Flavonoids from Aurantii Fructus Immaturus and Aurantii Fructus: promising phytomedicines for the treatment of liver diseases

Abstract

Background: Liver diseases and related complications are major sources of morbidity and mortality, which places a huge financial burden on patients and lead to nonnegligible social problems. Therefore, the discovery of novel therapeutic drugs for the treatment of liver diseases is urgently required. Aurantii Fructus Immaturus (AFI) and Aurantii Fructus (AF) are frequently used herbal medicines in traditional Chinese medicine (TCM) formulas for the treatment of diverse ailments. A variety of bioactive ingredients have been isolated and identified from AFI and AF, including alkaloids, flavonoids, coumarins and volatile oils. Main body: Emerging evidence suggests that flavonoids, especially hesperidin (HD), naringenin (NIN), nobiletin (NOB), naringin (NRG), tangeretin (TN), hesperetin (HT) and eriodictyol (ED) are major representative bioactive ingredients that alleviate diseases through multi-targeting mechanisms, including anti-oxidative stress, anti-cytotoxicity, anti-inflammation, anti-fibrosis and anti-tumor mechanisms. In the current review, we summarize the recent progress in the research of hepatoprotective effects of HD, NIN, NOB, NRG, TN, HT and ED and highlight the potential underlying molecular mechanisms. We also point out the limitations of the current studies and shed light on further in-depth pharmacological and pharmacokinetic studies of these bioactive flavonoids. Conclusion: This review outlines the recent advances in the literature and highlights the potential of these flavonoids isolated from AFI and AF as therapeutic agents for the treatment of liver diseases. Further pharmacological studies will accelerate the development of natural products in AFI and AF and their derivatives as medicines with tantalizing prospects in the clinical application.

Multi-Therapeutic Potential of Naringenin (4′,5,7-Trihydroxyflavonone): Experimental Evidence and Mechanisms

“…The groups of rats intoxicated with CCl4 have shown repression of caspase-3 and -9 levels [ 108 ]. In a recently published article by Wu et al, the hepatoprotective action of naringenin has been attributed to its potential in inhibiting hepatic oxidative stress and inflammation [ 109 ].…”

Morchella importuna Polysaccharides Alleviate Carbon Tetrachloride-Induced Hepatic Oxidative Injury in Mice

“…These metabolites were mainly involved in flavonoid biosynthesis, amino acid metabolism, energy metabolism, and toxicant degradation. Numerous studies have indicated multifunctional flavonoids isolated from Chinese medicines and plants as potential therapeutic agents for the improvement of the liver tissue via antioxidant, anti-inflammatory, and antifibrotic mechanisms (Gou et al, 2020 ; Wu et al, 2020a ). Serum metabolomic analysis revealed that metabolites (i.e., isoliquiritigenin and prunin) related to flavonoid biosynthesis were significantly reduced by CCl 4 intoxication.…”

Effects of Bergamot Polyphenols on Mitochondrial Dysfunction and Sarcoplasmic Reticulum Stress in Diabetic Cardiomyopathy

“…In this experimental model, naringin treatment alleviated damage to the myocardial structure, decreased the content of MDA, and significantly increased SOD activities. In addition, the protein expressions of GRP78 and CHOP were decreased, demonstrating a protective action of naringin on SR stress of on mitochondrial oxidative stress induced by diabetes [ 166 ]. In parallel, an in vitro study was conducted on vascular endothelial cells in which a condition of stress that was induced by serum starvation and naringin was tested under the same experimental conditions at different concentrations and for different times [ 167 ].…”