A porcine placental extract prevents steatohepatitis by suppressing activation of macrophages and stellate cells in mice

Abstract

Nonalcoholic fatty liver disease (NAFLD) is caused by ectopic fat accumulation in the liver. NAFLD is associated with hepatic inflammation and oxidative stress, resulting in nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Placental extracts have been used to treat various chronic diseases due to their antioxidative effect. However, the effects of the extracts on the development of NASH have yet to be elucidated. Here, we demonstrated that supplementation with an oral porcine placental extract (PPE) attenuated lipid accumulation and peroxidation, insulin resistance, inflammatory and stress signaling, and fibrogenesis in the liver of NASH model mice fed a high-cholesterol and high-fat diet. The PPE reduced the number of M1-like liver macrophages, but increased the number of anti-inflammatory M2-like macrophages, resulting in a predominance of M2 over M1 macrophage populations in the liver of NASH mice. Accordingly, the PPE suppressed lipopolysaccharide-induced M1 polarization in isolated murine peritoneal macrophages, whereas it facilitated interleukin 4-induced M2 polarization. Furthermore, the PPE reduced the hepatic stellate cell (HSC) activation associated with the attenuated transforming growth factor-β/Smad3 signaling, both in the liver of NASH mice and in RI-T cells, a HSC line. The PPE may be a potential approach to prevent NASH by limiting lipid peroxidation, promoting M2 macrophage polarization, and attenuating HSC activation.

Von Willebrand Factor Deficiency Improves Hepatic Steatosis, Insulin Resistance, and Inflammation in Mice Fed High‐Fat Diet

“…On the contrary, M2‐polarized macrophages secreted anti‐inflammatory cytokines and later contributed to the maintenance of insulin sensitivity . Coincident with previous data , our results showed increased obesity‐induced inflammation, M1‐type polarization of macrophages, and compromised insulin activities in WT mice exposed to an HFD for 12 weeks. In contrast, VWF −/− mice displayed decreased obesity‐induced inflammation and M1‐type polarization of macrophages.…”

Human placental extract attenuates neurological symptoms in the experimental autoimmune encephalomyelitis model of multiple sclerosis-a putative approach in MS disease?

“…Given the ability of IL-23 to promote the secretion of IL-10 and regulate IL-17 production by CD4 + T cells [ 42 ], one may propose that the administration of human placental extract in the first place, may suppress the destructive activity of autoreactive T cells in EAE. Similarly, human placental extract can suppress the secretion of several pro-inflammatory mediators, including IL-23 and several other mediators mentioned in different studies, resulting in the attenuation of inflammation and the mean clinical score in EAE mice [ 43 – 45 ].…”

Placental extract suppresses differentiation of 3T3-L1 preadipocytes to mature adipocytes via accelerated activation of p38 MAPK during the early phase of adipogenesis

“…The porcine placental extract (PPE) used in this study was produced by Snowden (Tokyo) using a combination of fermentation and proteolysis as previously described [27]. Briefly, the porcine placenta was obtained as afterbirth and was fermented with yeast ( Zygosaccharomyces sp.)…”

“…Since the placenta contains various nutrients including amino acids, nucleic acids, minerals, vitamins, hormones and some growth factors, it has been used in traditional medicines for fatigue, menopausal symptoms, skin whitening and antiaging from ancient times to the present [21–26]. Recent studies, in fact, have demonstrated that a hydrolyzed extract of the placenta, known simply as “placental extract”, has beneficial effects such as amelioration of non-alcoholic steatohepatitis (NASH) and other forms of liver regeneration, increased proliferation of skin fibroblasts and marrow cells, and anti-inflammatory and anti-oxidant activities [27–30]. In the present study, we examined the broad spectrum of effects of placental extract, with a focus on the influence of placental extract on adipogenesis.…”