Temporal lobe epilepsy (TLE) is a chronic neurological disorder that is often resistant to antiepileptic drugs. The pathogenesis of TLE is extremely complicated and remains elusive. Understanding the molecular mechanisms underlying TLE is crucial for its diagnosis and treatment. In the present study, a lithium-pilocarpine-induced TLE model was employed to reveal the pathological changes of hippocampus in rats. Hippocampal samples were taken for proteomic analysis at 2 weeks after the onset of spontaneous seizure (a chronic stage of epileptogenesis). Isobaric tag for relative and absolute quantization (iTRAQ) coupled with liquid chromatography-tandem mass spectrometry (LC–MS/MS) technique was applied for proteomic analysis of hippocampus. A total of 4173 proteins were identified from the hippocampi of epileptic rats and its control, of which 27 differentially expressed proteins (DEPs) were obtained with a and . Bioinformatics analysis indicated 27 DEPs were mainly enriched in “regulation of synaptic plasticity and structure” and “calmodulin-dependent protein kinase activity,” which implicate synaptic remodeling may play a vital role in the pathogenesis of TLE. Consequently, the synaptic plasticity-related proteins and synaptic structure were investigated to verify it. It has been demonstrated that CaMKII-α, CaMKII-β, and GFAP were significant upregulated coincidently with proteomic analysis in the hippocampus of TLE rats. Moreover, the increased dendritic spines and hippocampal sclerosis further proved that synaptic plasticity involves in the development of TLE. The present study may help to understand the molecular mechanisms underlying epileptogenesis and provide a basis for further studies on synaptic plasticity in TLE.

Background and Purpose: Temporal lobe epilepsy (TLE) is a common chronic neurological disease that is often invulnerable to anti-epileptic drugs. Increasing data have demonstrated that acetylcholine (ACh) and cholinergic neurotransmission are involved in the pathophysiology of epilepsy. Cytisine, a full agonist of α7 nicotinic acetylcholine receptors (α7nAChRs) and a partial agonist of α4β2nAChRs, has been widely applied for smoking cessation and has shown neuroprotection in neurological diseases. However, whether cytisine plays a role in treating TLE has not yet been determined.Experimental Approach: In this study, cytisine was injected intraperitoneally into pilocarpine-induced epileptic rats for three weeks. Alpha-bungarotoxin (α-bgt), a specific α7nAChR antagonist, was used to evaluate the mechanism of action of cytisine. Rats were assayed for the occurrence of seizures and cognitive function by video surveillance and Morris water maze. Hippocampal injuries and synaptic structure were assessed by Nissl staining and Golgi staining. Furthermore, levels of glutamate, γ-aminobutyric acid (GABA), ACh, and α7nAChRs were measured.Results: Cytisine significantly reduced seizures and hippocampal damage while improving cognition and inhibiting synaptic remodeling in TLE rats. Additionally, cytisine decreased glutamate levels without altering GABA levels, and increased ACh levels and α7nAChR expression in the hippocampi of TLE rats. α-bgt antagonized the above-mentioned effects of cytisine treatment.Conclusion and Implications: Taken together, these findings indicate that cytisine exerted an anti-epileptic and neuroprotective effect in TLE rats via activation of α7nAChRs, which was associated with a decrease in glutamate levels, inhibition of synaptic remodeling, and improvement of cholinergic transmission in the hippocampus. Hence, our findings not only suggest that cytisine represents a promising anti-epileptic drug, but provides evidence of α7nAChRs as a novel therapeutic target for TLE.

Background: Temporal lobe epilepsy (TLE), a prevalent chronic neurological disorder, affects millions of individuals and is often resistant to anti‐epileptic drugs. Increasing evidence has shown that acetylcholine (ACh) and cholinergic neurotransmission play a role in the pathophysiology of epilepsy. Tropisetron, an antiemetic drug used for chemotherapy in clinic, has displayed potential in the treatment of Alzheimer's disease, depression, and schizophrenia in animal models. However, as a partial agonist of α7 nicotinic acetylcholine receptors (α7nAChRs), whether tropisetron possesses the therapeutic potential for TLE has not yet been determined.Methods: In this study, tropisetron was intraperitoneally injected into pilocarpine‐induced epileptic rats for 3 weeks. Alpha‐bungarotoxin (α‐bgt), a specific α7nAChR antagonist, was applied to investigate the mechanism of tropisetron. Rats were assessed for spontaneous recurrent seizures (SRS) and cognitive function using video surveillance and Morris's water maze testing. Hippocampal impairment and synaptic structure were evaluated by Nissl staining, immunohistochemistry, and Golgi staining. Additionally, the levels of glutamate, γ‐aminobutyric acid (GABA), ACh, α7nAChRs, neuroinflammatory cytokines, glucocorticoids and their receptors, as well as synapse‐associated protein (F‐actin, cofilin‐1) were quantified.Results: The results showed that tropisetron significantly reduced SRS, improved cognitive function, alleviated hippocampal sclerosis, and concurrently suppressed synaptic remodeling and the m⁶A modification of cofilin‐1 in TLE rats. Furthermore, tropisetron lowered glutamate levels without affecting GABA levels, reduced neuroinflammation, and increased ACh levels and α7nAChR expression in the hippocampi of TLE rats. The effects of tropisetron treatment were counteracted by α‐bgt.Conclusion: In summary, these findings indicate that tropisetron exhibits an anti‐epileptic effect and provides neuroprotection in TLE rats through the activation of α7nAChRs. The potential mechanism may involve the reduction of glutamate levels, enhancement of cholinergic transmission, and suppression of synaptic remodeling. Consequently, the present study not only highlights the potential of tropisetron as an anti‐epileptic drug but also identifies α7nAChRs as a promising therapeutic target for the treatment of TLE.

Purpose: Sotatercept, an activin signalling inhibitor approved in March 2024 for pulmonary arterial hypertension (PAH), demonstrated efficacy in clinical trials. This pharmacovigilance study evaluated its real-world safety profile using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to identify postmarketing risks. Methods: FAERS reports from 2024 were analysed, focusing on cases where sotatercept was designated as the primary suspect. Duplicate entries were removed using standardised FDA protocols. Adverse events (AEs) were categorised using the Medical Dictionary for Regulatory Activities (MedDRA V.28.0). Disproportionality signals were assessed via reporting ORs (RORs; 95% CI lower limit >1 with ≥3 cases). Severity was classified using the EudraVigilance Important Medical Events (IMEs) list. Results: Among 1 484 350 deduplicated reports, 613 sotatercept-associated AEs (1717 occurrences, 395 MedDRA terms) were identified. Disproportionality analysis revealed 48 safety signals: 30 aligned with labelled risks (eg, haemoglobin elevation (ROR=272.2), telangiectasia (ROR=334.1)) and 18 novel signals. The most frequent AEs included headache (n=78), epistaxis (n=57) and diarrhoea (n=53). Two unlabelled events—cerebral haemorrhage and ascites—met criteria for critical IMEs. Most reports originated from the USA (98.5%) and involved females (73.6%). Conclusion: This study confirms sotatercept’s labelled risks (haematological and vascular effects) and identifies novel safety concerns, including cerebral haemorrhage and ascites, highlighting the need for vigilant monitoring in PAH management. Real-world data underscore the value of postmarketing surveillance for detecting rare or unanticipated AEs. Clinicians should prioritise monitoring for haematological abnormalities and bleeding risks. Longitudinal studies are warranted to clarify long-term safety outcomes.

Background: Human diseases remain a major global health challenge, requiring effective therapeutic strategies. Traditional Chinese medicine (TCM) has been widely used in clinical settings. Many natural compounds, such as flavonoids from TCM, exhibit diverse pharmacological activities. Alpinetin and pinocembrin are structurally related flavonoids. Alpinetin is derived from Zingiberaceae plants, and pinocembrin is extracted from wild marjoram (origanum vulgare) or other natural sources. They possess a wide range of pharmacological activities or biological effects, including anti-inflammatory, anti-tumor, liver and kidney protection, cardiovascular protection, and antibacterial activities. Methods: The present comparative review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using four major databases (PubMed, EMBASE, Web of Science, and Cochrane Library), as well as CNKI without language restrictions. Results: Pharmacokinetic studies reveal distinct absorption, metabolism, and excretion profiles. Alpinetin and pinocembrin undergo glucuronidation and interact with cytochrome P450 enzymes and transporters. However, alpinetin has demonstrated approximately 1.5-fold higher plasma exposure and slower clearance compared to pinocembrin. Mechanistically, alpinetin exerted therapeutic effects through modulation of the NF-κB/MAPK, PI3K/Akt, and PPAR-γ signaling pathways, resulting in a 2- to 3-fold reduction in pro-inflammatory cytokines. In contrast, pinocembrin exerted protective activity through the inhibition of HMGB1/TLR4 signaling, regulation of endoplasmic reticulum stress, and activation of Nrf2/HO-1, leading to a 1.8-fold increase in antioxidant enzyme activity. The minimum inhibitory concentrations were reduced by 2- to 4-fold against Gram-positive bacteria compared to alpinetin. Conclusions: These findings highlight the pharmacological potential of alpinetin and pinocembrin as promising candidates for the development of novel anti-tumor, anti-inflammatory, liver and kidney protection, cardiovascular protection, and antibacterial agents. However, research on the pharmacological actions of alpinetin and pinocembrin is still in the preclinical stage. Further research is required to validate their efficacy in clinical settings, especially for translation to clinical studies. This is critical to translating these natural flavonoids into effective therapeutic agents while addressing the regulatory challenges and pathways associated with botanical drugs in human diseases.