Apigenin Prevents Acetaminophen-Induced Liver Injury by Activating the SIRT1 Pathway

Zhao, Leilei; Zhang, Jiaqi; Hu, Cheng; Wang, Tao; Lü, Juan; Wu, Chenqu; Chen, Long; Jin, Mingming; Ji, Guang; Cao, Qing; Jiang, Yuanye

doi:10.3389/fphar.2020.00514

Cited by 37 publications

(22 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5(b)), implying NA has the different role to regulate the expression of Sirt1 and Nrf2 in physiological and pathological conditions. These results are consistent with other reports (21). In addition, NA pretreatment down regulated the expression level of Keap1 in APAP group (Fig.…”

Section: Na Activated Sirt1/nrf2 Signaling Pathwaysupporting

confidence: 93%

Nicotinic Acid against Acetaminophen-Induced Hepatotoxicity via Sirt1/Nrf2 Antioxidative Pathway in Mice

Zhang

Jiang

et al. 2021

J Nutr Sci Vitaminol

View full text Add to dashboard Cite

Acetaminophen (N-acetyl-p-aminophenol, APAP) overdose causes hepatotoxicity, even liver failure, and oxidative stress plays pivotal role in its pathogenesis. Nicotinic acid (NA) is one form of vitamin B3, which has been used to treat a series of diseases in clinic for decades. To date, several studies have evidenced that NA has anti-oxidative property. Therefore, NA may have the hepatoprotective potential against APAP-induced toxicity. Here, our aim was to investigate the beneficial effect of NA against hepatotoxicity induced by APAP and its mechanism in vivo. BALB/c mice were intraperitoneally injected with NA (100 mg/kg) 3 times at 24, 12 and 1 h before APAP (600 mg/kg or 400 mg/kg) challenge. The results showed that pretreatment of NA markedly improved the survival rate, alleviated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and mitigated the histopathological injuries compared to APAP-exposed mice. Furthermore, NA significantly elevated the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) content, while reduced malondialdehyde (MDA) level. Finally, the signaling pathway was probed. The western blot revealed that NA up-regulated Sirtuin1 (Sirt1), nuclear factor erythroid 2-related factor 2 (Nrf2) and NAD(P)H quinone dehydrogenase-1 (NQO-1) expression and down-regulated Kelch-like ECH-associated protein 1 (Keap1) level in liver followed APAP exposure, implying Sirt1/Nrf2 axis exerted an essential role in the protective mechanism of NA on APAP toxicity. In brief, pretreatment of NA effectively protects liver against hepatotoxicity due to overdose of APAP through an antioxidant dependent manner modulated by Sirt1/Nrf2 signaling pathway.

show abstract

Section: Na Activated Sirt1/nrf2 Signaling Pathwaysupporting

confidence: 93%

Nicotinic Acid against Acetaminophen-Induced Hepatotoxicity via Sirt1/Nrf2 Antioxidative Pathway in Mice

Zhang

Jiang

et al. 2021

J Nutr Sci Vitaminol

View full text Add to dashboard Cite

show abstract

“…Next, we determined whether H 2 O 2 or UVB induces cell-proliferation reduction in HS68 cells. The cells were exposed to different doses of H 2 O 2 (100, 150, 200, 250, and 300 µM) and UVB (25,30,40,50, and 60 mJ/cm 2 ) for 24 h. The results indicated that cell viability decreased in a dose-dependent manner following H 2 O 2 /UVB exposure (Figure 1C,D). Next, we examined the protective effects of galangin in H 2 O 2 -and UVB-exposed cells.…”

Section: Galangin Inhibited Uvb-and H 2 O 2 -Induced Proliferation Re...mentioning

confidence: 92%

Galangin Reverses H2O2-Induced Dermal Fibroblast Senescence via SIRT1-PGC-1α/Nrf2 Signaling

Lee

Hsu

et al. 2022

IJMS

View full text Add to dashboard Cite

UV radiation and H2O2 are the primary factors that cause skin aging. Both trigger oxidative stress and cellular aging. It has been reported that deacetylase silent information regulator 1 (SIRT1), a longevity gene, enhances activation of NF-E2-related factor-2 (Nrf2), as well as its downstream key antioxidant gene hemeoxygenase-1 (HO-1), to protect cells against oxidative damage by deacetylating the transcription coactivator PPARγ coactivator-1α (PGC-1α). Galangin, a flavonoid, possesses anti-oxidative and anti-inflammatory potential. In the present study, we applied Ultraviolet B/H2O2-induced human dermal fibroblast damage as an in vitro model and UVB-induced photoaging of C57BL/6J nude mice as an in vivo model to investigate the underlying dermo-protective mechanisms of galangin. Our results indicated that galangin treatment attenuates H2O2/UVB-induced cell viability reduction, dermal aging, and SIRT1/PGC-1α/Nrf2 signaling activation. Furthermore, galangin treatment enhanced Nrf2 activation and nuclear accumulation, in addition to inhibiting Nrf2 degradation. Interestingly, upregulation of antioxidant response element luciferase activity following galangin treatment indicated the transcriptional activation of Nrf2. However, knockdown of SIRT1, PGC-1α, or Nrf2 by siRNA reversed the antioxidant and anti-aging effects of galangin. In vivo evidence further showed that galangin treatment, at doses of 12 and 24 mg/kg on the dorsal skin cells of nude mice resulted in considerably reduced UVB-induced epidermal hyperplasia and skin senescence, and promoted SIRT1/PGC-1α/Nrf2 signaling. Furthermore, enhanced nuclear localization of Nrf2 was observed in galangin-treated mice following UVB irradiation. In conclusion, our data indicated that galangin exerts anti-photoaging and antioxidant effects by promoting SIRT1/PGC-1α/Nrf2 signaling. Therefore, galangin is a potentially promising agent for cosmetic skin care products against UV-induced skin aging.

show abstract

“…Recent studies have revealed that most fruits and vegetables are rich in flavonoids, which have anti-inflammatory and antioxidant effects (Gao et al, 2019;Zhang et al, 2020a;Zhao et al, 2020;Zhang et al, 2021). The hypoglycemic effects of flavonoids are associated with mechanisms, such as improved insulin resistance, inhibition of non-enzymatic glycosylation reactions of proteins, and reduction of blood lipids and oxidative stress levels (Sharma et al, 2015;Williamson, 2017).…”

Section: Introductionmentioning

confidence: 99%

Fisetin Attenuates Diabetic Nephropathy-Induced Podocyte Injury by Inhibiting NLRP3 Inflammasome

Dong

Jia

et al. 2022

Front. Pharmacol.

Self Cite

View full text Add to dashboard Cite

Diabetic nephropathy (DN) is one of the primary complications of diabetes. Fisetin is a flavonoid polyphenol that is present in several vegetables and fruits. The present study investigated the mechanisms of fisetin in DN-induced podocyte injury both in vitro and in vivo. The results revealed that fisetin ameliorated high glucose (HG)-induced podocyte injury and streptozotocin (STZ)-induced DN in mice. CDKN1B mRNA expression in the glomeruli of patients with DN decreased based on the Nephroseq dataset, and fisetin reversed CDKN1B expression at mRNA and protein levels in a dose-dependent manner in podocytes and mice kidney tissues. Furthermore, fisetin suppressed the phosphorylation of P70S6K, a downstream target of CDKN1B, activated autophagosome formation, and inhibited Nod-like receptor protein 3 (NLRP3) inflammasomes. Interfering CDKN1B reduced the protective effects of fisetin against high glucose-induced podocyte injury. Molecular docking results revealed a potential interaction between fisetin and CDKN1B. In summary, the present study revealed that fisetin alleviated high glucose-induced podocyte injury and STZ-induced DN in mice by restoring autophagy-mediated CDKN1B/P70S6K pathway and inhibiting NLRP3 inflammasome.

show abstract

Apigenin Prevents Acetaminophen-Induced Liver Injury by Activating the SIRT1 Pathway

Cited by 37 publications

References 62 publications

Nicotinic Acid against Acetaminophen-Induced Hepatotoxicity via Sirt1/Nrf2 Antioxidative Pathway in Mice

Nicotinic Acid against Acetaminophen-Induced Hepatotoxicity via Sirt1/Nrf2 Antioxidative Pathway in Mice

Galangin Reverses H2O2-Induced Dermal Fibroblast Senescence via SIRT1-PGC-1α/Nrf2 Signaling

Fisetin Attenuates Diabetic Nephropathy-Induced Podocyte Injury by Inhibiting NLRP3 Inflammasome

Contact Info

Product

Resources

About