Akebia Saponin D Decreases Hepatic Steatosis through Autophagy Modulation

Abstract

Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of the metabolic syndrome, and the incidence of NAFLD is increasing rapidly. However, appropriate drugs for treatment of NAFLD are lacking. This study aimed to elucidate the protective effects and mechanisms of Akebia saponin D (ASD) against NAFLD in ob/ob mice and Buffalo rat liver cells. ASD significantly decreased hepatic steatosis and hepatocyte apoptosis in ob/ob mice. ASD also significantly activated autophagic flux, as assessed by the decreased expression of light chain 3 (LC3)-II and P62 accumulation of autophagosomes. In Buffalo rat liver cells, ASD prevented oleic acid (OA)-induced lipid droplets and increased autophagic flux acting as increase the number of autolysosomes than autophagosomes in mTagRFP-mWasabi-LC3. ASD treatment also prevented OA-induced expression of LC3-II, P62, Beclin, and phospho-mammalian target of rapamycin. These effects were similar to those of cotreatment with rapamycin. ASD treatment could not prevent OA-increased, autophagy-related protein expression after treatment with chloroquine or small interfering RNA-mediated knockdown of atg7. These results suggest that ASD alleviates hepatic steatosis targeted at the fusion of autophagosomes to lysosomes, and autophagy modulation via ASD may offer a new strategy for treating NAFLD.

Amelioration of hepatic steatosis is associated with modulation of gut microbiota and suppression of hepatic miR-34a in Gynostemma pentaphylla (Thunb.) Makino treated mice

“…As a traditional Chinese medicine, GP contains various bioactive components including saponins, flavone, polysaccharide, amino acids, trace elements and vitamins. Saponins can decrease hepatic steatosis through autophagy modulation [ 43 ] and alleviate liver fibrosis induced by carbon tetrachloride (CCl4) in rats [ 44 ], which might mediate the beneficial effect of GP on NAFLD, polysaccharides, another main ingredients of GP, has antioxidative, immunomodulatory activities [ 45 ] and is able to protect liver from CCl4 injury in mice [ 46 ], while flavone was reported to induce cell death in human hepatoma HepG2 cell [ 47 ]. Therefore, the components in GP listed above, either acting alone or together, might be responsible for the effect of GP on NAFLD.…”

Herbal Medicine in the Treatment of Non-Alcoholic Fatty Liver Diseases-Efficacy, Action Mechanism, and Clinical Application

“…For example, Dioscin inhibits collagen synthesis through modulating the expressions of autophagic flux (P62 LC-I LC-II) (Xu et al, 2017). Administration of Akebia saponin D (extracts from Akebia quinata) resulted in the upregulation of autophagic flux (e.g., decreased P62 accumulation and increased the level of LC3-II expression) in the liver of ob/ob mice (Gong et al, 2016); Glycycoumarin (a coumarin compound isolated from Rhizoma Glycyrrhizae) inhibited hepatocyte lipo-apoptosis through reactivation of impaired autophagy and inactivation of GSK-3. In line with autophagy activation, mitochondrial apoptotic activation, and ER stress-mediated JNK pathway were also blocked by glycycoumarin ; Nobiletin (Yuk et al, 2018), ginsenoside Rb2 (extracted from Panax Ginseng C.A.Mey) and Tangshen formula , could reverse the repression of autophagic pathways in AMPK-SIRT1 dependent manner (Huang et al, 2017).…”

Fermented mulberry (Morus alba) leaves suppress high fat diet-induced hepatic steatosis through amelioration of the inflammatory response and autophagy pathway

“…Ginsenoside Rb2 partly activates the autophagic pathway through inhibition of the AMPK or SIRT1 pathway in db/db mice [58]. Also, resveratrol and akebia saponin D prevent hepatic steatosis, accompanied with up-regulation of autophagy markers such as LC3-II, Beclin 1 and p62 [59,60]. Similar effects on the induction of autophagy and prevention of hepatic steatosis have been reported in obesity animals and hepatic cell lines after exposure to the bergamot polyphenol fraction (BPF) and capsaicin [29,60,61].…”

“…A similar regulatory mechanism was observed after the treatment of several compounds with anti-obesity activity. Akebia saponin D (ASD) treatment prevent the oleic acid (OA)induced upregulation of LC3-II, Beclin and P62 expression as well as accumulation of lipid droplets in ob/ob mice [59]. Also, Lycium barbarum polysaccharides induced the down-regulation of p-mTOR and p62 level, while the expression level of Beclin and LC3 were enhanced in HFD-induced NASH rat model [69].…”