Epigallocatechin gallate-rich fraction alleviates histamine-induced neurotoxicity in rats via inactivating caspase-3/JNK signaling pathways

Ingestion of prominent levels of histamine (HIS) leads to dangerous effects on biological systems. The most frequent and active catechin in green tea is epigallocatechin gallate which has strong antioxidant properties. Our research intended to investigate the possible neuroprotective effect of epigallocatechin gallate-rich fraction (EGCGR) against HIS-inducing neurotoxicity. Six groups of male rats (n = 5) were used as follows: (1) Distilled water, (2&3) EGCGR (100–200 mg/kg BWT/day, respectively), (4) HIS (1750 mg/kg BWT/week, (5&6) HIS + EGCGR. Administration of HIS for 14 days induced severe neurobehavioral changes including depression, incoordination, and loss of spatial memory. Extensive neuronal degeneration with diffuse gliosis was the prominent histopathological lesion observed and confirmed by strong immunostaining of casp-3, Cox-2, and GFAP. Additionally, the HIS group showed a significantly higher MDA level with lower CAT and GSH activity than the control group. Moreover, HIS promoted apoptosis, which is indicated by increasing JNK, and Bax and decreasing Bcl-2 gene expressions. Otherwise, the oral intake of EGCGR with HIS improved all neurotoxicological parameters induced by HIS. We concluded that HIS could cause neurotoxicity via an upset of the equilibrium between oxidants and antioxidants which trigger apoptosis through modulation of JNK signaling pathway. Furthermore, EGCGR has either direct or indirect antihistaminic effects.