School of Pharmacy and Emerging Sciences, Baddi University of Emerging Sciences & Technology, Baddi, Solan - 173205, Himachal Pradesh, India.
Ashwagandha (Within somnifera) is also known as Indian ginseng or winter cherry. Ashwagandha is a highly valued herb in the Indian Ayurvedic medical system. In particular, it is utilized as a nervine tonic and for a variety of illness processes. Ashwagandha, an adaptogenic herb that is frequently used in traditional Ayurvedic medicine, has garnered a lot of attention because of its possible health benefits. Ashwagandha is well-known for its capacity to increase resilience to stress, enhance cognitive function and improve general vitality. Its therapeutic qualities are attributed to the presence of bioactive compounds like withanolides, alkaloids and saponins. Studies have demonstrated that Ashwagandha can lower cortisol levels, enhance immune function, improve sleep quality and modify the body’s stress response. . It has a cognitive promoting effect and has been helpful for memory loss in older adults and youngsters with memory deficits. It enhances energy levels and mitochondrial health and has an anxiolytic impact. Neurogenetic conditions like Parkinson’s and Alzheimer’s diseases has also been reported to benefit from it. It has also been investigated for its potential to treat neurodegenerative diseases, anxiety and depression. Modern scientific research and complementary medicine are interested in this herb because of its many potential uses.
Ashwagandha has been used for thousands of years as a Rasayana for its many health benefits, making it one of the most significant herbs in Ayurveda, India’s traditional medical system. Rasayana is herbal or metallic preparation that is said to expand happiness and youthful state of physical and mental health. There kinds of remedies are administered as tonics to young children and are also taken by middle-aged and older people to prolong their lives. Ashwagandha is most prominent among the ayurvedic Rasayana herbs. Most of the Rasayana herbs are adaptogen / anti-stress agents. Ashwagandha’s name comes from the word “Ashwa” which means horse. It is said that ingesting the root gives one abilities skin to those of a horse. The second part of the name “Gandha” which means fragrance, alludes to the distinct scent of the plant’s fresh root [1]. It has been used in traditional Indian medicine for almost 3,000 years. Its root has been used as stimulant, anthelmintic, diuretic, tonic, narcotic, and aphrodisiac. Although it is indigenous to India, it is also grown in the Mediterranean region, the Himalayan regions, Africa, the Canary Island, the Cape of Good Hope, and Australia [2]. Common forms of Ashwagandha include churna, a finely ground powder that can be combined with water, ghee or honey. It improves memory and the way the brain and nervous system work. It improves the functionality of the reproductive system that supports a balanced sexual and reproductive life. As a potent adaptogen, it enhances the body’s ability to handle stress. Ashwagandha strengthens the body’s resistance to illness by enhancing the cell-mediated immunity. It also has strong antioxidant qualities that help guard against free radical-include cellular damage [3].
2. History of Ashwagandha
The traditional medicine system has the potential to treat a variety of illnesses with few adverse effects, enhanced effectiveness and the ability to control the disease on several levels, including prevention and cure. In many traditional medical systems including Ayurveda, Unani, Siddha, Homeopathy, Chinese, Tibetan, African and other Ashwagandha is an essential herb. Withania somnifera widespread use as a neuroprotective is justified by the Latin word “somnifera”, which means “sleep inducer”. In various regions of India, it is referred to by distinct local names.
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Fig. 1. Schematic diagram of Ashwagandha
2.1 In Ayurveda: Ashwagandha is referred to as “odour of the horse”, because it roots look like a sweaty horse. Since thousands of years ago, it has been widely used to treat a variety of illnesses. The fresh roots are traditionally boiled in milk by Ayurvedic practitioners. The roots are also ground into a fine powder known as churna and blended it with liquids, honey and water. Other parts, such as leaves, shoots, seeds and berries have also been used to extend life and promote health. According to the Ayurvedic system, it is categorized as “Rasayana” which means “tonic” and primarily serves as a body rejuvenator, disease defense, aging slowing agent and memory enhancer [4].
2.2 In Unani: Traditional Unani medicine is practiced primarily in South Asian and Middle Eastern nations. It is founded on the idea of equilibrium and treatment use physical methods to treat illnesses. It uses the administrative of a particular diet or adjustments to the amount and quality of food. Natural remedies are used to treat illnesses, either as individual medications or in combination with two or more medications [5].
2.3 In Tibetan: One of the oldest known traditional medical systems in the world is the Tibetan system of medicine (TSM). It is mostly practiced by herbal doctors and Amchis in northern India, specifically in Ladakh, Lahul and Spiti. The Indian Buddhist literature serves as its foundation and it is also referred to as Sowa-Rigpa or science of healing [6].
2.4 In Homeopathy: The “theory of similarities” underpins homeopathy, a type of traditional medicine, which states that if a substance produces any symptoms in a healthy person, it will also successfully treat those same symptoms in a sick person. To treat the illness, this system only prepares tinctures which are higher dilutions of natural substances such as plants, animals, minerals and synthetic substances [7].
2.5 In China: It is called Indian ginseng in China. The Chinese traditional system (CTS) does not currently classify Ashwagandha from India. This could be because of the countries cultural distance and isolation from one another. However, Ashwagandha can be classified in CTS as “Tonify Qi” and “Tonify Blood and Essence based on comparisons with pertinent herbs [8].
2.6 In Africa: Withania somifera is a native plant in Africa that is primarily regarded as a weed of waste and contaminated areas. Leaves are applied as anti-inflammatory and anti-infection dressings. The roots is used as an ointment for sores and abscesses and is ground into affine powder and combined with animal fat [9].
3. Chemical Compounds
Ashwagandha is distinguished by its abundant phytochemical makeup. The raw material displays a varied composition of chemical compounds depending on its location. Withanolides and alkaloids are its active ingredients which are essential to its pharmacological action. Ergostane, which has a six-membered lactone ring at the C-8 or C-9 position, is the fundamental structural component of withanolides. Withanopherin A, withanolides A-Y, withanone, witadomniferin A and witasomniferols A-C are all members of the witanolide group. Witanin, somiferin, somnin, tropin, somniferinin, pseudotropin, choline, kuskohigrin, isopeletierin and anaferin are examples of alkaloids [10]. Flavonoids, such as 3-O-rutinoside, 6,8-dihydroxycemferol, quercetin and its glycosidic derivative, 3-O-rutinoside-7O-glucoside are also found in the raw material.
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Furthermore, the raw material also contains withanolid glycosides which have a structure with a glucose moiety at position C-27. Both sitoindoside IX and sitoindoside X are members of this group of compounds. Additionally, steroidal saponins with an acyl group- sitoindoside VII and VIII are found in Ashwagandha. The raw material has also been found to contain sterols, chlorogenic acid, coumarins, saponins, resins, lipids, carbohydrates and fatty acids [11].
4. Therapeutic uses of Ashwagandha
Ashwagandha has a long history of usage in Ayurvedic medicine. Additionally, preclinical studies have demonstrated the antitumor, anti-inflammatory, antidiabetic, anti-aging and neuroprotective qualities of Ashwagandha. Human clinical studies have demonstrated that Ashwagandha is safe and beneficial for variety of ailments. Ashwagandha is generally thought to be safe with only a few minor potential side effects.
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4.1 Ashwagandha in Breast cancer
Globally, cancer is the second leading cause of disease related mortality and its incidence is rising quickly. The most prevalent disease among women is breast cancer. Breast cancers are typically quite aggressive and metastatic in nature because of their extremely diverse makeup. By causing molecularly-level programmed cell death, particularly apoptosis, WS affects breast cancer cells. It has been discovered that ashwagandha may be used to treat breast cancer, particularly triple-negative and estrogen receptor/progesterone receptor (ER/PR) positive breast cancer.
4.1.1 Mechanism of Action
Using fluorescence microscopy and phosphorylation of the H3 histone at the Ser10 residue, early cell line experiments showed that WA caused mitotic arrest in MCF7 and MDA-MB-231 cells (12). Additionally, five weekly intraperitoneal (i.p.) injections of 4 mg WA/kg body weight resulted in significant tumor retardation in female nude mice injected with MDA-MB-231 cells, while in vitro studies on the same cells revealed FOXO3a and Bim-dependent apoptotic death. According to a different study, WA induces apoptosis in a novel way by inhibiting the levels of pro-survival proteins such as cellular inhibitor of apoptosis-2 (cIAP-2), X-linked inhibitor of apoptosis (XIAP), and surviving proteins after roughly 6 hours of treatment, whereas in the xenograft model, WA only inhibited the levels of survivin proteins [13]. Additionally, WA has been shown to suppress oxidative phosphorylation in breast cancer cells and have a role in reactive oxygen species (ROS)-induced apoptosis [14]. Additional molecular research by Thaiparambil and colleagues shown that WA enhanced vimentin's Ser56 residue phosphorylation, a sign of vimentin disintegration, and consequently provided anti-invasive and anti-metastatic properties in both in vitro and in vivo contexts. Furthermore, WA has the capacity to covalently alter the distinct cysteine residue (Cys328) of vimentin in HUVECs, which also led to vimentin fragmentation in vitro and prevented neovascularization [15]. Additionally, it was reported that Withania root extracts inhibited the Epithelial-Mesenchymal Transition (EMT) in a panel of breast cancer cell lines and in xenograft mice model injected with MDA-MB-231 cells [16]. Additionally, immunohistochemistry studies revealed that treating the tumors with root extracts decreased the expression of Ki67 and the Proliferating Cell Nuclear Antigen (PCNA) marker in female Spaghe-Dawley rats with methylnitrosurea-induced mammary cancer. Withaferin A demonstrated anti-estrogen characteristics by preventing the growth of ER-positive MCF7 and T47D cells. Interestingly, MDA-MB-231 cells transfected with ER-a showed protection against WA-induced apoptosis but not against WA-induced G2/M phase cell cycle arrest [17]. Under various experimental settings, numerous other papers have likewise hinted at WA's possible anti-proliferative qualities. According to epigenetic research, WA may have altered the methylation status of several genes implicated in TNBC and suppressed TNBC-specific traits, resulting in a less aggressive luminal breast cancer with better sensitivity and response to treatment [18]. When combined, these findings indicate that the active ingredients in WS reduce the invasive and proliferative properties of tumor cells through a variety of molecular mechanisms, thereby offering enormous therapeutic promise against breast cancer.
4.2 Typical brain conditions
The term “brain disorder” encompasses, to some extent, emotional disorders in additional to insanity and related conditions of mental derangement. When emotional factors deviate from normalcy and manifest as mental disorder syndromes. According to some estimates, the brain contains 100 billion neurons, each of which forms a communication network with numerous connection. These nerves cells have special job like thinking, learning, remembering, see, hear and smell. In order brain cells to communicating with one another, they process and store information.
4.2.1 Ashwagandha in Alzheimer’s Disease
The brain exhibits aberrant β-amyloid protein deposition throughout the progression of Alzheimer’s disease. It has a neurotoxic effect in its fibrillar form because it breaks down glucose transport in neurons and produces free radicals, which damage and kills cells [19]. Some studies conducted on human nerve cells. It has been demonstrated that Ashwagandha counteracts the harmful effects of β-amyloid in cells, which may contribute to neurocongnitive impairment during HIV infection. Rats given vitanon, an ingredient derived from the root of Withania somnifera, orally were used in a study. Amyloid b-42 inhibition was associated with significant improvements in cognitive function, as well as a decrease in lipid peroxidation, nitric oxide and pro-inflammatory cytokines TNF-a, IL-β, IL-6 and MCP-1 [20]. Furthermore, withaferin A, which is derived from Ashwagandha, seems to be a promising component for the treatment of Alzheimer’s disease. It functions by preventing the accumulation of t proteins and decreasing b-amyloid aggregation. Furthermore, withaferin A controls the expression of heat shock proteins (HSPs), which rise in response to stressors and inhibits oxidative and pro-inflammatory chemicals. Nevertheless, additional research is required to evaluate withaferin A’s safety and validate its neuroprotective benefits in the management of Alzheimer’s disease [21]. Derivatives of Withania somnifera were examined for their impact on the development of β-amyloid 42 deposits in Alzheimer’s disease. The hydrophobic core of β-amyloid1-42 was found to interact with withanolide A, withanolide B, withanoside IV and withanoside V in the form of an oligomer, which inhibits additional interaction with monomers and decreases aggregation [22].
4.2.2 Ashwagandha in Depression
A diverse disorder, depression is linked to brain health primarily through mood swings, thoughts, misbehavior, disappointments, sadness, hopelessness, loss of physical activities and low self-esteem. Additionally, depression is linked to changes in appetite and sleep patterns and other everyday tasks in addition to anxiety symptoms [23]. Experimental research has shown that Ashwagandha can help people with depression. It was in 2000 Bhattacharya and colleagues separated the bioactive substances glycowithanolides from Ashwagandha roots and examined its potential as an antidepressant at 20 and 50mg/kg. It was discovered that in behavioral despair and learned helplessness brought on by mandatory swim test, glycowithanolides had an antidepressant effect similar to imipramine [24].
4.2.3 Ashwagandha in Parkinson’s Disease
The main feature of Parkinson’s disease, an age-dependent neurodegenerative illness that progress over time, is the depletion of dopaminergic substantia nigra neurons brought on by a combination of environment and genetic factors. It is linked to abnormal protein aggregation, mitochondria dysfunction and oxidative stress. It has been discovered that ethanolic root extract from Ashwagandha can reverse the Parkinson’s like symptoms in MPTP-include Parkinson’s disease [25]. A study was carried out on rats that has Parkinson’s disease is caused by 6-hydroxdopamine. Ashwagandha was found to raise glutathione levels, decrease lipoperoxidation, increase glutathione, S-transferase, glutathione reductase, glutathione peroxides, superoxide dismutase and catalase activities, catecholamines, dopamine D2 receptor binding and tyrosine hydroxylase expression [26]. In comparison to the control group, Ashwagandha extract treatment improved biochemical parameters and decreased motor impairment in Parkinson’s disease-afflicted mice [27].
4.2.4 Ashwagandha in Huntington’s Disease
Huntington’s disease is a progressive neurodegenerative condition marketed by oxidative stress and the death of neurons in the basal ganglia. It is hereditary autosomal dominant syndrome linked to dementia, emotional instability and muscle dysfunction. It also encompasses issues with speech, language, movement, depression, short-term memory loss and lack of focus and concentration [28]. Huntington’s disease like abnormalities, especially oxidative stress, abnormal gait and mitochondria dysfunction are mimicked by nitropropionic acid induction. Additional behavioral, enzymatic and biochemical changes result from complex II inhibition. Additionally, it has been documented that the pathogenesis of Huntington’s disease involves the GABAergic system. Because of its GABAergic action and antioxidant properties, Ashwagandha can help treat Huntington’s disease by restoring the levels of the enzymes glutathione and acetylcholinesterase and enhancing cognitive function [29].
5. Extraction Techniques of Ashwagandha
Alkaloids, withanolides, and flavonoids are just a few of the many bioactive substances found in WS that give it its medicinal qualities. These bioactive chemicals are extracted from plant material using a variety of extraction procedures. When it comes to removing bioactive substances from WS, extraction methods are essential. The kind of bioactive components to be extracted, the required level of extract purity, and the extract's intended usage are some of the variables that influence the extraction technique selection. Maceration, infusion, reflux, and Soxhlet extraction are traditional techniques for obtaining phytochemicals from herbal plants. These techniques entail the diffusion of solvents into plant cells, the solubilization of phytochemicals in the plant matrix, and the diffusion of solvents containing phytoconstituents from plant cells. [30].
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Table 1. Extraction method of Ashwagandha
|
Plant part |
Extraction Method |
|
Roots |
Reflux |
|
UASE |
|
|
MASE |
|
|
Leaves |
Maceration |
|
Roots |
Maceration |
|
Root and Leaves |
Soxhlet Extraction |
5.1 Maceration Extraction
The process of maceration extraction entails immersing the herb for an extended length of time in a solvent. The active ingredients in the herb are progressively dissolved by the solvent during this period. This technique is frequently applied to extract non-heat-stable chemicals and delicate botanicals [31]. Because maceration extraction is a gentle technique that can retain the herb's delicate phytochemicals and antioxidants, it is also recommended for the extraction of WS [32]. Relatively recent methods like pressured liquid extraction and supercritical fluid extraction have gained popularity due to their superior performance in terms of high production, self-sufficiency, and cost. [33].
5.2 Reflux Extraction
In reflux extraction, the herb is boiled in a solvent, which is subsequently condensed and recycled back into the boiling vessel. The solvent is able to extract the active ingredients from the herb by repeating this procedure multiple times. Because it can effectively extract the necessary components and be readily scaled up for bigger batches, reflux extraction is a preferred technique for extracting WS [34].
5.3 Ultrasound-assisted Solvent Extraction
Ultrasound-assisted solvent extraction (UASE) is a nonthermal extraction technique that releases bioactive substances by breaking down the plant material's cell walls with high-frequency sound waves. The plant material is exposed to ultrasonic vibrations while submerged in a solvent, like water or ethanol. High yields of bioactive chemicals can be obtained quickly and effectively using ultrasonic extraction [35].
5.4 Microwave-Assisted Extraction
The quick and effective technique known as microwave-assisted extraction (MAE) heats the solvent using microwave energy to make it easier to extract bioactive components from WS. Although MAE is a relatively new method, its yield and extract purity have showed promise [36]. Utilizing techniques such as reflux, ultrasound-assisted solvent extraction (UASE), and microwave-assisted solvent extraction (MASE), WS powdered root raw material was extracted in one study utilizing varying ratios of extraction solvent, such as water, ethanol:water (9:1), and water. Reflux extraction required five hours, whereas UASE and MASE respectively took five, ten, and twenty minutes to extract. At 9.51%, the yield of the traditional extraction method is much lower than that of MASE (13.74%) and UASE (11.85%). Compared to traditional ethanolic extracts (4.79 μg/mg), UASE (8.66 μg/mg) and MASE (5.73 μg/mg) ethanol extracts also contain more total withanolides.
5.5 Supercritical Fluids Extraction
Supercritical fluids, such carbon dioxide, are used as the solvent in the contemporary process known as supercritical fluid extraction (SFE). Supercritical fluids are perfect solvents for removing bioactive substances from WS because of their special combination of liquid and gas characteristics. SFE is an effective and selective extraction technique that produces an extract with a high level of purity [37]. In order to obtain fatty acids with a 13% yield, pulverized and dried WS seeds were extracted using food-grade liquid carbon dioxide with backflow pressures of 450/80 and 555/40 bar/degree Celsius and CO2 flow of 60 g/min for 22 hours and 20 minutes. Additionally, it offers a more hygienic way to extract bioactive from plant matrices. The technique's main prerequisite is a proficient operational setup [38].
5.6 Soxhlet Extraction
Soxhlet extraction is a traditional method that uses a glass device called a Soxhlet extractor to extract chemicals from solid plant sources. A thimble is used to extract the sample using a solvent, such as ethanol or methanol. The extract is then left behind when the solvent has evaporated. A dependable but time-consuming method for removing different compounds from WS is soxhlet extraction [39]. The leaves are extracted by Soxhlet extraction, liquid partitioning with diethyl ether, and defatting with n-hexane. Moreover, n-hexane and methanol–water (90–70%, MeOH) at 35 °C were used to extract the leaves and roots of WS. The plant metabolite variety was separated into four fractions of different polarity (n-hexane, aqueous methanol, chloroform, and n-butanol) following liquid–liquid partitioning of the methanolic water layer using CHCl3 and n-BuOH. Particularly in the aqueous methanolic fraction, the amount of metabolite in leaves was substantially higher than in roots [40].
6. CONCLUSION
The incidence of cancer is still rising quickly, necessitating an efficient management strategy. Nowadays, a large number of anticancer medications are derived from plants and target tumour cells only, not healthy ones. The ancient Indian medical science known as Ayurveda is safe, has few adverse effects, and has positive therapeutic results. Ashwagandha and its components shown a range of activities against models of spinal cord damage and Alzheimer's disease.Additionally, extracts from ashwagandha demonstrated positive effects against models of other neurodegenerative illnesses, including Parkinson's and Huntington's,55–60, suggesting that ashwagandha may be helpful against a variety of neurodegenerative diseases. Withania somnifera, which has been reported in a number of studies pertaining to cancer, has undoubtedly demonstrated efficacy as an antitumor agent due to its pleiotropic mode of action, which targets multiple onco-genic pathways at once also helps to improve the general quality of life for cancer patients.
REFERENCES
Dr. Ravinesh Mishra*, Ishita Devi, Dr. Bhartendu Sharma, Priya Sharma, Ashwagandha: A Review of its Phytochemistry, Mechanisms of Action, and Clinical Applications, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 4, 1699-1710 https://doi.org/10.5281/zenodo.15209029
10.5281/zenodo.15209029
