Placental extract ameliorates non-alcoholic steatohepatitis (NASH) by exerting protective effects on endothelial cells

Yamauchi, Akira; Kamiyoshi, Akiko; Koyama, Teruhide; Iinuma, Nobuyoshi; Yamaguchi, Shumpei; Miyazaki, Hiroyuki; Hirano, Eiichi; Kaku, Taiichi; Shindo, Takayuki

doi:10.1016/j.heliyon.2017.e00416

Cited by 26 publications

(32 citation statements)

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“…In an earlier study, we generated a NASH model by feeding a methionine-and choline-deficient (MCD) diet with high-salt loading (8% NaCl in the drinking water) to mice deficient in the vasoprotective molecule RAMP2 for 5 weeks (36). In this model, fibrosis was observed in regions adjacent to the sinusoids in control mice but the fibrosis was less pronounced in hPE-treated mice.…”

Section: Methodsmentioning

confidence: 99%

“…6A). Regarding the molecular weight distributions of these In an earlier study, to accelerate the damage of sinusoidal endothelial cells, we modified the MCD model by combining it with high-salt loading and used mice deficient in Receptor activity modifying protein 2 (RAMP2), a molecule involved in mediating endothelial viability (36). Using that model, we showed that hPE treatment ameliorated NASH pathology by preventing the damage of sinusoidal endothelial cells.…”

Section: Effect Of Hpe Fractions On Suppressing Hepatic Stellate Ri-tmentioning

confidence: 99%

“…Among the several candidates for the second hit, we have focused on sinusoidal endothelial cells (2,12). We have used the MCD diet-induced liver injury model for NASH (36) because we found that fibrosis starts from the region adjacent to the sinusoids in that model. Our MCD diet is high in sucrose and fat (40% sucrose, 10% fat), and is deficient in methionine and choline, which are essential for hepatic β oxidation and production of very low-density lipoprotein (VLDL).…”

Section: Effect Of Hpe Fractions On Suppressing Hepatic Stellate Ri-tmentioning

confidence: 99%

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Placental extract ameliorates liver fibrosis in a methionine- and choline-deficient diet-induced mouse model of non-alcoholic steatohepatitis

et al. 2020

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Non-alcoholic steatohepatitis (NASH) is a severe form of fatty liver disease that is defined by the presence of inflammation and fibrosis, which ultimately leads to cirrhosis and hepatocellular carcinoma. We previously showed that human placental extract (hPE) was intramuscularly injected to ameliorates liver injury in a methionine-and choline-deficient (MCD) diet-induced NASH model. In the present study, we investigated the effects of hPE using dB/dB mice which exhibit obesity and insulin resistance and are thought to reproduce the pathological background of NASH. The MCD-diet induced liver atrophy accompanied by fibrosis around the liver sinusoids. hPE dosedependently reduced the perivascular fibrosis. Moreover, αSMA-positive activated hepatic stellate cells increased in number in mice on the MCD diet, with this effect reversed by hPE treatment. hPE significantly decreased expression of Acta2, Col1a1, and Tgfb1 genes in hepatic stellate cells, and inhibited Smad phosphorylation. Moreover, hPE treatment increased the expression of the antioxidative genes Hmox1, Nqo1, Cat, and Sod1, and significantly enhanced nuclear factor erythroid 2-related factor 2 activity. Furthermore, hPE decreased the expression of Nox4 and attenuated the levels of intracellular reactive oxygen species. These results, along with our previous study, suggest that hPE effectively ameliorates liver fibrosis in NASH. This beneficial effect may, in part, be due to suppression of hepatic stellate cell activation.

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Section: Methodsmentioning

confidence: 99%

Section: Effect Of Hpe Fractions On Suppressing Hepatic Stellate Ri-tmentioning

confidence: 99%

Section: Effect Of Hpe Fractions On Suppressing Hepatic Stellate Ri-tmentioning

confidence: 99%

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Placental extract ameliorates liver fibrosis in a methionine- and choline-deficient diet-induced mouse model of non-alcoholic steatohepatitis

et al. 2020

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“…Placental extract can be simply obtained by hydrolysis of the placenta via both hydrochloric acid and enzymatic digestion, and it has been reported to have many biological activities in vitro and in vivo (Bak et al, 2018(Bak et al, , 2019Ito, Yamada, Matsumoto, & Imamura, 2018;Yamauchi et al, 2017;Yoshimoto et al, 2018). There are now several placental extract products available, and these have been used as drugs or in health care.…”

Section: Introductionmentioning

confidence: 99%

Porcine placental extract facilitates memory and learning in aged mice

Yamauchi

Tone

Sugimoto

et al. 2019

Food Science & Nutrition

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Aging induces a decline in both memory and learning ability without predisposing an individual to diseases of the central nervous system, such as dementia. This decline can have a variety of adverse effects on daily life, and it can also gradually affect the individual and the people they are surrounded by. Since recent evidence indicated that placental extract has effects on brain function such as memory, we hypothesized that placental extract could ameliorate the age‐associated reduction in cognitive function in aging. Here, we investigated the effect of new modified porcine placental extract (SD‐F) on memory ability in aged mice at both the behavioral and molecular levels. Our results revealed that SD‐F significantly enhanced memory ability in the object recognition and object location tasks in a dose‐dependent manner in aged mice relative to controls. The numbers of Nissl‐positive cells in the hippocampal cornu ammonis 3 (CA3) and dentate gyrus (DG) regions were increased in SD‐F‐treated aged mice relative to controls. RNA‐seq analysis of the hippocampus of aged mice identified 542 differentially expressed genes, of which 216 were up‐regulated and 326 were down‐regulated in SD‐F‐treated mice relative to controls. Of the 216 up‐regulated genes, we identified four characteristic genes directly related to memory, including early growth response protein 1 (Egr1), growth arrest and DNA‐damage‐inducible, beta (Gadd45b), NGFI‐A binding protein 2 (Nab2), and vascular endothelial growth factor a (Vegfa). These results suggest that the efficacy of SD‐F involves upregulation of these genes.

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“…Normal diet (N), high-fat/high-sucrose diet (C), high-fat/high-sucrose diet containing carotene at a low dose (0.001% by mass) (LC), or high-fat/high-sucrose diet containing carotene at a high dose (0.004% by mass) (HC in mice was closely associated with reduced MMP-9 expression (Yamauchi et al, 2017). However, other proinflammatory cytokines may be related to liver fibrosis.…”

Section: Edmentioning

confidence: 99%

High-dose β-carotene exacerbates high-fat/high-sucrose diet-inducible fibrosis in the liver of Mongolian gerbils

Kondo

Hariya

Mochizuki

2019

Fundam. Toxicol. Sci.

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β-Carotene, a natural additive that is often used for food coloring, is converted into vitamin A in the body and it removes reactive oxygen species. β-Carotene accumulates in the liver and adipose tissue, where it can induce adverse effects if present in excess. In this study, we determined whether β-carotene supplementation of a high-fat/high-sucrose diet enhances liver inflammation and fibrosis in Mongolian gerbils, which accumulate β-carotene in the liver. Ten-week-old male Mongolian gerbils were divided into four groups and fed either a normal diet, a high-fat/high-sucrose diet, a high-fat/high-sucrose diet supplemented with a low dose of β-carotene (0.001%), or a high-fat/high-sucrose diet supplemented with a high dose of β-carotene (0.004%). An oral glucose tolerance testing was performed after 12 weeks, and non-fasted serum and tissue samples were collected after 13 weeks of diet feeding. The high dose of β-carotene increased triglycerides and total cholesterol serum concentrations. Intake of a high-fat/high-sucrose diet with a high dose of β-carotene increased the β-carotene content, volume occupied by fat droplets, degree of fibrosis, and protein levels of matrix metalloprotease-9 (a marker of inflammation in steatohepatitis) in the liver. These data suggest that the intake of excessive amounts of β-carotene for 13 weeks exacerbates high-fat/high-sucrose diet-inducible inflammation and fibrosis in the liver in Mongolian gerbils. This model is suitable for studying the mechanism of β-carotene-induced liver injury, including liver fibrosis.

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Placental extract ameliorates non-alcoholic steatohepatitis (NASH) by exerting protective effects on endothelial cells

Cited by 26 publications

References 32 publications

Placental extract ameliorates liver fibrosis in a methionine- and choline-deficient diet-induced mouse model of non-alcoholic steatohepatitis

Placental extract ameliorates liver fibrosis in a methionine- and choline-deficient diet-induced mouse model of non-alcoholic steatohepatitis

Porcine placental extract facilitates memory and learning in aged mice

High-dose β-carotene exacerbates high-fat/high-sucrose diet-inducible fibrosis in the liver of Mongolian gerbils

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