title: The inhibitory effects of Geranium thunbergii on interferon-γ- and LPS-induced inflammatory responses are mediated by Nrf2 activation.
abstract: Geranium thunbergii Sieb. et Zucc. (GT; which belongs to the Geraniaceae family) has been used as a traditional medicine in East Asia for the treatment of inflammatory diseases, including arthritis and diarrhea. However, the underlying mechanisms of the anti-inflammatory effects of GT remain poorly understood. In the present study, we examined the mechanisms responsible for the anti-inflammatory activity of GT in macrophages. The results revealed that GT significantly inhibited the lipopolysaccharide (LPS)- and interferon-γ (IFN-γ)-induced expression of pro-inflammatory genes, such as inducible nitric oxide synthase, tumor necrosis factor-α and interleukin-1β, as shown by RT-PCR. However, the inhibitory effects of GT on LPS- and IFN-γ-induced inflammation were associated with an enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) activity, but not with the suppression of nuclear factor (NF)-κB activity, as shown by western blot analysis. In addition, in bone marrow-derived macrophages (BMDM) isolated from Nrf2 knockout mice, GT did not exert any inhibitory effect on the LPS- and IFN-γ-induced inflammation. Taken together, our findings indicate that the anti-inflammatory effects of GT may be associated with the activation of Nrf2, an anti-inflammatory transcription factor.
authors.affiliation: Department of Pathology, College of Korean Medicine, Dongguk University, Siksa-dong, Ilsan, Gyeonggi-do, Republic of Korea.
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine and Korean Medicine Research Center for Healthy Aging, Pusan National University, Mulgeum-eup, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine and Korean Medicine Research Center for Healthy Aging, Pusan National University, Mulgeum-eup, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Mi-Ju
authors.initials: MJ
authors.lastname: Park
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine and Korean Medicine Research Center for Healthy Aging, Pusan National University, Mulgeum-eup, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Jeonju Biomaterials Institute, Jeonju, Republic of Korea.
authors.forename: Seung-Il
authors.initials: SI
authors.lastname: Jeong
authors.affiliation: Department of Korean Pathology, College of Korean Medicine, Sangji University, Wonju, Gangwon, Republic of Korea.
authors.forename: Seongoo
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine and Korean Medicine Research Center for Healthy Aging, Pusan National University, Mulgeum-eup, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Kyun Ha
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine and Korean Medicine Research Center for Healthy Aging, Pusan National University, Mulgeum-eup, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Myungsoo
authors.initials: M
authors.lastname: Joo
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine and Korean Medicine Research Center for Healthy Aging, Pusan National University, Mulgeum-eup, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Han-Sol
authors.initials: HS
authors.lastname: Jeong
authors.affiliation: Department of Pathology, College of Korean Medicine, Dongguk University, Siksa-dong, Ilsan, Gyeonggi-do, Republic of Korea.
authors.forename: Jai-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine and Korean Medicine Research Center for Healthy Aging, Pusan National University, Mulgeum-eup, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Ki-Tae
authors.initials: KT
authors.lastname: Ha
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D031315:Geranium / Q000737:chemistry*; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D007371:Interferon-gamma / Q000009:adverse effects*; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D010936:Plant Extracts; D007371:Interferon-gamma