Hepatic‐Targeted Nano‐enzyme with Resveratrol Loading for Precise Relief of Nonalcoholic Steatohepatitis

Abstract

Nonalcoholic steatohepatitis (NASH) is characterized by massive lipid deposition in hepatocytes and is often associated with hepatic inflammation and other severe metabolic syndromes. The intervention of NASH can prevent its further progression into hepatocarcinoma. In this study we have successfully constructed liver‐targeted Ce‐based hollow mesoporous nanocarriers loaded with bioactive drugs. This may provide an effective approach for eliminating NASH. Liver‐section‐specific targeting was realized by covalently linked galactose (Gal), which can be specifically recognized by receptors in the membranes of hepatocytes. Meanwhile, resveratrol (Res), a drug used to treat NASH, was efficiently loaded into the pores and cavity of CeO2 (Res@H−CeO2−Gal). In steatotic HepG2 cells (free fatty acid induction), this nanosystem was found to enhance cellular Res internalization for improved anti‐lipogenesis activity. In mice with NASH, Res@H−CeO2−Gal increased Res delivery to liver sections for a reduction in lipid accumulation and enhanced anti‐inflammatory activity from the antioxidant capacity of Ce‐based nanocarriers. This effectively recovered NASH mice to the normal state. These findings show that the hepatic targeting and Res delivery nanoplatform could act as a safe and promising strategy for the elimination of NASH and other liver diseases.

Gold Nanoparticles Encapsulated Resveratrol as an Anti-Aging Agent to Delay Cataract Development

“…Resveratrol (3,5,4-trihydroxy-trans-stilbene, Res) is a natural polyphenol found in plants such as peanuts, grapes, and strawberries [ 9 , 10 ]. Recently, many studies have reported that Res possesses anti-inflammatory, anti-cancer, and anti-bacterial properties [ 11 , 12 , 13 ]. Intriguingly, the ability of Res to induce antioxidant formation in many cell types has validated its anti-aging potential, which has, in turn, attracted extensive attention in the research community.…”

Human diet‐derived polyphenolic compounds and hepatic diseases: From therapeutic mechanisms to clinical utilization

“…were established for the treatment of NASH mice, and the results demonstrated increased resveratrol delivery to the liver, reduced lipid buildup, and enhanced anti-inflammatory activity (Tong et al, 2023).…”

“…This nanocarrier effectively alleviated lipid buildup and insulin resistance by modulating the AMPK/SIRT1/FAS/SREBP1c signaling pathway (Teng et al, 2019). Furthermore, similar resveratrol nanocarriers (resveratrol‐CeO2‐ galactose) were established for the treatment of NASH mice, and the results demonstrated increased resveratrol delivery to the liver, reduced lipid buildup, and enhanced anti‐inflammatory activity (Tong et al, 2023). Moreover, curcumin complexes with silver nanoparticles (AgNPs) were developed for the treatment of CCl4‐induced hepatic fibrosis.…”

Protective role of resveratrol against VCM-induced hepatotoxicity in male wistar rats

“…As well as protecting cells from oxidative stress, resveratrol also promotes the expression of antioxidative enzymes and their substrates ( Miguel et al, 2021 ; Santos et al, 2021 ). Recently, it has been suggested that resveratrol has hepatoprotection properties through its anti-inflammatory and antioxidant effects ( Chupradit et al, 2022 ; Ma et al, 2022 ; Tong et al, 2022 ). It has also been reported that resveratrol attenuates acetaminophen toxic metabolite N-acetyl-p-benzoquinone-imine and facilitates liver regeneration by modulating the silent mating type information regulation two homolog (SIRT1), tumor protein P53, and Tumor Necrosis Factor-alpha (TNF-α) ( Sener et al, 2006 ; Wang et al, 2015 ).…”