Treatment options for NAFLD
| Molecules | Target | Function | References |
|---|---|---|---|
| AAE | OS | AAE protected mitochondrial function and reduced OS by reducing lipid peroxidation and modulating the expression of antioxidant enzymes (e.g., glutathione reductase and catalase). | [79] |
| ISV | Oxidative and ER stress | ISV, a derivative of stevioside extracted from the plant Stevia Rebaudiana Bertoni, prevents FFA- and HFD-induced hepatic injury through modulating protein kinase C-β/Src-homology-2-domain-containing transforming protein 1-mediated oxidative and ER stress. ISV also decreased ER-mitochondrial interaction. | [80] |
| PK | Mitochondrial UCP-2 | PK promoted mitochondrial function by inhibiting HFD-induced increase of mitochondrial UCP-2 and HFD-induced decrease of cytochrome c and by up-regulating CPT-1, which alleviates NAFLD. | [81] |
| Melatonin | Mitochondrial fission | Melatonin supplementation halted mitochondrial fission but recovered mitophagy via blockade of NR4A1-DNA-PKcs-p53 pathway, conferring a protective effect to hepatocytes and mitochondrial function. | [83] |
| n-3 PUFA | ER stress and mitochondrial dysfunction | Analysis of hepatic proteomics and plasma lipidomics indicated that 6-month treatment with n-3 PUFA significantly ameliorated markers of lipid metabolism, ER stress, and mitochondrial functions in patients with NASH. | [89, 97] |
| MaR1 | SERCA2b | MaR1, a DHA-derived metabolite, inhibited hepatic lipid synthesis and steatosis via activating AMPK/SERCA2b-mediated suppression of ER stress in HFD-fed mice. | [81, 92] |
| Monounsaturated OA | ER stress, mitochondrial dysfunction, OS | Treatment with monounsaturated OA markedly improved PA-induced cellular apoptosis, OS, ER stress, mitochondrial dysfunction, as well as inflammation in hepatocytes. | [93] |
| Astragaloside IV (AS-IV) | ER stress | Treatment with AS-IV, a bioactive compound isolated from Astragali Radix, attenuated FFA-induced hepatic ER stress in a dose-dependent manner, evidenced by the reduction of the critical markers, GRP78, CHOP, and phospho-protein kinase R-like endoplasmic reticulum kinase (p-PERK). These results suggest that AS-IV is a promising therapeutic agent for hepatic steatosis and NAFLD. | [89, 97] |
| R-Tf-D-LP4 | VDAC1 | R-Tf-D-LP4 treatment eliminated hepatocyte ballooning degeneration, inflammation, and liver fibrosis associated with steatosis, NASH, and hepatocarcinoma, and it restored liver pathology-associated enzyme and glucose levels. | [98] |
| Silymarin | ER stress | Silymarin ameliorated NAFLD via inhibiting ER stress proteins GRP78 and XBP-1. | [99] |
