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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

Glucose intolerance and insulin resistance (IR) were attenuated by BTS. a Fasting plasma glucose, insulin levels and QUICKI: increased level of fasted plasma insulin and glucose were decreased, and QUICKI increased by treatment with 5 %BTS, and ITT confirmed severe IR doubleasteriskp < 0.01, tripleasteriskp < 0.001 vs GTG + HF, doubleplus symbolp < 0.01 vs 2 %BTS, n = 6. b Glucose tolerance test (GTT) and insulin tolerance test (ITT): GTT revealed severe glucose intolerance was attenuated, and ITT confirmed IR was attenuated by 5 %BTS. Asteriskp < 0.05 vs GTG + HF, n = 6. c Involvement of Akt in BTS reduction of IR: phosphorylation of Akt was involved in the reduction of IR by BTS treatment as reflected by increased phosphorylation of Akt in the livers of BTS treated mice upon insulin administration. Asteriskp < 0.05, doubleasteriskp < 0.01 vs GTG + HF, n = 4
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Fig5: Glucose intolerance and insulin resistance (IR) were attenuated by BTS. a Fasting plasma glucose, insulin levels and QUICKI: increased level of fasted plasma insulin and glucose were decreased, and QUICKI increased by treatment with 5 %BTS, and ITT confirmed severe IR doubleasteriskp < 0.01, tripleasteriskp < 0.001 vs GTG + HF, doubleplus symbolp < 0.01 vs 2 %BTS, n = 6. b Glucose tolerance test (GTT) and insulin tolerance test (ITT): GTT revealed severe glucose intolerance was attenuated, and ITT confirmed IR was attenuated by 5 %BTS. Asteriskp < 0.05 vs GTG + HF, n = 6. c Involvement of Akt in BTS reduction of IR: phosphorylation of Akt was involved in the reduction of IR by BTS treatment as reflected by increased phosphorylation of Akt in the livers of BTS treated mice upon insulin administration. Asteriskp < 0.05, doubleasteriskp < 0.01 vs GTG + HF, n = 4

Mentions: Since IR is regarded as a central pathogenic feature of NAFLD [25], we now investigated the effect of BTS treatment on IR. Fasting plasma glucose and insulin levels were markedly reduced in a dose dependent manner by BTS treatment, and QUICKI as an index of IR was also increased by BTS (Fig. 5a). We next evaluated the attenuation of glucose intolerance and IR using the GTT and the ITT in the presence of BTS. GTT revealed that treatment with BTS remarkably attenuated severe glucose intolerance induced by GTG + HF, and ITT showed that treatment with BTS attenuated IR induced by GTG + HF (Fig. 5b). The reduction of IR by BTS involved its promotion of the phosphorylation of Akt (Fig. 5c) an important factor in glucose metabolism [26].Fig. 5


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)

Glucose intolerance and insulin resistance (IR) were attenuated by BTS. a Fasting plasma glucose, insulin levels and QUICKI: increased level of fasted plasma insulin and glucose were decreased, and QUICKI increased by treatment with 5 %BTS, and ITT confirmed severe IR doubleasteriskp < 0.01, tripleasteriskp < 0.001 vs GTG + HF, doubleplus symbolp < 0.01 vs 2 %BTS, n = 6. b Glucose tolerance test (GTT) and insulin tolerance test (ITT): GTT revealed severe glucose intolerance was attenuated, and ITT confirmed IR was attenuated by 5 %BTS. Asteriskp < 0.05 vs GTG + HF, n = 6. c Involvement of Akt in BTS reduction of IR: phosphorylation of Akt was involved in the reduction of IR by BTS treatment as reflected by increased phosphorylation of Akt in the livers of BTS treated mice upon insulin administration. Asteriskp < 0.05, doubleasteriskp < 0.01 vs GTG + HF, n = 4
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4048468&req=5

Fig5: Glucose intolerance and insulin resistance (IR) were attenuated by BTS. a Fasting plasma glucose, insulin levels and QUICKI: increased level of fasted plasma insulin and glucose were decreased, and QUICKI increased by treatment with 5 %BTS, and ITT confirmed severe IR doubleasteriskp < 0.01, tripleasteriskp < 0.001 vs GTG + HF, doubleplus symbolp < 0.01 vs 2 %BTS, n = 6. b Glucose tolerance test (GTT) and insulin tolerance test (ITT): GTT revealed severe glucose intolerance was attenuated, and ITT confirmed IR was attenuated by 5 %BTS. Asteriskp < 0.05 vs GTG + HF, n = 6. c Involvement of Akt in BTS reduction of IR: phosphorylation of Akt was involved in the reduction of IR by BTS treatment as reflected by increased phosphorylation of Akt in the livers of BTS treated mice upon insulin administration. Asteriskp < 0.05, doubleasteriskp < 0.01 vs GTG + HF, n = 4
Mentions: Since IR is regarded as a central pathogenic feature of NAFLD [25], we now investigated the effect of BTS treatment on IR. Fasting plasma glucose and insulin levels were markedly reduced in a dose dependent manner by BTS treatment, and QUICKI as an index of IR was also increased by BTS (Fig. 5a). We next evaluated the attenuation of glucose intolerance and IR using the GTT and the ITT in the presence of BTS. GTT revealed that treatment with BTS remarkably attenuated severe glucose intolerance induced by GTG + HF, and ITT showed that treatment with BTS attenuated IR induced by GTG + HF (Fig. 5b). The reduction of IR by BTS involved its promotion of the phosphorylation of Akt (Fig. 5c) an important factor in glucose metabolism [26].Fig. 5

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