Neophytadiene (NPT) is a diterpene found in the methanolic extracts of Crataeva nurvala and Blumea lacera, plants reported with anxiolytic-like activity, sedative properties, and antidepressant-like actions; however, the contribution of neophytadiene to these effects is unknown. This study determined the neuropharmacological (anxiolytic-like, antidepressant-like, anticonvulsant, and sedative) effects of neophytadiene (0.1–10 mg/kg p.o.) and determined the mechanisms of action involved in the neuropharmacological actions using inhibitors such as flumazenil and analyzing the possible interaction of neophytadiene with GABA receptors using a molecular docking study. The behavioral tests were evaluated using the light–dark box, elevated plus-maze, open field, hole-board, convulsion, tail suspension, pentobarbital-induced sleeping, and rotarod. The results showed that neophytadiene exhibited anxiolytic-like activity only to the high dose (10 mg/kg) in the elevated plus-maze and hole-board tests, and anticonvulsant actions in the 4-aminopyridine and pentylenetetrazole-induced seizures test. The anxiolytic-like and anticonvulsant effects of neophytadiene were abolished with the pre-treatment with 2 mg/kg flumazenil. In addition, neophytadiene showed low antidepressant effects (about 3-fold lower) compared to fluoxetine. On other hand, neophytadiene had no sedative or locomotor effects. In conclusion, neophytadiene exerts anxiolytic-like and anticonvulsant activities with the probable participation of the GABAergic system.

Substantial evidence in the literature demonstrates the pleiotropic effects of the administration of recombinant human erythropoietin (rhEPO) and its molecular variants in different tissues and organs, including the brain. Some of these reports suggest that the chemical properties of this molecule by itself or in combination with other agents (e.g., growth factors) could provide the necessary pharmacological characteristics to be considered a potential protective agent in neurological disorders such as Alzheimer’s disease (AD). AD is a degenerative disorder of the brain, characterized by an aberrant accumulation of amyloid β (Aβ) and hyperphosphorylated tau (tau-p) proteins in the extracellular and intracellular space, respectively, leading to inflammation, oxidative stress, excitotoxicity, and other neuronal alterations that compromise cell viability, causing neurodegeneration in the hippocampus and the cerebral cortex. Unfortunately, to date, it lacks an effective therapeutic strategy for its treatment. Therefore, in this review, we analyze the evidence regarding the effects of exogenous EPOs (rhEPO and its molecular variants) in several in vivo and in vitro Aβ and tau-p models of AD-type neurodegeneration, to be considered as an alternative protective treatment to this condition. Particularly, we focus on analyzing the differential effect of molecular variants of rhEPO when changes in doses, route of administration, duration of treatment or application times, are evaluated for the improved cellular alterations generated in this disease. This narrative review shows the evidence of the effectiveness of the exogenous EPOs as potential therapeutic molecules, focused on the mechanisms that establish cellular damage and clinical manifestation in the AD.

Ceiba aesculifolia (Kunth) Britten & Baker f (Malvaceae) is used for the folk treatment of mood disorders. C. aesculifolia bark was extracted in ethanol, and the extract (CAE) was chemically standardized using gas chromatography–mass spectrometry (GC-MS). This study evaluated the effects of CAE (10–100 mg/kg p.o.) on anxiolytic-like activity, sedation, locomotor activity, depression-like activity, and spatial working memory using in vivo rodent models. A possible mechanism for the anxiolytic-like and antidepressant-like actions induced by CAE was assessed using neurotransmission pathway inhibitors. Myristic acid was one of the compounds found in CAE using GC-MS. This study also evaluated the anxiolytic-like activity and the sedative actions of myristic acid and assessed a possible mechanism of action using neurotransmission pathway inhibitors and an in silico analysis. CAE elicited anxiolytic-like activity and antidepressant-like effects (ED₅₀ = 57 mg/kg). CAE (10–100 mg/kg) did not affect locomotor coordination or induce sedation. The anxiolytic-like and antidepressant-like actions of CAE were reverted by prazosin, suggesting a possible participation of the noradrenergic system. The anxiolytic-like activity of myristic acid was reverted by the co-administration of prazosin and partially reverted by ketanserin. The docking study revealed that myristic acid can form favorable interactions within 5-HT2A and α1A-adrenoreceptor binding pockets.

Amyloid-β oligomers are a cytotoxic structure that is key for the establishment of the beginning stages of Alzheimer’s disease (AD). These structures promote subcellular alterations that cause synaptic dysfunction, loss of cell communication, and even cell death, generating cognitive deficits. The aim of this study was to investigate the cytotoxic effects of amyloid-β1-42 oligomers (AβOs) on the membranous organelles involved in protein processing: the endoplasmic reticulum (ER) and Golgi apparatus (GA). The results obtained with 10 μM AβOs in SH-SY5Y neuroblastoma cells showed that oligomeric structures are more toxic than monomers because they cause cell viability to decrease as exposure time increases. Survivor cells were analyzed to further understand the toxic effects of AβOs on intracellular organelles. Survivor cells showed morphological alterations associated with abnormal cytoskeleton modification 72–96 h after exposure to AβOs. Moreover, the ER and GA presented rearrangement throughout the cytoplasmic space, which could be attributed to a lack of constitutive protein processing or to previous abnormal cytoskeleton modification. Interestingly, the disorganization of both ER and GA organelles exposed to AβOs is likely an early pathological alteration that could be related to aberrant protein processing and accumulation in AD.

Stanhopea tigrina Bateman ex Lindl. (Orchidaceae) is an orchid endemic to Mexico, known as “Calavera” or “calaverita”, in the Huasteca Potosina (central region of Mexico). This plant species is used for the folk treatment of mental disorders and urological kidney disorders, according to the ethnomedicinal information obtained in this study. Ethanolic extracts of leaves (HE) and pseudobulb (PE) were obtained by microwave-assisted extraction (MAE). Gas Chromatography coupled with Mass Spectrometry (GC-MS) was used to carry out the chemical characterization of HE and PE. The pharmacological effects (antioxidant, diuretic, anxiolytic, locomotor, hypnotic, and sedative) of HE and PE were evaluated. The possible mechanism of action of the anxiolytic-like activity induced by HE was assessed using inhibitors of the GABAergic, adrenergic, and serotonergic systems. The possible mechanism of the diuretic action of HE was assessed using prostaglandin inhibitory antagonists and nitric oxide synthase (NOS) blockers. HE at 50 and 100 mg/kg exerted anxiolytic-like activity without inducing hypnosis or sedation. Flumazenil, prazosin, and ketanserin inhibited the anxiolytic-like activity shown by HE, which suggests the participation of GABA, α₁-adrenergic receptors, and 5-HT₂ receptors, respectively. The diuretic effect was reversed by the non-selective NOS inhibitor L-NAME, which caused the reduction in nitric oxide (NO). These results demonstrate that the ethanolic extract of S. tigrina leaves exhibited anxiolytic-like activity and diuretic effects without inducing hypnosis or sedation. This work validates the medicinal uses of this orchid species.

Septo-hippocampal pathway, crucial for physiological functions and involved in epilepsy. Clinical monitoring during epileptogenesis is complicated. We aim to evaluate tissue changes after lesioning the medial septum (MS) of normal rats and assess how the depletion of specific neuronal populations alters the animals’ behavior and susceptibility to establishing a pilocarpine-induced status epilepticus. Male Sprague–Dawley rats were injected into the MS with vehicle or saporins (to deplete GABAergic or cholinergic neurons; n = 16 per group). Thirty-two animals were used for diffusion tensor imaging (DTI); scanned before surgery and 14 and 49 days post-injection. Fractional anisotropy and apparent diffusion coefficient were evaluated in the fimbria, dorsal hippocampus, ventral hippocampus, dorso-medial thalamus, and amygdala. Between scans 2 and 3, animals were submitted to diverse behavioral tasks. Stainings were used to analyze tissue alterations. Twenty-four different animals received pilocarpine to evaluate the latency and severity of the status epilepticus 2 weeks after surgery. Additionally, eight different animals were only used to evaluate the neuronal damage inflicted on the MS 1 week after the molecular surgery. Progressive changes in DTI parameters in both white and gray matter structures of the four evaluated groups were observed. Behaviorally, the GAT1-saporin injection impacted spatial memory formation, while 192-IgG-saporin triggered anxiety-like behaviors. Histologically, the GABAergic toxin also induced aberrant mossy fiber sprouting, tissue damage, and neuronal death. Regarding the pilocarpine-induced status epilepticus, this agent provoked an increased mortality rate. Selective septo-hippocampal modulation impacts the integrity of limbic regions crucial for certain behavioral skills and could represent a precursor for epilepsy development.