QUOTE
1: Endocrinology. 2007 Sep 20; [Epub ahead of print] Links
Evodiamine improves diet-induced obesity in a UCP1-independent manner: Involvement of anti-adipogenic mechanism and ERK/MAPK signaling.
Wang T, Wang Y, Kontani Y, Kobayashi Y, Sato Y, Mori N, Yamashita H.
Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai 487-8501, Japan; Department of Surgery, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX75390, USA; Department of Food Science for Health, Minami-Kyushu University, Miyazaki 880-0032, Japan; Kitasato University, School of Pharmaceutical Sciences, Tokyo 108-8641, Japan; Department of Health Science, Faculty of Psychological and Physical Sciences, Aichi-Gakuin University, Nisshin 470-0195, Japan; Department of Anatomy and Neurobiology, Nagasaki University School of Medicine, Nagasaki 852-8523, Japan.
Evodiamine is an alkaloidal compound with anti-obesity effects that have been thought to be due to uncoupling protein-1 (UCP1) thermogenesis similar to the effects of capsaicin, but the underlying mechanisms are poorly understood. To clarify the mechanisms, we first examined whether the anti-obesity effect of evodiamine could be attributed to the involvement of UCP1. When UCP1-KO mice were fed a high fat diet with 0.03% evodiamine (w/w) for 2 months, the increases in body weight, adiposity, and the serum levels of leptin and insulin were reduced in a manner indistinguishable from control mice fed a high fat diet with evodiamine, suggesting that evodiamine triggered a UCP1-independent mechanism to prevent diet-induced obesity. By using preadipocyte cultures, we found that evodiamine, but not capsaicin, increased phosphorylation of extracellular signal-regulated kinase (ERK) / mitogen-activated protein kinases (MAPK), reduced the expression of transcription factors such as peroxisome proliferator-activated receptor gamma, and strongly inhibited adipocyte differentiation. Evodiamine treatment also reduced insulin-stimulated phosphorylation of Akt, a crucial regulator of adipocyte differentiation; and the reduction of phosphorylated-Akt and augmentation of phosphorylated-ERK were reversed by blockade of the MAPK kinase (MEK)/MAPK signaling pathway, restoring adipogenesis in the cultures. The changes in ERK and Akt phosphorylation levels were also observed in white adipose tissues of UCP1-KO mice fed the evodiamine diet. These findings suggest that evodiamine has a potential to prevent the development of diet-induced obesity in part by inhibiting adipocyte differentiation through ERK activation and its negative cross-talk with the insulin signaling pathway.
PMID: 17884939 [PubMed - as supplied by publisher]
Evodiamine improves diet-induced obesity in a UCP1-independent manner: Involvement of anti-adipogenic mechanism and ERK/MAPK signaling.
Wang T, Wang Y, Kontani Y, Kobayashi Y, Sato Y, Mori N, Yamashita H.
Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai 487-8501, Japan; Department of Surgery, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX75390, USA; Department of Food Science for Health, Minami-Kyushu University, Miyazaki 880-0032, Japan; Kitasato University, School of Pharmaceutical Sciences, Tokyo 108-8641, Japan; Department of Health Science, Faculty of Psychological and Physical Sciences, Aichi-Gakuin University, Nisshin 470-0195, Japan; Department of Anatomy and Neurobiology, Nagasaki University School of Medicine, Nagasaki 852-8523, Japan.
Evodiamine is an alkaloidal compound with anti-obesity effects that have been thought to be due to uncoupling protein-1 (UCP1) thermogenesis similar to the effects of capsaicin, but the underlying mechanisms are poorly understood. To clarify the mechanisms, we first examined whether the anti-obesity effect of evodiamine could be attributed to the involvement of UCP1. When UCP1-KO mice were fed a high fat diet with 0.03% evodiamine (w/w) for 2 months, the increases in body weight, adiposity, and the serum levels of leptin and insulin were reduced in a manner indistinguishable from control mice fed a high fat diet with evodiamine, suggesting that evodiamine triggered a UCP1-independent mechanism to prevent diet-induced obesity. By using preadipocyte cultures, we found that evodiamine, but not capsaicin, increased phosphorylation of extracellular signal-regulated kinase (ERK) / mitogen-activated protein kinases (MAPK), reduced the expression of transcription factors such as peroxisome proliferator-activated receptor gamma, and strongly inhibited adipocyte differentiation. Evodiamine treatment also reduced insulin-stimulated phosphorylation of Akt, a crucial regulator of adipocyte differentiation; and the reduction of phosphorylated-Akt and augmentation of phosphorylated-ERK were reversed by blockade of the MAPK kinase (MEK)/MAPK signaling pathway, restoring adipogenesis in the cultures. The changes in ERK and Akt phosphorylation levels were also observed in white adipose tissues of UCP1-KO mice fed the evodiamine diet. These findings suggest that evodiamine has a potential to prevent the development of diet-induced obesity in part by inhibiting adipocyte differentiation through ERK activation and its negative cross-talk with the insulin signaling pathway.
PMID: 17884939 [PubMed - as supplied by publisher]
QUOTE
1: Arch Pharm Res. 2006 Apr;29(4):293-7.
Related Articles, Links
Anti-inflammatory principles from the fruits of Evodia rutaecarpa and their cellular action mechanisms.
Choi YH, Shin EM, Kim YS, Cai XF, Lee JJ, Kim HP.
College of Pharmacy, Kangwon National University, Chunchon, Korea.
The fruits of Evodia rutaecarpa Benth (Rutaceae) has long been used for inflammatory disorders and some anti-inflammatory actions of its constituents such as dehydroevodiamine, evodiamine and rutaecarpine were previously reported. Since the pharmacological data is not sufficient to clearly establish the scientific rationale of anti-inflammatory medicinal use of this plant material and the search for its active principles is limited so far, three major constituents (evodiamine, rutaecarpine, goshuyuamide II) were evaluated for their anti-inflammatory cellular action mechanisms in the present study. From the results, evodiamine and rutaecarpine were found to strongly inhibit prostaglandin E2 synthesis from lipopolysaccharide-treated RAW 264.7 cells at 1-10 microM. Evodiamine inhibited cyclooxygenase-2 induction and NF-kappaB activation, while rutaecarpine did not. On the other hand, goshuyuamide II inhibited 5-lipoxygenase from RBL-1 cells (IC50 = 6.6 microM), resulting in the reduced synthesis of leukotrienes. However, these three compounds were not inhibitory against inducible nitric oxide synthase-mediated nitric oxide production from RAW cells up to 50 micorM. These pharmacological properties may provide the additional scientific rationale for anti-inflammatory use of the fruits of E. rutaecarpa.
Publication Types:
* Comparative Study
* Research Support, Non-U.S. Gov't
PMID: 16681034 [PubMed - indexed for MEDLINE]
Related Articles, Links
Anti-inflammatory principles from the fruits of Evodia rutaecarpa and their cellular action mechanisms.
Choi YH, Shin EM, Kim YS, Cai XF, Lee JJ, Kim HP.
College of Pharmacy, Kangwon National University, Chunchon, Korea.
The fruits of Evodia rutaecarpa Benth (Rutaceae) has long been used for inflammatory disorders and some anti-inflammatory actions of its constituents such as dehydroevodiamine, evodiamine and rutaecarpine were previously reported. Since the pharmacological data is not sufficient to clearly establish the scientific rationale of anti-inflammatory medicinal use of this plant material and the search for its active principles is limited so far, three major constituents (evodiamine, rutaecarpine, goshuyuamide II) were evaluated for their anti-inflammatory cellular action mechanisms in the present study. From the results, evodiamine and rutaecarpine were found to strongly inhibit prostaglandin E2 synthesis from lipopolysaccharide-treated RAW 264.7 cells at 1-10 microM. Evodiamine inhibited cyclooxygenase-2 induction and NF-kappaB activation, while rutaecarpine did not. On the other hand, goshuyuamide II inhibited 5-lipoxygenase from RBL-1 cells (IC50 = 6.6 microM), resulting in the reduced synthesis of leukotrienes. However, these three compounds were not inhibitory against inducible nitric oxide synthase-mediated nitric oxide production from RAW cells up to 50 micorM. These pharmacological properties may provide the additional scientific rationale for anti-inflammatory use of the fruits of E. rutaecarpa.
Publication Types:
* Comparative Study
* Research Support, Non-U.S. Gov't
PMID: 16681034 [PubMed - indexed for MEDLINE]
QUOTE
1: Biol Pharm Bull. 2007 Jan;30(1):197-9.
Related Articles, Links
In vitro and in vivo antiallergic effect of the fructus of Evodia rutaecarpa and its constituents.
Shin YW, Bae EA, Cai XF, Lee JJ, Kim DH.
College of Pharmacy, Kyung Hee University, Seoul, Korea.
The unripe fruit of Evodia rutaecarpa (JUSS) BENTH (ER, Family Rutaceae) has been used frequently as a traditional medicine against inflammatory diseases in Korea, China and Japan. To evaluate antiallergic effect of ER, we isolated its main constituents, evodiamine and rutaecarpine, and evaluated in vivo their inhibitory effects against passive cutaneous anaphylaxis (PCA) reaction induced by IgE-antigen complex and scratching behaviors by compound 48/80. ER and its constituents, evodiamine and rutaecarpine, potently inhibited PCA reaction and scratching behaviors in mice, although ER weakly inhibited scratching behaviors. Evodiamine and rutaecarpine inhibited TNF-alpha and IL-4 protein expression in RBL-2H3 cells induced by IgE-antigen complex, although these did not inhibit degranulation of RBL-2H3 cells induced by IgE-antigen complex and rat peritoneal mast cells induced by compound 48/80. These findings suggest that ER and its constituents, evodiamine and rutaecarpine, may be effective for IgE-induced allergic diseases such as atopic dermatitis and rhinitis.
Publication Types:
* Research Support, Non-U.S. Gov't
PMID: 17202687 [PubMed - indexed for MEDLINE]
Related Articles, Links
In vitro and in vivo antiallergic effect of the fructus of Evodia rutaecarpa and its constituents.
Shin YW, Bae EA, Cai XF, Lee JJ, Kim DH.
College of Pharmacy, Kyung Hee University, Seoul, Korea.
The unripe fruit of Evodia rutaecarpa (JUSS) BENTH (ER, Family Rutaceae) has been used frequently as a traditional medicine against inflammatory diseases in Korea, China and Japan. To evaluate antiallergic effect of ER, we isolated its main constituents, evodiamine and rutaecarpine, and evaluated in vivo their inhibitory effects against passive cutaneous anaphylaxis (PCA) reaction induced by IgE-antigen complex and scratching behaviors by compound 48/80. ER and its constituents, evodiamine and rutaecarpine, potently inhibited PCA reaction and scratching behaviors in mice, although ER weakly inhibited scratching behaviors. Evodiamine and rutaecarpine inhibited TNF-alpha and IL-4 protein expression in RBL-2H3 cells induced by IgE-antigen complex, although these did not inhibit degranulation of RBL-2H3 cells induced by IgE-antigen complex and rat peritoneal mast cells induced by compound 48/80. These findings suggest that ER and its constituents, evodiamine and rutaecarpine, may be effective for IgE-induced allergic diseases such as atopic dermatitis and rhinitis.
Publication Types:
* Research Support, Non-U.S. Gov't
PMID: 17202687 [PubMed - indexed for MEDLINE]