Withaninsams A and B: Phenylpropanoid Esters from the Roots of Indian Ginseng (Withania somnifera)

• Published in: Plants (Basel) 2019-11, Vol.8 (12), p.527
• Main Authors: Baek, Su Cheol, Lee, Seoyoung, Kim, Sil, Jo, Mun Seok, Yu, Jae Sik, Ko, Yoon-Joo, Cho, Young-Chang, Kim, Ki Hyun
• Format: Article
• Language: English
• Subjects: Analgesics; Analytical chemistry; Anti-inflammatory agents; Chromatography; Communication; Cytokines; Cytotoxicity; Diabetes mellitus; Disorders; Esters; Ginseng; Herbal medicine; inducible nitric oxide synthase; Inflammation; Ionization; Lipopolysaccharides; Liquid chromatography; Macrophages; Mass spectrometry; Mass spectroscopy; Medicinal plants; Natural products; Nervous system; Nitric oxide; Nitric-oxide synthase; NMR; Nuclear magnetic resonance; Phenolic compounds; Phenols; phenylpropanoid esters; Proteins; Pyrazole; Roots; Spectrum analysis; Transcription; Tumor necrosis factor-α; Western blotting; Withania somnifera; withaninsams a and b
• ISSN: 2223-7747; 2223-7747
• DOI: 10.3390/plants8120527

(L.) Dunal (Solanaceae), known as Indian ginseng or ashwagandha, has been used in Indian Ayurveda for the treatment of a variety of disorders, such as diabetes and reproductive and nervous system disorders. It is particularly used as a general health tonic, analgesic, and sedative. As part of continuing projects to discover unique bioactive natural products from medicinal plants, phytochemical investigation of the roots of combined with a liquid chromatography-mass spectrometry (LC/MS)-based analysis has led to the isolation of two novel phenylpropanoid esters, Withaninsams A (1) and B (2), as an inseparable mixture, along with three known phenolic compounds (3, 4, and 6) and a pyrazole alkaloid (5). The structures of the new compounds were elucidated using a combination of spectroscopic methods, including one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectroscopy (HR-ESIMS). Withaninsams A (1) and B (2) are phenylpropanoid esters that contain a side chain, 4-methyl-1,4-pentanediol unit. To the best of our knowledge, the present study is the first to report on phenylpropanoid esters with 4-methyl-1,4-pentanediol unit. The anti-inflammatory activity of the isolated compounds (1-6) was evaluated by determining their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, where compound 3 inhibited LPS-induced NO production (IC = 33.3 μM) and TNF-α production, a pro-inflammatory cytokine (IC = 40.9 μM). The anti-inflammatory mechanism through the inhibition of transcriptional iNOS protein expression was confirmed by western blotting experiments for the active compound , which showed decreased iNOS protein expression.