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               Effects  of  acetylated  glucomannan  derived  from  Dendrobium  Taiseed

               Tosnobile on non-alcoholic fatty liver disease and gut microbiota modulation

               in mice


                                                   ,3
                                1,2
               Chun-Hui Chiu,   Li-Chan Yang*

               1  Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung
                 University of Science and Technology, Taoyuan 333, Taiwan
               2  Department of Nephrology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
               3  Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing
                 University, Taichung 40227, Taiwan
               * E-mail: lcyang@dargon.nchu.edu.tw

               Abstract
                  Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition worldwide,
               often progressing to non-alcoholic steatohepatitis (NASH), fibrosis, and even hepatocellular
               carcinoma.  Current  treatments  are  limited,  with  a  growing  need  for  alternative  therapeutic
               options. This study investigated the effects of acetylated glucomannan polysaccharides derived
               from a cultivated hybrid medicinal Dendrobium, Dendrobium Taiseed Tosnobile (DTTPS), on
               NAFLD using a high-fat, high-cholesterol diet-induced mouse model. The chemical structure
               and acetylation degree of DTTPS and its deacetylated form (deac-DTTPS) were characterized.
               Mice were orally administered with DTTPS or deac-DTTPS for 16 weeks alongside high-fat
               feeding.  Results  demonstrated  that  DTTPS  significantly  ameliorated  liver  steatohepatitis,
               reduced  serum  levels  of  glucose,  triglycerides,  cholesterol,  ALT,  and  AST,  and  decreased
               hepatic lipid accumulation. These effects were accompanied by improved hepatic antioxidant
               status, including increased glutathione (GSH) content. Deacetylated polysaccharides exhibited
               moderately  diminished  efficacy,  highlighting  the  critical  role  of  acetyl  substituents  in
               bioactivity.  Importantly,  DTTPS  modulated  gut  microbiota  composition  by  increasing  the
               abundance of the beneficial bacterium Akkermansia muciniphila and elevated urinary levels of
               microbial metabolites indole-3-acetic acid and 4-hydroxyphenylacetic acid, which are known
               to have anti-inflammatory and antioxidative properties. These factors likely contributed to the
               observed liver protection through the gut-liver axis. In conclusion, acetylated glucomannan
               from Dendrobium Taiseed Tosnobile demonstrates promising hepatoprotective effects against
               diet-induced NAFLD by modulating gut microbiota and enhancing antioxidant defense. This
               study  supports  the  potential  development  of  DTTPS  as  a  functional  herbal  ingredient  for
               improving  metabolic  liver  diseases  and  highlights  the  importance  of  acetylation  in
               polysaccharide bioactivity.

               Keywords: Dendrobium Taiseed Tosnobile; Glucomannan; Acetyl group; Non-alcoholic fatty
                          liver disease; Gut microbiota
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