Withaferin A: From ayurvedic folk medicine to preclinical anti-cancer drug

Hassannia, Behrouz; Logie, Emilie; Vandenabeele, Peter; Berghe, Tom Vanden; Berghe, Wim Vanden

doi:10.1016/j.bcp.2019.08.004

Cited by 82 publications

(47 citation statements)

References 146 publications

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“…In this regard, withanolides, naturally occurring C-28-steroidal lactones on an ergostane framework [9], have attracted considerable attention due to their diverse pharmacological properties [10], including anti-inflammatory, immunomodulatory, neurological disorders, and antitumor potential. Withaferin A (WA), the prototype of natural products with withanolide-type skeleton, was investigated for the first time in 1967 as an anticancer agent [11], and since then, a growing list of reports on WA's broad spectrum antitumor properties [12] and multifunctional molecular mechanism of action [13] have been disclosed. WA molecular biochemical targets against leukemia [14] have also been described.…”

Section: Introductionmentioning

confidence: 99%

Withanolide-Type Steroids from Withania aristata as Potential Anti-Leukemic Agents

et al. 2020

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Leukemia is a blood or bone marrow cancer with increasing incidence in developed regions of the world. Currently, there is an ongoing need for novel and safe anti-leukemic agents, as no fully effective chemotherapy is available to treat this life-threatening disease. Herein, are reported the isolation, structural elucidation, and anti-leukemic evaluation of twenty-nine withanolide-type steroids (1–29) from Withania aristata. Among them, the new isolated withanolides, withaperoxidins A–D (1–4) have an unusual six-membered cyclic peroxide moiety on the withasteroid skeleton as a structural novelty. Their structures have been elucidated by means of spectroscopic analyses, including 2D NMR experiments. In addition, extensive structure–activity relationships and in silico ADME studies were employed to understand the pharmacophore and pharmacokinetic properties of this series of withasteroids. Compounds 15, 16, and 22 together with withaferin A (14) were identified as having improved antiproliferative effect (IC50 ranging from 0.2 to 0.7 μM) on human leukemia HL-60 cell lines compared with the reference drug, etoposide. This cytotoxic potency was also coupled with good selectivity index (SI 33.0–9.2) on non-tumoral Vero cell line and in silico drug likeness. These findings revealed that these natural withasteroids are potential candidates as chemotherapeutic agents in the treatment of leukemia.

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Section: Introductionmentioning

confidence: 99%

Withanolide-Type Steroids from Withania aristata as Potential Anti-Leukemic Agents

et al. 2020

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“…In this regard, we investigated Withaferin A (WA), a natural steroidal lactone isolated from Withania somnifera , known for a broad range of medicinal properties including its antiinflammatory and immunomodulatory activities 18 , 19 . Previous reports including our own have shown that mechanistically, WA inhibits NF-κB activation by binding to inhibitor of NF-κB subunit beta (IKKβ), preventing phosphorylation of Iκβ 20 – 22 .…”

Section: Introductionmentioning

confidence: 99%

Withaferin A inhibits lymphocyte proliferation, dendritic cell maturation in vitro and prolongs islet allograft survival

Kumano

Kanak

Saravanan

et al. 2021

Sci Rep

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The immunosuppressive regimen for clinical allogeneic islet transplantation uses beta cell–toxic compounds such as tacrolimus that cause islet graft loss. Previously we reported that the plant-derived steroidal lactone Withaferin A (WA) can protect islet grafts by inhibiting nuclear factor-kappa B (NF-κB). Since the NF-κB signaling pathway is essential for T-cell activation, we hypothesized that long-term WA administration may also provide an immunosuppressive effect. Treatment of BALB/c donor islets and C57BL/6N recipients with WA alone resulted in 80% islet graft long-term survival vs. 40% in low-dose FK506-treated mice. In vitro, WA significantly blocked mouse and human T-cell proliferation by CD3/CD28 bead stimulation and in mixed lymphocyte reaction assay. Treatment of immature dendritic cells with WA prevented their maturation in response to inflammatory stimuli, as seen by decreased expression of CD83 and human leukocyte antigen–DR isotype. Exosomes released by islets treated with WA contained significantly fewer proinflammatory molecules interleukin-6, interleukin-8, monocyte chemoattractant protein-1, interferon-gamma-induced protein-10, inducible nitric oxide synthase, and cyclooxygenase-2. In conclusion, WA treatment not only reduced inflammation but also prolonged allograft survival, possibly through suppression of dendritic cell maturation and T-cell proliferation. WA has the potential to inhibit both the innate and adaptive immune response to prolong allograft survival.

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“…While our predecessors hardly understood the underlying mechanisms and chemical mediators responsible for the efficacy of these plants, recent advancement in technology (which includes techniques, instrumentation, and automation in isolation and structural characterization) allows us to learn the underlying mechanisms of these herbal treatments in depth [5,6] and discover the full potential for the usage of these plants full of potent medicinal properties and nutritive values [7,8]. An updated medicinal plant database will enhance the scientific community to advance in the field of drug discovery (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

MPDB 2.0: A Large Scale and Integrated Medicinal Plant Database of Bangladesh

Hussain¹,

Chando²,

Abir³

et al. 2021

Preprint

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Medicinal plants are generally defined as rare herbals with potent medicinal activities that can be used as an alternative treatment for diseases. Recent studies exploring novel medicine developments, originating from folk-medicinal practices challenges this notion and suggests that both the circumference of the term medicinal plant and their potential application covers a substantially extensive verse than previously suggested. While medicinal plants are not limited to the borders of any country, Bangladesh and its south-east Asian neighbors do boast a huge collection of potent medicinal plants with considerable folk-medicine history compared to most other countries of the world. MPDB 2.0 is the continuation of MPDB 1.0, it serves as both a data repertoire for medicinal of Bangladesh and a user-friendly interface for researchers, health practitioners, drug developers, and students who wish to study the various medicinal & nutritive plants scattered around Bangladesh and the underlying phytochemicals contributing to their efficacy in folk medicine. While in developing MPDB 2.0 human diseases have been highly focused upon, the information in this database is not limited in its application for human diseases or diseases only, as many of the plants indexed here can serve in developing biofuel or bioremediation technologies or nutritive diets or cosmetics, etc. MPDB 2.0 comprises a collection of more than five hundred medicinal plants from Bangladesh along with a record of their corresponding scientific, family, and local names together with their utilized parts, information regarding ailments, active compounds, and PubMed ID of related publications.

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Withaferin A: From ayurvedic folk medicine to preclinical anti-cancer drug

Cited by 82 publications

References 146 publications

Withanolide-Type Steroids from Withania aristata as Potential Anti-Leukemic Agents

Withanolide-Type Steroids from Withania aristata as Potential Anti-Leukemic Agents

Withaferin A inhibits lymphocyte proliferation, dendritic cell maturation in vitro and prolongs islet allograft survival

MPDB 2.0: A Large Scale and Integrated Medicinal Plant Database of Bangladesh

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