Hepatoprotective effect of kaempferol glycosides isolated from Cedrela odorata L. leaves in albino mice

Abstract

Background and purpose: Paracetamol is the most implicated xenobiotic in inducing hepatotoxicity. Our study aimed to determine the impact of some kaempferol glycosides isolated from the leaves of Cedrela odorata L. on paracetamol hepatotoxicity. Experimental approach: The methanolic extract of dried leaves of C. odorata L . was subjected to the combination of spectroscopic methods ( 1 H and 13 CNMR). Six kaempferol glycosides were isolated: kaempferol-3- O -β-D-glycopyranoside (astragalin), kaempferol-3- O -β-L-rhamnopyranoside, kaempferol-3- O -β-D-rutinoside, kaempferide-3- O -β-D-rutinoside, kaempferide-3- O -β-Drutinosyl-7- O -β-D-rhamnopyranoside, and kaempferol-3- O -β-D- rutinosyl-7- O -a-D-arabinopyranoside. Fifty-four female Swiss Albino mice were divided randomly into 9 groups including (1) control negative (1 mL/kg saline; IP), (2) control positive (paracetamol 300 mg/kg; IP), (3) silymarin 50 mg/kg (IP). Animals of groups 4-9 were injected with 6 different samples of isolated compounds at 100 mg/kg (IP). One h later, groups 3-9 were injected with paracetamol (300 mg/kg IP). Two h later, tissue samples were taken from all animals to assess nitrotyrosine, c-Jun N-terminal protein kinase (c-JNK), Raf -1kinase, and oxidative stress biomarkers viz . reduced glutathione (GSH) and malondialdehyde (MDA). Findings/Results: Isolated glycosides had a prominent anti-apoptotic effect via inhibition of c-JNK and Raf-1 kinase. They also exerted a powerful antioxidant effect by modulating the oxidative stress induced by paracetamol via increasing GSH, reducing MDA and nitrotyrosine concentrations compared to positive control. The glycoside (1) showed a better effect than silymarin (standard) in ameliorating the formation of nitrotyrosine, Raf-1 kinase, c-JNK, and GSH. Conclusion and implication: Kaempferol glycosides isolated for the first time from C. odorata L. leaves exerted antioxidant and antiapoptotic effects via amelioration of oxidative stress and inhibition of Raf/MAPK pathway.

Kaempferol sophoroside glucoside mitigates acetaminophen-induced hepatotoxicity: Role of Nrf2/NF-κB and JNK/ASK-1 signaling pathways

“…Interestingly, pretreatment with KSG significantly alleviated the pathological lesions and reduced the elevated levels of transaminases, ALP, LDH, and γ-GT, indicating protection of the liver's integrity and function by KSG. Importantly, the hepatoprotective activity of different derivatives of kaempferol against experimental hepatic injury has been shown previously [ 30 , 31 , 56 , 57 ].…”

Acacia sieberiana (Fabaceae) Attenuates Paracetamol and Bile Duct Ligation-Induced Hepatotoxicity via Modulation of Biochemical and Oxidative Stress Biomarkers

“…For instance, flavonoids compounds such as catechin and kaempferol fight against free radicals and inhibit liver disease pathogenesis (Okaiyeto et al, 2018). Also, glycosides act as an antioxidant to provide hepatoprotective efficacy (Asaad et al, 2021; Siddiqui et al, 2018). Besides, (Huang et al, 2014) reported the hepatic protection of triterpenoids and saponins.…”

Acacia sieberiana (Fabaceae) attenuates paracetamol and Bile Duct Ligation-Induced hepatotoxicity via modulation of biochemical and oxidative stress biomarkers

“…For instance, flavonoids compounds such as catechin and kaempferol fight against free radicals and inhibit liver disease pathogenesis (Okaiyeto et al, 2018). Also, glycosides act as an antioxidant to provide hepatoprotective efficacy (Siddiqui et al, 2018;Asaad et al, 2021). Besides, (Huang et al, 2014), reported the hepatic protection of triterpenoids and saponins.…”