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Bofutsushosan, a Japanese herbal (Kampo) medicine, attenuates progression of nonalcoholic steatohepatitis in mice.

Ono M, Ogasawara M, Hirose A, Mogami S, Ootake N, Aritake K, Higuchi T, Okamoto N, Sakamoto S, Yamamoto M, Urade Y, Saibara T, Oben JA - J. Gastroenterol. (2013)

Bottom Line: The effectiveness of BTS in attenuating features of NASH and the mechanisms through which BTS attenuated NASH were then assayed through an assessment of the anthropometric, radiological, biochemical and histological parameters.BTS attenuated the progression of NASH through induction of adiponectin and its receptors along with an induction of PPAR-α and PPAR-γ, decreased expression of SREBP-1c, increased hepatic fatty acid oxidation and increased hepatic export of triglycerides.BTS moreover, reduced IR through phosphorylation of the protein kinase, Akt.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology and Hepatology, Kochi Medical School, Kohasu, Nankoku, Kochi, 783-8505, Japan, onom@kochi-u.ac.jp.

ABSTRACT

Background: Obesity-induced liver disease (nonalcoholic fatty liver disease, NAFLD) is now the commonest cause of chronic liver disease in affluent nations. There are presently no proven treatments for NAFLD or its more severe stage, nonalcoholic steatohepatitis (NASH). Bofutsushosan (BTS), a Japanese herbal (Kampo) medicine, long used as an anti-obesity medicine in Japan and other Asian countries, has been shown to reduce body weight and improve insulin resistance (IR) and hepatic steatosis. The precise mechanism of action of BTS, however, remains unclear. To evaluate the ability of BTS to prevent the development of NASH, and determine the mediators and pathways involved.

Methods: C57BL/6 mice were injected intra-peritoneally with gold-thioglucose and fed a high-fat diet (HF) or HF diet admixed with either 2 or 5 % BTS for 12 weeks. The effectiveness of BTS in attenuating features of NASH and the mechanisms through which BTS attenuated NASH were then assayed through an assessment of the anthropometric, radiological, biochemical and histological parameters.

Results: BTS attenuated the progression of NASH through induction of adiponectin and its receptors along with an induction of PPAR-α and PPAR-γ, decreased expression of SREBP-1c, increased hepatic fatty acid oxidation and increased hepatic export of triglycerides. BTS moreover, reduced IR through phosphorylation of the protein kinase, Akt.

Conclusions: BTS through induction of adiponectin signaling and Akt attenuated development of NASH. Identification of the active entity in BTS should allow development of novel treatments for NASH.

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Related in: MedlinePlus

BTS treatment reduces hepatic inflammation and oxidative stress. a The extent of hepatic inflammation was markedly attenuated with BTS: hepatocyte ballooning and Mallory–Denk bodies in the livers of GTG + HF fed mice were absent in BTS treatment livers. Filled arrow ballooning hepatocyte, arrow Mallory–Denk body. b Oxidative stress and TNF-α expression: BTS reduced hepatic oxidative stress as shown by reduction of numbers of nuclei stained positive for 8-OHdG in GTG + HF mice. BTS similarly reduced hepatic TNF-α mRNA expression. Triple asteriskp < 0.001, asteriskp < 0.01 vs GTG + HF, Triple plus symbol p < 0.001 vs 2 %BTS, n = 6
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Fig3: BTS treatment reduces hepatic inflammation and oxidative stress. a The extent of hepatic inflammation was markedly attenuated with BTS: hepatocyte ballooning and Mallory–Denk bodies in the livers of GTG + HF fed mice were absent in BTS treatment livers. Filled arrow ballooning hepatocyte, arrow Mallory–Denk body. b Oxidative stress and TNF-α expression: BTS reduced hepatic oxidative stress as shown by reduction of numbers of nuclei stained positive for 8-OHdG in GTG + HF mice. BTS similarly reduced hepatic TNF-α mRNA expression. Triple asteriskp < 0.001, asteriskp < 0.01 vs GTG + HF, Triple plus symbol p < 0.001 vs 2 %BTS, n = 6

Mentions: Mice administered GTG and then fed a HF diet (GTG + HF), had a comprehensive histological and dysmetabolic phenotype resembling human NASH as reported recently [9]. To then evaluate the effectiveness of BTS in the GTG + HF model, we studied the anthropometric, radiological, biochemical and histological parameters as detailed above in the presence or absence of BTS 2 or 5 % admixed with the HF component of the GTG + HF. Administration of BTS attenuated weight gain in a dose dependent manner (Fig. 1a). Unexpectedly, GTG + HF induced increase in the volume of the visceral and subcutaneous fat were not markedly attenuated by treatment with BTS (Fig. 1b). However, hepatic steatosis on H&E or Oil Red-O staining in 12 weeks was attenuated in a dose dependent manner by BTS treatment (Figs. 2a, 3a). Additionally, BTS treatment also attenuated GTG + HF induced hepatomegaly in a dose-dependent manner (Fig. 2b).Fig. 1


Bofutsushosan, a Japanese herbal (Kampo) medicine, attenuates progression of nonalcoholic steatohepatitis in mice.

Ono M, Ogasawara M, Hirose A, Mogami S, Ootake N, Aritake K, Higuchi T, Okamoto N, Sakamoto S, Yamamoto M, Urade Y, Saibara T, Oben JA - J. Gastroenterol. (2013)

BTS treatment reduces hepatic inflammation and oxidative stress. a The extent of hepatic inflammation was markedly attenuated with BTS: hepatocyte ballooning and Mallory–Denk bodies in the livers of GTG + HF fed mice were absent in BTS treatment livers. Filled arrow ballooning hepatocyte, arrow Mallory–Denk body. b Oxidative stress and TNF-α expression: BTS reduced hepatic oxidative stress as shown by reduction of numbers of nuclei stained positive for 8-OHdG in GTG + HF mice. BTS similarly reduced hepatic TNF-α mRNA expression. Triple asteriskp < 0.001, asteriskp < 0.01 vs GTG + HF, Triple plus symbol p < 0.001 vs 2 %BTS, n = 6
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4048468&req=5

Fig3: BTS treatment reduces hepatic inflammation and oxidative stress. a The extent of hepatic inflammation was markedly attenuated with BTS: hepatocyte ballooning and Mallory–Denk bodies in the livers of GTG + HF fed mice were absent in BTS treatment livers. Filled arrow ballooning hepatocyte, arrow Mallory–Denk body. b Oxidative stress and TNF-α expression: BTS reduced hepatic oxidative stress as shown by reduction of numbers of nuclei stained positive for 8-OHdG in GTG + HF mice. BTS similarly reduced hepatic TNF-α mRNA expression. Triple asteriskp < 0.001, asteriskp < 0.01 vs GTG + HF, Triple plus symbol p < 0.001 vs 2 %BTS, n = 6
Mentions: Mice administered GTG and then fed a HF diet (GTG + HF), had a comprehensive histological and dysmetabolic phenotype resembling human NASH as reported recently [9]. To then evaluate the effectiveness of BTS in the GTG + HF model, we studied the anthropometric, radiological, biochemical and histological parameters as detailed above in the presence or absence of BTS 2 or 5 % admixed with the HF component of the GTG + HF. Administration of BTS attenuated weight gain in a dose dependent manner (Fig. 1a). Unexpectedly, GTG + HF induced increase in the volume of the visceral and subcutaneous fat were not markedly attenuated by treatment with BTS (Fig. 1b). However, hepatic steatosis on H&E or Oil Red-O staining in 12 weeks was attenuated in a dose dependent manner by BTS treatment (Figs. 2a, 3a). Additionally, BTS treatment also attenuated GTG + HF induced hepatomegaly in a dose-dependent manner (Fig. 2b).Fig. 1

Bottom Line: The effectiveness of BTS in attenuating features of NASH and the mechanisms through which BTS attenuated NASH were then assayed through an assessment of the anthropometric, radiological, biochemical and histological parameters.BTS attenuated the progression of NASH through induction of adiponectin and its receptors along with an induction of PPAR-α and PPAR-γ, decreased expression of SREBP-1c, increased hepatic fatty acid oxidation and increased hepatic export of triglycerides.BTS moreover, reduced IR through phosphorylation of the protein kinase, Akt.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology and Hepatology, Kochi Medical School, Kohasu, Nankoku, Kochi, 783-8505, Japan, onom@kochi-u.ac.jp.

ABSTRACT

Background: Obesity-induced liver disease (nonalcoholic fatty liver disease, NAFLD) is now the commonest cause of chronic liver disease in affluent nations. There are presently no proven treatments for NAFLD or its more severe stage, nonalcoholic steatohepatitis (NASH). Bofutsushosan (BTS), a Japanese herbal (Kampo) medicine, long used as an anti-obesity medicine in Japan and other Asian countries, has been shown to reduce body weight and improve insulin resistance (IR) and hepatic steatosis. The precise mechanism of action of BTS, however, remains unclear. To evaluate the ability of BTS to prevent the development of NASH, and determine the mediators and pathways involved.

Methods: C57BL/6 mice were injected intra-peritoneally with gold-thioglucose and fed a high-fat diet (HF) or HF diet admixed with either 2 or 5 % BTS for 12 weeks. The effectiveness of BTS in attenuating features of NASH and the mechanisms through which BTS attenuated NASH were then assayed through an assessment of the anthropometric, radiological, biochemical and histological parameters.

Results: BTS attenuated the progression of NASH through induction of adiponectin and its receptors along with an induction of PPAR-α and PPAR-γ, decreased expression of SREBP-1c, increased hepatic fatty acid oxidation and increased hepatic export of triglycerides. BTS moreover, reduced IR through phosphorylation of the protein kinase, Akt.

Conclusions: BTS through induction of adiponectin signaling and Akt attenuated development of NASH. Identification of the active entity in BTS should allow development of novel treatments for NASH.

Show MeSH
Related in: MedlinePlus