Hesperetin modulates the Sirt1/Nrf2 signaling pathway in counteracting myocardial ischemia through suppression of oxidative stress, inflammation, and apoptosis

Li, Panpan; Li, Jinghan; Liu, Miaomiao; Xue, Yucong; Zhang, Yuanyuan; Han, Xue; Jing, Xuan; Chu, Li

doi:10.1016/j.biopha.2021.111552

Cited by 62 publications

(31 citation statements)

References 54 publications

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“…Hesperidin and hesperetin have both been observed to confer protective properties on neurons in both in vitro and animal models of various neurological diseases such as Alzheimer disease, epilepsy, Huntington disease, and Parkinson disease, in which cytotoxicity was induced by inflammatory stimuli, oxidative stress, or neurotoxic stress in animal models [ 23 , 28 ]. In addition, hesperetin supplementation led to decreased oxidative stress, inflammation, and apoptosis in a murine model of myocardial ischemia [ 29 ]. Several flavonoids, including hesperetin, appear to increase the barrier integrity of the tight junction in human intestinal Caco-2 cells [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Feeding Fiber-Bound Polyphenol Ingredients at Different Levels Modulates Colonic Postbiotics to Improve Gut Health in Dogs

Jewell

Jackson

Cochrane

et al. 2022

Animals

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This study assessed changes in canine fecal metabolites and microbiota with the consumption of foods with increasing concentrations of a fiber bundle including pecan shells, flax seed, and powders of cranberry, citrus, and beet that was previously shown (at 14% w/w) to improve stool quality, shift fecal bacterial metabolism from proteolysis to saccharolysis, increase abundance of saccharolytic bacteria, and decrease abundance of proteolytic bacteria. In this study, 48 healthy adult dogs were split evenly to consume different inclusion levels (0%, 1%, 2%, and 4%) of the fiber bundle for a 31-day period following a 28-day pre-feed period. Increases from baseline in the fecal short-chain fatty acids butyric acid, valeric acid, and hexanoic acid were observed only in the dogs that consumed the food with the 4% fiber bundle. With addition of any level of the fiber bundle, increases were seen in the polyphenols hesperidin, hesperetin, ponciretin, secoisolariciresinol diglucoside, secoisolariciresinol, and enterodiol. However, fecal microbiota and their metabolism, and stool scores were largely unaffected by the fiber bundle. Overall, addition of the fiber bundle appeared to increase bioactive metabolites of increased antioxidant and anti-inflammatory potency for beneficial to health and, at levels ≥4%, shifted gut bacterial metabolism toward saccharolysis.

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Section: Discussionmentioning

confidence: 99%

Feeding Fiber-Bound Polyphenol Ingredients at Different Levels Modulates Colonic Postbiotics to Improve Gut Health in Dogs

Jewell

Jackson

Cochrane

et al. 2022

Animals

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“…The chemical structure of HES is shown in Figure 1 and its IUPAC name is ((S)-2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4 methoxy-phenyl)-4H-1-benzopyran-4-one). Similar to most flavonoids, HES is also a natural antioxidant and has anti-inflammatory, anti-atherosclerotic, and anti-diabetic properties [14][15][16][17][18]. Several studies have reported that HES can ameliorates anxiety and depression-like behaviors by enhancing Glo-1 and activating the Nrf2/ARE pathway in the brain of diabetic rats and high glucose cultured SH-SY5Y cells [19].…”

Section: Introductionmentioning

confidence: 99%

Crystal Structure, Solubility, and Pharmacokinetic Study on a Hesperetin Cocrystal with Piperine as Coformer

et al. 2022

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Hesperetin (HES) is a key biological active ingredient in citrus peels, and is one of the natural flavonoids that attract the attention of researchers due to its numerous therapeutic bioactivities that have been identified in vitro. As a bioenhancer, piperine (PIP) can effectively improve the absorption of insoluble drugs in vivo. In the present study, a cocrystal of HES and PIP was successfully obtained through solution crystallization. The single-crystal structure was illustrated and comprehensive characterization of the cocrystal was conducted. The cocrystal was formed by two drug molecules at a molar ratio of 1:1, which contained O–H–O hydrogen bonds between the carbonyl and ether oxygen of PIP and the phenolic hydroxyl group of HES. In addition, a solubility experiment was performed on powder cocrystal in simulated gastrointestinal fluid, and the result revealed that the cocrystal improves the dissolution behavior of HES compared with that of the pure substance. Furthermore, HES’s bioavailability in the cocrystal was six times higher than that of pristine drugs. These results may provide an efficient oral formulation for HES.

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“…Then, the question arises of how FGF20 alleviates oxidative stress in the heart. Emerging evidence indicates that SIRT1, a nicotinamide adenosine dinucleotide (NAD+)-dependent protein deacetylase, is a redox-resistant factor in the heart [ 15 , 45 , 46 ]. Importantly, the increased oxidative stress correlated with decreased SIRT1 expression during the development of heart failure [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Fibroblast growth factor 20 attenuates pathological cardiac hypertrophy by activating the SIRT1 signaling pathway

et al. 2022

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Cardiac hypertrophy occurs initially in response to an increased cardiac load as a compensatory mechanism to maintain cardiac output. However, sustained pathological hypertrophy can develop into heart failure and cause sudden death. Fibroblast growth factor 20 (FGF20) is a member of the fibroblast growth factor family, which involved in apoptosis, aging, inflammation, and autophagy. The precise function of FGF20 in pathological cardiac hypertrophy is unclear. In this study, we demonstrated that FGF20 was significantly decreased in response to hypertrophic stimulation. In contrast, overexpression of FGF20 protected against pressure overload-induced cardiac hypertrophy. Mechanistically, we found that FGF20 upregulates SIRT1 expression, causing deacetylation of FOXO1; this effect promotes the transcription of downstream antioxidant genes, thus inhibits oxidative stress. In content, the anti-hypertrophic effect of FGF20 was largely counteracted in SIRT1-knockout mice, accompanied by an increase in oxidative stress. In summary, our findings reveal a previously unknown protective effect of FGF20 on pathological cardiac hypertrophy by reducing oxidative stress through activation of the SIRT1 signaling pathway. FGF20 is a potential novel molecular target for preventing and treating pressure overload-induced myocardial injury.

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Hesperetin modulates the Sirt1/Nrf2 signaling pathway in counteracting myocardial ischemia through suppression of oxidative stress, inflammation, and apoptosis

Cited by 62 publications

References 54 publications

Feeding Fiber-Bound Polyphenol Ingredients at Different Levels Modulates Colonic Postbiotics to Improve Gut Health in Dogs

Feeding Fiber-Bound Polyphenol Ingredients at Different Levels Modulates Colonic Postbiotics to Improve Gut Health in Dogs

Crystal Structure, Solubility, and Pharmacokinetic Study on a Hesperetin Cocrystal with Piperine as Coformer

Fibroblast growth factor 20 attenuates pathological cardiac hypertrophy by activating the SIRT1 signaling pathway

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