title: Effects of natural phytochemicals in Angelica sinensis (Danggui) on Nrf2-mediated gene expression of phase II drug metabolizing enzymes and anti-inflammation.
abstract: The root of Angelica sinensis (Oliv.) Diels (abbreviated as AS) (Danggui) has a long history in Asian herbal medicine. Recently, it was demonstrated that AS possesses anti-cancer and anti-oxidant activities. Because the transcription factor Nrf2 mediates the expression of many cellular anti-oxidative stress genes, including genes that are involved in phase II drug metabolism and anti-oxidative stress, this study sought to investigate whether pure compounds from AS or an AS extract could activate antioxidant response element (ARE)-mediated gene expression and induce anti-inflammatory activities. Z-Ligustilide (Ligu), 3-butylidenephthalide (Buty) and CO2 supercritical fluid-extracted lipophilic AS extract (SFE) were tested in HepG2-C8 cells stabilized with ARE luciferase reporter gene. Ligu and Buty caused significant toxicity only at 100 μm. All three samples induced ARE-luciferase activity; however, SFE at 8.5 µg/ml induced ARE-luciferase activity 2-3 fold more potently than did either of the pure compounds. SFE also significantly increased the endogenous mRNA of Nrf2 and the Nrf2 target anti-oxidative gene NAD(P)H dehydrogenase, quinone 1 (NQO1). The protein expression of NQO1 was also significantly induced by SFE. In RAW 264.7 cells, SFE suppressed lipopolysaccharide (LPS)-induced IL-1β and TNF-α expression about 2 fold stronger than sulforaphane, whereas both pure compounds and SFE suppressed inflammatory nitric oxide (NO) production. In summary, this study demonstrates that AS has anti-inflammatory effects and activates the Nrf2 pathway, which protects against oxidative stress.
authors: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors: Constance Lay Lay
authors: CL
authors: Saw
authors: Qing
authors: Q
authors: Wu
authors: Zheng-Yuan
authors: ZY
authors: Su
authors: Hu
authors: H
authors: Wang
authors: Yinhua
authors: Y
authors: Yang
authors: Xiaoting
authors: X
authors: Xu
authors: Ying
authors: Y
authors: Huang
authors: Tin Oo
authors: TO
authors: Khor
authors: Ah-Ng Tony
authors: AN
authors: Kong
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D029971:Angelica sinensis; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015870:Gene Expression; D056945:Hep G2 Cells; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010796:Phthalic Anhydrides / Q000494:pharmacology*; D064209:Phytochemicals / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D051267:NF-E2-Related Factor 2; D010796:Phthalic Anhydrides; D064209:Phytochemicals; D010936:Plant Extracts; D012333:RNA, Messenger; C000606290:SOD1 protein, human; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C027820:ligustilide; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D015107:4-Butyrolactone; C026105:butylidenephthalide
keywords: 3-butylidenephthalide; Angelica sinensis, anti-inflammatory; Danggui; anti-oxidative; antioxidant response element (ARE); ligustilide; nuclear factor (erythroid-derived 2)-like 2 (Nrf2)