acyl esters of picroside-I, picroside-II, catalpol, agnuside and negundoside have been synthesized by this enzymatic trans-esterification methodology
Synthesis and in vitro study of 14-aryl-14H-dibenzo[a.j]xanthenes as cytotoxic agents
No full textA simple and expedient method for the synthesis of a series of 14-aryl-14H-dibenzo[a.j]xanthenes is described through a one-pot condensation of b-naphthol with aryl aldehydes catalysed by TaCl5 under solvent-free conventional heating. The major advantages of the present method are: high yields, less reaction time, solvent-free condition and easy purification of the products. The synthesized 14-aryl-
14H-dibenzo[a.j]xanthenes were evaluated against a panel of six human cancer lines of different tissues.Synthesized compound 3o showed IC50 of 37.9 and 41.3 lM against Colo-205 and 502713, respectively,whereas 3g showed IC50 of 41.9 lM against Colo-205
Boswellic acids: a group of medicinally important compounds
No full textThis review, containing over 276 references, covers the progress made in the chemistry and bioactivity of this important group of triterpenoids. Though initially known for their anti-inflammatory and antiarthritic activities through a unique 5-LO inhibition mechanism, boswellic acids have recently attained significance due to their anti-cancer properties. The phytochemistry and chemical modifications,
including mechanism of action, are discussed
Protocol for In Vitro Regeneration and Marker Glycoside Assessment in Swertia chirata Buch-Ham
No full textWe have developed a rapid in vitro propagation system, via axillary shoot formation from nodal explants
of Swertia chirata Buch Ham. Culture medium supplemented with 2 mg/L. BAP is best for direct shoot regeneration initially formed adventitious buds from axils of the nodal explants after 30 days. The reduced BAP concentration 0.5 mg/L proliferate shoots effectively. Kept the number of hyperhydrated shoots to minimal and induced on an average 22–38 shoots per flask (4.3 cm average length). The regenerated shoots (5- to 6-m long) formed roots very well in Murashige and Skoog (MS) medium devoid of any growth regulator and followed by acclimatization of plants in pre-sterilized sand containing 1% Trichoderma viride and Azatobactor chrococcum as bioinoculants. The regenerated plants don’t show any genomic alterations. This protocol also outlines procedure of assessment of marker iridoid glycosides(amarogentin and amaroswerin) from callus, roots, multiple shoots, regenerated plants, and mother plant. High propagation frequency, reproducibility of procedure, molecular, and phenotypic and chemical stability ensures the efficiency of the developed protocol
Saponins as novel TNF-α inhibitors: isolation of saponins and a nor-pseudoguaianolide from Parthenium hysterophorus
No full textTwo novel saponins and a 13-nor-pseudoguaianolide designated as hysterolactone were isolated from Parthenium hysterophorus. The two saponins were found to be potent inhibitors of TNF-a. Their mode of inhibition was studied through molecular modeling. The wet lab results were in concordance with the data obtained from docking experiments
Arthrobacter sp. lipase immobilization for preparation of enantiopure masked β-amino alcohols
No full textRecent reports on immobilization of lipase from Arthrobacter sp. (ABL, MTCC 5125; IIIM isolate) on insoluble
polymers have shown altered properties including stability and enantioselectivity. Present work demonstrates a facile method for the preparation of enantiopure b-amino alcohols by modulation of ABL enzyme properties via immobilization on insoluble as well as soluble supports using entrapment/
covalent binding techniques. Efficacies of immobilized ABL on insoluble supports prepared from tetraethylorthosilicate/
aminopropyltriethoxy silane and soluble supports derived from copolymerization of Nvinyl pyrrolidone-allylglycidyl ether (ANP type)/N-vinyl pyrrolidone-glycidyl methacrylate (GNP type) for kinetic resolution of masked b-amino alcohols have been studied vis-à-vis free ABL enzyme/wet cell biomass. The immobilized lipase on different insoluble/soluble supports has shown 21–110 mg/g protein
binding and 30–700 U/g activity for hydrolyzing tributyrin substrate. The findings have shown a significant
enhancement in enantioselectivity (ee 99%) vis-à-vis wet cell biomass providing ee 70–90% for resolution
of b-amino alcohols
Immunomodulatory activity of Asparagus racemosus on systemic Th1/Th2 immunity: Implications for immunoadjuvant potential
No full textEthnopharmacological relevance: Roots of Asparagus racemosus Willd (Shatavari in vernacular) are widely
used in Ayurveda as Rasayana for immunostimulation, galactogogue as also in treatment of conditions like ulcers and cancer. Various studies have indicated immunomodulatory properties of Shatavari root extracts and formulations.
Aim of the study: To study the effect of standardized Asparagus racemosus root aqueous extract (ARE) on systemic Th1/Th2 immunity of SRBC sensitized animals.
Materials and methods:We used HPTLC to quantify steroidal saponins (Shatavarin IV, Immunoside®) and flow cytometry to study effects of ARE on Th1/Th2 immunity. SRBC specific antibody titres and DTH responses were also monitored as markers of Th2 and Th1 responses, respectively. We also studied lymphocyte proliferation. Cyclosporin, cyclophosphamide and levamisole were used as controls.
Results: Treatment with ARE (100 mg/(kg b.w. p.o.)) resulted in significant increase of CD3+ and CD4/CD8+
percentages suggesting its effect on T cell activation. ARE treated animals showed significant up-regulation of Th1 (IL-2, IFN-g) and Th2 (IL-4) cytokines suggesting its mixed Th1/Th2 adjuvant activity. Consistent to this, ARE also showed higher antibody titres and DTH responses. ARE, in combination with LPS, Con A or SRBC, produced a significant proliferation suggesting effect on activated lymphocytes.
Conclusion: The study suggests mixed Th1/Th2 activity of ARE supports its immunoadjuvant potential
Semi-synthetic analogs of pinitol as potential inhibitors of TNF-α cytokine expression in human neutrophils
No full textSemi-synthetic analogs of pinitol were subjected to screening by determining TNF-a expression in human neutrophils using flowcytometry. Among the tested compounds, three derivatives displayed more than 50% inhibition of TNF-a cytokine secretion in LPS induced stimulated neutrophils and can be considered as potent anti-inflammatory moieties