Induction of Nrf2-mediated genes by Antrodia salmonea inhibits ROS generation and inflammatory effects in lipopolysaccharide-stimulated RAW264.7 macrophages.
Antrodia salmonea (AS), a well-known medicinal mushroom in Taiwan, has been reported to exhibit anti-oxidant, anti-angiogenic, anti-atherogenic, and anti-inflammatory effects. In the present study, we investigated the activation of Nrf2-mediated antioxidant genes in RAW264.7 macrophages by the fermented culture broth of AS, studied the resulting protection against lipopolysaccharide (LPS)-stimulated inflammation, and revealed the molecular mechanisms underlying these protective effects. We found that non-cytotoxic concentrations of AS (25-100 μg mL⁻¹) protected macrophages from LPS-induced cell death and ROS generation in a dose-dependent manner. The antioxidant potential of AS was directly correlated with the increased expression of the antioxidant genes HO-1, NQO-1, and γ-GCLC, as well as the level of intracellular GSH followed by an increase in the nuclear translocation and transcriptional activation of the Nrf2-ARE pathway. Furthermore, Nrf2 knockdown diminished the protective effects of AS, as evidenced by the increased production of pro-inflammatory cytokines and chemokines, including PGE₂, NO, TNF-α, and IL-1β, in LPS-stimulated macrophages. Notably, AS treatment significantly inhibited LPS-induced ICAM-1 expression in macrophages. Our data suggest that the anti-inflammatory potential of Antrodia salmonea is mediated by the activation of Nrf2-dependent antioxidant defense mechanisms. Results support the traditional usage of this beneficial mushroom for the treatment of free radical-related diseases and inflammation.
Institute of Nutrition, China Medical University, Taichung 40402, Taiwan.
Hsin-Ling
HL
Yang
Shu-Wei
SW
Lin
Chuan-Chen
CC
Lee
Kai-Yuan
KY
Lin
Chun-Huei
CH
Liao
Ting-Yu
TY
Yang
Hui-Min
HM
Wang
Hui-Chi
HC
Huang
Chi-Rei
CR
Wu
You-Cheng
YC
Hseu
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D055491:Antrodia / Q000254:growth & development / Q000378:metabolism*; D002461:Cell Line, Transformed; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects*; D020834:Ethnopharmacology; D005285:Fermentation; D020868:Gene Silencing; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008518:Medicine, East Asian Traditional; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013624:Taiwan
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D017077:Culture Media, Conditioned; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; D005721:Glutamate-Cysteine Ligase