A Critical Analysis of Medicinal plants for Anti-Depressant action with their Phyto-Constituent and Mechanism of Action

 

Shanti Bhushan Mishra¹*, Priya Mishra²

¹Department of Pharmacognosy, United Institute of Pharmacy, Prayagraj 211010, India.

²Department of Pharmacology, United Institute of Pharmacy, Prayagraj 211010, India.

 

ABSTRACT:

Depression or stress refers to a state of sad feelings and loss of interest in pleasurable activities characterized by retardation of thoughts and actions, appetite and weight changes, restlessness as well as in sleep disturbance. All the current evidences implicate alteration in the firing pattern of a subset of biogenic amines in the central nervous system. There are adequate number of synthetic drugs used to treat depression as standard treatment for clinically depressed patient, however only 30% of patients respond satisfactorily to the existing medicines and the remaining do not attain full recovery. Many scientists are investigating on herbal drugs for mitigating this disorder that shown antidepressant properties by virtue of synergistic effect of their phyto constituents. In this review article we emphasize to give an outline of certain medicinal plants with their constituents and mechanism of action which have been explored for their antidepressant action.

 

 

 

INTRODUCTION:

In the current scenario, depression is the leading mental health disorder which badly impacts citizens’s life and daily routine. Depression/Disturbance of mood, sleep, loss of interest, energy, poor concentration, diminished appetite, feeling of worthlessness, suicidal thoughts and excessive guilts are the major leading symptoms of this disorder¹. There are two types of depressive syndrome mostly occur; first is unipolar depression in which mood swings always go in the identical direction and second is bipolar mood disorder; in which the depression alternates with the mania². According to the World Health Organization, approximately 280 million people are suffering from depression and estimated that it will be the leading disease in near future.

 
There are many factors which plays an major role in the progress of depression viz. biological, psychological and inherited factors are involved in the development of depression as per reported literature³. In context of the mechanistic approach, it causes dysfunctions in neural and neurotransmission systems basically reduction in monoamines and their intermediates, as well as the corresponding precursors and transporters. This is the most widely used theoretical perception for the etiology of depression because most pharmacological agents used to treat the ailment target this neurological pathway⁴. Recently, multiple internal stressors such as variations in serum levels of triglyceride, sugar cholesterol, and coagulation factors have been reported to be concerned in the development of depression.  With oxidative stress, one of mechanisms for assessing active compounds investigates their influences on either the oxidative enzymes or nuclear factor erythroid 2-like 2 involved in the expression of different genes, comprising those for antioxidant enzymes⁵. Recent investigations have demonstrated that depressive patients normally present with altered mitochondrial membrane depolarization, manifesting as oxidized mitochondrial DNA, promoting high concentrations of central and peripheral reactive oxygen species. In the brain, the consequences of ROS, which are mostly due to peroxidation, are well recognized and involve apoptosis, neuronal damage, DNA and protein injury, lowers antioxidant defenses, and neuroinflammation⁶.

 

Researchers are currently looking for more specific drugs with better safety and lower cost. There is a series of research papers that have dealt intensively with medicinal plants acting on psychiatric disorders and cause fewer adverse effects than conventional and chemical drugs⁷.

 

The objective of this manuscript is to review the observations of the research on antidepressant outcomes and mechanism of action of various chemical constituents of medicinal plants responsible for the antidepressant action.

 

METHODOLOGY AND DATA COMPILATION:

The knowledge and information about the medicinal plants with anti-depressant properties was gathered from a variety of national and international peer review journals and databases viz. PubMed, Google Scholar, Scopus and web of science by using the keywords depression, antidepressant, plant extract, medicinal plants, phytoconstituents, Neurological disorders and mechanism of action. Moreover, the information was also collected to examine the classes of phytoconstituent responsible for antidepressant action as the plants belonging to a particular family may have similar types of chemical composition and mechanisms of action.  In the following data collection, the method was changed from generalisation to specification of categories. The screening was done and compilation of data on 130 medicinal plants with their local names families, classes of phytoconstituents acts on various mechanisms of depression. A list of plants with antidepressant function is included in Table 1. Fig.2 shows various chemical constituents responsible for antidepressant action.

 

Pathophysiology of Depression

The pathophysiology of depression involves an alteration in both the function as well as structure of the brain. In many patients with depression, excess production of corticotropin-releasing hormone leads to hyperactivity of the hypothalamic-pituitary-adrenal axis⁸. Anatomical changes in cerebral depression include a reduction in the size of the hippocampus, reduced frontal lobe volume, and an increased proportion of the cerebral ventricles^9-10. Moreover, neurotransmitters play a important role in the pathophysiology of depression including decreased levels of monoamines, particularly norepinephrine and serotonin¹¹.

 

 

Figure 1: Diagram showing mechanism believed to be involved in the pathophysiology of depression

Serotonin is critical to the development of depression and has been shown in several retrospective and prospective studies to decrease in the brains of depressed individuals.  In addition to serotonin, its precursor tryptophan is also found in lower concentrations in the brain in depression¹². Catecholamines, including both norepinephrine and dopamine have also been linked to depression.  In addition, other neurotransmitters may be abnormal during the depression such as altered levels of glutamate and GABA in various regions of the brain such as prefrontal cortex and occipital lobe can be expected¹³. The Mechanism of action and pathophysiology of depression mentioned in Figure 1.

 

Research on Appropriate Models of Depression

How to improve a model that meets the intention of the investigation determines the results of the experiments and has become the track that researchers have been discovering in recent time. Martínez et al¹⁴. developed a model based on predictions to assess factors that are able to modifying the treatment pathway for depression. Nie et al¹⁵. continued the work on prediction-based modelling of treatment-resistant depression that can launch a predictive model for treatment-of depression. Behavioural testing and rational modelling methods allow for more comprehensive research into depression, with more comprehensive investigations and more scientifically valid results.

 

Research on Mechanisms/pathways of Depression

Research founded on the mechanisms of depression comprises the assessment of disease pathogenesis, the analysis of drug action mechanisms, and the study of disease dealing mechanisms. Research on the pathogenesis of depression is more attentive on the study of the hypothalamic-pituitary-adrenal axis. Societal stress can alter the hypothalamic-pituitary-adrenal axis¹⁶. Experiments on the mechanism of action of drugs are mostly depend on their effects on the central nervous system. The antidepressant action of Tanshinone IIA is facilitated by the ERK-CREB-BDNF pathway in the hippocampus region of mice¹⁷. Research on the various mechanisms of depression treatment has also focused on the central nervous system. It has been established that the vagus nerve can convey the signals to the brain that can lead to a lessening in depressive behavior^18-20.

 

Table 1. Medicinal plants explored for anti-depressant action with in vivo models and MOA^21-24.

 

 

Fig. 2 Chemical Constituents for antidepressant action

 

CONCLUSION:

Pathological alterations in the concentration of neurotransmitters, which helps in interaction between nerve cells within the brain, describe depression, a condition of mental illnesses. example Dopamine, Norepinephrine, and Serotonin. The effectiveness of botanicals in lowering the level of depression has been demonstrated by scientific validation of numerous plant species. The natural compounds that have been taken into consideration show promise as potential antidepressant treatments. Treatment for a variety of neurological illnesses like anxiety and depression might benefit greatly from the use of these medications in the creation of a multi-component herbal formulation. A thorough and well-planned study in this field would demonstrate to be a new direction in herbal medicines.

 

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this investigation.

 

ABBREVIATIONS:

CRF, corticotrophinreleasing factor; ACTH, adrenocorticotropic hormone; AFST, acute forced swim test; AO, antioxidant; AT, anhedonic test; BDNF, brain-derived neurotrophic factor; BDZR, benzodiazepine receptors; CDM, chick depression model; cHE, cyclohexane extract; CIS, chronic immobilization stress; CMS, chronic mild stress; Cort, corticosterone; CRF, corticotrophin releasing factor; CRS, chronic restraint stress; CSDS, chronic social defeat stress; CST, coat state test; CUMS, chronic unpredicted mild stress; DA, dopamine, DAT, dopamine uptake; EDM, escape, deficit model; EMP, elevated plus maze; FST, forced swim test; Glut, glutamate; 5-HT, serotonin; HBT, hole-board test; HF, heart failure; HIC, haloperidol-induced catalepsy; HPA, hypothalamic-pituitary-adrenal; HWT, horizontal wire test; KLF11, Krueppel-like factor 11; LAT, locomotor activity test; LDT, light-dark transition test; LHT, learned helplessness test; MOA, mechanism of action; MWM, Morris water maze; NA, noradrenaline, NART, noradrenaline transporter; NAT, noradrenaline uptake; NGF, nerve growth factor; NMDA, Nmethyl-Daspartic acid; NSF, novelty-suppressed feeding test; OFT, open-field test; PH-50, standardized extract of Hypericum perfoliatum; PSD-95, synaptic protein-95; RIH, reserpine-induced hyperthermia; SERT, serotonin transporter; SFST, sub-chronic forced swim test; SIRT1, NAD-dependent deacetylase sirtuin-1; SPT, sucrose preference test; TDT, tank diving test; TST, tail suspension test; TrKB, kinase linked receptor, Ap, aerial parts, Bk, bark; Bu, bulb; Fr, fruit; Ju, juice; Le, leaf; Pp, plant powder; Rh, rhizome; Ro, root; SB, stem bark; Se, seed; Wp, whole plant; ^{AE, acetone extract; CE, chloroform extract; CO}2^{E, supercritical fluids CO2-extract; DE, dichloromethane extract; dEtE, diethyl ether extract; EAE, ethyl acetate extract; EE,} ethanol extract; EO, essential oil; ME, methanol extract; iPE, isopropanol extract; SDE, spray dried extract; SE, standardized extract; WE, water extract (aqueous extract); WEE, hydro-ethanol extract; WME, hydro-methanol extract; Alk, alkaloids; DTerp, diterpenoids; Gly, glycosides; Flav, flavonoids; MTerp, monoterpenoids; MX, methylxanthines; Phe, phenolics; PPhe, polyphenols; PSac, polysaccharides; STerp, sesquiterpenoids; Terp, terpenoids, Terp-lact, terpene-lactones; TTerp, triterpenoids, ip, intraperitoneally; ivt, intraventricular; po, per os (orally); sc, subcutaneous.

 

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Received on 17.03.2023           Modified on 14.06.2023

Accepted on 31.07.2023   ©Asian Pharma Press All Right Reserved