Human placental extract treatment for non‐alcoholic steatohepatitis non‐responsive to lifestyle intervention: A pilot study

Shimokobe, Hideto; Sumida, Yoshio; Tanaka, Saiyu; Mori, Kumiko; Kitamura, Yoko; Fukumoto, Kohei; Kakutani, Akira; Ohno, Tomoyuki; Kanemasa, Kazuyuki; Imai, Shoichi; Hibino, Sawako; Yoshikawa, Toshikazu

doi:10.1111/hepr.12432

Cited by 16 publications

(15 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In an experimental animal model of hepatitis, hPE reportedly ameliorated hepatic injury through liver regeneration and inhibition of inflammatory reactions and hepatocyte apoptosis (15,32). Moreover, Shimokobe et al reported that hPE is effective in NASH patients who were unresponsive to lifestyle intervention (26). In that study, patients treated for eight weeks with a hPE formulation exhibited a significant reduction in serum transaminases, and suppression of inflammation and hepatocyte damage was noted in liver biopsies.…”

Section: Methodsmentioning

confidence: 94%

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

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

Section: Methodsmentioning

confidence: 94%

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

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In experimental animal model of hepatitis, HPE reportedly ameliorates hepatic injury through liver regeneration and inhibition of inflammatory reactions and hepatocyte apoptosis ( Jung et al, 2011 ; Wu et al, 2008 ). Moreover, Shimokobe et al recently reported that HPE is effective in NASH patients who were unresponsive to lifestyle intervention ( Shimokobe et al, 2014 ). They treated patients with Laennec, a HPE formulation, for 8 weeks, and obtained significant reductions in serum transaminases (AST and ALT).…”

Section: Introductionmentioning

confidence: 99%

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

Yamauchi

Kamiyoshi

Koyama

et al. 2017

Heliyon

View full text Add to dashboard Cite

Non-alcoholic steatohepatitis (NASH) is a severe form of fatty liver disease that is defined by the presence of inflammation and fibrosis, ultimately leading to cirrhosis and hepatocellular carcinoma. Treatment with human placental extract (HPE) reportedly ameliorates the hepatic injury. We evaluated the effect of HPE treatment in a mouse model of NASH. In the methione- and choline-deficient (MCD) diet-induced liver injury model, fibrosis started from regions adjacent to the sinusoids. We administered the MCD diet with high-salt loading (8% NaCl in the drinking water) to mice deficient in the vasoprotective molecule RAMP2 for 5 weeks, with or without HPE. In both the HPE and control groups, fibrosis was seen in regions adjacent to the sinusoids, but the fibrosis was less pronounced in the HPE-treated mice. Levels of TNF-α and MMP9 expression were also significantly reduced in HPE-treated mice, and oxidative stress was suppressed in the perivascular region. In addition, HPE dose-dependently increased survival of cultured endothelial cells exposed to 100 μM H2O2, and it upregulated expression of eNOS and the anti-apoptotic factors bcl-2 and bcl-xL. From these observations, we conclude that HPE ameliorates NASH-associated pathologies by suppressing inflammation, oxidative stress and fibrosis. These beneficially effects of HPE are in part attributable to its protective effects on liver sinusoidal endothelial cells. HPE could thus be an attractive therapeutic candidate with which to suppress progression from simple fatty liver to NASH.

show abstract

“…Approximately 59% of the antioxidative effects of human placenta extract can be explained by the actions of these components. 11) In previous studies that used the same hPH, it was confirmed that hPH contains various amino acids, including arginine (0.08%), lysine (0.1%), phenylalanine (0.08%), tyrosine (0.03%), leucine (0.12%), methionine (0.03%), valine (0.04%), alanine (0.08%), serine (0.07%), and threonine (0.06%). 50) Therefore, it can be assumed that these amino acids have a role in removing oxidative stress and increasing antioxidant enzymes.…”

Section: Discussionmentioning

confidence: 99%

“…8,9) Many of these factors possibly act in an autocrine and/or paracrine fashion within the human placenta and regulate the production of other biologically active substances, which may hold potential for therapeutic agents as suggested in previous studies, where fractions of human placenta hydrolysate (hPH) stimulated tissue repair processes. 10,11) Over the last few decades, hPH has been prescribed clinically to treat chronic hepatitis, 12,13) liver cirrhosis 14) and other hepatic diseases. 15) hPH reportedly ameliorated hepatic injury through liver regeneration 9) and inhibited inflammatory reactions and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Human Placenta Hydrolysate Promotes Liver Regeneration <i>via</i> Activation of the Cytokine/Growth Factor-Mediated Pathway and Anti-oxidative Effect

Lee

Park

Jang

et al. 2019

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Liver regeneration is a very complex process and is regulated by several cytokines and growth factors. It is also known that liver transplantation and the regeneration process cause massive oxidative stress, which interferes with liver regeneration. The placenta is known to contain various physiologically active ingredients such as cytokines, growth factors, and amino acids. In particular, human placenta hydrolysate (hPH) has been found to contain many amino acids. Most of the growth factors found in the placenta are known to be closely related to liver regeneration. Therefore, in this study, we investigated whether hPH is effective in promoting liver regeneration in rats undergoing partial hepatectomy. We confirmed that cell proliferation was significantly increased in HepG2 and human primary cells. Hepatocyte proliferation was also promoted in partial hepatectomized rats by hPH treatment. hPH increased liver regeneration rate, double nucleic cell ratio, mitotic cell ratio, proliferating cell nuclear antigen (PCNA), and K i-67 positive cells in vivo as well as interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), and hepatocyte growth factor (HGF). Moreover, Kupffer cells secreting IL-6 and TNF-α were activated by hPH treatment. In addition, hPH reduced thiobarbituric acid reactive substances (TBARs) and significantly increased glutathione (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Taken together, these results suggest that hPH promotes liver regeneration by activating cytokines and growth factors associated with liver regeneration and eliminating oxidative stress.

show abstract

Human placental extract treatment for non‐alcoholic steatohepatitis non‐responsive to lifestyle intervention: A pilot study

Abstract: In NASH patients who received HPE treatment, significant reductions in serum liver enzymes were obtained after 8 weeks. Histological efficacy may be better in obese patients than in non-obese ones.

Cited by 16 publications

References 27 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

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

Human Placenta Hydrolysate Promotes Liver Regeneration <i>via</i> Activation of the Cytokine/Growth Factor-Mediated Pathway and Anti-oxidative Effect

Contact Info

Product

Resources

About