title: Involvement of heme oxygenase-1 induction in the cytoprotective and neuroinflammatory activities of Siegesbeckia Pubescens isolated from 5,3'-dihydroxy-3,7,4'-trimethoxyflavone in HT22 cells and BV2 cells.
abstract: Glutamate-induced oxidative injury contributes to neuronal degeneration such as Alzheimer's disease, Parkinson's disease and Huntington's disease in the central nervous system (CNS). Siegesbeckia pubescens is used in oriental medicine to treat arthritis, stroke, rash, edema, and skin itching eczema in South-East Asia. This study provides evidence that 5,3'-dihydroxy-3,7,4'-trimethoxyflavone (DTMF), a compound isolated from 90% MeOH extract of Siegesbeckia pubescens, effectively has neuroprotective and anti-neuroinflammatory activities. DTMF has cytoprotective and reactive oxygen species (ROS) reductive effects in HT22 cells. DTMF also decreased LPS-induced inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2) expression but attenuated LPS-induced nitrite (NO) and prostaglandin E2(PGE2), as well as TNF-α and IL-1β production. In addition, DTMF induced Heme oxygenase (HO)-1 expression, HO activity, nuclear transcription factor erythroid-2 related factor 2 (Nrf2) nuclear translocation, and antioxidant response element (ARE)-luciferase activity. DTMF increased p38 phosphorylation in HT22 cells and JNK phosphorylation in BV2 microglia cells. Thus, p38 inhibitor (SB203580) in HT22 cells and JNK inhibitor (SP600125) in BV2 microglia cells significantly suppressed HO-1 expression by DTMF. Furthermore, treatment with SnPP (an inhibitor of HO activity) significantly blocked the cytoprotective effects and the anti-neuroinflammatory action of DTMF. In addition, activated microglia-mediated cell death of mouse hippocampal HT22 cells was significantly repressed by DTMF. We also investigated the protective effect of DTMF on the death of glutamate-induced primary mouse hippocampal neurons. These results demonstrated that DTMF may be a good therapeutic agent against neurodegenerative diseases induced by oxidative stress.
authors: College of Pharmacy, Chosun University, Dong-gu, Gwangju, 61452, Republic of Korea.
authors: Dong-Sung
authors: DS
authors: Lee
authors: Department of Pharmacy, Suncheon University, Suncheon-Si, Jeonnam, 540-950, Republic of Korea.
authors: Mina
authors: M
authors: Lee
authors: College of Pharmacy, Seoul University, Seoul 151-742, Republic of Korea.
authors: Sang Hyun
authors: SH
authors: Sung
authors: College of Pharmacy, Keimyung University, Daegu 704-701, Republic of Korea. Electronic address: gsjeong@kmu.ac.kr.
authors: Gil Saeng
authors: GS
authors: Jeong
mesh_terms: D000818:Animals; D019659:Asteraceae; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D044950:Flavanones; D005419:Flavonoids; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C459623:ayanin; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D015232:Dinoprostone
keywords: 5,3′-dihydroxy-3,7,4′-trimethoxyflavone; BV2 microglial cells; HT22 cells; Heme oxygenase-1; Siegesbeckia pubescens