Prophylactic effect of myricetin and apigenin against lipopolysaccharide-induced acute liver injury

Abstract

Background Liver has an important role in the initiation and progression of multiple organ failure that occurs in sepsis. Many natural active substances can be used to reduce the liver injury caused by sepsis. For this aim, the effects of myricetin and apigenin on mice model of acute liver injury was evaluated in this study. Methods and resultsThirty-six mice were randomly divided into six groups as; control, lipopolysaccharide (LPS) (5 mg/kg), LPS + myricetin (100 mg/kg), LPS + myricetin (200 mg/kg), LPS + apigenin (100 mg/kg), and LPS + apigenin (200 mg/kg) groups. Myricetin and apigenin were administered orally for 7 days, and LPS was administered intraperitoneally only on the 7th day of the study. 24 h after LPS application, all animals were sacrificed and serum biochemical parameters, histopathology and oxidative stress and inflammation markers of liver tissue were examined. Myricetin and apigenin pre-treatments increased serum albumin and total protein levels, liver GSH level and catalase and SOD activities and decreased serum ALT, AST, ALP, γ-GT, CRP, total and direct bilirubin levels, liver MPO activity, MDA, NOx, PGE 2 , TNF-α, IL-1β, and IL-6 levels, iNOS and COX-2 mRNA levels, phosphorylation of NF-κB p65, IκB, and IKK proteins but not p38, ERK, and JNK proteins in LPS-treated mice. Myricetin and apigenin administration also regained the hepatic architecture disrupted during LPS application. Conclusion Myricetin and apigenin pre-treatments led to reduction of liver injury indices and oxidative stress and inflammatory events and these flavonoids has probably hepatoprotective effects in acute liver injury.

Beneficial Effects of Bauhinia rufa Leaves on Oxidative Stress, Prevention, and Treatment of Obesity in High-Fat Diet-Fed C57BL/6 Mice

“…MEBr increased the activity of the antioxidant enzymes SOD and CAT. It has been shown that components present in MEBr such as quercetin, myricetin, kaempferol, and p-coumaroyl increase the activity of the antioxidant enzymes SOD and CAT [38][39][40][41][42][43]. SOD is responsible for dismuting the radical superoxide anion (O2 •-) to H 2 O 2 , which is neutralized by CAT, limiting the production of hydroxyl radicals ( • OH) [44].…”

Apigenin attenuates inflammatory response in allergic rhinitis mice by inhibiting the TLR4/MyD88/NF‐κB signaling pathway

“…On days 21-25 after the beginning of the sensitization period, mice were sensitized by instillation of OVA solution into the bilateral nasal cavities by using a micropipette (100 μg/mice) once a day. Apigenin (100 μl/mice) at doses of 50, 100 or 200 mg/kg body weight 22,23 or dexamethasone (100 μl/mice) at a dose of 5 mg/kg body weight were orally administered to OVA-sensitized animals once daily from days 15 to 20. Mice in control group were given saline alone on the same schedule.…”

Phytochemicals, Biological Activities, Molecular Mechanisms, and Future Prospects of Plantago asiatica L.

“…Apigenin ( 1 ) and plantamajoside ( 25 ) can reduce pro-inflammation mediators (TNF-α, IL-1β, IL-6, IL-17A, NO, PGE2, iNOS, COX-2, NLRP3, and NF-κB); improve anti-inflammation cytokines (TGF-β and IL-10); and restrain the phosphorylation of NF-κB, IκB, and IKK proteins to inhibit inflammatory responses. ,− Similarly, luteolin ( 2 ), acteoside ( 27 ), and isoacteoside ( 28 ) regulate the expression of factors in the anti-inflammatory function, including (I) inflammatory mediators COX-2, iNOS, PGE2, NO, TLR4, Myd88, ICAM-1, and VCAM-1; (II) pro-inflammatory cytokines (like TNF-α, NLRP3, IL-1β, IL-17, and IL-18); (III) anti-inflammatory factors [such as arginase 1 (Arg-1), TGF-β, IL-4, IL-6, IL-10, and NO synthase-2]; and (IV) chemoattractant cytokines, such as C–C motif chemokine ligands (CCL)-2 and CCL-3 and the CXC motif chemokine ligands (CXCL)-1, CXCL-2, and CXCL-10. ,− It is reported that polysaccharides inhibit the secretion of TNF-α, IL-6, IL-10, IL-2, and IL-1β induced by LPS to prevent liver injury …”

“…Studies have shown that apigenin ( 1 ) administration blocks the secretion of pro-inflammatory cytokines and the activation of NF-κB; downregulates the expression of NLRP-3, TLR4, TNF-α, AMPK, and NF-κB; , and decreases the transcriptional activity of NF-κB and the phosphorylation of NF-κB, IκB, IKK, Lyn, Syk, MAPK, ERK, and JNK. , Similarly, luteolin ( 2 ) exerts an anti-inflammatory effect by downregulating the TLR4-mediated NF-κB/NLRP-3 and NF-κB phosphorylation. ,− The protective effects of acteoside ( 27 ) and isoacteoside ( 28 ) are mediated by phosphorylation of IKK, IκBα, NF-κB, and MAPK and the inactivation of TLR4-mediated NF-κB to modulate inflammation. ,− , Additionally, acteoside ( 27 ) restrains the inflammatory responses (TNF-α, IFN-γ, IL-6, and IL-12) by suppressing the JAK/STAT signaling pathway . Furthermore, plantamajoside ( 25 ) has anti-inflammatory properties via inhibition of the phosphorylation of IκBα, JNK, and MAPK, as well as nuclear translocation of NF-κB. , Unexpectedly, on the basis of the MAPK and NF-κB pathway, polysaccharides induce expression of MHC-II and CD86 to promote maturation of dendritic cells (DCs) and then accelerate the secretion of TNF-α and IL-12p70 so it may promote inflammatory effects .…”

“…Studies have shown that apigenin (1) administration blocks the secretion of pro-inflammatory cytokines and the activation of NF-κB; 38 downregulates the expression of NLRP-3, TLR4, TNF-α, AMPK, and NF-κB; 63,64 and decreases the transcriptional activity of NF-κB 65 and the phosphorylation of NF-κB, IκB, IKK, Lyn, Syk, MAPK, ERK, and JNK. 50,66 Similarly, luteolin (2) exerts an anti-inflammatory effect by downregulating the TLR4-mediated NF-κB/NLRP-3 and NF-κB phosphorylation. 53,67−69 The protective effects of acteoside (27) and isoacteoside ( 28) are mediated by phosphorylation of IKK, IκBα, NF-κB, and MAPK and the inactivation of TLR4-mediated NF-κB to modulate inflammation.…”