Beta-caryophyllene mitigates the cognitive impairment caused by repeated exposure to aspartame in rats: Putative role of BDNF-TrKB signaling pathway and acetylcholinesterase activity.

Aspartame (ASP) is a common sweetener, but studies show it can harm the nervous system, causing learning and memory deficits. ß-caryophyllene (BCP), a natural compound found in foods, including bread, coffee, alcoholic beverages, and spices, has already described as a neuroprotector agent. Remarkably, ASP and BCP are commonly consumed, including in the same meal. Therefore, considering that (a) the BCP displays plenty of beneficial effects; (b) the ASP toxicity; and (c) that they can be consumed in the same meal, this study sought to investigate if the BCP would mitigate the memory impairment induced by ASP in rats and investigate the involvement of the brain-derived neurotrophic factor (BDNF)/ tropomyosin receptor kinase B (TrKB) signaling pathway and acetylcholinesterase (AChE) activity. Young male Wistar rats received ASP (75 mg/kg; i.g.) and/or BCP (100 mg/kg; i.p.) once daily, for 14 days. At the end of the treatment, the animals were evaluated in the open field and object recognition tests. The cerebral cortex and hippocampus samples were collected for biochemical and molecular analyses. Results showed that the BCP effectively protected against the cognitive damage caused by ASP in short and long-term memories. In addition, BCP mitigated the increase in AChE activity caused by ASP. Molecular insights revealed augmented BDNF and TrKB levels in the hippocampus of rats treated with BCP, indicating greater activation of this pathway. In conclusion, BCP protected against ASP-induced memory impairment. AChE activity and the BDNF/TrkB signaling pathway seem to be potential targets of BCP modulatory role in this study.

Myricetin attenuates the severity of seizures and neuroapoptosis in pentylenetetrazole kindled mice by regulating the of BDNF-TrkB signaling pathway and modulating matrix metalloproteinase-9 and GABAA.

Currently available antiepileptic drugs are effective; however, frequently associated with adverse effects that limit their therapeutic value. Compounds that target the molecular events underlying epilepsy, with minor or no adverse effects, would be of clinical value. Matrix metalloproteinase-9 (MMP-9) and the brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling pathway may be involved in epileptogenesis. The current study investigated the effects of the plant-derived hydroxyflavone, myricetin, in a pentylenetetrazole (PTZ)-induced mouse model of epilepsy. Mice received an intraperitoneal injection of 35 mg/kg body weight PTZ on alternate days (13 injections) and were observed for 30 min following each PTZ injection. Myricetin (100 or 200 mg/kg body weight) was administered orally to the treatment groups (n=18/group) for 26 days, 30 min prior to each PTZ injection. Treatment with myricetin reduced seizure and mortality rates. Increased apoptotic cell count and elevated expression levels of apoptotic proteins caused by PTZ kindling were downregulated following treatment with myricetin. The BDNF-TrkB signaling pathway and MMP-9 expression levels were regulated by myricetin. Expression of γ-aminobutyric acid A (GABA) receptor and glutamic acid decarboxylase 65, as well as the glutamate/GABA balance, were restored following treatment with myricetin. The results of the present study indicated that myricetin may exert protective effects by regulating the molecular events associated with epileptogenesis.