Current Pharmaceutical Design - Volume 31, Issue 17, 2025

Psychosis, marked by detachment from reality, includes symptoms like hallucinations and delusions. Traditional herbal remedies like kratom are gaining attention for psychiatric conditions. This was aimed at comprehending the molecular mechanisms of Kratom's antipsychotic effects utilizing a multi-modal computational approach.

This study employed network pharmacology followed by molecular docking and molecular dynamics simulation study to investigate the potential antipsychotic properties of kratom compounds by identifying their key molecular targets and interactions.

Compounds present in kratom interact with a variety of receptors and proteins that play a pivotal role in neurotransmission, neurodevelopment, and cellular signaling. These interactions, particularly with dopamine and serotonin receptors, various proteins, and pathways, suggest a complex influence on psychiatric conditions. Both mitragynine and zotepine (an atypical antipsychotic drug) display significant binding affinities for 5HTR2A receptors, suggesting their potential for modulating related physiological pathways. Mitragynine displayed higher flexibility in binding compared to zotepine, which showed a more stable interaction. Hydrogen bond analysis revealed a more variable interaction profile for mitragynine than zotepine.

The research findings suggest that the interaction between kratom compounds and essential brain receptors could influence psychiatric conditions. Notably, both mitragynine (a key kratom component) and zotepine (an antipsychotic) bind to the 5HTR2A receptor, suggesting the potential for kratom to modulate similar pathways. Interestingly, mitragynine's flexible binding mode compared to zotepine might indicate a more diverse range of effects. Overall, the findings suggest complex interactions between kratom and the brain's signaling system, warranting further investigation into its potential therapeutic effects.

This study aimed to evaluate the effectiveness and safety of Altibrain^® in combination with standard Autism Spectrum Disorder (ASD) treatment compared to standard ASD treatment alone in individuals diagnosed with ASD.

A randomized, open-label trial was conducted involving 120 participants aged 3 to 17 years, randomly assigned to either the Standard ASD Treatment group or the Altibrain^® + Standard ASD Treatment group. Sixty patients were randomly allocated to each Standard ASD Treatment group or the Altibrain^® + Standard ASD Treatment group. Participant allocation was done by computer-generated randomization. Participants had confirmed ASD diagnoses based on DSM-V or ICD-11 criteria and demonstrated moderate to severe core ASD symptoms. Informed consent was obtained from caregivers. A total number of 120 subjects were included, consisting of 71 male and 49 female patients. Participants received either standard ASD treatment alone or Altibrain^® in addition to standard ASD treatment orally once daily for 24 weeks. A total of 7 study visits/24 weeks to analyze the intervention efficacy of the Standard ASD Treatment group or the Altibrain^® + Standard ASD Treatment group. Primary outcomes included changes in core ASD symptoms measured by the Autism Diagnostic Observation Schedule (ADOS) and safety assessments. Secondary outcomes included alterations in social communication skills, reduction in repetitive behaviors, overall functional improvements, safety and tolerability of Altibrain^®.

Altibrain^® significantly improved qualitative deficits in social interaction and repetitive behaviors compared to standard ASD treatment alone (p < 0.0001). The Altibrain^® + Standard ASD Treatment group demonstrated significant improvements in social functioning, social awareness, cognition, communication, and motivation compared to the Standard ASD Treatment group (p < 0.0001). Additionally, Altibrain^® showed superior efficacy in reducing hyperactivity/noncompliance, inappropriate speech, irritability, lethargy/ social withdrawal, stereotypic behavior, and aberrant behavior compared to standard treatment alone (p < 0.0001). Additionally, Altibrain^® exhibited a favorable safety profile as per the 4-week post-treatment safety follow-up.

Overall, Altibrain^® holds promise as a valuable therapeutic option for individuals with ASD and their families. Limitations of the study include neuroimaging and biomarkers analysis and larger cohort studies.

The aim of the current study was to explore nano-formulation for effective neuroprotection by auranofin.

Currently, the treatment options for various CNS disorders, particularly neurodegenerative disorders, are greatly constrained. A significant obstacle in this pursuit is the blood-brain barrier, a shielding covering that hinders the route of numerous biochemical treatments into the brain. To overcome this problem, nanoformulation-based approaches are gaining interest, increasing the compound's BBB penetrability.

The objective of this study was to evaluate whether nanoparticles fabricated from poly(lactic-co-glycolic acid) encapsulated with auranofin could oppose aluminium chloride-induced Alzheimer's disease.

Auranofin-encapsulated PLGA nanoparticles were prepared, and their particle size, entrapment efficiency (EE), distribution of particles, morphological surface charge, and structural characteristics were characterized. During the in vivo study, rats were orally administered AlCl3 at 100 mg/kg for 21 days. Meanwhile, auranofin and auranofin nanoparticles were orally administered at doses of 5 and 10 mg/kg and 2.5 and 5 mg/kg, respectively, within 2 weeks. After the course therapy, the rats were decapitated, and the hippocampus was collected for the estimated biochemical and neuroinflammatory markers.

The auranofin nanoparticles were characterized, revealing % entrapment efficiency (98%) and % loading dose (76%). The nanoparticles exhibited a morphological surface charge of 27.5 ± 5.10 mV, a polydispersity index of 0.438 ± 0.12, and a mean particle size of 101.5 ± 10.3 nm. In the in vivo study, administering a gold compound (auranofin) and formulation (auranofin nanoparticles) resulted in a significant improvement in cognitive deficits, changes in biochemical parameters, and markers of neuroinflammation triggered with aluminium chloride.

The results have suggested that auranofin nanoparticles demonstrate abilities to protect neurons compared to auranofin alone. The noticed therapeutic benefits of the auranofin-encapsulated PLGA nanoparticles can be attributed to modulation in particle size with antioxidative and anti-inflammatory impacts of auranofin. Consequently, the outcome of the research has revealed that gold compound nanoparticles hold the potential to be a promising option for altering the therapeutic course of Alzheimer's disease.