Pharmacological Effects of Withanolides

anti-inflammatory and cytotoxic effects of withanolides have been reported. Its pharmacological targets are more focused on the NF- κ B and STAT3 signaling pathways. NF- κ B regulates a great deal of physiological processes including cellular proliferation, development, differentiation, immunity, apoptosis, inﬂammation and metabolism [7]. Abnormal STAT3 activity dysregulates growth and survival, promotes angiogenesis [8], migration and invasion of tumor cells, and induces tumor-immune tolerance. The activation and interaction between STAT3 and NF- κ B plays a pivotal role in control of the communication between cancer cells and inﬂammatory cells [8]. In addition, the anti-cancer activities of TNF- α are enhanced when combined Abstract Withanolides is a class of active compounds widely found in Solanaceae plants. In traditional applications, it has a long history and a wide range of functions. With the progress of drug structure and pharmacological research, more and more reports point to its excellent anticancer effect. Solanaceae is widely distributed, providing a large number of sources for the structure and pharmacological research of its natural products. At the same time, in the light of market demand, the circulation of such medicinal materials is enormous. Based on the pharmacological action of inhibiting NF-κB signaling pathway, withanolides has become a research hotspot in natural medicine. Perhaps combining traditional clinical practice will point out a new research direction to provide basic information for the development of new drugs for difficult cases.


Introduction
: The chemical structure of withaferin A.
Withania somnifera (L.) Dunal (Family, Solanaceae) commonly known as Ashwagandha or winter cherry is one of the top medicinal herbs used in Ayurveda-the holistic system of Indian medicine. The principle bioactive components, a group of secondary metabolites collectively called withanolides, are C-28 steroidal lactones [1]. Withaferin A, a steroidal lactone that was initially isolated from Withania somnifera (winter cherry) in 1965 and was the first member of the withanolides to be discovered ( Figure 1). Withanolides is a series of small molecules widely found in Solanaceae. The solanaceae plant is traditionally used to treat asthma, parasitic disease, constipation, edema, glaucoma, headache, hepatopathy, reducing swelling and inflammation, postpartum pain, skin diseases [2][3][4]. In the past decade, with the rapid development and application of various separation techniques and spectral analysis techniques, especially nuclear magnetic resonance spectroscopy, the research speed of the compounds in the solanaceae has been greatly accelerated, and its structural research has made great progress. Up to now, more than 900 kinds of withanolides have been separated from the whole world [5,6].
In recent years, many anti-inflammatory and cytotoxic effects of withanolides have been reported. Its pharmacological targets are more focused on the NF-κB and STAT3 signaling pathways.
NF-κB regulates a great deal of physiological processes including cellular proliferation, development, differentiation, immunity,

Antitumor Action
Despite the development of a wide variety of anticancer drugs, the global incidence of various cancers, and the mortality thereof, is still on the rise. The number of cancer-related deaths is presumed to increase by two-fold in the next 50 years [14]. Different kinds of solanol lactone can show differences in anticancer activity and target, but anticancer is their common pharmacological characteristics [15]. NF-κB is a classic signal pathway for tumorigenesis [7,16,17]. A crosstalk between TP53 and NF-κB pathways was    [47]. It suggests that Withania somnifera leaf water extract inhibits microglial activation and migration and may prove to be a potential therapeutic candidate for the suppression of neuroinflammation in the treatment of neurodegenerative diseases [48]. Kallol Dutta,et al. tested an extract of W. somnifera that had the potency to reduce in a dosedependent fashion the activity of NF-κB P65-luciferase reporter in the microglial cultured BV2 cells [49]. Withania somnifera water extract reduces LPS-induced NF-κB activity in DI TNC1 astrocytes [50]. Withaferin A may be an eligible candidate for the treatment of neuroinflammatory and stress conditions characterized by an important astrocytic input [51]. Perhaps inhibiting mitochondrial oxidative stress is the initial role of withanolides [52].

Discussion and Future Direction
In addition to Withaferin A, many of the withanolides are isolated from Solanaceae plants [11,53,54]. Through the understanding of Psoriasis, a chronic inflammatory dermatosis, which contains all the characteristics of the autoimmune disease [55], and it needs a highly effective and inexpensive drug containing all of the above functions. The two signaling pathways of NF-κB and STAT3 have been proved to play an important role in the pathological process of psoriasis [56][57][58], and there may be interactions between them [59,60]. In the clinical application of traditional Chinese medicine, the extract of Flos Daturae has achieved exact effect in the treatment of psoriasis [61][62][63] (Figure 4). It is preliminarily believed that the substance base of this effect is withanolides. The Relationship of its structure-activity still needs further study.  46. Grover A, Shandilya A, Punetha A, Bisaria VS, Sundar D (2010) Inhibition of the NEMO/IKKβ association complex formation, a novel mechanism associated with the NF-κB activation suppression by Withania