Polysaccharides fatty acid esters glycosides iridoids anthra

Polysaccharides, fatty MPI-0479605 esters, glycosides, iridoids, anthraquinones, flavonoids, phytosterols, carotenoids, vitamin A, antraquinones, potassium, and others have been identified as putative active ingredients in NJ. Our previous report indicated that gentisic, p-hydroxybenoic, and chlorogenic acids have been characterized as the major phenolic acids in our fermented NJ, while the hepatic antioxidant and antiinflammation effects of NJ in a high-fat diet were partially attributed to its phenolic acid. Furthermore, the major mineral in NJ is potassium (K), followed by magnesium (Mg), and sodium (Na). Interestingly, some trace minerals, i.e., zinc (Zn), manganese (Mn), and selenium (Se) were also found in this fermented NJ. In addition, this naturally fermented NJ contains polysaccharides (2141.52 mg/100 mL), and its antiinflammatory effects against alcoholic liver disease also significantly result from its polysaccharide contents. It has been reported that polysaccharides can downregulate the phosphorylation of ERK and JNK, and then suppress NFκB activation, which influences tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) secretions. Therefore, we speculated that the bioactive compounds (polyphenols, polysaccharides, and minerals) in the naturally fermented NJ may also contribute to increased hepatic antioxidant capacities and antiinflammatory responses in TAA-induced liver fibrosis. Although NJ showed hypolipidemic, antioxidative, and antiinflammatory effects in a high-fat/cholesterol diet and liquid alcohol diet fed to hamsters and mice, respectively, the protective mechanism of NJ against TAA-induced rat liver fibrosis is still lacking. Therefore, by employing a TAA-induced liver fibrosis rat model, the present study addressed the protective effects of NJ via: (1) increased antioxidative capacities; (2) downregulation of inflammatory and ER stress; and (3) inhibited collagen accumulation.
Methods
Results
Discussion Growing understandings of the pathophysiology behind liver fibrosis has contributed to the development of agents that could potentially inhibit and reverse the fibrotic process in livers. In the present study, the damage and inflammation of hepatocytes were observed and measured by serum biochemical values, liver cytokines, and H&E and Masson’s trichrome stainings. Our results showed that an application of 100 mg TAA/kg BW three times weekly successfully induces chronic liver fibrosis in rats, which also confirmed the observation from a previous report. According to the histopathological observations, NJ cotreatment showed amelioration of liver damage in TAA-treated rats. It has been reported that the hepatoprotection of silymarin on TAA-induced chronic liver damage is attributed to downregulation of hepatic MMP-2, MMP-13, TIMP-1, TIMP-2, activator protein 1, Kruppel-like factor 6, transforming growth factor beta 1, alpha smooth muscle actin, and collagen alpha 1. Based on our results, there was a remarkable reduction in liver fibrotic scars of TAA-treated rats cotreated with NJ (Fig. 3C), which warrants clarifying the protective molecular mechanisms of NJ on the liver of TAA-treated rats. Furthermore, serum ALT and AST values are also important criteria for the evaluation of liver injuries where the TAA induction results in significant increases. Rats intoxicated with TAA experienced hepatic injury evidenced by significant changes (Fig. 1) in serum liver biomarkers when compared to control rats. Cotreatments of low, medium, and high dosages of NJ in TAA-treated rats significantly lowered the ALT level by 20.01%, 29.2%, and 35.7%, respectively, as well as the AST level by 45.72%, 55.26%, and 56.65%, respectively; this is compared with those without NJ, indicating a potential hepatoprotection effect of NJ supplementation against TAA-induced liver damage (Figs. 1C and 1D). In conclusion, the current study presents solid evidence showing the hepatic oxidative stress and damage, along with lipid accumulation, inflammation, ER stress and its associated cell death, fibrotic responses, and consequently hepatic dysfunctions in TAA-treated rats. It also demonstrated that supplementing with naturally fermented NJ in TAA-treated rats alleviates these pathological changes, including ER stress (Fig. 4), lipid accumulation (Fig. 2), inflammation (Table 2), and fibrosis development (Figs. 3 and 4).Therefore, it is speculated that the synergistic effect of bioactive compounds (polyphenol, polysaccharide, Zn, Mn, and Se) in this naturally fermented NJ may offer the liver protection against the TAA intoxication. In summary, naturally fermented NJ can attract considerable attention in the functional-food market for its ameliorative effect against chronic liver fibrosis.