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Effect of ashwagandha and shilajit on central nervous system neurotransmitter levels. (a) Changes in serotonin levels before and after treatment. Ashwagandha (500 mg/kg) as well as combined ashwagandha and shilajit treatment (day 21–30) lead to significant increase (P < 0.01) increase in corticohippocampal serotonin compared to untreated animals on ethanol (30 days). However, treatment with shilajit (50 mg/kg) alone or diazepam failed to increase serotonin levels compared to alcohol treated group. (b) Changes in dopamine levels before and after treatment. Shilajit (50 mg/kg) as well as ashwagandha and shilajit combination treatment (day 21–30) led to significant increase (P < 0.01) in corticohippocampal dopamine compared to untreated animals on ethanol (30 days). However, treatment with ashwagandha (500 mg/kg) alone or diazepam failed to increase serotonin levels compared to alcohol treated group. (c) Changes in gamma‑aminobutyric acid levels before and after treatment. Ashwagandha (500 mg/kg) as well as combined ashwagandha and shilajit treatment (day 21–30) led to significant increase (P < 0.01) increase in corticohippocampal gamma‑aminobutyric acid levels compared to untreated animals on ethanol (30 days). However, treatment with shilajit (50 mg/kg) alone failed to increase serotonin levels compared to alcohol‑treated group. Diazepam treatment also showed a significant increase (P < 0.001) increase in corticohippocampal gamma‑aminobutyric acid levels. Values represent mean ± standard error of the mean n = 5
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Background: Alcohol addiction is a social problem leading to both loss of health and economic prosperity among addicted individuals. Common properties of anti‑addictive compounds include anti‑anxiety, anticonvulsants, anti‑depressant, and nootropic actions primarily through modulation of gamma‑aminobutyric acid (GABA) and serotonergic systems. Obje...
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Context 1
... treatment with shilajit (50 mg/kg) as well as ashwagandha and shilajit combination leads to a significant increase (P < 0.01) in dopamine levels compared to animals on ethanol (30 days). Diazepam treatment had little effect on dopamine and serotonin levels [ Figure 4]. ...
Citations
... On the other hand, diabetic groups that received 100 & 200 mg/kg BW of ashwagandha demonstrated a significant rise in serum serotonin levels when compared with the DC group. This is in line with an earlier study by Bansal and Banerjee (2016) who found that chronic ashwagandha administration significantly increased serotonin levels. Also, Priyanka et al. (2020) pointed to the ability of ashwagandha in increasing serotonin concentrations. ...
Evaluation of the efficacy of ashwagandha root extract to ameliorate the oxidative stress and depression resulting from diabetes in male rats was conducted in the current study. Thirty-six male albino rats were randomly grouped into two main groups: normal (n=18) and diabetic (n=18), diabetes was induced by a single dose of 150 mg/kg BW alloxan injected intraperitoneally. After six weeks, both normal and diabetic groups were further subdivided into six subgroups ; normal control, 100 & 200 mg/kg BW ashwagandha treated normal, diabetic control, 100 and 200 mg/kg BW ashwagandha treated diabetic groups, for another six weeks. The forced swim test was used to assess depression, and serum serotonin levels were measured. In brain tissue homogenates, the glutathione reduced content, superoxide dismutase, and catalase activity were measured, as well as the total antioxidant capacity, total oxidative capacity, and malondialdehyde levels. Moreover, histo-pathological examination of the brain (cerebral cortex and cerebellum) were conducted. The obtained results revealed that the administration of ashwagandha extract to diabetic rats reduced immobility time during the forced swim test while increasing the serotonin levels significantly when compared with the diabetic group. Similar to this, brain total antioxidant capacity, glutathione reduced content, superoxide dismutase, and cata-lase activity increased significantly, while brain total oxidative capacity, oxidative stress index, and malondi-aldehyde levels decreased significantly when compared with the diabetic group. Furthermore, the histopatho-logical changes in brain sections were reversed by ashwagandha root extract. In conclusion, ashwagandha root extract can be used to ameliorate the brain oxidative stress and depression brought on by diabetes mellitus at doses of 100 and 200 mg/kg BW.
... Another study reported that in chronic alcohol exposure Ashwagandha churna causes reduction in both withdrawal anxiety and intake of ethanol. Dominantly, the mechanism involved in anti-addiction is via modulation of GABAergic and serotonergic system (Bansal and Banerjee, 2016). In view of several above studies, Ashwagandha is found to be effective in reversing addiction. ...
Ethnopharmacological relevance: Withania somnifera (Family: Solanaceae), commonly known as Ashwagandha or
Indian ginseng is distributed widely in India, Nepal, China and Yemen. The roots of plant consist of active
phytoconstituents mainly withanolides, alkaloids and sitoindosides and are conventionally used for the treatment of multiple brain disorders.
Aim of the review: This review aims to critically assess and summarize the current state and implication of
Ashwagandha in brain disorders. We have mainly focussed on the reported neuroactive phytoconstituents,
available marketed products, pharmacological studies, mechanism of action and recent patents published related
to neuroprotective effects of Ashwagandha in brain disorders.
Materials and methods: All the information and data was collected on Ashwagandha using keywords
“Ashwagandha” along with “Phytoconstituents”, “Ayurvedic, Unani and Homeopathy marketed formulation”,
“Brain disorders”, “Mechanism” and “Patents”. Following sources were searched for data collection: electronic
scientific databases such as Science Direct, Google Scholar, Elsevier, PubMed, Wiley On-line Library, Taylor and
Francis, Springer; books such as AYUSH Pharmacopoeia; authentic textbooks and formularies.
Results: Identified neuroprotective phytoconstituents of Ashwagandha are sitoindosides VII–X, withaferin A,
withanosides IV, withanols, withanolide A, withanolide B, anaferine, beta-sitosterol, withanolide D with key
pharmacological effects in brain disorders mainly anxiety, Alzheimer's, Parkinson's, Schizophrenia, Huntington's
disease, dyslexia, depression, autism, addiction, amyotrophic lateral sclerosis, attention deficit hyperactivity
disorder and bipolar disorders. The literature survey does not highlight any toxic effects of Ashwagandha.
Further, multiple available marketed products and patents recognized its beneficial role in various brain disorders; however, very few data is available on mechanistic pathway and clinical studies of Ashwagandha for
various brain disorders is scarce and not promising.
Conclusion: The review concludes the results of recent studies on Ashwagandha suggesting its extensive potential
as neuroprotective in various brain disorders as supported by preclinical studies, clinical trials and published
patents. However vague understanding of the mechanistic pathways involved in imparting the neuroprotective
effect of Ashwagandha warrants further study to promote it as a promising drug candidate.
... Another study reported that in chronic alcohol exposure Ashwagandha churna causes reduction in both withdrawal anxiety and intake of ethanol. Dominantly, the mechanism involved in anti-addiction is via modulation of GABAergic and serotonergic system (Bansal and Banerjee, 2016). In view of several above studies, Ashwagandha is found to be effective in reversing addiction. ...
Ethnopharmacological relevance
Withania somnifera (Family: Solanaceae), commonly known as Ashwagandha or Indian ginseng is distributed widely in India, Nepal, China and Yemen. The roots of plant consist of active phytoconstituents mainly withanolides, alkaloids and sitoindosides and are conventionally used for the treatment of multiple brain disorders.
Aim of the review: This review aims to critically assess and summarize the current state and implication of Ashwagandha in brain disorders. We have mainly focussed on the reported neuroactive phytoconstituents, available marketed products, pharmacological studies, mechanism of action and recent patents published related to neuroprotective effects of Ashwagandha in brain disorders.
Materials and methods
All the information and data was collected on Ashwagandha using keywords “Ashwagandha” along with “Phytoconstituents”, “Ayurvedic, Unani and Homeopathy marketed formulation”, “Brain disorders”, “Mechanism” and “Patents”. Following sources were searched for data collection: electronic scientific databases such as Science Direct, Google Scholar, Elsevier, PubMed, Wiley On-line Library, Taylor and Francis, Springer; books such as AYUSH Pharmacopoeia; authentic textbooks and formularies.
Results
Identified neuroprotective phytoconstituents of Ashwagandha are sitoindosides VII–X, withaferin A, withanosides IV, withanols, withanolide A, withanolide B, anaferine, beta-sitosterol, withanolide D with key pharmacological effects in brain disorders mainly anxiety, Alzheimer's, Parkinson's, Schizophrenia, Huntington's disease, dyslexia, depression, autism, addiction, amyotrophic lateral sclerosis, attention deficit hyperactivity disorder and bipolar disorders. The literature survey does not highlight any toxic effects of Ashwagandha. Further, multiple available marketed products and patents recognized its beneficial role in various brain disorders; however, very few data is available on mechanistic pathway and clinical studies of Ashwagandha for various brain disorders is scarce and not promising.
Conclusion
The review concludes the results of recent studies on Ashwagandha suggesting its extensive potential as neuroprotective in various brain disorders as supported by preclinical studies, clinical trials and published patents. However vague understanding of the mechanistic pathways involved in imparting the neuroprotective effect of Ashwagandha warrants further study to promote it as a promising drug candidate.
... [42][43][44][45] Withania somnifera is also often used by practitioners of Ayurveda for combating addiction, obsession, and diverse so-called "lifestyle disorders" [46] and numerous preclinical and clinical studies conducted with its different types of extract have continued to justify such traditionally known medicinal uses of different parts of the plant. [28,30,31,[47][48][49][50] However, the therapy relevant questions concerning their doses and treatment regimen necessary for prevention and cure of such disorders still remain unanswered or speculative only. ...
Background:
The objective of the study is to compare stress resistance-promoting effect of triethylene glycol (TEG) and root extract of Ashwagandha (Withaniasomnifera) i.e. withanolide-free root extract of Withaniasomnifera (WFWS).
Materials and methods:
Mice groups treated orally with 10 mg/kg TEG or WFWS (3.3, 10, 33.3, or 100 mg/kg) for 12 consecutive days were subjected to foot shock stress-triggered hyperthermia test on the 1st, 5th, 7th and 10th day and to marble-burying test on the following 2 days. Effects of treatment on stress-triggered alteration in body weight, core temperature, blood glucose, insulin and cortisol level were quantified and statistically analyzed.
Results:
WFWS doses up to 10 mg/kg/day were as effective as TEG in affording protection against stress-triggered alteration in body weight, core temperature and marble-burying behavior. Protection against stress-triggered alteration in blood glucose and insulin level, as well as antidepressants or anxiolytic-like activities in the behavioral test, were observed in the higher two WFWS doses (33.3 and 100 mg/kg) treated groups only.
Conclusion:
Ashwagandha metabolites other than withanolides contribute to its stress resistance increasing effects. The observations suggest that modulation of physiological functions of gut microbiota may be involved in the mode of action of Withaniasomnifera root extracts.
... However, under stressful condition there is depletion of GABA receptor binding in the CNS [43,44] which leads to the activation of the HPA axis. Studies have shown that extracts and active compounds of ashwagandha have GABA-like activity and also increase the production of GABA in brain [45][46][47]. Therefore, it is suggested that IC might induce higher levels of GABA or exert GABA like action in brain under the stressful condition and thereby suppress the activation of the HPA axis and the subsequent increase in serum level of corticosterone which is to be substantiated by future studies. ...
Objective: To find out whether an isolated compound (IC) from the ethanolic extract of roots of ashwagandha prevents stress-induced hyperglycemia by direct interference with the action of increased concentration of corticosterone on hepatocytes or by preventing hyper-secretion of corticosterone or both.Methods: A group of rats served as controls, and those in another group were subjected to restraint (1 h) and forced swimming exercise (15 min), after a gap of 4 h daily for 4 w. The third group of rats received orally IC (5 mg/kg bw/rat) 1 h prior to exposure to stressors. After the last treatment period, a blood sample was collected and serum was separated for the estimation of corticosterone and glucose. In in vitro experiment, hepatocytes were treated with different concentrations of corticosterone (100, 200, 300, 400 and 500 ng/ml). In another set of experiment, hepatocytes were treated with different doses of IC (1, 10, 100, 1000 and 10 000 μg/ml of medium) along with corticosterone (400ng/ml). The concentration of glucose and activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were determined after the treatment.Results: Stress exposure caused a significant increase in serum concentration of corticosterone and glucose whereas, administration of IC did not result in similar changes. Further, treatment of corticosterone in in vitro significantly increased the activities of PEPCK and G6Pase and concentration of glucose in a dose-dependent manner in hepatocytes. However, treatment with IC did not interfere with the corticosterone-induced an increase in the activities of PEPCK and G6Pase as well as the concentration of glucose in hepatocytes.Conclusion: The in vivo and in vitro results put together reveal that IC does not directly interfere with the action of corticosterone on hepatocytes. However, it prevents stress-induced hyperglycemia by suppressing hyper-secretion of corticosterone.
... Both epidemiological and animal studies have shown obesity to be a risk factor for mood disorders including depression. [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] Diabetic rats have also been shown to develop signs of depression. 40,41 However, how obesity or diabetes may lead to depression is not very well characterized. ...
Metabolic syndrome (MetS) is associated with high blood glucose, insulin resistance, dyslipidemia, central obesity, and hypertension. There is clinical evidence of the coexistence of depression and MetS, however, pathways associating these diseases are far from clear. In the present study, we evaluate and determine the pathogenesis of depression in MetS animals. Methods: Diet induced (High-fat diet long with 20% fructose water; HFHC diet for 4 weeks) MetS was developed in swiss albino mice. Fasting blood glucose levels, Lipids and blood pressure (BP) was measured in these animals. Development of depression in these animals was determined using forced swim and tail suspension tests. This was followed by measurement of GABA, dopamine, serotonin and norepinephrine levels in these animals. We also evaluated the effect of various antidepressants, on MetS associated depression. Results: MetS was induced using high fat and high carbohydrate (HFHC) diet in Swiss albino mice with high fasting blood glucose levels (>250 mg/dl), significantly increased LDL (p<0.001) and triglyceride (p<0.01) and reduced HDL levels (p<0.05) and significant increase in systolic BP; p<0.001) compared to normal controls. MetS animals showed signs of depression with significantly higher (p<0.001) immobility time in forced swim and tail suspension tests. These animals showed significantly lower corticohippocampal norepinephrine (NE) levels (p<0.01) compared to controls. Nortryptaline, showed a dose dependent decrease in immobility time in MetS animals (p<0.001) in both forced swim and tail suspension tests thus reversing MetS induced depression. Conclusion: The above results suggest that MetS may lead to depression in mice which is primarily mediated by NE system. © 2018, Association of Pharmaceutical Teachers of India. All rights reserved.
... The ability of shilajit to reduce alcohol withdrawal anxiety has been studied in mice (Bansal and Banerjee, 2016). Shilajit treatment significantly decreased ethanol intake and increased water consumption. ...
Nitric oxide (NO) is a gaseous signaling molecule with a short half-life that's known to exert its biological functions through cyclic guanosine monophosphate. In our system, nitric oxide is produced by nitric oxide synthase enzymes, which use substrates l-arginine, reduced nicotinamide adenine dinucleotide phosphate (NADPH), and oxygen by producing citrulline, nicotinamide adenine dinucleotide phosphate (NADP⁺), and NO. Nitric oxide can react with superoxide to produce peroxynitrite (ONOO?), which can cause irreversible modification and inhibition of different biological molecules, including mitochondrial membrane complexes and antioxidant defense enzymes through oxidizing reactions. This chapter focuses on the direct and indirect role of NO in terms of energy metabolism. Nitric oxide in this context governs and regulates metabolism, heat production, and body composition, which overall change the tissue distribution of oxygen, adenosine triphosphate production, blood flow, glucose utilization, and supply of other nutrients by resulting in altered tissue functions and physical activities.
... [24] After 30 days of chronic ethanol intake, animals showed increased corticohippocampal levels of GABA as we reported previously. [25] Decrease in GABAergic function after chronic administration of alcohol in experimental animals has been widely attributed to decrease in GABA A receptor expression and function. [26] Shankhpushpi treatment significantly increased GABA levels in the cortico-hippocampal lysates over ethanol-treated animals. ...
Alcohol addiction is a worldwide problem. It has mainly two components: dependence and withdrawal. Characteristic properties of most anti-addictive compounds include anti-anxiety, anticonvulsant, antidepressant, and nootropic actions. Shankhpushpi (Convolvulus pluricaulis. Convolvulaceae), known ethnopharmacologically as brain tonic, possess all the properties mentioned above. Here, we screen shankhpushpi for possible anti-addictive potential. Effect of shankhpushpi churna was measured on ethanol withdrawal anxiety using elevated plus maze. The role of shankhpushpi on chronic ethanol consumption (21 days) was measured using two bottle choice protocol of voluntary drinking. We also measured the effect of the above herb on cortico-hippocampal GABA levels. Shankhpushpi was found to reduce alcohol withdrawal anxiety in a dose-dependent manner. The herb also decreased ethanol intake and increased water intake significantly (P < 0.001) after 4 days of administration. Both these effects were blocked (P < 0.001) by GABAA antagonist suggesting the role of GABAA receptor. Chronic administration of shankhpushpi also significantly (P < 0.01) increased cortico-hippocampal GABA levels in mice. Shankhpushpi reduced both alcohol dependence and withdrawal in a GABAA-dependent manner, thus showing anti-addictive potential.
SUMMARY
Shankhpushpi prevented ethanol withdrawal anxiety and alcohol addiction in a GABAA-dependent manner.
Abbreviations used: GABA: Gamma-Aminobutyric Acid, HIV: Human Immunodeficiency Virus, CNS: Central Nervous System
Substance use disorders are a growing concern for all ages, including adolescents. Even though there is an increase in recreational substance use and a wider variety of drugs is available to this young population, treatment options remain scarce. Most medications have limited evidence in this population. Few specialists treat individuals struggling with addiction along with mental health disorders. As the evidence grows, these treatments are usually included in complementary and integrative medicine. This article discusses available evidence for many complementary and integrative treatment approaches while briefly describing existing psychotherapeutic and psychotropic medications.
