Abstract
Withaferin A (WA), a manifold studied, C28-steroidal lactone withanolide found in Withania somnifera. Given its unique beneficial effects, it has gathered attention in the era of modern science. Cancer, being considered a “hopeless case and the leading cause of death worldwide, and the available conventional therapies have many lacunae in the form of side effects. The poly pharmaceutical natural compound, WA treatment, displayed attenuation of various cancer hallmarks by altering oxidative stress, promoting apoptosis, and autophagy, inhibiting cell proliferation, reducing angiogenesis, and metastasis progression. The cellular proteins associated with antitumor pathways were also discussed. WA structural modifications attack multiple signal transduction pathways and enhance the therapeutic outcomes in various diseases. Moreover, it has shown validated pharmacological effects against multiple neurodegenerative diseases by inhibiting acetylcholesterinases and butyrylcholinesterases enzyme activity, antidiabetic activity by upregulating adiponectin and preventing the phosphorylation of peroxisome proliferator-activated receptors (PPARγ), cardioprotective activity by AMP-activated protein kinase (AMPK) activation and suppressing mitochondrial apoptosis. The current review is an extensive survey of various WA associated disease targets, its pharmacokinetics, synergistic combination, modifications, and biological activities.
Highlights
Phytotherapy is the frequent therapeutic approach in complementary as well as in traditional medicine since time immemorial
Withaferin A (WA) down-regulates the expression of Notch1, pAKT, and NF-κB and other markers of inflammation (interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and cyclooxygenase-2) [79], highlighting that this therapeutic agent has a vital role in colon carcinogenesis prevention
Various pathways involve kelch like ECH associated protein 1, glycogen synthase kinase 3 [154]. These findings suggest that WA effectively protects cells from Nonalcoholic steatohepatitis (NASH), further studies are still required to know the exact mechanism
Summary
Phytotherapy is the frequent therapeutic approach in complementary as well as in traditional medicine since time immemorial It is utilized by 60% of the global population and has a vital role in the health care system due to ease of availability and reduced cost compared with synthetic compounds. Today medicinal plantsmedicinal are evaluated modern technologies, technologies, including screening and functional assays [8]. Alkylation nucleophilic site chemical structure displayed positions that mayproteins. Nucleophilic site binding reactions occurs through the A-ring at position C3 and the epoxide. These sites are most vulnerable attack reaction; WAalkylation interacts network in C24. The current review is an extensive survey of various WA associated disease targets, summarizing the pharmacokinetics, structural modifications, potential pharmacological activities, and WA formulations, and evaluating the available evidence to predict the potential targets. More than 150 References, indexed in the most relevant data basis (MDPI, ESEVIER, PubMed, NCBI, Springer, etc.) were found describing parts of our topic
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