Nootropics or smart drugs are well‐known compounds or supplements that enhance the cognitive performance. They work by increasing the mental function such as memory, creativity, motivation, and attention. Recent researches were focused on establishing a new potential nootropic derived from synthetic and natural products. The influence of nootropic in the brain has been studied widely. The nootropic affects the brain performances through number of mechanisms or pathways, for example, dopaminergic pathway. Previous researches have reported the influence of nootropics on treating memory disorders, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. Those disorders are observed to impair the same pathways of the nootropics. Thus, recent established nootropics are designed sensitively and effectively towards the pathways. Natural nootropics such asGinkgo bilobahave been widely studied to support the beneficial effects of the compounds. Present review is concentrated on the main pathways, namely, dopaminergic and cholinergic system, and the involvement of amyloid precursor protein and secondary messenger in improving the cognitive performance.

Neurogenesis is influenced by various external factors such as enriched environments. Some researchers had postulated that neurogenesis has contributed to the hippocampal learning and memory. This project was designed to observe the effect of Delta-9-tetrahydrocannabinol (∆⁹-THC) in cognitive performance that influenced by the neurogenesis. Different doses of ∆⁹-THC were used for observing the neurogenesis mechanism occurs in the hippocampus of rats. The brains were stained with antibodies, namely BrdU, glial fibrillary acidic protein (GFAP), nestin, doublecortin (DCX) and class III β-tubulin (TuJ-1). The cognitive test was used novel-object discrimination test (NOD) while the proteins involved, DCX and brain-derived neurotrophic factor (BDNF), were measured. Throughout this study, ∆⁹-THC enhanced the markers involved in all stages of neurogenesis mechanism. Simultaneously, the cognitive behaviour of rat also showed improvement in learning and memory functions observed in behavioural test and molecular perspective. Administration of ∆⁹-THC was observed to enhance the neurogenesis in the brain, especially in hippocampus thus improved the cognitive function of rats.

Opiate abuse has been studied to cause adaptive changes observed in the presynaptic release and the mediated‐synaptic plasticity proteins. The involvement of neuronal SNARE proteins reveals the role of the neurotransmitter release in expressing the opioid actions. The present study was designed to determine the effect of the alkaloid extract ofErythroxylum cuneatum(E. cuneatum) against chronic morphine and the influences ofE. cuneatumon neurotransmission processes observedin vitro. The human neuroblastoma cell line, SK‐N‐SH, was treated with the morphine, methadone, orE. cuneatum. The cell lysates were collected and tested forα‐synuclein, calmodulin, vesicle‐associated membrane protein 2 (VAMP 2), and synaptotagmin 1. The extract ofE. cuneatumwas observed to upregulate the decreased expression of dependence proteins, namely,α‐synuclein and calmodulin. The effects were comparable to methadone and control. The expressions of VAMP 2 and synaptotagmin 1 were normalised by the plant and methadone. The extract ofE. cuneatumwas postulated to treat dependence symptoms after chronic morphine and improve the soluble N‐ethylmaleimide‐sensitive factor activating protein receptor (SNARE) protein involved in synaptic vesicle after.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disorder characterised by synovial joint destruction and systemic complications. Central to its pathogenesis is the formation and deposition of immune complexes (ICs), which result from antigen-antibody interactions involving autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs). These ICs infiltrate joint tissues, activate the complement system, and initiate a cascade of inflammatory responses. The ensuing recruitment of polymorphonuclear leukocytes and release of pro-inflammatory cytokines and chemokines contribute to sustained inflammation, tissue degradation, and joint deformity. RA is thus classified as a type III hypersensitivity disorder, wherein IC-mediated mechanisms perpetuate a self-amplifying inflammatory loop. This review explores the evolving understanding of IC-driven pathophysiology in RA, emphasising the three-stage progression of IC formation, deposition, and inflammatory activation. By elucidating the interplay between hypersensitivity reactions and immune-mediated mechanisms in RA, the review underscores potential therapeutic targets that may help disrupt this pathogenic cycle. Enhanced comprehension of IC dynamics not only deepens insight into RA progression but also opens avenues for more precise and effective interventions in autoimmune diseases.

Evaluation of toxicity induced in laboratory animals is paramount to the screening step in the assessment of the safety profile of all compounds. 3-(2,5-dimethoxyphenyl)-1-(5-methyl furan-2-yl) prop-2-en-1-one (DMPF-1); synthetic chalcone derivative has been investigated due to its pharmacological properties, including its antinociceptive and anti-inflammatory. However, the safety profile of this compound is yet to be determined. The present study seeks to highlight the toxicity effect of this compound using acute and subacute toxicity studies in the mice model. A single highest dose (1000 mg/kg) and repeated dose (0.1, 0.5, 1, 5 and 10 mg/kg) of DMPF-1 supplementation were executed. All toxicity study performed was supported by behavioural and body weight changes, haematological, serum biochemical analysis, macroscopic and microscopic analysis of the vital organs. The present result simplifies that DMPF-1 compound supplementation for four weeks is non-toxic as it caused no significant alteration in mice body weight and behaviour. Besides, no significant changes in haematological and biochemical parameters were observed. Further evaluation of its safety profile was confirmed by the normal architecture of the tissues organs obtained. Collectively, this report showed that DMPF-1 was safe to be consumed.

Chronic morphine exposure disrupts receptor signalling by inhibiting receptor internalisation, leading to receptor desensitisation and reduced availability of active receptors. This process significantly contributes to morphine addiction, a condition with limited effective and accessible treatments. Current pharmacological interventions, such as methadone, face challenges including restricted availability, risk of misuse, and adverse effects, leaving a substantial treatment gap for individuals with opioid use disorder (OUD). To address this, alkaloid extract of Erythroxylum cuneatum (E. cuneatum) was investigated as a potential alternative treatment. Using the human neuroblastoma cell line (SK-N-SH), 2 experimental designs were employed: Antagonistic treatment and pre-treatment with morphine. The antagonistic design evaluated the direct interaction between morphine and E. cuneatum, while the pre-treatment model assessed its anti-addictive properties during morphine withdrawal. Methadone served as a positive control. Cytosolic protein fractions were analysed to determine the expression of G protein-coupled receptor kinase 2 (GRK2), β-arrestin 1/2, and clathrin heavy chain, essential for receptor internalisation and resensitisation. Morphine exposure significantly downregulated these proteins, indicating impaired receptor function. Treatment with the alkaloid extract of E. cuneatum reversed these effects, restoring protein levels to those comparable with methadone. These findings highlight the alkaloid extract of E. cuneatum as a promising candidate for mitigating morphine addiction by targeting the molecular mechanisms underlying receptor desensitisation and resensitisation. E. cuneatum addresses a critical gap in addiction management by providing a potential alternative therapy that overcomes some limitations of existing treatments. HIGHLIGHTS Erythroxylum cuneatum alkaloid extract effectively counteracts morphine-induced receptor desensitisation and dysregulation in neuroblastoma cell lines. Dose-dependent restoration of GRK2, β-arrestin 1/2, and clathrin heavy chain by cuneatum highlights its role in promoting receptor internalisation and desensitisation. The antagonist effects of cuneatum are comparable to methadone, suggesting its potential as a natural alternative for opioid addiction treatment. The study proposes a novel mechanism of action for cuneatum, targeting the receptor trafficking machinery to restore μ-opioid receptor (MOR) function. cuneatum represents a promising plant-based therapeutic agent with lower dependency risks, offering a safer alternative to conventional opioid replacement therapies. GRAPHICAL ABSTRACT