INTRODUCTION:

Withania somnifera, commonly referred to as Ashwagandha and a member of the Solanaceae family, is also known as "Indian Winter cherry" or "Indian Ginseng." This herb has held a central role in Ayurveda, the traditional Indian system of medicine, for countless years¹. It is recognized as a Rasayana, a remedy that promotes both physical and mental well-being, fostering happiness and vitality.

In Ayurveda, Rasayana preparations are given to children as tonics and are taken by adults, especially the elderly, to enhance longevity. Among the Rasayana herbs in Ayurveda, Ashwagandha stands out as a prominent "Sattvic Kapha Rasayana" herb, known for its adaptogenic and anti-stress properties.²

Ashwagandha is commonly found in the form of churna, which is a finely sifted powder that can be blended with water, ghee (clarified butter), or honey. It plays a supportive role in enhancing brain and nervous system functions, aiding in memory improvement. Furthermore, it contributes to maintaining a healthy balance in the reproductive system, promoting overall sexual and reproductive well-being. Acting as a potent adaptogen, it strengthens the body's capacity to handle stress. Ashwagandha also fortifies the body's defense mechanisms against illnesses by boosting cell-mediated immunity and possesses strong antioxidant properties, protecting against cellular damage caused by free radicals.^3-4

Ashwagandha has a rich history in traditional medicine, valued for its diverse range of properties including anti-stress, narcotic, diuretic, treatment for anemia, and aphrodisiac qualities, among others⁵. Its applications span a wide spectrum, addressing various issues such as constipation, worm infestations, liver ailments, leprosy, inflammation, cardiovascular problems, joint pain, bacterial infections, nervous system disorders, and arthritis, among others^6-7. The pharmacological activities associated with Withania somnifera encompass anti-inflammatory, analgesic, anti-arthritic, hepatoprotective, anticancer, anti-epileptic, anti-Alzheimer, antiparkinson, cardioprotective, neuroprotective, antimicrobial, antifungal, antioxidant, immunomodulatory, antidepressant, antidiabetic, antiplatelet, and fibrinolytic properties.^8-11

Regarding administration, solid medications such as tablets, powders, capsules, and cachets are prevalent choices¹². These forms fall under the category of solid unit dose forms since they deliver a precise amount of medication for a single dose. Tablets and capsules, in particular, make up a substantial portion of global pharmaceutical production. This is primarily attributed to their benefits, stringent formulation standards, and the necessity for large-scale manufacturing to fulfill healthcare needs.^13-14

Tablets exhibit diverse shapes, sizes, and weights, tailored to the therapeutic ingredients and intended administration. This document provides a concise overview of the primary constituents commonly present in tablets, the manufacturing procedures employed, and underscores both their advantages and drawbacks. Tablets stand as the most widespread dosage form currently employed, with approximately 70% of all medications being dispensed in this format.

Table No 1: Taxonomical Classification

Taxonomical classification
Kingdom	Plantae, plant
Subkingdom	Tracheobionta, Vascular plant
Super division	Spermatophyte, seeds plant
Division	Angiosperma
Class	Dicotyledons
Subclass	Magnoliopsida
Order	Solanales

Fig No. 1: Ashwagandha (Withania somnifera)

BOTANICAL DESCRIPTION:

Withania somnifera, also known as WS, is a small woody shrub from the Solanaceae family. It usually attains a height of approximately two feet and can be found growing in various regions such as Africa, the Mediterranean, and India. It appears as an erect, evergreen plant with a fuzzy texture, ranging from 30 to 150 centimeters in height. WS flourishes in arid parts of India and is frequently observed in abandoned locations and along riverbanks.

The plant exhibits stout and fleshy whitish-brown roots, simple ovate leaves devoid of hair, with smaller leaves positioned opposite each other in the flowering area. Its flowers are not very conspicuous, often appearing greenish or slightly yellow, clustered in umbrella-like arrangements within the leaf axils. As late autumn approaches, small round orange-red berries emerge, enclosed within the persistent calyx. These berries contain yellow, kidney-shaped seeds. For medicinal purposes, the primary plant part used is its roots. In late autumn, the vibrant red fruits are harvested, and the seeds are dried to be planted in the following spring.

Parts used:

Whole plant, roots, leaves, stem, green berries, fruits, seeds, bark are used.

SYNONYMS:

Sanskrit	Ashwagandha, Turangi-gandha
English	Winter Cherry.
Hindi	Punir, Asgandh
Bengali	Ashwagandha
Gujarati	Ghodakun, Ghoda, Asada, Asan
Telagu	Pulivendram, Panneru-gadda, Panneru
Tamil	Amukkura, Amkulang, Amukkuram-Kilangu, Aswagandhi,
Goa	Fatarfoda
Panjabi	Asgand, Isgand
Bombay	Asgund, Asvagandha

PHYTOCHEMISTRY:

The isolation and detailed analysis of secondary metabolites found in plants are of atmost importance in the development of innovative treatments for a broad spectrum of health issues. Extensive research has been conducted on Withania somnifera (W. somnifera), leading to the identification of a multitude of phytochemical compounds. Various analytical methods, including column chromatography, gas chromatography-mass spectrometry (GCMS), liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR), and X-Ray diffraction etc., have been employed in this process^.6,15

The essential process of isolating and characterizing secondary metabolites from plants plays a critical role in the development of innovative therapeutics for a diverse array of health conditions. Extensive research has focused on Withania somnifera (W. somnifera), leading to the discovery of a wide range of phytochemicals. This identification has been made possible through the application of various analytical techniques, including column chromatography, gas chromatography-mass spectrometry (GCMS), liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR), and X-Ray diffraction.

Phytochemical studies have revealed a wide spectrum of bioactive components in various parts of W. somnifera. Initial analyses have identified the presence of steroidal lactones, alkaloids, saponins, flavonoids, tannins, starch, phenolic compounds, carbohydrates, withanolides, sitoindosides, anaferine, anahygrine, ß-sitosterol, chlorogenic acid, cysteine, cuscohygrine, pseudotropine, withanine, scopoletin, withananine, somniferinine, somniferiene, tropanol, 14-α-hydroxywithanone, and 6,7β-Epoxywithanon.¹⁶

In specific research carried out by Power and Salway, they successfully extracted various phytochemicals, including withaniol, somnirol, somnitol, withanic acid, phytosterols, ipuranol, as well as alkaloids like somniferine, somniferinine, withamine, withanmine, pseudowithamine, and withanaminine from alcoholic extracts of both W. somnifera leaves and roots. The initial withanolide identified in W. somnifera was Withaferin-A, and other withanolides such as Withanolide-A, Withanolide-E, and Withanone were also found to be present.¹⁷

Furthermore, the methanolic leaf extract was found to contain a variety of compounds, including tisopelletierine, 3α-tigloyloxtropine, cuscohygrine, hentriacontane, visamine, as well as components like reducing sugars, ducitol, starch, iron, and amino acids such as glutamic acid, cysteine, and tryptophan. The plant also contains steroids like cholesterol, diosgenin, stigmastadien, and sitoinosides VII-X. Additionally, from the methanol root extract of W. somnifera, seven new withanosides glycosides, named withanosides I-VII, were isolated, along with four known compounds, including withaferin A, 5α,20αF (R)-dihydroxy-6α,7α-epoxy-1-oxowitha-2,24-dienolide, physagulin D, and coagulin Q.

These bioactive compounds have demonstrated a range of documented biological activities, which add to the therapeutic promise of W. somnifera.¹⁸

1. Withaferin A (Leaf):- 2.Withanone (Fruit):-

Biological Activity: -Neuroprotective and Cardioprotective Biological Activity:- Anti-inflammatory

3.Withanolide A (Root): - 4. Withanolide D(Leaf):-

Biological Activity: -Immunomodulator Biological Activity:-Anti-cancer

5.Withanolide E(Leaf):-6. Withanolide F(Leaf):

Biological Activity: -Anti-cancer Biological Activity: Anticancer

PHARMACOLOGICAL ACTIVITY:

Anti-inflammatory/antiarthritic/analgesic activity:

Withaferin-A, a component present in W. somnifera, exhibits strong anti-inflammatory characteristics in both laboratory-based and live animal experiments. It proves to be an effective treatment for diverse inflammatory conditions linked to ailments such as arthritis, cystic fibrosis, and inflammatory bowel disease, employing distinct mechanisms. These mechanisms involve the suppression of nuclear factor kappa B (NF-κB) activation and the reduction of cyclooxygenase-2 (COX-2) production.

Furthermore, Withaferin-A boosts the expression of a transcription factor specific to osteoblasts, fostering osteoblast differentiation and proliferation. This is advantageous for conditions such as menopausal osteoporosis and bone injuries.

Additionally, Withaferin-A mitigates the shedding of endothelial protein C receptor (EPCR) triggered by cecal ligation and puncture (CLP) in mice by reducing both the expression and activity of tumor necrosis factor-α converting enzyme.

Furthermore, the unrefined ethanolic extract derived from W. somnifera has demonstrated the ability to inhibit the release of pro-inflammatory cytokines in synovial fluid mononuclear cells taken from individuals with rheumatoid arthritis. This effect may be achieved through the suppression of the nuclear translocation of certain transcription factors.^3,6

Antiparkinson Activity:

Parkinson's disease (PD) is associated with disturbances in mitochondrial function and oxidative stress, affecting different aspects of neurodegeneration such as dopaminergic neurons and cholinergic receptors. This initiates a sequence of events that involves mitochondrial challenges and neuroinflammatory responses.

Leucine-Rich Repeat Kinase 2 (LRRK2), also known as dardarin, is a large protein that undergoes mutations in familial PD cases. Elevated levels of this protein can be detrimental to neurons. Its stability is maintained through the assistance of the chaperone heat shock protein 90 (Hsp90) and its co-chaperone Cdc37. When the microglial cell line N9 is exposed to withaferin-A, it reduces LRRK2 levels in a concentration and time-dependent manner. This disrupts the interaction between Hsp90, Cdc37, and LRRK2, ultimately causing instability and downregulation of LRRK2.

The oral intake of a 300 mg/kg/day ethanolic root extract from W. somnifera has been found to improve grip strength, motor skills, and dopamine levels in the striatum of male Wistar rats across different Parkinson's disease models. This enhancement is achieved by reducing the presence of free radicals, thus protecting dopaminergic neurons. Furthermore, antioxidant enzymes like glutathione peroxidase, catalase, and glutathione reductase show an increase, while indicators of oxidative stress, such as lipid peroxidation and nitrite levels, exhibit a decrease.^6,19

Anticancer Activity:

Cancer is defined by unregulated cell proliferation, and existing chemotherapy approaches aim to disrupt various cellular signaling pathways to directly eliminate cancer cells and impede their proliferation. Nevertheless, these treatments frequently result in side effects that diminish their efficacy.

W. somnifera has exhibited a reassuring safety record and significant anti-cancer potential in animal research. Withaferin-A, a compound present in W. somnifera, induces programmed cell death (apoptosis) in cancer cells through multiple pathways. It hinders the activation of NF-κB by blocking TNF-triggered activation of IκB kinase ß through a redox mechanism that is sensitive to thioalkylation. Furthermore, it activates tumor suppressor proteins like p53 and pRB. Withaferin-A also enhances the expression of death receptor-5, initiating signals that induce apoptosis and ultimately lead to the death of cancer cells.

In prostate cancer cells, Withaferin-A halts the G2/M phase of the cell cycle and blocks mitosis. It achieves this by increasing the levels of phosphorylated Wee1, phosphorylated histone H3, p21, and targets related to aurora B. In breast cancer cells, it hinders cell migration and invasion by reducing the activity of signal transducer and activator of transcription (STAT3). Moreover, in B cell lymphoma, Withaferin-A diminishes cell survival by reducing the expression of heat shock protein 90 (HSP90), a protein that stabilizes various key proteins required for tumor growth.

The root extract of W. somnifera reduces cell viability and prompts the arrest of the cell cycle at the G2/M phase in a prostate cell line (PC3). This effect is achieved by suppressing transcription factors, resulting in decreased synthesis of IL8 and COX-2 enzymes.⁶

Neuroprotective activity:

W. somnifera has demonstrated its capacity for neuroprotection, both in preclinical and clinical investigations. When administered as a root extract, it effectively reduced the generation of nitric oxide (NO) by interacting with neuronal nitric oxide synthase (nNOS). This inhibition of NO production curbed the stress-induced activation of NADPH-diaphorase. This was accomplished by reducing corticosterone release and promoting the activation of choline acetyltransferase, subsequently leading to increased serotonin levels in the hippocampus. These interconnected effects effectively inhibited NADPH-d activity in adult Swiss albino mice subjected to chronic stress.

The neuroprotective attributes of W. somnifera were reaffirmed in experiments involving C6 cells exposed to lead nitrite. In this scenario, the root extract of W. somnifera played a pivotal role in preserving the equilibrium of factors such as glial fibrillary acidic protein (GFAP) expression, heat shock protein (HSP70) levels, and neural cell adhesion molecule (NCAM) expression. An imbalance in these factors is linked to neurodegenerative mechanisms.⁶

Anti-epileptic activity:

W. somnifera and its bioactive constituents, notably withanolides, have been subjected to scrutiny using diverse in-vitro and in-vivo models, illustrating their capacity to diminish epileptic seizures through a range of mechanisms.

In experiments using pentylenetetrazol-induced seizures, both W. somnifera extracts and withanolides were observed to elevate the seizure threshold in the brain. This outcome was attained when a sub-protective dose of GABA or diazepam was co-administered, and the underlying mechanism involved the modulation of the GABAergic system.

The oral administration of W. somnifera root extract and withanolide-A at doses of 100 mg/kg/day and 10 mol/kg/day, respectively, over a 15-day duration, successfully alleviated spatial memory impairments in male Wistar rats with epilepsy induced by pilocarpine. This improvement was achieved by counteracting oxidative stress-induced changes in glutamergic transmission within the brain, specifically by diminishing the expression of N-methyl-D-aspartate (NMDA) receptors.

Furthermore, in a pilocarpine-induced epilepsy model, the inhibition of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPA receptors) enhanced motor learning.^6,8

Anti-Alzheimer activity:

Withafera somnifera root extract and its active components have shown potential in the treatment of Alzheimer's disease, as demonstrated in various in vivo and in vitro studies. They influence several pathological processes, including the reduction of amyloid beta plaques in the brain and the enhancement of muscarinic receptor binding affinity.

The root extract inhibits the production of Aβ, leading to a decrease in neuronal apoptosis by promoting the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus. Nrf2 is a transcription factor that regulates the activity of antioxidant enzymes, protecting cells from oxidative damage. It also elevates the expression of the neuroprotective enzyme heme oxygenase-1.

Furthermore, Withaferin A inhibits heat shock protein 90 (Hsp90) and induces heat shock proteins 70 and 27 (Hsp70 and Hsp27). While Hsp90 promotes the aggregation of τ protein, a hallmark of Alzheimer's disease, Hsp27 plays a protective role by preventing amyloid-beta oligomerization in mouse and drosophila larval models of Alzheimer's disease.

In Alzheimer's disease, the NF-κB pathway hampers Aβ fibril phagocytosis, resulting in the accumulation of Aβ fibrils and neuroinflammation in the brain. Withaferin-A has been shown to inhibit NF-κB activation by preventing NF-κB phosphorylation through the inhibition of IκB kinase stimulation. It also inhibits NF-κB activation by targeting the catalytic site of IκB kinase, thereby mitigating neuroinflammation.⁶

Hepatoprotective activity:

Numerous research studies have emphasized the liver-protective properties of W. somnifera and its active constituents. Withaferin-A, in particular, has demonstrated its ability to mitigate acute liver failure induced by D-galactosamine/ lipopolysaccharide in wild-type mice. It accomplishes this by suppressing the activation of macrophages. This compound effectively mitigates liver damage caused by GalN/LPS by specifically targeting macrophages. Importantly, its mode of action involves partially inhibiting NLRP3 and is largely unrelated to NRF2 signaling, autophagy induction, hepatic AMPKα1, and IκκB.⁶

Cardioprotective activity:

W. somnifera has a traditional use in addressing cardiovascular conditions due to its beneficial effects on heart health, which have been substantiated by numerous animal studies. One of its bioactive compounds, Withaferin-A, has exhibited anti-platelet properties and the ability to enhance fibrinolysis in post-myocardial infarction scenarios.²⁰

This was achieved by assessing activated partial thromboplastin time (aPTT) and prothrombin time (PT) in normal human plasma. Furthermore, when human umbilical vein endothelial cells (HUVECs) were stimulated by TNF-α, Withaferin-A effectively inhibited the production of plasminogen activator inhibitor type 1 (PAI-1) without directly affecting tissue plasminogen activator (tPA). This resulted in a lowered PAI-1/t-PA ratio, ultimately promoting fibrinolytic effects.^6,21

Cognition enhancing activity:

Numerous preclinical and clinical studies have provided evidence that W. somnifera can enhance cognitive function in individuals dealing with conditions like neurodegenerative disorders and cognitive impairment induced by anxiety.⁶

Antiviral activity against SARS-CoV-2:

Multiple in silico investigations have suggested that bioactive compounds derived from the plant possess the capability to interact with specific enzymes and the primary spike protein linked to SARS-CoV-2. Withanoside and Somniferine, as revealed by molecular docking and dynamic simulations, exhibit a robust binding affinity for the SARS-CoV-2 main protease enzyme (Mpro), indicating their potential as therapeutics for combatting COVID-19.

Moreover, Withanoside-V and Withanoside-X, as indicated by docking studies, demonstrate significant binding affinity for the viral S-glycoprotein, which plays a crucial role in attaching to the human ACE2 receptor. This underscores their potential as therapeutic agents against the disease. Nevertheless, further comprehensive in vitro and in vivo investigations are necessary to explore the extracts and bioactive compounds from W. somnifera, as well as their modes of action against the SARS-CoV-2 virus.^3-6,10

Scientific Studies on Ashwagandha¹

Adaptogenic/Anti-stress effect:

Ashwagandha is often likened to Eleutherococcus senticosus (Siberian Ginseng) and Panax Ginseng (Chinese/Korean Ginseng) due to its adaptogenic qualities, earning it the moniker "Indian Ginseng." Extensive research conducted on animal models has demonstrated that Ashwagandha effectively enhances physical endurance, shields against stress-induced gastric ulcers, and mitigates carbon tetrachloride (CCl4)-induced liver damage and mortality. In the case of rats, Ashwagandha demonstrates similar anti-stress properties, employing an oral dosage of 100mg/kg of an aqueous suspension of Ashwagandha root in these experiments.

The findings reveal a substantial rise in plasma corticosterone levels, phagocytic index, and avidity index in rats exposed to cold swimming stress. However, in rats pre-administered with Ashwagandha, these parameters reverted to levels close to normal, accompanied by an increase in swimming endurance. These observations point to the potency of crude Withania somnifera as an effective anti-stress agent.^1,6

Collectively, these investigations lend credence to the traditional Ayurvedic principles of tonics, revitalizers, and rejuvenators. They suggest that Withania somnifera could have practical clinical applications in averting and addressing stress-related conditions, including arteriosclerosis, premature aging, arthritis, diabetes, hypertension, and malignancies.^7,22

Effect on swimming performance:

In experiments conducted with adult rats using a swimming endurance stress test, Ashwagandha showcased its capacity to improve swimming performance significantly. The rats treated with Ashwagandha demonstrated a substantial boost in their swimming endurance when compared to the control group. While the control mice swam for an average of 385 minutes, the Ashwagandha-treated animals continued swimming for an average of 740 minutes. In essence, Withania somnifera (WS) treatment approximately doubled the swimming duration.

Effect on cortisol and ascorbic acid contents of adrenals:

When animals underwent 5 hours of continuous swimming, there was a notable decrease in cortisol levels in their adrenal glands compared to the non-swimming group. However, prior treatment with Withania somnifera (WS) thwarted this decline in adrenal cortisol content. Additionally, the levels of ascorbic acid significantly diminished after 5 hours of swimming when compared to the non-swimming group. Nevertheless, pre-treatment with WS prevented this decline in ascorbic acid levels induced by the stress of swimming. In summary, Withania somnifera treatment effectively safeguards against the reduction in adrenal cortisol and ascorbic acid levels typically associated with the stress of swimming.

Anti-ulcerogenic effect:

Ashwagandha has proven its efficacy in preventing stress-induced ulcers within the gastrointestinal tract. It provided significant protection against ulcers induced by various stressors, including 18hours of immobilization, a combination of cold exposure and 4-hour immobilization, and aspirin-induced gastric ulcers in rats. Moreover, it led to a reduction in the average ulcer index in these rat experiments.

Effect on leukocytosis:

The administration of Ashwagandha to a group of mice in conjunction with milk injections led to a reduction in leukocytosis.

Anti-tumor effect:

Effect on Chinese Hamster Ovary (CHO) cells carcinoma:

The roots of Withania demonstrated a 49% decrease in colony forming efficiency for CHO cells, resulting in the inhibition of cell growth and the prevention of cell attachment. This prolonged inhibition of CHO cell growth was influenced by both cell density and the duration of exposure to Ashwagandha. This data can hold significance for oncologists contemplating the incorporation of Ashwagandha alongside conventional chemotherapy or radiation therapy to potentially augment their efficacy.

Effect on Urethane induced lung-adenoma in mice and other studies:

In its unrefined state, Ashwagandha displayed notable effectiveness in experimental carcinogenesis. It efficiently thwarted the formation of urethane-induced lung adenomas in mice and alleviated other adverse effects provoked by urethane, including leucopenia. Urethane, a chemical stressor, usually triggers a range of adverse effects, all of which were effectively mitigated by Withania.

This adaptable herbal remedy can function as a supplementary strategy alongside cancer chemotherapy or radiotherapy. In addition to its anti-cancer attributes, it holds the promise of alleviating the typical side effects associated with anti-cancer treatments, which frequently have an adverse impact on immunity and overall well-being. Withania somnifera also serves as an immune modulator, potentially enhancing the lifespan of cancer patients by addressing issues related to compromised immunity.

Our research outcomes strongly endorse the utilization of Ashwagandha as an anti-tumor agent. These studies have presented compelling indications that this remarkable herb holds remarkable potential for the treatment of conditions related to tumors, including cancer. Furthermore, it has demonstrated the capability to improve white cell count (WBC) and function, which are typically depleted during chemotherapy for cancer.

Moreover, Ashwagandha has shown potential in the management of uterine fibroid tumors. It plays a role in diminishing uterine bleeding tendencies and, with extended treatment, contributes to the eventual disappearance of fibroids.

Effect on Central Nervous System:

Cognition Promoting Effect:

Ashwagandha is a well-known Ayurvedic Rasayana belonging to the category of Medhyarasayanas, a subgroup recognized for their ability to enhance mental and intellectual capacities. The term "Medhya" primarily relates to the mind and cognitive abilities. Therefore, Medhya Rasayanas like Ashwagandha are utilized to enhance intelligence and memory.

The cognitive-enhancing benefits of Medhya Rasayanas are particularly noticeable in scenarios involving children with memory deficits, individuals facing memory challenges resulting from head injuries or prolonged illnesses, and among the elderly population.

Effect on neurodegenerative diseases such as Parkinson’s, Huntington’s, and Alzheimer’s diseases:

In individuals diagnosed with Alzheimer's disease, cognitive decline is primarily associated with neuritic atrophy and synaptic loss, as evidenced by post-mortem neuropathological examinations of the brain. Likewise, patients with other neurodegenerative disorders such as Parkinson's disease, Huntington's disease, and Creutzfeldt-Jakob disease have also demonstrated substantial neuritic atrophy as a fundamental aspect of the conditions.

Multiple research investigations have illustrated Ashwagandha's capacity to decelerate, halt, reverse, or alleviate neuritic atrophy and synaptic loss. As a result, Ashwagandha holds potential in the management of neurodegenerative conditions like Alzheimer's, Parkinson's, Huntington's, and others, irrespective of the disease's progression stage. This encompasses early stages when individuals may be encountering mild forgetfulness.

Certain compounds present in Ashwagandha, such as glycowithanolides, withaferin-A, and sitoindosides VII-X, have been extracted from its roots and demonstrated substantial efficacy in alleviating cognitive deficits induced by ibotenic acid in an Alzheimer's disease model.

Ashwagandha is traditionally recognized in Ayurveda as a nervine tonic and is a frequent component in Ayurvedic tonics. Within Ayurveda, these tonics, rejuvenators, and vitalizers are thought to combat illnesses, boost immunity, and foster longevity in those who consume them.

Furthermore, prior administration of Ashwagandha extract has been demonstrated to forestall a range of modifications linked to Parkinson's disease in a rat model induced by 6-hydroxydopamine (6-OHDA). These modifications encompass shifts in antioxidant enzyme activities, catecholamine levels, binding of dopaminergic D2 receptors, and the expression of tyrosine hydroxylase. This suggests that Ashwagandha may play a protective role in ameliorating neuronal damage in Parkinson's disease.

Anxiolytic effect:

Ashwagandha exhibited an anxiolytic effect, reducing anxiety to a degree comparable to the drug Lorazepam in three well-established anxiety tests: the elevated plus-maze, social interaction, and feeding latency in an unfamiliar environment. Furthermore, both Ashwagandha and Lorazepam successfully reduced elevated levels of tribulin, a clinical anxiety marker in the rat brain induced by the anxiogenic agent pentylenetetrazole.

Additionally, Ashwagandha demonstrated an antidepressant effect akin to imipramine in two well-established assessments: the "behavioral despair" test induced by forced swim and the "learned helplessness" test. These results suggest the potential utility of Ashwagandha as a mood regulator in clinical scenarios associated with anxiety and depression.

Effect on Energy levels and Mitochondrial Health:

Researchers explored how Ashwagandha influenced glycosaminoglycan synthesis in the granulation tissue of carrageenin-induced air pouch granuloma. Their findings indicated that Ashwagandha notably impeded the integration of ribosome-35S into the granulation tissue. Moreover, the study observed that Ashwagandha disrupted oxidative phosphorylation, resulting in a decrease in the ADP/O ratio within the mitochondria of the granulation tissue.

Moreover, Ashwagandha had an impact on the Mg2+-dependent ATPase activity in the granulation tissue. Additionally, it was observed to reduce the activity of the succinate dehydrogenase enzyme within the mitochondria of the granulation tissue.

Anti-inflammatory effect due to Withaferin:

Withaferin A and 3-β-hydroxy-2,3-dihydrowithanolide F, derived from Withania somnifera, demonstrate noteworthy potential due to their antibacterial, antitumoral, immunomodulatory, and anti-inflammatory properties.

Anti-arthritic effect:

Ashwagandha functions as an analgesic, effectively soothing the nervous system's reaction to pain. Its strong anti-arthritic properties are well-recognized and well-documented, and it has also demonstrated effectiveness as both an antipyretic and analgesic.

When given orally at a dose of 1000mg/kg, Ashwagandha exhibited substantial analgesic effects in rats during heat-induced analgesia assessments using the hot plate method. The maximum analgesic effect, which reached 78.03 percent, was observed two hours after the administration.

To explore the role of pain mediators such as prostaglandins and 5-hydroxytryptamine in the analgesic effects of Ashwagandha, pre-treatment with paracetamol (100 mg/kg, ip) and cyproheptadine (10 mg/kg, ip) was conducted. Ashwagandha's analgesic effects.

DISCUSSION AND CONCLUSION:

Ashwagandha plays a prominent role in Indian households, valued as a potent tonic suitable for both the elderly and children. Among young individuals, it carries a reputation as an aphrodisiac. In the realm of Ayurveda, the ancient medical system, Ashwagandha holds a distinguished status as one of the finest nervine tonics.

Drawing from our clinical expertise, Ashwagandha has exhibited potential in addressing diverse neurological conditions. This includes its ability to enhance the condition of patients affected by paralysis and neuronal deficits resulting from brain strokes after extended treatment. Moreover, we have incorporated Ashwagandha into the treatment regimen for various cancer types, including advanced stages of prostate and lung cancers. Remarkably, some patients with lung cancer who opted not to pursue modern therapies have witnessed tangible health improvements through our Ashwagandha-based treatment approach.

Ashwagandha harbors bioactive components, notably withanolides, which hold therapeutic promise in addressing a spectrum of conditions impacting the central nervous system, such as cyclical vomiting syndrome (CVS), inflammatory ailments, and liver disorders. These compounds target diverse biomolecules relevant to these disorders and have demonstrated benefits in animal models of these conditions. Withanolides, including withaferin-A, exert influence over multiple pathways tied to inflammation, cancer, neurodegenerative illnesses, and more. Nevertheless, further clinical trials spanning various health conditions, including cancer, are imperative. While Ashwagandha boasts a low incidence of side effects, confirming its efficacy in human studies is essential.

Scientific evidence available to date substantiates Ashwagandha's role as a robust regenerative tonic, aligning with the Ayurvedic concept of "Rasayana." This reputation arises from its multifaceted pharmacological actions, encompassing anti-stress, neuroprotective, antitumor, anti-arthritic, analgesic, and anti-inflammatory properties. Ashwagandha's potential applications extend to a spectrum of conditions, including Parkinson's disease, dementia, memory impairment, stress relatedInterestingly, cyproheptadine significantly enhanced Ashwagandha's analgesic activity, while paracetamol did not produce any significant alteration, suggesting that serotonin, rather than prostaglandins, contributes to disorders, malignancies, and beyond.

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Received on 04.12.2023 Modified on 01.02.2024

Res. J. Pharmacognosy and Phytochem. 2024; 16(2):112-120.

DOI: 10.52711/0975-4385.2024.00022