Anti-aging effect of phlorizin on D-galactose–induced aging in mice through antioxidant and anti-inflammatory activity, prevention of apoptosis, and regulation of the gut microbiota

Chen, Huiying; Dong, Ling; Chen, Xueyan; Ding, Chuanbo; Hao, Mingqian; Peng, Xiaojuan; Zhang, Yue; Zhu, Hongyan; Liu, Wencong

doi:10.1016/j.exger.2022.111769

Cited by 35 publications

(22 citation statements)

References 70 publications

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“…In addition, the hepatic CAT activity was remarkably increased in LPS-treated mice with L. paracasei CCFM1222 pretreatment. CAT is a vital endogenous enzyme that relieves the symptoms of in ammation by eliminating the reactive oxygen species in the body [29].…”

Section: Discussionmentioning

confidence: 99%

Intestinal Microbiomics and Metabolomics Insights into the Hepatoprotective Effects of Lactobacillus paracasei CCFM1222 Against the Acute Liver Injury in Mice

Guo

Cui

Tang

et al. 2022

Probiotics & Antimicro. Prot.

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In recent years, acute liver injury (ALI) has received wide-range attention in the world due to its relatively high morbidity and mortality. This study aimed to explore the hepatoprotective effect of Lactobacillus paracasei CCFM1222 against lipopolysaccharide (LPS)-induced ALI mice, and further elaborate its mechanism of action from the perspective of intestinal microbiomics and metabolomics. The results displayed that L. paracasei CCFM1222 pretreatment signi cantly decreased the serum ALT, and AST levels, inhibited the releases of hepatic TNF-α, IL-1β, and IL-6 levels, and activated the SOD, CAT, and GSH-Px activities in LPS-treated mice. The cecal short-chain fatty acid (SCFAs) levels were increased in LPStreated mice with L. paracasei CCFM1222 pretreatment. In addition, L. paracasei CCFM1222 pretreatment remarkably shifted the intestinal microbiota composition, including the higher abundance of Faecalibaculum, Bi dobacterium, and lower abundance of Prevotellaceae NK3B31 group, which is positively associated with the cecal propionic, butyric, valeric, isobutyric, and isovaleric acids. The metabolomics based on UPLC-QTOF/MS revealed that L. paracasei CCFM1222 pretreatment signi cantly regulated the composition of feces metabolites in LPS-treated mice, especially the potential biomarkersrelated butanoate metabolism, vitamin B6 metabolism, D-glutamine and D-glutamate metabolism, tryptophan metabolism, caffeine metabolism, arginine biosynthesis, arginine, and proline metabolism. Moreover, L. paracasei CCFM1222 pretreatment remarkably regulated the expression of genes-associated ALI (including Tlr4, Myd88, Nf-kβ, iNOS, Cox2, Iκ-Bα, Nrf2, and Sirt-1). In conclusion, these results suggest the possibility that L. paracasei CCFM1222 supplementation has bene cial effects on preventing the occurrence and development of ALI by inhibiting the in ammatory responses, altering intestinal microbiota composition and their metabolites, and mediating the Tlr4/Nf-kβ pathway.

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Section: Discussionmentioning

confidence: 99%

Intestinal Microbiomics and Metabolomics Insights into the Hepatoprotective Effects of Lactobacillus paracasei CCFM1222 Against the Acute Liver Injury in Mice

Guo

Cui

Tang

et al. 2022

Probiotics & Antimicro. Prot.

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“…At the phylum level, F/B was significantly higher in the M group than in the C group, while the ratio in the H and L groups was significantly decreased after EA intervention. Studies have shown that the F/B ratio was significantly increased in D-galinduced aging mice 45 as well as in humans with age. 46 At the genus level, compared with the M group, in the H group, a relatively increased abundance of Akkermansia, Bif idobacterium, Clostridium_sensu_stricto_1, Turicibacter, and Lactobacillus were observed after EA intervention.…”

Section: Discussionmentioning

confidence: 99%

Ameliorative Effect of Ellagic Acid on Aging in Rats with the Potential Mechanism Relying on the Gut Microbiota and Urolithin A-Producing Ability

Xian

Deng

Yang

et al. 2023

J. Agric. Food Chem.

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Ellagic acid (EA) exhibits potential antiaging activity. Differences in individual ability to produce urolithins may result in large interindividual variability in the health effects of EA. Therefore, the effects and mechanism of EA on d-galactose-induced aging, considering urolithin A-producing ability, were investigated. Our results showed that EA improved cognitive impairment and hippocampal damage, increased the GABA (by 107.84–117.86%) and 5-HT (by 72.56–100.85%) levels, and suppressed the inflammatory and oxidative stress in aging rats. Thirteen plasma metabolites and 12 brain metabolites were improved by EA administration in aging rats. In particular, EA showed a better anti-aging effect in high-UroA-producing rats than in the low counterparts, while antibiotic intervention almost offset EA-alleviated aging induced by d-gal. Furthermore, the lower ratio of Firmicutes and Bacteroidota as well as the greater abundances of Akkermansia (by 139.21%), Bifidobacterium (by 88.04%), Clostridium_sensu_stricto_1 (by 183.47%), Lactobacillus (by 97.23%), and Turicibacter (by 83.06%) were observed in the high-UroA-producing group compared with the model group (p < 0.05). These findings provide novel insights into the anti-aging effects of EA and suggest that the ability of the gut microbiota responding to EA largely determines EA’s anti-aging performance.

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“…We showed that dietary supplementation with phlorizin exhibited beneficial effects in disease models of AD, DM, and PD. A previous study has shown that phlorizin reduced neuronal damage and improved learning and memory abilities in D-galactose-induced aged mice [ 50 ]. In streptozotocin-induced dementia of AD, phlorizin alleviated cognitive decline and neuropathological conditions with AD [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-Oxidant and Anti-Aging Effects of Phlorizin Are Mediated by DAF-16-Induced Stress Response and Autophagy in Caenorhabditis elegans

Park

2022

Antioxidants

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Phlorizin (phloridzin) is a polyphenolic phytochemical primarily found in unripe Malus (apple). It is a glucoside of phloretin and acts as an inhibitor of renal glucose transport, thus lowering blood glucose. The objective of this study was to determine effects of dietary supplementation with phlorizin on stress response, aging, and age-related diseases using Caenorhabditis elegans as a model system. Survival after oxidative stress or ultraviolet irradiation was significantly increased by pre-treatment of phlorizin. Dietary supplementation with phlorizin also significantly extended lifespans without reducing fertility. Age-related decline of muscle function was delayed by supplementation with phlorizin. Phlorizin induced the expression of stress-responsive genes hsp-16.2 and sod-3 and nuclear localization of DAF-16, a FOXO transcription factor modulating stress response and lifespan in C. elegans. Amyloid-beta-induced toxicity was significantly reduced by phlorizin. This effect was dependent on DAF-16 and SKN-1. Increased mortality induced with a high-glucose diet was partially prevented by phlorizin via SKN-1. Inactivation of dopaminergic neurons observed in a Parkinson’s disease model was completely recovered by supplementation with phlorizin. Genetic analysis suggests that lifespan extension by phlorizin is mediated through oxidative stress response and autophagy. Taken together, these data suggest that phlorizin has strong anti-oxidant and anti-aging activities with potential to be developed as a novel anti-oxidant nutraceutical against aging and age-related diseases.

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Anti-aging effect of phlorizin on D-galactose–induced aging in mice through antioxidant and anti-inflammatory activity, prevention of apoptosis, and regulation of the gut microbiota

Cited by 35 publications

References 70 publications

Intestinal Microbiomics and Metabolomics Insights into the Hepatoprotective Effects of Lactobacillus paracasei CCFM1222 Against the Acute Liver Injury in Mice

Intestinal Microbiomics and Metabolomics Insights into the Hepatoprotective Effects of Lactobacillus paracasei CCFM1222 Against the Acute Liver Injury in Mice

Ameliorative Effect of Ellagic Acid on Aging in Rats with the Potential Mechanism Relying on the Gut Microbiota and Urolithin A-Producing Ability

Anti-Oxidant and Anti-Aging Effects of Phlorizin Are Mediated by DAF-16-Induced Stress Response and Autophagy in Caenorhabditis elegans

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