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Withaferin A

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https://www.readbyqxmd.com/read/27915154/lipopolysaccharides-stimulated-macrophage-products-enhance-withaferin-a-induced-apoptosis-via-activation-of-caspases-and-inhibition-of-nf-%C3%AE%C2%BAb-pathway-in-human-cancer-cells
#1
Liang Piao, Zhao Canguo, Lu Wenjie, Cheng Xiaoli, Shi Wenli, Lu Li
Macrophages, as a major cellular component in tumor microenvironment, play an important role in tumor progression. However, their roles in modulation of cytotoxic chemotherapy are still not fully understood. Here, we investigated the influence of Lipoplysaccharides (LPS)-stimulated macrophage products (LSMP) on Withaferin A (WA), a natural compound that derived from the medicinal plant Withania somnifera, as an antitumor agent in human breast cancer cells MDA-MB-231 and prostate cancer cells PC-3. Our results revealed that LSMP may enhance WA-induced apoptosis in both cell lines, the underlying mechanisms of which are closely associated with activation of caspase-8, -9 and -3, cleavage of poly ADP-ribose polymerase (PARP), as well as specifically inhibiting the translocation of nuclear factor-κB (NF-κB) and down-regulation of anti-apoptotic proteins X-linked inhibitor of apoptosis protein (XIAP) and inhibitor of apoptosis protein (cIAP1/2)...
December 1, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27867044/mitochondrial-dysfunction-in-cancer-chemoprevention-by-phytochemicals-from-dietary-and-medicinal-plants
#2
REVIEW
Anuradha Sehrawat, Ruchi Roy, Subrata K Pore, Eun-Ryeong Hahm, Suman K Samanta, Krishna B Singh, Su-Hyeong Kim, Kamayani Singh, Shivendra V Singh
Cancer chemoprevention, a scientific term coined by Dr. Sporn in the late seventies, implies use of natural or synthetic chemicals to block, delay or reverse carcinogenesis. Phytochemicals derived from edible and medicinal plants have been studied rather extensively for cancer chemoprevention using preclinical models in the past few decades. Nevertheless, some of these agents (e.g., isothiocyanates from cruciferous vegetables like broccoli and watercress) have already entered into clinical investigations. Examples of widely studied and highly promising phytochemicals from edible and medicinal plants include cruciferous vegetables constituents (phenethyl isothiocyanate, benzyl isothiocyanate, and sulforaphane), withaferin A (WA) derived from a medicinal plant (Withania somnifera) used heavily in Asia, and an oriental medicine plant component honokiol (HNK)...
November 17, 2016: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/27859734/withanolides-against-tlr4-activated-innate-inflammatory-signalling-pathways-a-comparative-computational-and-experimental-study
#3
Preethi M Purushotham, Jin-Man Kim, Eun-Kyeong Jo, Kalaiselvi Senthil
Innate inflammations are dominant causes of poor health and high mortality. The pathogen-associated molecular pattern and lipopolysaccharide (LPS) are sensed by immune cells through activation of toll-like receptor 4 leading to mitogen-activated protein kinases (MAPKs) and NF-κB activations. Controlled MAPK and Nf-κB inhibitors have been proposed as potential antiinflammatory drugs. Withania somnifera is an important medicinal herb with known antiinflammatory activity. In this study, the selected Withania somnifera extracts and withanolides were analysed on LPS-induced macrophages comparatively...
November 17, 2016: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/27837436/withaferin-a-and-its-potential-role-in-glioblastoma-gbm
#4
REVIEW
Jasdeep Dhami, Edwin Chang, Sanjiv S Gambhir
Within the Ayurvedic medical tradition of India, Ashwagandha (Withania somnifera) is a well-known herb. A large number of withanolides have been isolated from both its roots and its leaves and many have been assessed for their pharmacological activities. Amongst them, Withaferin A is one of its most bioactive phytoconstituents. Due to the lactonal steroid's potential to modulate multiple oncogenic pathways, Withaferin A has gained much attention as a possible anti-neoplastic agent. This review focuses on the use of Withaferin A alone, or in combination with other treatments, as a newer option for therapy against the most aggressive variant of brain tumors, Glioblastoma...
November 11, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27773717/cardioprotective-effects-of-monocyte-locomotion-inhibitory-factor-on-myocardial-ischemic-injury-by-targeting-vimentin
#5
Shu Jiang, Yulan Liu, Jing Wang, Yue Zhang, Yaocheng Rui, Yuefan Zhang, Tiejun Li
Monocyte locomotion inhibitory factor (MLIF), a heat-stable pentapeptide produced by Entamoeba histolytica, has anti-inflammatory function and protective effect on ischemic stroke. In this study, we evaluated the effect of MLIF on myocardial ischemia. The myocardial ischemia reperfusion (I/R) model was established by ligation of the left anterior descending branch (LAD) using 8-0 silk suture for 30min followed by 3h reperfusion in mice. After sacrifice, the serum concentrations of cardiac troponin I (cTnI), creatine kinase (CK), lactate dehydrogenase (LDH) as well as the heart infarct size were measured...
October 20, 2016: Life Sciences
https://www.readbyqxmd.com/read/27743505/metabolite-profiling-of-withania-somnifera-roots-hydroalcoholic-extract-using-lc-ms-gc-ms-and-nmr-spectroscopy
#6
Mahendra Kumar Trivedi, Parthasarathi Panda, Kalyan Kumar Sethi, Snehasis Jana
Ashwagandha (Withania somnifera) is a very well-known herbal medicine and it was well studied for its active metabolites throughout the World. Although, nearly 40 withanolides were isolated from W. somnifera root extract, still there is remaining unidentified metabolites due to very low abundance and natural variation. Advanced separation technology with online identification by mass and nuclear magnetic resonance (NMR) are now-a-days used to find out the new compounds in the crude herbal extract. This article described the metabolite profiling of ashwagandha root hydroalcoholic extract using ultra-performance liquid chromatography coupled with a positive ion electrospray ionization tandem mass spectrometry through gas chromatography mass spectrometry (GC-MS) and NMR analysis...
October 15, 2016: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/27717869/withaferin-a-induces-nrf2-dependent-protection-against-liver-injury-role-of-keap1-independent-mechanisms
#7
Dushani L Palliyaguru, Dionysios V Chartoumpekis, Nobunao Wakabayashi, John J Skoko, Yoko Yagishita, Shivendra V Singh, Thomas W Kensler
Small molecules of plant origin offer presumptively safe opportunities to prevent carcinogenesis, mutagenesis and other forms of toxicity in humans. However, the mechanisms of action of such plant-based agents remain largely unknown. In recent years the stress responsive transcription factor Nrf2 has been validated as a target for disease chemoprevention. Withania somnifera (WS) is a herb used in Ayurveda (an ancient form of medicine in South Asia). In the recent past, withanolides isolated from WS, such as Withaferin A (WA) have been demonstrated to be preventive and therapeutic against multiple diseases in experimental models...
October 4, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27709727/leaf-spot-disease-adversely-affects-human-health-promoting-constituents-and-withanolide-biosynthesis-in-withania-somnifera-l-dunal
#8
V Singh, B Singh, A Sharma, K Kaur, A P Gupta, R K Salar, V Hallan, P K Pati
AIMS: The present work investigates the implication of leaf spot disease on the antioxidant potential and commercial value of pharmaceutically important constituents of Withania somnifera, a high-valued medicinal plant. METHODS AND RESULTS: Leaf spot disease was induced in W. somnifera by inoculating Alternaria alternata (Fr.) Keiss. pathogen. Total polyphenolic content and antioxidant potential showed a significant decrease during leaf spot disease. Evaluation of pharmaceutically active constituents withaferin A, withanone and withanolide A utilizing high-performance liquid chromatography showed a significant decrease in diseased samples as compared to healthy ones...
October 6, 2016: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/27703308/citrullination-of-glial-intermediate-filaments-is-an-early-response-in-retinal-injury
#9
John W Wizeman, Anthony P Nicholas, Akihito Ishigami, Royce Mohan
PURPOSE: A hallmark of retinal gliosis is the increased detection and modification of the type III intermediate filament (IF) proteins vimentin and glial fibrillary acidic protein (GFAP). Here, we investigated vimentin and GFAP in Müller glia in a mouse model of alkali injury, focusing on the posttranslational modification of citrullination. METHODS: Mice were injured by corneal exposure to 1.0 N NaOH, and eyes were enucleated at different time points following injury...
2016: Molecular Vision
https://www.readbyqxmd.com/read/27697094/determination-of-withanolides-in-withania-somnifera-by-liquid-chromatography-single-laboratory-validation-first-action-2015-17
#10
Mayachari Shivanand Anand, Sharon L Brunelle, Balasubramanian Murali, Rojison Koshy
An LC method was developed and validated in 2007 for analyzing Withania somnifera raw material (root) and dried extracts for withanolide content, including withanoside IV, withanoside V, withaferin A, 12-deoxywithastromonolide, withanolide A, and withanolide B. The method involved the extraction of the analytes with methanol, their subsequent filtration, and then analysis on a C18 column with an acetonitrile gradient and UV detection. Single-laboratory validation yielded linearity generally in the range of 20 to 200 μg/mL for each analyte, with a repeatability precision of RSD < 3% in most cases, and recovery in the range of 90 to 105%...
September 30, 2016: Journal of AOAC International
https://www.readbyqxmd.com/read/27685630/pharmacologic-inhibition-of-reactive-gliosis-blocks-tnf-%C3%AE-mediated-neuronal-apoptosis
#11
Izhar Livne-Bar, Susy Lam, Darren Chan, Xiaoxin Guo, Idil Askar, Adrian Nahirnyj, John G Flanagan, Jeremy M Sivak
Reactive gliosis is an early pathological feature common to most neurodegenerative diseases, yet its regulation and impact remain poorly understood. Normally astrocytes maintain a critical homeostatic balance. After stress or injury they undergo rapid parainflammatory activation, characterized by hypertrophy, and increased polymerization of type III intermediate filaments (IFs), particularly glial fibrillary acidic protein and vimentin. However, the consequences of IF dynamics in the adult CNS remains unclear, and no pharmacologic tools have been available to target this mechanism in vivo...
2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27671823/natural-withanolides-in-the-treatment-of-chronic-diseases
#12
Peter T White, Chitra Subramanian, Hashim F Motiwala, Mark S Cohen
Withanolides, and in particular extracts from Withania somnifera, have been used for over 3,000 years in traditional Ayurvedic and Unani Indian medical systems as well as within several other Asian countries. Traditionally, the extracts were ascribed a wide range of pharmacologic properties with corresponding medical uses, including adaptogenic, diuretic, anti-inflammatory, sedative/anxiolytic, cytotoxic, antitussive, and immunomodulatory. Since the discovery of the archetype withaferin A in 1965, approximately 900 of these naturally occurring, polyoxygenated steroidal lactones with 28-carbon ergostane skeletons have been discovered across 24 diverse structural types...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27668267/doxil-when-combined-with-withaferin-a-wfa-targets-aldh1-positive-cancer-stem-cells-in-ovarian-cancer
#13
Sham S Kakar, Christopher A Worth, Zhenglong Wang, Kelsey Carter, Mariusz Ratajczak, Pranesh Gunjal
Ovarian cancer is a highly aggressive and deadly disease. Currently, the treatment for ovarian cancer entails cytoreductive surgery followed by chemotherapy, mainly cisplatin or carboplatin combined with paclitaxel. Although this regimen is initially effective in a high percentage of cases, unfortunately, after few months of initial treatment, tumor relapse occurs due to platinum-resistance. DOXIL (liposomal preparation of doxorubicin) is a choice of drug for recurrent ovarian cancer. However, its response rate is very low and is accompanied by myocardial toxicity...
2016: Journal of Cancer Stem Cell Research
https://www.readbyqxmd.com/read/27622735/glucocorticoid-receptor-mediated-delivery-of-nano-gold-withaferin-conjugates-for-reversal-of-epithelial-to-mesenchymal-transition-and-tumor-regression
#14
Pritha Agarwalla, Sudip Mukherjee, Bojja Sreedhar, Rajkumar Banerjee
AIM: To explore the potential of glucocorticoid receptor-targeted nano-gold formulation as antitumor drug sensitizing agent. MATERIALS & METHODS: Simultaneous conjugation of gold nanoparticle with thiol-modified dexamethasone, a synthetic glucocorticoid and anticancer drug withaferin A afforded stable gold nanoparticle-modifed dexamethasone-withaferin A nanoconjugate. RESULTS: This metallic nanoparticle formulation showed glucocorticoid receptor-dependent cancer cell selective cytotoxicity, inhibited growth of aggressive mouse melanoma tumor, reduced mice mortality, while reversing epithelial-to-mesenchymal transition in tumor cells...
October 2016: Nanomedicine
https://www.readbyqxmd.com/read/27556820/high-expression-of-vimentin-is-associated-with-progression-and-a-poor-outcome-in-glioblastoma
#15
Jiaxin Zhao, Liqiu Zhang, Xingli Dong, Lu Liu, Linman Huo, Huirong Chen
Glioblastoma multiforme (GBM) has a high recurrence and mortality rate. Because of a poor understanding of the mechanism for this disease, treatment regimens have remained limited. Vimentin, one of the major cytoskeletal proteins, is associated with cellular structure. However, the function of vimentin in GBM is still undefined. In the present study, we investigated the expression level of vimentin in 179 GBM tissues using immunohistochemistry. We found that the vimentin expression level was associated with the time to progression (P=0...
August 23, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/27550017/aqueous-extract-from-the-withania-somnifera-leaves-as-a-potential-anti-neuroinflammatory-agent-a-mechanistic-study
#16
Muskan Gupta, Gurcharan Kaur
BACKGROUND: Microglial-mediated neuroinflammation is a key factor underlying the pathogenesis of various neurodegenerative diseases and also an important target for the development of the neuroinflammation-targeted therapeutics. Conventionally, the nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed, but they are associated with long-term potential risks. Natural products are the cornerstone of modern therapeutics, and Ashwagandha is one such plant which is well known for its immunomodulatory properties in Ayurveda...
2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27479085/withaferin-a-is-a-leptin-sensitizer-with-strong-antidiabetic-properties-in-mice
#17
Jaemin Lee, Junli Liu, Xudong Feng, Mario Andrés Salazar Hernández, Patrick Mucka, Dorina Ibi, Jae Won Choi, Umut Ozcan
The increasing global prevalence of obesity and its associated disorders points to an urgent need for the development of novel and effective therapeutic strategies that induce healthy weight loss. Obesity is characterized by hyperleptinemia and central leptin resistance. In an attempt to identify compounds that could reverse leptin resistance and thus promote weight loss, we analyzed a library of small molecules that have mRNA expression profiles similar to that of celastrol, a naturally occurring compound that we previously identified as a leptin sensitizer...
September 2016: Nature Medicine
https://www.readbyqxmd.com/read/27474152/erbb2-overexpression-establishes-erbb3-dependent-hypersensitivity-of-breast-cancer-cells-to-withaferin-a
#18
Wenjun Liu, Annalise R Barnette, Samita Andreansky, Ralf Landgraf
The catalytically deficient ERBB3 strongly synergizes with the receptor tyrosine kinase ERBB2, and elevated levels represent an overall risk factor for unfavorable disease outcomes in breast cancer. Although itself not a target of pan-ERBB kinase inhibitors, it contributes to resistance in ERBB2-targeted treatment regiments. The steroidal lactone Withaferin A (WA) has established broad anticancer properties through several modes of action and was shown to be effective against triple-negative breast cancers at elevated concentrations...
July 29, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27457692/evaluation-of-herb-drug-interaction-of-a-polyherbal-ayurvedic-formulation-through-high-throughput-cytochrome-p450-enzyme-inhibition-assay
#19
Subrata Pandit, Satyajyoti Kanjilal, Anshumali Awasthi, Anika Chaudhary, Dipankar Banerjee, B N Bhatt, Avinash Narwaria, Rahul Singh, Kakoli Dutta, Manu Jaggi, Anu T Singh, Neena Sharma, Chandra Kant Katiyar
ETHNOPHARMACOLOGICAL RELEVANCE: Arishtas are Ayurvedic formulation made with decoction of herbs. Arjunarishta formulation is being used in Ayurveda for cardio-protective activity. Ashwagandharishta formulation possesses antioxidant, anti-atherosclerotic and anti-stress properties. Ridayarishta, a novel empirical formulation was prepared using combination of selected ingredients from these two formulations to support healthy heart functions and to reduce stress. AIM OF THE STUDY: Aim of the Study was to investigate herb-drug interaction (HDI) of Ridayarishta formulation through human hepatic cytochrome P450 (CYP450) enzyme inhibition assay...
July 25, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27447565/oral-administration-of-withaferin-a-inhibits-carcinogenesis-of-prostate-in-tramp-model
#20
Suman Suman, Trinath P Das, Jim Moselhy, Deeksha Pal, Venkatesh Kolluru, Houda Alatassi, Murali K Ankem, Chendil Damodaran
We previously reported that withaferin A (WA), a natural compound, deters prostate cancer by inhibiting AKT while inducing apoptosis. In the current study, we examined its chemopreventive efficacy against carcinogenesis in the prostate using the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Two distinct sets of experiments were conducted. To determine whether WA delays tumor progression, it was given before cancer onset, at week 6, and until week 44. To determine its effect after the onset of prostate cancer, it was given from weeks 12 to 35...
July 20, 2016: Oncotarget
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