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Withaferin A

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
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
Varinder Singh, Baldev Singh, Ashutosh Sharma, Kulwinder Kaur, Ajai Prakash Gupta, Raj Kumar Salar, Vipin Hallan, Pratap Kumar Pati
AIMS: The present work investigates the implication of leaf spot disease on the antioxidant potentials 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 (TPC) 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 (HPLC) showed a significant decrease in diseased samples as compared to healthy ones...
October 6, 2016: Journal of Applied Microbiology
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
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
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
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
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
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
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
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
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
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
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 22, 2016: Journal of Ethnopharmacology
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
Mazhar A Kanak, Rauf Shahbazov, Gumpei Yoshimatsu, Marlon F Levy, Michael C Lawrence, Bashoo Naziruddin
BACKGROUND: The underlying molecular mechanism that leads to development of chronic pancreatitis remains elusive. The aim of this study is to understand the downstream inflammatory signaling involved in progression of chronic pancreatitis, and to use withaferin A (WA), a small molecule inhibitor of nuclear factor κB (NFκB), to prevent progression of chronic pancreatitis. METHODS: Two different protocols were used to induce pancreatitis in mice: standard and stringent administration of cerulein...
July 14, 2016: Journal of Gastroenterology
Megan M Marlow, Sumedh S Shah, Eduardo A Véliz, Michael E Ivan, Regina M Graham
Resistance mechanisms employed by high-grade gliomas allow them to successfully evade current standard treatment of chemotherapy and radiation treatment. Withaferin A (WA), utilized in Ayurvedic medicine for centuries, is attracting attention for its antitumor capabilities. Here we review pertinent literature on WA as a high-grade glioma treatment, and discuss the cancerous mechanisms it affects. WA is relatively nontoxic and has shown potential in crossing the blood-brain barrier. WA prevents p53 alterations and inactivates overexpressed MDM2 through ARF and ROS production...
July 2, 2016: Journal of Natural Medicines
Shuichiro Okamoto, Takayuki Tsujioka, Shin-Ichiro Suemori, Jun-Ichiro Kida, Toshinori Kondo, Yumi Tohyama, Kaoru Tohyama
Treatment outcomes for acute myeloid leukemia and myelodysplastic syndromes (MDS) remain unsatisfactory despite progress in various types of chemotherapy and hematopoietic stem cell transplantation. Therefore, there is a need for the development of new treatment options. We investigated the growth-suppressive effects of withaferin A (WA), a natural plant steroidal lactone, on myelodysplasia and leukemia cell lines. WA exhibited growth-suppressive effects on the cell lines, MDS-L, HL-60, THP-1, Jurkat and Ramos, and induction of cell cycle arrest at G2/M phase at relatively low doses...
September 2016: Cancer Science
Xu Li, Feng Zhu, Jianxin Jiang, Chengyi Sun, Qing Zhong, Ming Shen, Xin Wang, Rui Tian, Chengjian Shi, Meng Xu, Feng Peng, Xingjun Guo, Jun Hu, Dawei Ye, Min Wang, Renyi Qin
In contrast to normal tissue, cancer cells display profound alterations in protein synthesis and degradation. Therefore, proteins that regulate endoplasmic reticulum (ER) homeostasis are being increasingly recognized as potential therapeutic targets. The ubiquitin-proteasome system and autophagy are crucially important for proteostasis in cells. However, interactions between autophagy, the proteasome, and ER stress pathways in cancer remain largely undefined. This study demonstrated that withaferin-A (WA), the biologically active withanolide extracted from Withania somnifera, significantly increased autophagosomes, but blocked the degradation of autophagic cargo by inhibiting SNARE-mediated fusion of autophagosomes and lysosomes in human pancreatic cancer (PC) cells...
September 2016: Autophagy
Shruti B Patel, Nirav J Rao, Lal L Hingorani
BACKGROUND: The use of Withania somnifera is increasing due to a number of its chemical constituents found useful for health. OBJECTIVE: The present study was carried out to investigate the potential adverse effects (if any) of a standardized Withania somnifera extract (WSE) in rats following acute and sub chronic administration. MATERIALS AND METHODS: The toxicity study was performed in Wistar rats by oral administration. An acute toxicity study was done at the dose of 2000 mg/kg...
March 2016: Journal of Ayurveda and Integrative Medicine
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