Reserpine

BackgroundWith increased social pressure, individuals face a high risk of depression. Subsequently, depression affects cognitive behaviour and negatively impacts daily life. Fortunately, the Traditional Chinese Medicine Jia Wei Xiao Yao (JWXY) capsule is effective in reducing depression and improving cognitive behaviour.MethodsThe constituents of JWXY capsule were identified by ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry analyses. We analysed behaviours of depression-like zebrafish in the novel tank with an automatic 3D video-tracking system and conducted the colour preference test, as well detected physiological changes after sertraline and JWXY capsule treatments.ResultsBoth sertraline and JWXY capsule rescued the decreased locomotive behaviour and depression phenotype of zebrafish caused by reserpine. JWXY capsule especially improved the inhibited exploratory behaviour caused by reserpine. In addition, with the onset of depressive behaviour, zebrafish exhibited alterations in cognitive behaviour as indicated by colour preference changes. However, compared with sertraline, JWXY capsule was more efficaciously in rescuing this change in the colour preference pattern. Moreover, an increased level of cortisol, increased expression of tyrosine hydroxylase (TH) and decreased monoamine neurotransmitters, including serotonin (5-HT) and noradrenaline, were involved in the depressive behaviours. In addition, sertraline and JWXY capsule rescued the depressive phenotype and cognitive behaviour of zebrafish by altering the levels of endogenous cortisol and monoamine neurotransmitters.ConclusionsJWXY capsule was more effectively than sertraline in rescuing reserpine-induced depression and cognitive disorder in zebrafish. Potentially, our study can provide new insights into the clinical treatment of depression and the mechanism of action of JWXY capsule.

BackgroundReserpine is an effective antihypertensive drug, but its role in routine practice has declined such that it is rarely used. This is largely based on the assumption that reserpine causes depression. This assumption was a foundation for the original monoamine hypothesis of depression. However, there remains conflicting evidence as to whether reserpine causes depression, and no systematic review of available evidence.AimsWe systematically reviewed evidence on effects of reserpine on depressive and related symptoms (e.g. anxiety, suicidal ideation).MethodElectronic searches of MEDLINE, Embase and PsycINFO were conducted to identify studies up to 14 February 2021. Studies of any methodological design involving reserpine-treated and reserpine-untreated conditions, in any adult human population, were included and a narrative synthesis of findings was undertaken. Risk of bias (RoB) was examined using ROBINS-I.ResultsOf the 35 studies meeting inclusion criteria, 9 were randomised controlled trials. Eleven studies reported some depressogenic effects, 13 reported no effect and 11 reported putative antidepressant effects. Studies identifying depressive effects were more likely to examine people without psychiatric disorders at baseline, while studies identifying a potential antidepressant effect tended to treat fewer participants for shorter durations, at higher doses. Around one-third of studies conducted in people with psychiatric disorders showed beneficial effects on depression symptoms. 30/35 studies were at high RoB.ConclusionsAssociations between reserpine and depression are inconsistent and limited by a lack of high-quality evidence. Due to reserpine's apparently complex effects, we urge nuance rather than simplicity surrounding the monoamine hypothesis of depression.

Alzheimer's disease (AD) is a multifactorial disorder characterized by exponential loss of memory and cognitive deficit involving several disease modifying targets (amyloid beta, beta-secretase, monoaminoxidase-B, and cholinesterase). The present study explores multi-target directed ligand approach using secondary metabolite reserpine (RES) and ajmalicine (AJM) obtained from Rauwolfia serpentina roots. Novel LCMS and HPLC methods were developed for identification and quantification of reserpine and ajmalicine. In vitro enzyme inhibition assays were performed to evaluate anti-cholinesterase, β-site amyloid cleaving enzyme (BACE-1) inhibition and monoamine oxidase-B (MAO-B) inhibition, further analyzed with in silico analysis. Anti-amyloidogenic potential was studied using anti-aggregation studies along with TEM and circular dichroism (CD) analysis. In vitro neuroprotective potential against Aβ toxicity and anti-oxidative stress was demonstrated using PC12 cell cultures. Reserpine is a more potent dual cholinesterase inhibitor than ajmalicine (IC50 values of 1.7 μM (AChE) and 2.8 μM (BuChE)). The anti-aggregation activity of reserpine (68%) was more than ajmalicine (56%). Both compounds demonstrated neuroprotective activity against Aβ42 (92%) and H2O2 (93%) induced toxicity in PC12 cells against controls. Phytocompounds also inhibited MAO-B and BACE-1 enzymes in concentration dependent manner. Molecular docking studies indicated the strong binding of compounds to the catalytic site of targets. This novel study demonstrated that reserpine and ajmalicine as a multi-target directed ligand that have disease modifying potential for amelioration of AD.

Fibromyalgia (FM) is a chronic condition characterized by widespread musculoskeletal pain, fatigue, psychological disturbances, and sleep issues. Honokiol (HNK) is a bioactive compound known for its medicinal properties. This study evaluated HNK's effectiveness in alleviating pain, depression, and anxiety in a reserpine-induced FM rat model. Thirty male rats were divided into three groups: control, RES (FM-induced), and RES + HNK. HNK was supplemented to RES + HNK in a dose of 8 mg/kg for 21 days. Behavioral assessments included the open field, elevated plus maze, and forced swim tests, while pain was evaluated using treadmill endurance, tail flick latency, paintbrush, and rotarod tests. Brain homogenates were analyzed for neurotransmitters, antioxidants, pro-inflammatory cytokines, and gene expressions. Histopathological evaluation of spinal cords assessed markers of inflammation and apoptosis. Results showed that HNK administration improved behavior and reduced pain. This was linked to reduced levels of malondialdehyde, tumor necrosis factor-α, and prostaglandin E2, alongside increased superoxide dismutase and interleukin-10. Additionally, HNK downregulated the expression of calcitonin gene-related peptide and the JAK/STAT3 gene. These findings suggest that HNK alleviates FM symptoms through its antioxidant, anti-inflammatory, neuroprotective, and anti-apoptotic properties, indicating its potential as a therapeutic agent for FM.