Induction of Quinone Reductase by Withanolides

Abstract

Thirty-seven naturally occurring withanolides (1-37), previously isolated in our laboratories, were evaluated for their potential to induce quinone reductase with cultured murine hepatoma cells (Hepa 1c1c7). Spiranoid (29, 32) and 18-functionalized withanolides (2-5, 7-9, 24) were found to be potent inducers of the enzyme, while 5alpha-substituted derivatives exhibited weak activity. Preliminary studies were performed with compound 29 to evaluate enzyme-inducing capacity in multiple organ sites of BALB/c mice. Significant induction was observed in liver and colon, but not in lung, stomach, or mammary gland.

Withanolides and Related Steroids

“…One such compound, the spiranoid, jaborosalactone P (389), was selected to test its capacity to induce steady-state levels of quinone reductase in multiple organ sites of BALB/c mice. With jaborosalactone P-treated mice, a significant induction was observed in liver and colon, but not in lung, stomach, or mammary gland (253). This in vivo study confirmed the in vitro results, indicating that withanolides may function as potent phase II enzyme inducers.…”

“…In a broader study comprising withanolides from 13 Solanaceae species, 37 withanolides representative of a variety of structural types were evaluated for their potential to induce quinone reductase (253). Jaborosalactone 1 (397), jaborosalactone O (353), jaborosalactone P (389), trechonolide A (368), and withaphysalin J (320), were significant QR inducers with CD values in the range of 0.27-1.52 mM.…”

Withanolides potentiate apoptosis, inhibit invasion, and abolish osteoclastogenesis through suppression of nuclear factor-κB (NF-κB) activation and NF-κB–regulated gene expression

“…A pharmacologic study conducted on this plant indicated that a component withanolide, withaferin A, inhibits angiogenesis (4). Withanolides have also been reported to inhibit metastasis (5) and quinone reductase activity (6). Some of them have been shown to preferentially affect events in the cholinergic signal transduction cascade of the cortical and basal forebrain, indicating their promise for the treatment of Alzheimer's disease (7).…”

Derivados citotóxicos de vitanolidos isolados das folhas de Acnistus arborescens

“…Estes foram primeiramente citados na literatura em 1962, mas sua elucidação estrutural só aconteceu em 1966 com a descrição estereoquímica da vitaferina 1 (Figura 1) isolada das folhas de Withania somnifera, popularmente conhecida na Índia como Ashwaganha. 2 Os vitanolidos têm sido isolados de plantas de vários gêneros, como exemplo podem ser citados: Acnistus, [3][4][5][6][7][8] Datura, 9 Jaborosa, 10 Physalis 11 e Withania, 12,13 todos da família Solanaceae, e despertam interesse por apresentarem diversas atividades biológicas, algumas delas como antitumoral, 4-8 diurética, 13 indução de quinona redutase 5,14 e imunossupressora. 15 Outros esteroides que são encontrados na famíla Solanaceae incluem glicosídeos e alcaloides esteroidais, compostos presentes nos gêneros Cestrum e Solanum, sendo este último gênero o que possui o maior número de espécies catalogadas.…”