Diosgenin attenuates nonalcoholic hepatic steatosis through the hepatic FXR-SHP-SREBP1C/PPARα/CD36 pathway

Chen, Suwen; Sun, Shenghua; Feng, Yanan; Li, Xiu; Yin, Guoliang; Liang, Pengpeng; Yu, Wenfei; Meng, Decheng; Zhang, Xin; Liu, Hongshuai; Zhang, Fengxia

doi:10.1016/j.ejphar.2023.175808

Cited by 15 publications

(5 citation statements)

References 49 publications

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“…Currently, NAFLD has emerged as the primary cause of chronic liver disease in children and adolescents, impacting their growth and development. Mounting evidence suggests that traditional Chinese medicine exhibits characteristics of multi-target action in the treatment of NAFLD, accompanied by relatively few side effects [22,23].…”

Section: Discussionmentioning

confidence: 99%

Artesunate Inhibits Lipid Accumulation and Inflammation by Regulating the NLRP3 Inflammasome in Nonalcoholic Fatty Liver Disease

Sun,

Chen,

Wang

2024

Discovery Medicine

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Background: Non-alcoholic fatty liver disease (NAFLD), recognized as a chronic liver condition, has emerged as one of the most prevalent worldwide. This study explores the impact of artesunate (ART) on lipid accumulation and inflammatory factors within NAFLD model cells. Methods: LO2 cells were subjected to treatment with oleic acid (OA) to establish NAFLD cell model. Subsequently, these cells were categorized into distinct groups: a control group, an OA group, an OA + 2.5 µm ART group, and an OA + 5 µm ART group. The activity of LO2 cells was determined using the Cell Counting Kit-8 (CCK-8) method. The presence of intracellular lipid droplets was examined through oil red O staining. Levels of triglycerides (TG), total cholesterol (TC), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated using enzyme-linked immunosorbent assay (ELISA). Additionally, the protein expressions of nucleotide-binding oligomerization domain (NOD), leucine-rich repeat (LRR), and pyrin domain-containing protein 3 (NLRP3), Cleaved caspase-1, N-terminus of Gasdermin-D (GSDMD-N), and apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) were measured via Western blot assay. Results: In comparison to the control group, the OA group exhibited a significant increase in the contents of lipid droplets, TC, and TG (p < 0.01). Notably, ART effectively reversed the impact of OA (p < 0.01). Following OA stimulation, there was a pronounced elevation in the levels of IL-6 (p < 0.01), IL-1β (p < 0.01), and TNF-α (p < 0.05). In comparison to the OA group, the 2.5 µm ART group showed no significant difference in TNF-α content (p > 0.05), while the 5 µm ART group significantly reduced TNF-α content (p < 0.05). Furthermore, both the 2.5 µm ART (p < 0.05) and 5 µm ART (p < 0.01) groups notably reduced IL-1β and IL-6 content. When compared to the control group, the expressions of NLRP3, ASC, GSDMD-N, and Cleaved caspase-1 in the OA group significantly increased (p < 0.01). ART, however, mitigated this heightened expression trend (p < 0.05). Conclusions: ART demonstrated a reduction in TC and TG content, improvement in the deposit of intracellular lipid droplets, and a decrease in the release of inflammatory factors in LO2 cells. This effect was achieved through the regulation of the NLRP3 inflammasome, presenting a novel approach to the treatment of NAFLD.

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Section: Discussionmentioning

confidence: 99%

Artesunate Inhibits Lipid Accumulation and Inflammation by Regulating the NLRP3 Inflammasome in Nonalcoholic Fatty Liver Disease

Sun,

Chen,

Wang

2024

Discovery Medicine

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“…Concomitantly, the downstream mediator of the FXR signaling pathway, SHP, exhibited discernible involvement [ 29 ]. A cascade emerged wherein SHP’s upregulation correlated with the inhibition of ACC1 transcription, thus abating fatty acid synthesis [ 30 ]. Notably, AG treatment conspicuously augmented the expression of SHP within the murine liver, reinforcing the potential of AG in the attenuation of fatty acid synthesis and uptake.…”

Section: Discussionmentioning

confidence: 99%

Alanyl-Glutamine Dipeptide Attenuates Non-Alcoholic Fatty Liver Disease Induced by a High-Fat Diet in Mice by Improving Gut Microbiota Dysbiosis

Zheng,

Ying,

Shi

et al. 2023

Nutrients

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Non-alcoholic fatty liver disease (NAFLD) manifests as a persistent liver ailment marked by the excessive buildup of lipids within the hepatic organ accompanied by inflammatory responses and oxidative stress. Alanyl-glutamine (AG), a dipeptide comprising alanine and glutamine, is commonly employed as a nutritional supplement in clinical settings. This research aims to evaluate the impact of AG on NAFLD triggered by a high-fat diet (HFD), while concurrently delving into the potential mechanisms underlying its effects. The results presented herein demonstrate a notable reduction in the elevated body weight, liver mass, and liver index induced by a HFD upon AG administration. These alterations coincide with the amelioration of liver injury and the attenuation of hepatic histological advancement. Furthermore, AG treatment manifests a discernible diminution in oil-red-O-stained regions and triglyceride (TG) levels within the liver. Noteworthy alterations encompass lowered plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) concentrations, coupled with elevated high-density lipoprotein cholesterol (HDLC) concentrations. The mitigation of hepatic lipid accumulation resultant from AG administration is aligned with the downregulation of ACC1, SCD1, PPAR-γ, and CD36 expression, in conjunction with the upregulation of FXR and SHP expression. Concomitantly, AG administration leads to a reduction in the accumulation of F4/80-positive macrophages within the liver, likely attributable to the downregulated expression of MCP-1. Furthermore, AG treatment yields a decline in hepatic MDA levels and a concurrent increase in the activities of SOD and GPX. A pivotal observation underscores the effect of AG in rectifying the imbalance of gut microbiota in HFD-fed mice. Consequently, this study sheds light on the protective attributes of AG against HFD-induced NAFLD through the modulation of gut microbiota composition.

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“…The polyphenolic compounds including ferulic acid and p-coumaric acid from Setaria italica alleviated MAFLD mainly by downregulating FABP and CD36 [267]. Recent studies have also reported that diosgenin extracted from Trigonella foenum-graecum attenuates MAFLD by regulating fatty acid uptake through the inhibition of fatty acid transporters such as CD36, FATP2, and FABP, which is at least partly achieved by the SIRT6 and FXR pathways [268,269].…”

Section: Natural Products Against Mafld Via the Modulation Of Nutrien...mentioning

confidence: 99%

“…Total alkaloids extracted from Corydalis saxicola Bunting can reduce DNL-induced lipid accumulation in hepatocytes by hindering SREBP1 maturation through the activation of AMPK [330]. Diosgenin, in addition to reducing fatty acid uptake, can also inhibit hepatic DNL by activating AMPK and downregulating SREBP1c, thereby alleviating MAFLD [269,271]. Gallic acid, an abundant polyphenolic compound found in vegetables and fruits, can ameliorate fructose-induced hepatic steatosis by inhibiting hepatic DNL through AMPK-dependent mechanisms [272].…”

Section: Natural Products and Dnl In Mafldmentioning

confidence: 99%

Examining the Pathogenesis of MAFLD and the Medicinal Properties of Natural Products from a Metabolic Perspective

Fu,

Wang,

Qin

2024

Metabolites

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Metabolic-associated fatty liver disease (MAFLD), characterized primarily by hepatic steatosis, has become the most prevalent liver disease worldwide, affecting approximately two-fifths of the global population. The pathogenesis of MAFLD is extremely complex, and to date, there are no approved therapeutic drugs for clinical use. Considerable evidence indicates that various metabolic disorders play a pivotal role in the progression of MAFLD, including lipids, carbohydrates, amino acids, and micronutrients. In recent years, the medicinal properties of natural products have attracted widespread attention, and numerous studies have reported their efficacy in ameliorating metabolic disorders and subsequently alleviating MAFLD. This review aims to summarize the metabolic-associated pathological mechanisms of MAFLD, as well as the natural products that regulate metabolic pathways to alleviate MAFLD.

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Diosgenin attenuates nonalcoholic hepatic steatosis through the hepatic FXR-SHP-SREBP1C/PPARα/CD36 pathway

Cited by 15 publications

References 49 publications

Artesunate Inhibits Lipid Accumulation and Inflammation by Regulating the NLRP3 Inflammasome in Nonalcoholic Fatty Liver Disease

Artesunate Inhibits Lipid Accumulation and Inflammation by Regulating the NLRP3 Inflammasome in Nonalcoholic Fatty Liver Disease

Alanyl-Glutamine Dipeptide Attenuates Non-Alcoholic Fatty Liver Disease Induced by a High-Fat Diet in Mice by Improving Gut Microbiota Dysbiosis

Examining the Pathogenesis of MAFLD and the Medicinal Properties of Natural Products from a Metabolic Perspective

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