Noni Fruit Polysaccharide Alleviates Hepatic Oxidative Stress And Inflammation And Its Mechanisms

The progress of non-alcoholic fatty liver disease(NAFLD)is a slow and gradual process.Hepatic oxidative stress and inflammation induced by high-fat diet play an important role in the development of NAFLD.Therefore,it is of great significance to prevent and alleviate hepatic oxidative stress and inflammation to reduce the risk of NAFLD.Noni(Morinda citrifolia L.)is an evergreen tree or shrub of the Rubiaceae family,and its roots,branches,leaves,and fruits of noni have wide range of pharmacological effects.Polysaccharides with antitumor,antioxidant,anti-inflammatory,and other physiological activities,are one of the main active components in noni fruit juice.In this study,the phytochemical analysis of noni fruit water extract(NFW)and noni fruit polysaccharide(NFP)obtained by hot water extraction were measured.Moreover,we compared the effects of NFW and NFP on hepatic oxidative stress and inflammation induced by high-fat diet(HFD),and verified whether NFP was an important antioxidant and anti-inflammatory active ingredient in NFW.In addition,the mechanisms by which NFP improved hepatic oxidative stress and inflammation induced by HFD was eveluated.The main results were as follows:1.The physical and chemical properties of NFW and NFP were analyzed,and the structure of NFP was further explained by infrared spectrum and scanning electron microscope.The results showed that the main chemical constituent in NFW was crude polysaccharides,and the contents of water-soluble protein,total flavonoids,total polyphenols,and mineral elements were also relatively rich.Furthermore,the total carbohydrate content of NFP was 93.87%,of which uronic acid(acid polysaccharide)accounted for 77.34%,and other chemical components were very lower,indicating that the purity of NFP was high.In addition,the infrared spectrum analysis results of NFP showed that NFP had the typical characteristic absorption peaks of polysaccharides and mainly was a polysaccharide with α-and β-pyranoside bonds.And scanning electron microscope results showed that the surface of NFP powder was mainly sheet-like.2.In this study,mice were induced to develop hepatic oxidative stress and inflammation through HFD.Treatment was performed via the administration of NFW(10 mL per kg bw)and NFP(50,100,and 200 mg per kg bw)for 4 weeks.The results showed that both NFW and NFP reduced hepatic MDA level in mice under HFD,and increased TEAC,SOD,GSH-Px,and Nrf2 levels in livers of HFD mice,as well as attenuated inflammation(the serum and hepatic TNF-α,IL-6,NO levels,and the hepatic NF-κB level were reduced),and the effects of medium and high dosage of NFP(100 and 200 mg per kg bw)were better,indicating that NFP was an important antioxidant and anti-inflammatory active ingredient in NFW.3.We aimed to investigate the mechanism by which NFP improved hepatic oxidative stress and inflammation in rats under HFD.In this study,rats were induced to hepatic oxidative stress,inflammation,and gut dysbiosis through feeding HFD for 4 weeks,followed by intervention via administration of NFP(100 mg per kg bw)for 5 weeks.NFP positively affected the production of SCFAs(decrement of the acetate content in the cecum,and significant increment of the butyrate content)and reversed the HFD-induced gut dysbiosis as indicated by the improved microbiota diversity and composition,such as the improvement in the levels of Lactobacillus,[Eubacterium] coprostanoligenes group,Parasutterella,Ruminococcaceae＿UCG＿014,and Ruminococcus＿1,as well as the decrement in the levels of Prevotella＿9,Collinsella,Bacteroides,and Turicibacter.Furthermore,NFP reduced the colonic permeability(increased the mRNA relative expression of CCL5,ZO-1,and occludin in the colon,and decreased the serum CCL5 level),and decreased the LPS level in the serum,thus ameliorating metabolic endotoxemia,eventually improving hepatic lipid accumulation,oxidative stress and inflammation in rats under HFD.In conclusion,the main chemical constituent in NFW was crude polysaccharides,and NFP was an important antioxidant and anti-inflammatory active ingredient in NFW.In addition,the effect of NFP on hepatic oxidative stress and inflammation induced by HFD may be related to the improvement of the intestinal microflora,SCFAs production,and the reduction of colonic barrier permeability and metabolic endotoxemia.Therefore,NFP can be used as prebiotic to improve NAFLD and related metabolic diseases.