Protective activity of tovophyllin A, a xanthone isolated from Garcinia mangostana pericarps, against acetaminophen-induced liver damage: role of Nrf2 activation

Abstract

Garcinia mangostana L. (GM, family Guttiferae) is one of the most widely recognized tropical fruits. GM is a wealthy pool of xanthones that exhibit a wide range of bioactivities. Tovophyllin A (TA) separated from GM pericarps was tested for its efficacy to ameliorate acetaminophen (APAP)-induced liver injury. Mice were injected with a single dose of APAP with or without TA pretreatment. The protective effects of TA against APAP-induced liver damage were evident through amelioration of serum indices of hepatotoxicity and improvement of hepatic histopathologic lesions. TA has antioxidant activity because it inhibited APAP-induced lipid peroxidation and improved the antioxidant capacity of the liver. Also, TA enhanced the mRNA expression of nuclear erythroid-related factor 2 (Nrf2) and its target genes. Protein expression of Nrf2 and heme oxygenase-1 was enhanced remarkably in TA-pretreated groups. TA suppressed activation of nuclear factor-kappa B (NF-κB) and the subsequent release of pro-inflammatory cytokines. In conclusion, TA has a marked protective activity against APAP-induced hepatotoxicity which may be linked to its ability to activate Nrf2 and inhibit the NF-κB signaling pathway.

Hepatoprotective Activity of the Ethanolic Extract of Polygonum multiflorum Thunb. against Oxidative Stress‐Induced Liver Injury

“…In addition, constant Nrf2 activation increased the basal hepatic GSH levels and accelerated their recovery after APAP treatment [ 20 ]. Recent data also support alleviation of APAP-induced liver injury through activation of the Nrf2 antioxidant pathway [ 21 , 22 ]. In the current study, PME induced activation of the Nrf2 pathway and decreased ROS production in vitro.…”

Genetic polymorphisms of long noncoding RNA RP11‐37B2.1 associate with susceptibility of tuberculosis and adverse events of antituberculosis drugs in west China

“…18 Ameliorate acetaminophen (APAP)-induced liver injury was attenuated by Tovophyllin A by activate Nrf2 and inhibit the NF-κB signaling pathway. 19 Therefore, it is speculated that these SNPs within RP11-37B2.1 may affect the occurrence of adverse reactions to antituberculosis drugs. In general, TB is a complex disease and immune factors affect its occurrence, development, and even adverse drug reactions.…”

“…RIPK2 interaction with NOD2 enhances NF‐kB activity making it an important player in immune response . Ameliorate acetaminophen (APAP)‐induced liver injury was attenuated by Tovophyllin A by activate Nrf2 and inhibit the NF‐κB signaling pathway . Therefore, it is speculated that these SNPs within RP11‐37B2.1 may affect the occurrence of adverse reactions to antituberculosis drugs.…”

Neuroprotection Against Parkinson’s Disease Through the Activation of Akt/GSK3β Signaling Pathway by Tovophyllin A

“…The structure of this compound was assigned by NMR and validated by comparing with the literature and spectroscopic and physical data (Ibrahim et al, 2018).…”