| Reference | [1]. Mediators Inflamm. 2017;2017:7250968. doi: 10.1155/2017/7250968. Epub 2017 Feb 20.<br />
Torilin Inhibits Inflammation by Limiting TAK1-Mediated MAP Kinase and NF-κB Activation.<br />
Endale M(1), Kim TH(2), Kwak YS(3), Kim NM(3), Kim SH(4), Cho JY(5), Yun BS(6), Rhee MH(2).<br />
Author information: (1)Division of Neonatology and Pulmonary Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH, USA. (2)College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea. (3)Research and Development Headquarters, Korea Ginseng Corporation, Daejon 305-805, Republic of Korea. (4)Institute of Traditional Medicine & Bioscience, Daejeon University, Daejeon 300-716, Republic of Korea. (5)Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea. (6)College of Environmental & Bioresource Sciences, Chonbuk National University, Iksan 570-752, Republic of Korea.<br />
Torilin, a sesquiterpene isolated from the fruits of Torilis japonica, has shown antimicrobial, anticancer, and anti-inflammatory properties. However, data on the mechanism of torilin action against inflammation is limited. This study aimed at determining the anti-inflammatory property of torilin in LPS-induced inflammation using in vitro model of inflammation. We examined torilin's effect on expression levels of inflammatory mediators and cytokines in LPS-stimulated RAW 264.7 macrophages. The involvement of NF-kB and AP-1, MAP kinases, and adaptor proteins were assessed. Torilin strongly inhibited LPS-induced NO release, iNOS, PGE2, COX-2, NF-α, IL-1β, IL-6, and GM-CSF gene and protein expressions. In addition, MAPKs were also suppressed by torilin pretreatment. Involvement of ERK1/2, P38MAPK, and JNK1/2 was further confirmed by PD98059, SB203580, and SP600125 mediated suppression of iNOS and COX-2 proteins. Furthermore, torilin attenuated NF-kB and AP-1 translocation, DNA binding, and reporter gene transcription. Interestingly, torilin inhibited TAK1 kinase activation with the subsequent suppression of MAPK-mediated JNK, p38, ERK1/2, and AP-1 (ATF-2 and c-jun) activation and IKK-mediated I-κBα degradation, p65/p50 activation, and translocation. Together, the results revealed the suppression of NF-κB and AP-1 regulated inflammatory mediator and cytokine expressions, suggesting the test compound's potential as a candidate anti-inflammatory agent.<br />
DOI: 10.1155/2017/7250968 PMCID: PMC5337842 PMID: 28316375 [Indexed for MEDLINE]<br />
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[2]. Int Immunopharmacol. 2013 Jun;16(2):232-42. doi: 10.1016/j.intimp.2013.04.012. Epub 2013 Apr 24.<br />
Torilin ameliorates type II collagen-induced arthritis in mouse model of rheumatoid arthritis.<br />
Endale M(1), Lee WM, Kwak YS, Kim NM, Kim BK, Kim SH, Cho J, Kim S, Park SC, Yun BS, Ko D, Rhee M.<br />
Author information: (1)Deparment of Molecular & Cellular Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.<br />
Advancements in rheumatoid-arthritis-(RA) therapies have shown considerable progresses in the comprehension of disease. However, the development of new potential agents with relative safety and efficacy continues and natural compounds have been considered as alternatives to identify new entities. Since previous in-vivo data and our in-vitro findings showed that torilin has a strong anti-inflammatory property, we further investigated its effect against collagen-induced-arthritis-(CIA) in mice. CIA-induced DBA/1J mice were treated with torilin or methotrexate (MTX) for 5-weeks. Arthritis severity was evaluated by arthritic score and joint histopathology. Draining lymph node (dLN), joint and peripheral-blood mononuclear-cell (PBMC) counts, and activation/localization of T-/B-lymphocytes, dendritic cells (DCs) and neutrophils were examined by FACS analysis. Serum anti-type-II-collagen-(CII) antibody levels and cultured-splenocyte and serum cytokines were also evaluated. Torilin markedly reduced CIA-induced arthritic score, histopathology and leukocyte counts. Besides, torilin suppressed CIA-activated T-cells including CD3+, CD3+/CD69+, CD8+, CD4+ and CD4+/CD25+ in dLNs or joints. It also modified CD19+ or CD20+/CD23+ (B-cells), MHCII+/CD11c+ (DCs) and Gr-1+/CD11b+ (neutrophil) subpopulations. It further depressed total anti-CII-IgG, anti-CII-IgG1 and anti-CII-IgG2a antibody productions. Moreover, while IFN-γ and IL-10 were not affected, torilin suppressed CIA-induced serum TNF-α, IL-1β and IL-6 levels. Interestingly, torilin also blocked IFN-γ, IL-17 and IL-6 cytokines while it did not affect IL-10 but enhanced IL-4 in splenocytes. These results show that torilin attenuated arthritis severity, modified leukocyte activations in dLNs or joints, and restored serum and splenocyte cytokine imbalances. Torilin may have immunomodulatory and anti-inflammatory properties with the capacity to ameliorate the inflammatory response in CIA-mice.<br />
DOI: 10.1016/j.intimp.2013.04.012 PMID: 23623942 [Indexed for MEDLINE]<br />
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[3]. Tetrahedron. 1969 Oct;25(19):4751-65. doi: 10.1016/s0040-4020(01)83016-7.<br />
Structure of torilin.<br />
Chikamatsu H, Maeda M, Nakazaki M.<br />
DOI: 10.1016/s0040-4020(01)83016-7 PMID: 5356923 [Indexed for MEDLINE]<br />
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[4]. Int J Cancer. 2000 Jul 15;87(2):269-75.<br />
Anti-angiogenic activity of torilin, a sesquiterpene compound isolated from Torilis japonica.<br />
Kim MS(1), Lee YM, Moon EJ, Kim SE, Lee JJ, Kim KW.<br />
Author information: (1)Department of Molecular Biology, Pusan National University, Pusan, South Korea.<br />
Torilin is a sesquiterpene compound purified from fruits of Torilis japonica (Umbelliferae). In this study, we demonstrated the anti-angiogenic activity of torilin using in vivo and in vitro assay systems. Torilin decreased both neovascularization of chick embryos in the chorioallantoic membrane assay and basic fibroblast growth factor-induced vessel formation in the mouse Matrigel plug assay. Torilin also reduced the proliferation and tube formation of human umbilical vein endothelial cells. In addition, the concentrated conditioned media obtained from torilin-treated HepG2 human hepatoblastoma cells blocked the angiogenic activation of torilin-untreated concentrated conditioned media, indicating that torilin may have an inhibitory effect on tumor-induced angiogenesis. To determine what molecules were involved in the anti-angiogenic activity, we examined the expression of hypoxia-inducible angiogenic factors in torilin-treated HepG2 cells. Torilin significantly down-regulated the expression of hypoxia-inducible vascular endothelial growth factor and insulin-like growth factor-II. Taken together, our data suggest that torilin may be a strong angiogenic inhibitor with the ability to decrease tube formation of vascular endothelial cells and to reduce expression of angiogenic factors of tumor cells.<br />
PMID: 10861486 [Indexed for MEDLINE]<br />
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[5]. Planta Med. 2009 Nov;75(14):1505-8. doi: 10.1055/s-0029-1185803. Epub 2009 Jun 16.<br />
Torilin from Torilis japonica inhibits melanin production in alpha-melanocyte stimulating hormone-activated B16 melanoma cells.<br />
Yun CY(1), Kim D, Lee WH, Park YM, Lee SH, Na M, Jahng Y, Hwang BY, Lee MK, Han SB, Kim Y.<br />
Author information: (1)College of Pharmacy & Research Center for Bioresource and Health, Chungbuk National University, Cheongju, Korea.<br />
Epidermal melanocytes synthesize melanin pigments and transfer them to keratinocytes, which is responsible for skin pigmentation. However, abnormal accumulation of melanin pigments causes hyperpigmentation disorders, which are substantially improved with treatment of tyrosinase inhibitor. In our ongoing study, Torilis japonica DC. (Umbelliferae) was found to inhibit melanin production. A goal of this study is to elucidate the hypopigmenting principle of T. japonica. A sesquiterpene structure of torilin was isolated from the plant extracts via bioassay-guided phytochemical analysis. Torilin dose-dependently inhibited melanin production, with an IC(50) value of 25 microM, in alpha-melanocyte stimulating hormone (alpha-MSH)-activated B16 melanoma cells. Arbutin, a positive control of skin whitener, also inhibited alpha-MSH-induced melanin production with an IC(50) value of 170 microM. As to the mode of action, torilin downregulated alpha-MSH-induced protein levels of tyrosinase without directly inhibiting catalytic activity of the enzyme. Taken together, this study shows that torilin contributes to the hypopigmenting principle of T. japonica, and suggests its pharmacological potential in melanin-associated hyperpigmentation disorders.<br />
Georg Thieme Verlag KG Stuttgart, New York.<br />
DOI: 10.1055/s-0029-1185803 PMID: 19533579 [Indexed for MEDLINE]
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