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.

Z‐Ligustilide inhibits benzo(a)pyrene‐induced CYP1A1 upregulation in cultured human keratinocytes via ROS‐dependent Nrf2 activation

“…Z‐Ligustilide is an active ingredient in C. officinale and A. acutiloba and shows several biological activities . In the present study, we investigated the inhibitory effect of Z‐Ligustilide on BaP‐induced CYP1A1 upregulation and its underlying mechanism in cultured human keratinocytes.…”

Danggui Buxue Tang Attenuates Tubulointerstitial Fibrosis via Suppressing NLRP3 Inflammasome in a Rat Model of Unilateral Ureteral Obstruction

“…Ma and Bai found that Z-ligustilide significantly inhibited NF- κ B activation and the production of IL-1 β and TNF- α in experimental ovariectomized (OVX) osteopenic rats and endotoxin-induced uveitis rats [49, 50]. Generally speaking, FA and Z-ligustilide, two major compounds in RA, activated the Nrf2 pathway and decreased NF- κ B luciferase activity, which may contribute to the anti-inflammatory activity of RA [51]. …”

Tumor Inhibition Effects and Mechanisms of Angelica sinensis and Sophorae flavescentis ait Decoction Combined with Cisplatin in Xenograft Mice

“…Currently, extracts from Angelica sinensis possess anti-cancer and anti-oxidant activities, which activate the Nrf2 pathway to mediate the expression of many cellular anti-oxidative stress genes, protect organs and tissues against oxidative stress (Saw et al, 2013); extracts from Angelica sinensis can also suppress the growth of malignant brain tumor cells, up-regulate expression of p53 protein, cyclin kinase inhibitors p16, decrease the phosphorylation of Rb proteins, leading to arrest at the G0-G1 phase and activation of apoptosisassociated proteins in p53 pathway, significantly prolong patient survival (Lin et al, 2013). Angelica sinensis can decrease the adhesive, invasive and migratory ability of human lung adenocarcinoma A549 cells, down-regulate the expressions of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) at both the protein and mRNA levels, inhibit the enzymatic activity of MMP-2 and MMP-9, possesses anti-growth and antimetastasis activity against lung cancer cells (Gao et al,…”