02288nas a2200265 4500008004100000022001400041245012100055210006900176260007300245300000900318490000900327520130900336653003701645653000901682653001301691653002601704653001301730653001801743100001901761700002201780700002901802700002701831700003701858856012701895 2014 eng d a0021-967300aExpedient preparative isolation and tandem mass spectrometric characterization of C-seco triterpenoids from neem oil0 aExpedient preparative isolation and tandem mass spectrometric ch aPO BOX 211, 1000 AE AMSTERDAM, NETHERLANDSbELSEVIER SCIENCE BVcOCT a1-140 v13663 a

C-seco triterpenoids are widely bioactive class of natural products with high structural complexity and diversity. The preparative isolation of these molecules with high purity is greatly desirable, although restricted due to the complexity of natural extracts. In this article we have demonstrated a Medium Pressure Liquid Chromatography (MPLC) based protocol for the isolation of eight major C-seco triterpenoids of salannin skeleton from Neem (Azadirachta indica) oil. Successive application of normal phase pre-packed silica-gel columns for the fractionation followed by reverse phase in automated MPLC system expedited the process and furnished highly pure metabolites. Furthermore, eight isolated triterpenoids along with five semi-synthesized derivatives were characterized using ultra performance liquid chromatography-electrospray ionization-quadrupole/orbitrap-MS/MS spectrometry as a rapid and sensitive identification technique. The structure-fragment relationships were established on the basis of plausible mechanistic pathway for the generation of daughter ions. The MS/MS spectral information of the triterpenoids was further utilized for the identification of studied molecules in the complex extract of stem and bark tissues from Neem. (C) 2014 Elsevier B.V. All rights reserved.

10aESI(+)-quadrupole/orbitrap-MS/MS10aMPLC10aNeem oil10aPreparative isolation10aSalannin10aTriterpenoids1 aHaldar, Saikat1 aMulani, Fayaj, A.1 aAarthy, Thiagarayaselvam1 aDandekar, Devdutta, S.1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/expedient-preparative-isolation-and-tandem-mass-spectrometric-characterization-c-seco-002898nas a2200313 4500008004100000022001400041245015200055210006900207260000800276300000700284490000700291520187700298653001702175653001402192653001802206653001402224653001502238653000902253100001802262700001902280700002002299700001902319700002202338700002002360700001702380700003702397700002102434856012902455 2018 eng d a1471-240700aEpoxyazadiradione suppresses breast tumor growth through mitochondrial depolarization and caspase-dependent apoptosis by targeting PI3K/Akt pathway0 aEpoxyazadiradione suppresses breast tumor growth through mitocho cJAN a520 v183 a

Background: Breast cancer is one of the most commonly diagnosed invasive cancers among women around the world. Among several subtypes, triple negative breast cancer (TNBC) is highly aggressive and chemoresistant. Treatment of TNBC patients has been challenging due to heterogeneity and devoid of well-defined molecular targets. Thus, identification of novel effective and selective agents against TNBC is essential. Methods: We used epoxyazadiradione to assess the cell viability, mitochondrial potential, ROS level, cell migration, apoptosis and protein expression in cell culture models of TNBC MDA-MB-231 and ER+MCF-7 breast cancer cells. The molecular mechanism was examined in two different type of breast cancer cells in response to epoxyazadiradione. We have also analyzed the effect of epoxyazadiradione on breast tumor growth using in vivo mice model. Results: In this study, we for the first time investigated that out of 10 major limonoids isolated from Azadirachta indica, epoxyazadiradione exhibits most potent anti-cancer activity in both TNBC and ER+breast cancer cells. Epoxyazadiradione induces apoptosis and inhibits PI3K/Akt-mediated mitochondrial potential, cell viability, migration and angiogenesis. It also inhibits the expression of pro-angiogenic and pro-metastatic genes such as Cox2, OPN, VEGF and MMP-9 in these cells. Furthermore, epoxyazadiradione attenuates PI3K/Akt- mediated AP-1 activation. Our in vivo data revealed that epoxyazadiradione suppresses breast tumor growth and angiogenesis in orthotopic NOD/SCID mice model. Conclusion: Our findings demonstrate that epoxyazadiradione inhibits PI3K/Akt-dependent mitochondrial depolarisation, induces apoptosis and attenuates cell migration, angiogenesis and breast tumor growth suggesting that this compound may act as a potent therapeutic agent for the management of breast cancer.

10aAngiogenesis10aApoptosis10aBreast cancer10aLimonoids10aMetastasis10aPI3K1 aKumar, Dhiraj1 aHaldar, Saikat1 aGorain, Mahadeo1 aKumar, Santosh1 aMulani, Fayaj, A.1 aYadav, Amit, S.1 aMiele, Lucio1 aThulasiram, Hirekodathakallu, V.1 aKundu, Gopal, C. uhttps://library.ncl.res.in/content/epoxyazadiradione-suppresses-breast-tumor-growth-through-mitochondrial-depolarization-and02116nas a2200313 4500008004100000022001400041245012800055210006900183260000800252300001600260490000800276520108500284653000801369653002001377653001301397653001901410653002101429100002301450700001801473700002001491700001801511700001901529700002201548700002501570700002401595700003301619700001801652856013201670 2019 eng d a0021-954100aEstrogen receptor activation in response to Azadirachtin A stimulates osteoblast differentiation and bone formation in mice0 aEstrogen receptor activation in response to Azadirachtin A stimu cDEC a23719-237350 v2343 a

The positive effectsof the sex hormone in sustaining bone homeostasis areexercised by maintaining the equilibrium betweencell activity and apoptosis. In this regard, the importance of estrogen receptors in maintaining the bone is that it is anattractive drug target,if devoid of known side effects. In this study, we show that a natural pure compound Azadirachtin A (Aza A) isolated from Azadirachta indica binds selectively to a site in the estrogen receptor, identifying itself to bea selective tissue modifier. Using computational and medicinal chemistry, we show that Aza A binds potentially and selectively to estrogen receptor-alpha (ER alpha) as compared with ER beta. This preferential binding of Aza A to ER alpha with good pharmacokinetic distribution in the body forms metabolites, showing that it is well absorbed. In in vivo estrogen deficiency models for osteoporosis, Aza A at a much lower dose enhances new bone formation at both sites of the trabecular and cortical bone with increased bone strength and presentswith no hyperplastic effect in the uterus.

10aALP10aGene expression10amicro-CT10amineralization10aosteoblast cells1 aKushwaha, Priyanka1 aAhmad, Naseer1 aDhar, Yogeshwar1 aVerma, Ashwni1 aHaldar, Saikat1 aMulani, Fayaj, A.1 aTrivedi, Prabodh, K.1 aMishra, Prabhat, R.1 aThulasiram, Hirekodathakallu1 aTrivedi, Ritu uhttps://library.ncl.res.in/content/estrogen-receptor-activation-response-azadirachtin-stimulates-osteoblast-differentiation-and