The anticonvulsant effect of saiga horn on febrile seizures by regulating brain serotonin content and inhibiting neuroinflammation

Abstract

Ethnopharmacological relevance: Saiga antelope horn (SAH) is derived from the Saiga antelope (Saiga tatarica Linnaeus) of the bovidae family. SAH has been used for the treatment of febrile seizures (FS) in children for thousands of years in China. Due to the biological protection of Saiga antelope and its ethical reasons, the application of SAH has been widely restricted. Unfortunately, the field of artificial manufacturing of SAH is still blank at present. The mechanism of SAH in the treatment of FS is still unclear, which seriously hinders the further development of artificial antelope horns and the search for substitutes for SAH. At present, there is an urgent need to determine the mechanism of SAH in the treatment of FS, so as to provide a theoretical basis for artificial antelope horn and its substitutes.

Aim of the study: To explore the anti-FS effect of natural SAH on FS rat model and its possible mechanism, and to provide a theoretical basis for the subsequent manufacture of artificial antelope horns and the search for the best substitutes.

Materials and methods: FS was induced by a warm water bath (48 ± 0.5 °C). The latency and seizure grade of FS were observed and recorded. Hematoxylin-eosin (HE) staining was used to observe the functional defect of hippocampal cells. The contents of tryptophan (TRP), serotonin (5-HT), IL-1β and TNF-a in rat brain tissue were determined by ELISA. qRT-PCR and Western blot were used to detect the expression of 5-HT synthesis related neurotransmitter receptors, catalytic enzymes and inflammatory factors in hippocampus. Immunofluorescence was used to observe the expression of TPH2 protein in the dorsal raphe nucleus of rat brain.

Results: After pretreating rats with SAH, the seizure grade of FS was significantly reduced and the latency was prolonged. SAH can reduce the histological damage of hippocampal tissue induced by FS in rats. Further analysis of ELISA results showed that SAH significantly increased the levels of TRP and 5-HT in the brain of FS rats, and significantly decreased the levels of IL-1β and TNF-a. The results of QPCR showed that SAH could up-regulate the expression of ER-β and TPH2 mRNA and down-regulate the expression of IL-1β and TNF-ɑ mRNA in the hippocampus of rats. In addition, WB and immunofluorescence results showed that SAH could significantly up-regulate the expression of ER-β/TPH2/5-HT pathway in the hippocampus of FS rats and the expression of TPH2 protein in the raphe nucleus, but had no significant effect on SERT protein in the hippocampus of FS rats. In addition, ER-β protein inhibitor PHTPP significantly inhibited the therapeutic effect of SAH on FS rats.

Conclusions: The present study demonstrates that SAH has a significant anticonvulsant effect on the FS rat model. The mechanism may be related to the increase of TRP content and up-regulation the expression of ER-β/TPH2/5-HT signaling pathway in the brain of FS rats, thereby increasing the content of 5-HT in the brain and reducing the content of IL-1β and TNF-a in the brain.

Keywords: ER-β/TPH2/5-HT; Febrile seizures; PHTPP; Saiga antelope horn.