Identification of different extracts and phytoconstituents of Callistemon viminalis Cheel for their anti-anxiety effects based on pharmacognostic, toxicological, and pharmacological strategies

Article

Author: Sharma, Arun K. ; Sharma, Arun K ; Mittal, Arun ; Kumari, Neelam ; Rana, Arpana

BackgroundPsychiatric disorders like depression and anxiety are global challenges, exacerbated by the limitations of synthetic medications, including addiction and toxic side effects.MethodsThis study meticulously investigated the pharmacognostic, phytochemical, toxicological, and pharmacological properties of Callistemon viminalis Cheel. Toxicological assessments, including hemocompatibility assays, LD₅₀ studies, FOB analysis, biochemical parameters, and structural integrity of vital organs, were conducted on aqueous, methanolic, chloroform, and petroleum ether extracts of leaves and stems. Phytochemical profiling via qualitative tests and GC-MS screened extracts for molecular docking against key receptors. Categorically screened extracts were evaluated for therapeutic potential against LPS-induced anxiety in mice.ResultsToxicological evaluations on experimental animals demonstrated the safety of various extracts, evidenced by no in vitro and in vivo toxicity. GC-MS identified numerous phytochemicals that passed "Lipinski's Rule of Five." These compounds were screened for molecular docking, revealing significant binding affinities with CB1, SERT, α2A-AR, and GABAβ2 receptors, suggesting potential therapeutic effects against anxiety. The phytoconstituents with the highest docking scores, particularly in aqueous and methanolic extracts, were further validated for their therapeutic efficacy. Preliminary analysis based on the EPM test and serum cortisol levels confirmed these extracts' superior therapeutic effectiveness.ConclusionIn conclusion, aqueous and methanolic extracts of Callistemon viminalis Cheel's leaf and stem showed promising potential as therapeutic interventions for anxiety disorders.

01 Jul 2023·Molecular Psychiatry

Towards precision medicine for anxiety disorders: objective assessment, risk prediction, pharmacogenomics, and repurposed drugs

Article

Author: Shekhar, A ; Pina, N ; Palkowitz, S ; Anastasiadis, W A ; Bhagar, R ; Kurian, S M ; Roseberry, K ; Levey, D F ; Rogers, J ; Gill, S S ; Le-Niculescu, H ; Niculescu, A B ; Soe, K

AbstractAnxiety disorders are increasingly prevalent, affect people’s ability to do things, and decrease quality of life. Due to lack of objective tests, they are underdiagnosed and sub-optimally treated, resulting in adverse life events and/or addictions. We endeavored to discover blood biomarkers for anxiety, using a four-step approach. First, we used a longitudinal within-subject design in individuals with psychiatric disorders to discover blood gene expression changes between self-reported low anxiety and high anxiety states. Second, we prioritized the list of candidate biomarkers with a Convergent Functional Genomics approach using other evidence in the field. Third, we validated our top biomarkers from discovery and prioritization in an independent cohort of psychiatric subjects with clinically severe anxiety. Fourth, we tested these candidate biomarkers for clinical utility, i.e. ability to predict anxiety severity state, and future clinical worsening (hospitalizations with anxiety as a contributory cause), in another independent cohort of psychiatric subjects. We showed increased accuracy of individual biomarkers with a personalized approach, by gender and diagnosis, particularly in women. The biomarkers with the best overall evidence were GAD1, NTRK3, ADRA2A, FZD10, GRK4, and SLC6A4. Finally, we identified which of our biomarkers are targets of existing drugs (such as a valproate, omega-3 fatty acids, fluoxetine, lithium, sertraline, benzodiazepines, and ketamine), and thus can be used to match patients to medications and measure response to treatment. We also used our biomarker gene expression signature to identify drugs that could be repurposed for treating anxiety, such as estradiol, pirenperone, loperamide, and disopyramide. Given the detrimental impact of untreated anxiety, the current lack of objective measures to guide treatment, and the addiction potential of existing benzodiazepines-based anxiety medications, there is a urgent need for more precise and personalized approaches like the one we developed.

01 Jan 2023·Pharmacogenomics

Pharmacogenetics of Anxiety and Depression in Alzheimer’s Disease

Review

Author: Naidoo, Vinogran ; Muñiz, Adriana ; Pego, Rocío ; Carril, Juan C ; Corzo, Lola ; Cacabelos, Ramón ; Martínez-Iglesias, Olaia ; Alcaraz, Margarita ; Cacabelos, Natalia

Anxiety and depression coexist with cognitive impairment in Alzheimer's disease along with other concomitant disorders (>60%), which require multipurpose treatments. Polypharmaceutical regimens cause drug–drug interactions and adverse drug reactions, potentially avoidable in number and severity with the implementation of pharmacogenetic procedures. The accumulation of defective variants (>30 genes per patient in more than 50% of cases) in pharmagenes (pathogenic, mechanistic, metabolic, transporter, pleiotropic) influences the therapeutic response to antidementia, antidepressant and anxiolytic drugs in polyvalent regimens. APOE, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, CYP4F2, COMT, MAOB, CHAT, GSTP1, NAT2, SLC30A8, SLCO1B1, ADRA2A, ADRB2, BCHE, GABRA1, HMGCR, HTR2C, IFNL3, NBEA, UGT1A1, ABCB1, ABCC2, ABCG2, SLC6A2, SLC6A3, SLC6A4, MTHFR and OPRM1 variants affect anxiety and depression in Alzheimer's disease.

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