Natural-Product-Mediated Autophagy in the Treatment of Various Liver Diseases

Abstract

Autophagy is essential for the maintenance of hepatic homeostasis, and autophagic malfunction has been linked to the pathogenesis of substantial liver diseases. As a popular source of drug discovery, natural products have been used for centuries to effectively prevent the progression of various liver diseases. Emerging evidence has suggested that autophagy regulation is a critical mechanism underlying the therapeutic effects of these natural products. In this review, relevant studies are retrieved from scientific databases published between 2011 and 2022, and a novel scoring system was established to critically evaluate the completeness and scientific significance of the reviewed literature. We observed that numerous natural products were suggested to regulate autophagic flux. Depending on the therapeutic or pathogenic role autophagy plays in different liver diseases, autophagy-regulative natural products exhibit different therapeutic effects. According to our novel scoring system, in a considerable amount of the involved studies, convincing and reasonable evidence to elucidate the regulatory effects and underlying mechanisms of natural-product-mediated autophagy regulation was missing and needed further illustration. We highlight that autophagy-regulative natural products are valuable drug candidates with promising prospects for the treatment of liver diseases and deserve more attention in the future.

An aqueous olive leaf extract (OLE) ameliorates parameters of oxidative stress associated with lipid accumulation and induces lipophagy in human hepatic cells

“…Our data are in line with those of recent work describing the ability of polyphenol-rich natural products to treat various liver diseases through the regulation of the autophagic process. 87 Overall, our data provide important results because the use of low temperatures and water makes the olive leaf extract safe and at the same time guarantees the total preservation of its beneficial properties on the liver.…”

“…Our data are in line with those of recent work describing the ability of polyphenol-rich natural products to treat various liver diseases through the regulation of the autophagic process. 87…”

Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy

“…The transformation of phagophores into autophagosomes requires the Atg12–Atg5–Atg16 complex and the phosphatidylethanolamine (PE)-conjugated LC3II (Atg8) system. Finally, the autophagosome fuses with the lysosome for the degradation of the contents, which thereby degrades the autophagosomal contents ( Figure 1 ) [ 255 , 256 ].…”

“…Regorafenib resistance is due to reduction in the drug-induced apoptosis by topoisomerase IIα (TOP2A)-upregulated gene, which is involved in the resistance to regorafenib [ 499 ]. Interestingly, many natural products are effective, inhibiting protective autophagy or inducing autophagic death and the apoptosis of HCC cells [ 256 ].…”

Nutriepigenomics in Environmental-Associated Oxidative Stress

“…In this context, it is interesting to note that autophagy is also regulated at epigenetic levels [ 246 , 247 ] and a variety of nutrients and natural dietary products with antioxidant properties also stimulate autophagy via epigenetic mechanisms [ 248 , 249 , 250 ]. Particularly, plant- and fruit-derived polyphenols and flavonoids, such as, for example, curcumin, resveratrol, quercetin and catechins, exert anti-inflammatory activity and protect against disease through the epigenetic modulation of autophagy [ 251 , 252 , 253 , 254 ]. In the next paragraph, we shall discuss in detail the epigenetic mechanisms through which the most relevant nutrients and dietary phytochemicals act.…”