Polysaccharides from Dicliptera chinensis ameliorate liver disturbance by regulating TLR‐4/NF‐κB and AMPK/Nrf2 signalling pathways

Abstract

The purpose of this study was to alleviate liver disturbance by applying polysaccharides from Dicliptera chinensis (DCP) to act on the adenosine monophosphate–activated protein kinase/ nuclear factor erythroid 2‐related factor 2 (AMPK/ Nrf2) oxidative stress pathway and the Toll‐like receptor 4 (TLR‐4)/ nuclear factor kappa‐B (NF‐κB) inflammatory pathway and to establish an in vivo liver disturbance model using male C57BL/6J and TLR‐4 knockout (−/−) mice. For this, we evaluated the expression levels of SREBP‐1 and Nrf2 after silencing the expression of AMPK using siRNA technology. Our results show that with regard to the TLR‐4/ NF‐κB inflammatory pathway, DCP inhibits TLR‐4, up‐regulates the expression of peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), reduces the expression of phospho(p)‐NF‐κB and leads to the reduction of downstream inflammatory factors, such as tumour necrosis factor‐α (TNF‐α), interleukin (IL)‐6 and IL‐1β, thereby inhibiting the inflammatory response. Regarding the AMPK/ Nrf2 oxidative stress pathway, DCP up‐regulates the expression of p‐AMPK and Nrf2, in addition to regulating glucose and lipid metabolism, oxidative stress and ameliorating liver disturbance symptoms. In summary, our study shows that DCP alleviates liver disturbances by inhibiting mechanisms used during liver inflammation and oxidative stress depression, which provides a new strategy for the clinical treatment of liver disturbance.

Chlorogenic Acid Protects against Advanced Alcoholic Steatohepatitis in Rats via Modulation of Redox Homeostasis, Inflammation, and Lipogenesis

“…Thus, further studies need to be performed to check the level of phosphorylated by AMPK target proteins such as pACC or pSREBP1, which, after phosphorylation, should exhibit decreased activity. Some authors have described that the inhibition of the TLR4/NF-κB signaling pathway, which is related to inflammatory response in chronic liver damage, also helps to protect hepatocytes against steatosis and fibrosis [59,60]. Chronic alcohol intoxication promotes hepatic inflammation by activating Kupffer cells, which play a crucial role in early-stage ALD via the production of inflammatory cytokines and chemokines through TLR4 mediated signaling.…”

Advances in health-promoting effects of natural polysaccharides: Regulation on Nrf2 antioxidant pathway

“…According to Supplementary Table 1 , NPs having regulation on Nrf2 antioxidant pathway can be isolated by water extraction ( 16 , 30 – 33 ), ultrasonic-assisted extraction ( 34 – 36 ), ethanol precipitation ( 37 – 41 ) and enzymatic hydrolysis ( 24 , 42 – 44 ). For acquiring homogeneous fractions, NPs can be further purified by stepwise ethanol precipitation ( 36 , 45 – 47 ) and/or column chromatography ( 31 , 42 , 43 , 48 – 53 ).…”

“…In terms of NPs having regulation on Nrf2 antioxidant pathway from herbs, M w values of them have been determined to range from 2.273 to 2,617 kDa ( 41 , 54 – 56 ). The polysaccharides were composed of fucose (Fuc), ribose (Rib), mannose (Man), glucose (Glc), arabinose (Ara), galactose (Gal), rhamnose (Rha), xylose (Xyl), glucuronic acid (GlcA), galacturonic acid (GalA), glucosamine (GlcN), and/or galactosamine (GalN) ( 18 , 56 – 58 ).…”

“…The polysaccharides were composed of fucose (Fuc), ribose (Rib), mannose (Man), glucose (Glc), arabinose (Ara), galactose (Gal), rhamnose (Rha), xylose (Xyl), glucuronic acid (GlcA), galacturonic acid (GalA), glucosamine (GlcN), and/or galactosamine (GalN) ( 18 , 56 – 58 ). Moreover, Glc, Ara, Gal, and Rha were four monosaccharide types widely discovered in the polysaccharides ( 18 , 41 , 54 , 55 , 57 – 62 ).…”

Toll-Like Receptor 4 (TLR4) and AMPK Relevance in Cardiovascular Disease

“…67 Accumulating evidence from in vitro and in vivo experiments indicates the involvement of AMPK as a negative regulator of immune/inflammatory responses, and shaping the cell's metabolic status at sites of inflammation may serve as a novel and promising therapeutic approach in the pathophysiology of several immune-mediated inflammatory diseases. The antiinflammatory effects of AMPK activators have been shown to confer benefits in Colitis, 6,68 hepatitis and liver disturbances, 69,70 autoimmune encephalomyelitis, 71 osteoarthritis, 72 A c c e p t e d M a n u s c r i p t endotoxemia, [73][74][75] myocardial infarction, 76 angiogenesis, 77 acute kidney injuries, 78 and mouse lung injury model. 79 AMPK is consistent with the suppressed production of pro-inflammatory mediators and the promotion of anti-inflammatory cytokines.…”