Withanolides: Chemistry and Antitumor Activity

Choudhary, M. Iqbal; Yousuf, Sammer; Atta-ur-Rahman, _

doi:10.1007/978-3-642-22144-6_150

Cited by 12 publications

(13 citation statements)

References 99 publications

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“…Srinivasan et al showed that WA, by inducing the proapoptotic protein in the prostate apoptosis response-4 (Par-4), caused the arrest of prostate cancer cell growth ( 13 ). Several studies have indicated that WA can stop the G2/M cell cycle and decrease the expression of NF-kβ and TNF-α, and thus it has antiproliferative activity and induces apoptosis in cancerous cells ( 34 , 35 ). It was found that WA also increased the activation of p21 in prostate cancer cells ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

Antiproliferative and Antioxidant Effects of Withania coagulans Extract on Benign Prostatic Hyperplasia in Rats

et al. 2016

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Background:Benign prostate hyperplasia (BPH) is a common urological disorder in elderly men. Phytotherapy is frequently used to alleviate the symptoms of this condition.Objectives:The present study investigated the effect of Withania coagulans extract (WCE), which is known to have antioxidant, anti-inflammatory, antihyperglycemic, and anti-cancer properties, on testosterone-induced BPH in rats.Materials and Methods:Forty Wistar rats were divided into five groups (each n = 8): the control group, the untreated BPH group, and three WCE-treated groups (WCE250, 500, and 1000). BPH was induced with 3 mg/kg subcutaneous injections of testosterone propionate for four weeks. WCE was concomitantly administrated by oral gavage. At the end of the induction schedule, the animals were sacrificed and their prostate glands were dissected, weighed, and fixed for histological examination (H&E and proliferating cell nuclear antigen [PCNA] staining). Half of each sample was prepared for measurement of malondialdehyde (MDA) and total antioxidant capacity (TAC) levels in the prostate.Results:The present study revealed that BPH caused elevation of MDA levels, suppression of TAC levels, and increased PCNA expression in the prostate gland. Interestingly, in a dose-dependent manner, WCE caused decreased MDA levels and increased TAC levels in the prostate gland, compared to the untreated BPH group. Histopathological examinations showed a reduction in PCNA expression in the prostate epithelium of the WCE animals.Conclusions:W. coagulans inhibits the development of BPH can be useful for the treatment of this condition.

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Section: Discussionmentioning

confidence: 99%

Antiproliferative and Antioxidant Effects of Withania coagulans Extract on Benign Prostatic Hyperplasia in Rats

et al. 2016

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“…In this study, we demonstrated the in vitro antileukemic effect of the root extract of W. somnifera in a T-lymphoblastoid cell line. The high-performance liquid chromatography (HPLC) analysis performed on WE revealed the presence of WFA, WDA and to a lesser extent withanolide B. Withanolides, in particular WFA and its acetyl derivative, are highly bioactive and show anticancer activity [ 19 , 20 , 21 ]. Of note, its dihydroderivative is not active, thus suggesting that an unsaturated lactone moiety in ring A of WFA is important for its biological activity.…”

Section: Discussionmentioning

confidence: 99%

Withania somnifera Induces Cytotoxic and Cytostatic Effects on Human T Leukemia Cells

Turrini

Calcabrini

Sestili

et al. 2016

Toxins

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Cancer chemotherapy is characterized by an elevated intrinsic toxicity and the development of drug resistance. Thus, there is a compelling need for new intervention strategies with an improved therapeutic profile. Immunogenic cell death (ICD) represents an innovative anticancer strategy where dying cancer cells release damage-associated molecular patterns promoting tumor-specific immune responses. The roots of Withania somnifera (W. somnifera) are used in the Indian traditional medicine for their anti-inflammatory, immunomodulating, neuroprotective, and anticancer activities. The present study is designed to explore the antileukemic activity of the dimethyl sulfoxide extract obtained from the roots of W. somnifera (WE). We studied its cytostatic and cytotoxic activity, its ability to induce ICD, and its genotoxic potential on a human T-lymphoblastoid cell line by using different flow cytometric assays. Our results show that WE has a significant cytotoxic and cytostatic potential, and induces ICD. Its proapoptotic mechanism involves intracellular Ca2+ accumulation and the generation of reactive oxygen species. In our experimental conditions, the extract possesses a genotoxic potential. Since the use of Withania is suggested in different contexts including anti-infertility and osteoarthritis care, its genotoxicity should be carefully considered for an accurate assessment of its risk–benefit profile.

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“…The study of natural products' biosynthetic pathways and patterns is important because it offers new approaches in total synthesis. Withanolides are a signature secondary metabolite (Sangwan et al 2004) and have significant and multiple bioactivities including immunomodulation, anti-cancer, neuroprotection, anti-hyperglycemic and the reversal of Alzheimer's disease (AD) (Choudhary et al 2013;Kushwaha et al 2012;Akizuki et al 2013;Sehgal et al 2012). Although structure and pharmacological activity have been studied and summarized during the last two decades, limited attempts have been made to illuminate the biosynthetic routes and identification of the key regulatory genes involved in withanolide biosynthesis.…”

Section: Biosynthesismentioning

confidence: 99%

“…The complex structures and diverse bioactivities of withanolides have attracted increasing attention from numerous researchers, and several reviews about their classification, complicated and changeable structures, and extensive biological activities have been published over the past thirty years (Kirson and Glotter 1981;Glotter 1991;Anjaneyyulu et al 1998;Chen et al 2011;Misico et al 2011;Choudhary et al 2013). The withanolides exhibit characteristic spectroscopic behaviors that contribute to their structural elucidation.…”

Section: Introductionmentioning

confidence: 99%

Phytochemistry and biosynthesis of δ-lactone withanolides

et al. 2015

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Withanolides are highly oxygenated natural products. These C 28 steroids with ergostane-based skeletons functionalized at C-22 and C-26 form sixmembered d-lactone rings. Withanolides containing a d-lactone side chain often occur in Solanaceae and have a variety of biological activities because of their complicated structures. Characteristic spectroscopic behaviors and biosynthesis of withanolides are conducive to their structural elucidation and ''biomimetic synthesis'', respectively. However, the last review to summarize their spectroscopic features and biosynthesis was in 1996. Since then, many withanolides with novel structures have been described by their spectra with biosynthesis investigated with many bioassays. This review surveys d-lactone withanolides and emphasizes their spectral features, configurations and biosynthetic genes. The period reviewed includes through January 2014. We also include phytochemical species.

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Withanolides: Chemistry and Antitumor Activity

Cited by 12 publications

References 99 publications

Antiproliferative and Antioxidant Effects of Withania coagulans Extract on Benign Prostatic Hyperplasia in Rats

Antiproliferative and Antioxidant Effects of Withania coagulans Extract on Benign Prostatic Hyperplasia in Rats

Withania somnifera Induces Cytotoxic and Cytostatic Effects on Human T Leukemia Cells

Phytochemistry and biosynthesis of δ-lactone withanolides

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