Current Neuropharmacology - Volume 23, Issue 12, 2025

Neurodegenerative diseases (NDDs) refer to a progressive degeneration of the nervous system and are on the rise. Researchers are trying to reveal the crucial mechanisms behind NDDs to find novel therapeutic candidates with higher efficacy and lower side effects. Increasing evidence highlights the auspicious role of inflammatory mechanisms in the pathogenesis of NDDs.

Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline, a systematic and comprehensive review was done to evaluate the effect of medicinal herbs in restoring gut-brain function and anti-inflammatory mechanisms in combating neuroprotection. The electronic databases, including Scopus, PubMed, and ScienceDirect, were searched for the literature review. The manual search of reference lists and citations was also employed falling within the authors’ expertise.

As with other mechanisms, the bidirectional communication between the brain and gut, known as the gut-brain axis, has emerged as a potential target for therapeutic interventions. Since the gut-brain axis covers multiple mechanisms, especially inflammatory mechanisms in NDDs, it urges the need for finding novel multi-targeting agents. Medicinal herbs, with their rich repertoire of natural products, are multi-targeting candidates in combating several diseases. In this systematic and comprehensive review, we explore the potential of medicinal herbs in restoring gut-brain function and promoting neuroprotection by suppressing inflammatory pathways. Novel delivery systems and clinical applications of medicinal herbs are also highlighted to drawback the pharmacokinetic limitation in regulating the gut-brain axis-associated NDDs.

Medicinal herbs provide neuroprotective responses through the modulation of gut-brain function and related inflammatory mediators.

Methcathinone, a synthetic cathinone derivative similar to amphetamine, has transitioned from a 1920s ephedrine precursor and Soviet-era antidepressant to a recreationally used substance since the 1970s-1980s, raising public health concerns due to its addiction potential and neurotoxicity-related health risks.

This review comprehensively analyzes methcathinone's impact on adult offspring, synthesizing recent advancements and critiquing literature to pinpoint key findings, challenges, and future research directions.

The systematic review adhered to PRISMA guidelines and encompassed case series, prospective and retrospective studies, as well as short communications published in English. An electronic search was conducted on PubMed, Elsevier, and CNKI. The focus was on methcathinone and its neuropsychological disorders and physical health complications, specifically in adult offspring.

A total of 8 studies met the inclusion criteria, resulting in a dataset of methcathinone on neurobehavioral and cognitive functions. These studies mainly found that prenatal methcathinone exposure in rats led to delayed physical development and induced anxiety-like behavior in offspring, with changes observed in neurobehavioral tests and the concentration of serotonin and dopamine. Furthermore, neurochemical effects were identified, showing dose- and time-dependent increases in extracellular dopamine and serotonin concentrations, and neurotoxic potential towards brain dopamine neurons.

This study concludes that methcathinone poses severe risks, including neurotoxicity for users and developmental harm for offspring, necessitating ongoing research to comprehend associated risks and inform public health interventions.

Early-life stress can severely impact brain health and neuronal plasticity, potentially leading to psychiatric disorders, with excitatory and inhibitory neurotransmission changes being key to understanding and mitigating these effects.

We investigated the effects of Perinatal Stress (PRS) on the balance of excitatory and inhibitory neurotransmission, particularly focusing on AMPA and GABAA receptor protein levels and their relationship with cognition and risk-taking behavior in male and female Sprague-Dawley rats.

Adult PRS (3-4 months old) offspring of dams exposed to 10 days of gestational restraint stress, which led to reduced maternal care, were evaluated at 3-4 months for behavioral responses to novelty, adverse environments, and recognition memory, with biochemical analyses conducted in the prefrontal cortex and the ventral and dorsal hippocampus.

PRS and sex notably affected behavior and AMPA/GABAA receptor subunit expression. PRS males showed reduced risk-taking behavior when exposed to novel and adverse environments and impaired recognition memory, while PRS females demonstrated better behavioral performance compared to both PRS males and control females. In the dorsal hippocampus, PRS increased the GluA2:GluA1 ratio and GABAA-α1 subunit in females but reduced them in males, modulating the AMPA/GABAA balance to enhance synaptic GABAergic inhibition and behavioral resilience in PRS females and control males.

Our findings indicate that increased synaptic inhibition and reduced excitatory noise may underlie enhanced recognition memory and risk-taking behavior. The sex differences in PRS rats suggest that targeting AMPA or GABAA receptors could help treat early-life stress-related disorders and underscore the need for developing gender-specific therapies.

Brain aging is a complex process involving genetic, neurodevelopmental, and environmental factors. Inherent features of this process are cellular senescence, the development of senescence-associated secretory phenotype (SASP), and prolonged inflammation.

Recently, progress has been made in understanding the biological roles of FPR2 receptors and their ligands in the mechanism of inflammation resolution (RoI) in the brain. However, the number of studies comparing the influence of prenatal stress (PS) on RoI in physiological aging and neurodegenerative disorders pathology is very limited, and the data need to be more consistent. Here, we examined whether PS can condition the pattern of age-dependent cognitive and RoI changes in the prefrontal cortex and hippocampus in wild-type and hAPP^NL-F/NL-F KI male mice.

We discovered that in aging, the memory deficits are accompanied by the limitation of the availability of pro-resolving FPR2 ligands, the rising proinflammatory microglia polarization, and inflammatory ligands mediated FPR2 overactivation. Moreover, the present study suggested the subtle role of the RoI deficits in creating brain cells' senescence and shifting the immunomodulators to the proinflammatory direction. PS has been revealed as a substantial factor modulating the profile of inflame-aging in a manner strongly determined by the age of animals and the brain structure under study, mainly in hAPP^NL-F/NL-F KI male mice.

Our results identify the FPR2 receptors as a driver regulating the RoI process in the brain and highlight that PS has diversified the picture of age-dependent neurodegenerative pathology.

Amyotrophic lateral sclerosis (ALS) is an idiopathic, fatal, and rapidly progressive neurodegenerative disease. At present, neurofilament light (NFL) and phosphorylated neurofilament heavy (pNfH) proteins in biological fluids are commonly known prognostic biomarkers, but their levels stabilize over time. Thus, there is a critical gap in the field to identify unique biomarkers that can aid disease diagnosis, progression and monitoring the therapy response.

To evaluate the presence of extracellular domain of p75 (p75ecd) in urine of ALS patients and healthy control volunteers in the North American cohort.

An enzyme-linked immunoassay (ELISA) and creatinine assay was used to determine the levels of p75ecd and creatinine in the urine of ALS patients and healthy control volunteers respectively. This assay demonstrated clear discrimination in the levels of the p75ecd in the urine samples of ALS patients as compared to healthy individuals.

It was found that the concentration of p75ecd in ALS samples was significantly higher than that of healthy controls group. Additionally, high p75ecd levels were segregated with respect to age, sex, family history, occupation and drug treatment, medication status. Moreover, we observed differential expression patterns among the different stages of the disease. Our results followed the pattern that was observed in the Chinese, and Australian cohort.

Altogether, our results indicate that the development of an efficient system for the detection of elevated levels of p75ecd in the urine could serve as a useful modality for early ALS diagnosis, disease progression, and monitoring the effectiveness of therapeutic interventions.

This work aimed to develop a new and simple method to establish a mouse model of vascular dementia (VD). We investigated whether a new nitric oxide metabolite in the botanical mixture (a NO-donating botanical mixture, NOBM) improved learning and memory in mice that underwent bilateral carotid artery stenosis (BCAS).

C57BL/6N mice received the NOBM orally (0.1 mL twice a day) after BCAS, from days 1 to 28. We assessed spatial memory using the Y maze and place recognition tests at 1 week and 4 weeks after the induction of BCAS. We quantified the parvalbumin protein in the cortex and hippocampus at 1 week and 4 weeks. We also quantified expression levels of neuronal nuclei, brain-derived neurotrophic factor, glial fibrillary acidic protein, and the number of dead neurons performed Fluoro-Jade B staining 31 days after BCAS.

NOBM significantly improved learning and memory behaviour in BCAS mice. Immunohistochemistry staining and Western blotting data showed a significantly higher protein expression of parvalbumin in the cortex and hippocampus of NOBM-treated BCAS animals, especially in the early stage of BCAS. Moreover, NOBM reduces neuronal loss in the cortex and reduces neuroinflammation and oxidative stress. The observed effect suggests that the NOBM reduced the loss of parvalbumin inhibitory interneurons in the early stage of VD and inhibited neuroinflammation in the VD mice model.

Our results reveal a potential neuroprotective and therapeutic use of NOBM for cognitive dysfunction associated with cerebral hypoperfusion in a mouse model of VD.