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provides coniferyl ferulate(CAS#:5119-48-2) MSDS, density, melting point, boiling point, structure, formula, molecular weight etc. Articles of coniferyl ferulate are included as well.>> amp version: coniferyl ferulate
Cancer is still considered a “hopeless case”, besides all of the advancements in oncology research. On the other hand, the natural products, as effective lead molecules, have gained significant interest for research due to the absence of toxic and harmful side effects usually associated with conventional treatment methods. Medicinal properties of herbal plants are strongly evidenced in traditional medicine from ancient times. In the context above, withaferin A (WA) was identified as the active principle of the plant Withania somnifera, its molecule being reported to have excellent anticancer and tumour inhibition activities in various cell lines. Furthermore, the in silico approaches in the medicinal chemistry of WA revealed the biological targets and gave momentum for the research that leads to many amazing pharmacological activities of WA which are not yet explored. This includes a broad spectrum of anticancer actions manifested in different organs (breast, pancreas, colon), melanoma and B cell lymphoma, etc. This review is an extensive survey of the most recent anticancer studies reported for WA, along with its mechanism of action and details about its in vitro and/or in vivo behaviour.
Anticancer activity; Traditional medicine; Tumour inhibition; Withaferin; Withania somnifera.
Overview of the anticancer activity of withaferin A, an active constituent of the Indian ginseng Withania somnifera
Vishnu Sankar Sivasankarapillai 1, Reshmi Madhu Kumar Nair 2, Abbas Rahdar 3, Simona Bungau 4, Dana Carmen Zaha 5, Lotfi Aleya 6, Delia Mirela Tit 4
The bioconversion of Withania somnifera extract by the fungus Beauveria bassiana leads to cysteine and glutathione derivatives of withaferin A at the C-6 position. The compounds were purified and fully characterized by 1D-NMR, 2D-NMR, and HRMS analysis. The glutathione derivative CR-777 was evaluated as a neuroprotective agent from damage caused by different neurotoxins mimicking molecular symptoms in Parkinson´s disease (PD), including 1-methyl-4-phenylpyridinium (MPP+), 6-hydroxydopamine (6-OHDA), and α-synuclein (α-Syn). CR-777, at nanomolar concentrations, protected dopaminergic and cortical neurons. In 6-OHDA-treated neurons, CR-777 increased cell survival and neurite network and decreased the expression of α-Syn. Using specific inhibitors of cell toxicity signaling pathways and specific staining experiments, the observed role of CR-777 seemed to involve the PI3K/mTOR pathway. CR-777 could be considered as a protective agent against a large panel of neuronal stressors and was engaged in further therapeutic development steps.
Alzheimer’s disease; Parkinson’s disease; Withania somnifera; bioconversion; glutathione conjugate; neuroprotection; withaferin A.
Neuroprotective Effect of CR-777, a Glutathione Derivative of Withaferin A, Obtained through the Bioconversion of Withania somnifera (L.) Dunal Extract by the Fungus Beauveria bassiana
Cherif Rabhi 1, Guillaume Arcile 2, Geraldine Le Goff 2, Christian Da Costa Noble 1, Jamal Ouazzani 2
2019 Dec 16;
Background: Ovarian cancer is the fifth leading cause of cancer-related deaths amongst women in the United States. Cachexia is the primary cause of death in approximately 30% of cancer patients, and is often evidenced in ovarian cancer patients. We tested the steroidal lactone Withaferin A to examine if it could ameliorate ovarian cancer-induced cachexia.
Methods: Six-week-old severely immunodeficient female mice were xenografted with the ovarian cancer cell line A2780 followed by treatment with Withaferin A or vehicle. Changes in functional grip strength were assessed on a weekly basis. Postmortem, H&E staining was performed on skeletal muscle sections and immunofluorescent immunohistochemistry was performed on skeletal muscle and tumor sections. The levels of NF-κB-related proinflammatory cytokines were assessed in the xenografted tumors and in resident host skeletal muscle.
Results: Xenografting of the A2780 cell line resulted in a significant rate of mortality, which was attenuated by a therapeutic dosage of Withaferin A. Mice that received vehicle treatment following xenografting exhibited functional muscle decline over the course of the study. The therapeutic dosage Withaferin A treatment attenuated this reduction in grip strength, whereas the supratherapeutic dosage of Withaferin A was found to be toxic/lethal and demonstrated a further decline in functional muscle strength and an increased rate of mortality on par with vehicle treatment. At a histological level, the vehicle treated tumor-bearing mice exhibited a profound reduction in myofibrillar cross-sectional area compared to the vehicle treated tumor-free control group. The atrophic changes induced by the xenografted tumor were significantly ameliorated by treatment with Withaferin A. The combination of functional muscle weakening and induction of myofibrillar atrophy corroborate a cachectic phenotype, which was functionally rescued by Withaferin A. Further, treatment completely abolished the slow-to-fast myofiber type conversion observed in the settings of cancer-induced cachexia. In both host resident skeletal muscle and the xenografted tumors, we report an increase in NF-κB-related proinflammatory cytokines that was reversed by Withaferin A treatment. Finally, we demonstrated that Withaferin A significantly downregulates cytosolic and nuclear levels of phospho-p65, the active canonical NF-κB transcription factor, in xenografted tumors.
Conclusions: Cumulatively, our results demonstrate a previously overlooked role of Withaferin A in a xenograft model of ovarian cancer. We propose mechanisms by which Withaferin A reduces NF-κB-dependent pro-inflammatory cytokine production leading to an attenuation of the cachectic phenotype in an i.p. xenograft model of ovarian cancer.
Cachexia; Cancer; Cytokine; Inflammation; NF-κB; Ovarian Cancer; Skeletal muscle.
Withaferin A ameliorates ovarian cancer-induced cachexia and proinflammatory signaling
Alex R Straughn 1, Sham S Kakar 2 3
2019 Nov 25