Preventive Effects of Bofutsushosan on Obesity and Various Metabolic Disorders

Shimada, Tsutomu; Kudo, Toshiyuki; Akase, Tomoko; Aburada, Masaki

doi:10.1248/bpb.31.1362

Cited by 51 publications

(47 citation statements)

References 19 publications

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“…Thus far, it has been reported that blood TG levels in TSOD mice are greater than those in TSNO mice. 29,33 These data suggest that the hepatic dysfunction observed early in time is associated with the development of fatty liver disease in TSOD mice. In the visceral fat, enlargement of adipocytes, perivascular and pericapsular CD8-positive lymphoid aggregations, and CLSs with macrophage aggregation were observed after 4 months of age.…”

Section: Discussionmentioning

confidence: 76%

Spontaneous onset of nonalcoholic steatohepatitis and hepatocellular carcinoma in a mouse model of metabolic syndrome

Nishida

Tsuneyama

Fujimoto

et al. 2013

Laboratory Investigation

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Metabolic syndrome is a worldwide healthcare issue and a dominant risk factor for the development of incurable diseases that affect the entire body. The hepatic manifestations of this syndrome include nonalcoholic fatty liver disease (NAFLD) and its progressive variant nonalcoholic steatohepatitis (NASH). The basic pathogenesis of NAFLD/NASH remains controversial because it is difficult to clarify the disease process of NASH on the basis of metabolic syndrome alone. To determine the pathogenesis and effective treatment, an excellent animal model of NASH is required. Tsumura Suzuki obese diabetes (TSOD) male mice spontaneously develop diabetes mellitus, obesity, glucosuria, hyperglycemia, and hyperinsulinemia without any special treatments such as gene manipulation. In this study, we examined the histopathological characteristics of visceral fat and liver of 56 male TSOD mice aged 4-17 months and 9 male Tsumura Suzuki non-obesity (control) mice aged 6-12 months. In the visceral fat, enlargement of adipocytes and perivascular and pericapsular CD8-positive lymphoid aggregation were observed in 4-month-old mice. Abnormal expression of tumor necrosis factor-a, interleukin-6, and lipid peroxidation endo products was observed in macrophages. In the liver, microvesicular steatosis, hepatocellular ballooning, and Mallory bodies were observed in 4-month-old mice, with severity worsening with increasing time. These pathological findings in the liver mimic those seen in patients with NASH. Interestingly, small liver nodules with high cellularity and absence of portal tracts were frequently observed after 12 months. Most of them showed nuclear and structural atypia, and mimicked human hepatocellular carcinoma. The degree of steatosis in the non-tumor portions of the liver improved when the liver nodules developed. These findings were not observed in control mice. Here, we report that TSOD male mice spontaneously developed NAFLD without any special treatment, and that these mice are a valuable model for assessing NASH and NASH carcinogenesis owing to metabolic syndrome.

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Section: Discussionmentioning

confidence: 76%

Spontaneous onset of nonalcoholic steatohepatitis and hepatocellular carcinoma in a mouse model of metabolic syndrome

Nishida

Tsuneyama

Fujimoto

et al. 2013

Laboratory Investigation

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“…CT-based analysis of body composition was performed after 12 wk of Aloe vera gel treatment (at 23 wk of age). The rats were anesthetized with isoflurane (Dainippon Sumitomo Pharma, Osaka, Japan) and scanned from xiphisternum to sacrum at 2 mm intervals using LaTheta (LCT-100A), an experimental X-ray CT instrument (Aloka Co., Ltd., Tokyo) ( 19 ). The estimated amounts of visceral and subcutaneous fat tissues, and percentage of body fat were calculated using LaTheta software.…”

Section: Methodsmentioning

confidence: 99%

Administration of Dried Aloe vera Gel Powder Reduced Body Fat Mass in Diet-Induced Obesity (DIO) Rats

Misawa

Tanaka

Nabeshima

et al. 2012

J Nutr Sci Vitaminol

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SummaryThe aim of the present study was to investigate the anti-obesity effects of Aloe vera gel administration in male Sprague-Dawley (SD) rats with diet-induced obesity (DIO). SD rats at 7 wk of age were fed either a standard diet (10 kcal% fat) (StdD) or high-fat (60 kcal% fat) diet (HFD) during the experimental period. Four weeks after of HFD-feeding, DIO rats (11 wk of age) were orally administered with two doses of Aloe vera gel powder (20 and 200 mg/kg/d) for 90 d. Body weights (g) and body fat (%) of HFD fed rats were significantly higher than those of StdD-fed rats. Although a modest decrease of body weight (g) was observed with the administration of dried Aloe vera gel powder, both subcutaneous and visceral fat weight (g) and body fat (%) were reduced significantly in Aloe vera gel-treated rats. Serum lipid parameters elevated by HFD were also improved by the Aloe vera gel treatment. The oxygen consumption (VO 2 ), an index of energy expenditure, was decreased in HFD-fed rats compared with that in StdD-fed rats. Administration of Aloe vera gel reversed the change in VO 2 in the HFD-fed rats. These results suggest that intake of Aloe vera gel reduced body fat accumulation, in part, by stimulation of energy expenditure. Aloe vera gel might be beneficial for the prevention and improvement of diet-induced obesity.

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“…23,24) Geniposide showed preventative effects on various metabolic disease symptoms in the TSOD mice. The body weight increase seen in the TSOD mice was significantly suppressed by geniposide from the 5th week after starting the treatment.…”

Section: Discussionmentioning

confidence: 95%

Preventive Effect of Geniposide on Metabolic Disease Status in Spontaneously Obese Type 2 Diabetic Mice and Free Fatty Acid-Treated HepG2 Cells

Kojima

Shimada

Nagareda

et al. 2011

Biological & Pharmaceutical Bulletin

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Obesity, diabetes, hyperlipidemia and hypertension, which are caused by hypernutrition and lack of exercise, are often found in the same person. These symptoms used to be called "the deadly quartet," "Syndrome X" or "insulin resistance syndrome," but these names have recently been collectively replaced with "metabolic syndrome (MS)," since the presence of visceral fat accumulation-type obesity has been recognized as the major disease base. It should be noted that progression of MS increases the risk of future onset of ischemic cardiac diseases and cerebrovascular diseases, and the importance of "prevention" and "early therapy" of MS is emphasized.Gardeniae fructus, the fruit of Gardenia jasminoides ELLIS, is widely used in Asian countries as a natural colorant, and it is also used as a Japanese and Chinese traditional medicine since it has a homeostatic effect, an antiphlogistic effect, an analgesic effect, an antipyretic effect, a hepatoprotective effect and a hypolipidaemic effect.1,2) Geniposide, an iridoid glycoside contained in Gardeniae fructus, is reported to have a hepatoprotective effect, an antioxidant effect, a hypoglycemic effect, a vascular endothelial cell adhesion-suppressing effect, an anti-lipopolysaccharide (LPS) effect, a neuroprotective effect, and an anti-inflammatory effect. [3][4][5][6][7][8][9] In addition, genipin, which is the aglycone portion of geniposide and is formed as a metabolite, is also reported to have an anti-inflammatory effect, a bile secretion-enhancing effect, and an anti-thrombotic effect. [10][11][12] Geniposide is promising as a seed compound for developing therapeutic medicines for metabolic diseases. However, no publication has reported the effect of geniposide on various metabolic disease symptoms based on visceral fat accumulation. TSOD mice are model animals showing spontaneously multifactorial genetic Type 2 diabetes based on visceral fat accumulation. [13][14][15][16][17][18] Since the cause of onset and the symptoms are very similar to those of human MS, this model is regarded as promising for the study of MS. In the present study, we investigated the effect of geniposide on various metabolic disease symptoms based on visceral fat accumulation using TSOD mice. In addition, a fatty liver model was prepared by adding a free fatty acid to human liver cancer cells (HepG2 cells), 19) and the direct effect of genipin on the liver was investigated. MATERIALS AND METHODSReagents Geniposide and genipin (Fig. 1) were supplied by Tsumura and Co. (Ibaraki, Japan). Palmitic acid powder was purchased from Sigma-Aldrich (MO, U.S.A.). The other reagents used were of the highest grade available.Animal Experiments Experimental Animals: Male TSOD mice and corresponding control animals (TSNO mice) were purchased from the Institute for Animal Reproduction (Ibaraki) at the age of 3 weeks. They were acclimated under controlled circumstances (temperature: 23Ϯ1°C, humidity: 55Ϯ5%, lighting hours: 12 h) for one week. During the acclimation period, the animals were given ordinary powder ...

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Preventive Effects of Bofutsushosan on Obesity and Various Metabolic Disorders

Cited by 51 publications

References 19 publications

Spontaneous onset of nonalcoholic steatohepatitis and hepatocellular carcinoma in a mouse model of metabolic syndrome

Spontaneous onset of nonalcoholic steatohepatitis and hepatocellular carcinoma in a mouse model of metabolic syndrome

Administration of Dried Aloe vera Gel Powder Reduced Body Fat Mass in Diet-Induced Obesity (DIO) Rats

Preventive Effect of Geniposide on Metabolic Disease Status in Spontaneously Obese Type 2 Diabetic Mice and Free Fatty Acid-Treated HepG2 Cells

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