Exploring the neuroprotective role of Asparagus racemosus (Shatavari) in Alzheimer’s disease: mechanisms, evidence, and future directions

Abstract

Alzheimer’s disease (AD), a progressive neurodegenerative disease, is characterized by cognitive decline, memory loss, and pathological features such as amyloid-beta plaques, tau hyperphosphorylation, oxidative stress, and neuroinflammation. Current therapies do not adequately address the disease’s fundamental causes, even while they provide symptomatic relief. Asparagus racemosus (Shatavari), a traditional Ayurvedic medicinal herb, has drawn interest for its neuroprotective potential in the hunt for safer and multi-targeted substitutes. It is abundant with various bioactive components, such as alkaloids, flavonoids, and steroidal saponins (shatavarins); A. racemosus has adaptogenic, anti-inflammatory, and antioxidant properties. By lowering oxidative stress, regulating neuroinflammation, and preventing the development of amyloid-beta, these may mitigate the pathophysiology of AD. In addition, preclinical research indicates that it maintains neuronal integrity, encourages neurogenesis, and increases acetylcholine levels by inhibiting cholinesterase. Moreover, via controlling the hypothalamic–pituitary–adrenal (HPA) axis, its adaptogenic actions may lessen stress-induced neurotoxicity. Preclinical evidence is encouraging, but there are still important limits. There are few human clinical trials available, and there are still unanswered questions about extract standardization, bioavailability, and long-term safety. Moreover, thorough mechanistic research is required to elucidate its therapeutic targets and interactions due to the intricacy of its phytochemical makeup. To improve effectiveness and bioavailability, future studies should focus on creating standardized formulations, including cutting-edge delivery methods like nanoformulations. To confirm its therapeutic potential and safety profile in AD patients, extensive, rigorous clinical studies are necessary. By addressing these issues, Asparagus racemosus may be positioned as a viable alternative or adjuvant in the treatment of AD.

Introduction

Alzheimer’s disease (AD) is a chronic, progressive neurological condition that is the leading cause of dementia globally (Rayathala et al. 2022). It is the most prevalent kind of dementia, accounting for 60–80% of all cases globally (World Health O. 2018). It is a gradual, irreversible neurological condition that predominantly affects elderly people (Tripathi et al. 2024). Clinically, it is marked by progressive cognitive decline, memory loss, language impairment, and executive dysfunction, which eventually leads to severe disability and reliance (Mahendra 2024). The disease’s degenerative development starts years before symptoms manifest, with the complex interplay between genetic, environmental, and lifestyle variables (Suresh et al. 2023; Prajapati et al. 2025). It is becoming a major public health problem as the world’s population ages and life expectancy rises (World Health O. 2018; Sharma et al. 2024). In 2023, more than 55 million individuals worldwide were living with dementia, with AD accounting for the vast majority. By 2050, this figure is expected to approach 139 million, owing to an aging population, particularly in low- and middle-income nations (Chen et al. 2024). AD prevalence is greater in North America and Europe owing to improved healthcare access and longer life expectancies (Nandi, et al. 2019). In the United States, around 6.5 million individuals aged 65 and over were living with AD in 2023, with the figure predicted to quadruple by 2060 (Chowdhary et al. 2022). There are several key pathological features such as amyloid-beta (Aβ) plaques, tau hyperphosphorylation, oxidative stress, neuroinflammation, synaptic dysfunction, and neurodegeneration, causing AD (Siddiqui et al. 2024). Amyloid-beta (Aβ) plaques characteristic of AD are the deposition of Aβ peptides in the brain’s extracellular spaces. These peptides, formed by the cleavage of amyloid precursor protein (APP), accumulate into insoluble plaques. Aβ plaques cause synaptic dysfunction, oxidative stress, and neuroinflammatory reactions, leading to neuronal death (Zhang et al. 2021; Agrawal et al. 2024). In AD, tau is a microtubule-associated protein that undergoes aberrant phosphorylation (Reddy and Oliver 2019). Hyperphosphorylated tau detaches from microtubules, resulting in neurofibrillary tangles (NFTs) inside neurons. The instability of the cytoskeleton hampers intracellular transport, resulting in synaptic dysfunction and neuron death (Guha et al. 2020; Akram, et al. 2023). AD is characterized by excessive reactive oxygen species (ROS) generation and inadequate antioxidant defenses. Oxidative damage damages lipids, proteins, and DNA, causing neural malfunction (Srivastava et al. 2019). Mitochondrial failure contributes significantly to oxidative stress in AD (Bhatt et al. 2021). Chronic activation of microglia, the brain’s resident immune cells, is a key factor in AD pathogenesis. Aβ plaques and injured neurons activate microglia, leading to the production of pro-inflammatory cytokines such as IL-1β and TNF-α. Sustained inflammation exacerbates neuronal damage and speeds up disease development (Cai et al. 2022). The loss of synaptic connections is closely related to cognitive deterioration in AD. Neuronal death in certain locations, including the hippocampus and cerebral cortex, causes brain atrophy and a gradual loss of cognitive function (Danysz and Parsons 2003). AD is being treated with a variety of synthetic medications, including acetylcholinesterase inhibitors, glutamate antagonists, and other neuroprotective treatments (Akıncıoğlu and Gülçin 2020). However, they are often coupled with substantial side effects, such as gastrointestinal problems, disorientation, and cognitive side effects, all of which may influence patients’ quality of life (Fantuzzi 2024). As a result, there is an increasing need for alternative medicines that have fewer adverse effects. Shatavari (Asparagus racemosus), a natural Ayurvedic treatment, offers a viable alternative owing to its low toxicity, chemical variety, and wide therapeutic potential (Alok et al. 2013). Shatavari has shown neuroprotective, anti-inflammatory, antioxidant, and adaptogenic characteristics, making it a promising choice for reducing the side effects of traditional AD therapies. Furthermore, it is inexpensive, safe for long-term usage, and has great potential to boost cognitive function. Shatavari, with its natural origin and multi-targeted biological activity, is a favored alternative for AD therapy over synthetic medications, providing patients with an effective, low-risk approach.

Shatavari

Asparagus racemosus, well recognized as Shatavari, is a highly esteemed therapeutic plant in ancient Ayurvedic medicine. The term “Shatavari” means “the plant of a hundred roots,” representing its adaptogenic and restorative properties. It has been used for ages as a general health tonic and as a “Rasayana” herb, a classification in Ayurveda designed to enhance lifespan, vigor, and mental clarity (Thakur et al. 2021). Shatavari’s extensive history in Ayurveda as a neuroprotective and cognitive-enhancing herb underpins contemporary research, which is actively investigating its possible use in the treatment of neurodegenerative illnesses, including AD (Singh 2018). It has been continuously used since ancient times for cognitive health problems. It is classified as a “Medhya Rasayana,” a category of herbs used to improve memory, learning, and cognitive functions. Ancient Ayurvedic scriptures characterize Shatavari as a cerebral tonic that enhances mental concentration, sharpens intelligence (buddhi), and bolsters cognitive resilience, particularly in the context of age or stress (Upadhyay, et al. 2021). It was historically used to safeguard the neurological system against degeneration and stress-related harm. It was advised for ailments associated with forgetfulness, cognitive tiredness, and stress-related problems. Apart from neuroprotective, it has cardioprotective, hepatoprotective, nephroprotective, anti-ulcer, antioxidant, anti-inflammatory, and antiviral action (Fig. 1) (Westfall and Pratap 2017).

Fig. 1.

Biological therapeutic effects of Asparagus racemosus (Shatavari) in various diseases

It was a strong Ayurvedic therapy against stress in ancient days. Stress is a recognized factor in neurodegenerative illnesses, and Shatavari’s adaptogenic characteristics assist in regulating the hypothalamic–pituitary–adrenal (HPA) axis, alleviating stress, and promoting mental well-being. Its capacity to soothe the mind and equilibrate the body’s stress reaction was especially esteemed among persons susceptible to anxiety or cognitive deterioration (Singh, et al. 2023; Akram, et al. 2024). Historically, Shatavari was used in treatments to enhance mental clarity, emotional equilibrium, and resistance against age-associated cognitive deterioration. Ayurvedic formulations also recognize it as improving general cognitive function and neuronal regeneration (Upadhyay, et al. 2021).

The cultivation and geographic distribution of Asparagus racemosus is Indigenous to portions of Southeast Asia and India (Kohli et al. 2023). Although it is grown in certain places, the plant does not grow as well outside of them. The worldwide supply is impacted by this geographic limitation, and crop yields, local agricultural techniques, and climate all have an impact on its availability (Farooq et al. 2023). Accessibility in other parts of the globe may be enhanced by extending cultivation outside of typical areas. Its market availability is widely accessible in nations like India in a variety of forms, including powders, extracts, and capsules, and is often used in Ayurvedic formulations (Akhtar et al. 2024). Its availability may be more restricted in Western nations, however, where it is usually obtained at marketplaces for alternative medicines or specialty health shops. Growing knowledge of its possible advantages for AD may spur demand and increase its supply on the international market (Kohli et al. 2023).

Principal bioactive constituents in Shatavari

Asparagus racemosus, often known as Shatavari, is a popular Ayurvedic plant noted for its many pharmacological properties. Shatavari roots contain diverse bioactive components that contribute to its many therapeutic benefits, such as neuroprotective, anti-inflammatory, adaptogenic, and antioxidant activity (Akhtar et al. 2024). The following is a full description of the main bioactive components found in Shatavari (Fig. 2).

Fig. 2.

Biochemical constituents in Asparagus racemosus (Shatavari)

Flavonoids

Flavonoids are a varied set of polyphenolic compounds that influence the pharmacological activities of Asparagus racemosus (Shatavari). These bioactive compounds are well known for their antioxidant, anti-inflammatory, and neuroprotective properties, making them essential for improving general health and well-being. The most abundant flavonoids in Shatavari are kaempferol, quercetin, and rutin, which contribute significantly to the plant’s therapeutic usefulness (Akhtara 2022). The antioxidant properties of Shatavari’s flavonoids are very noteworthy. Flavonoids neutralize free radicals and decrease oxidative stress, which is a major contributor to aging and the development of chronic illnesses such as cardiovascular disease, cancer, and neurological disorders including Alzheimer’s and Parkinson’s disease (Ayaz et al. 2019). These flavonoids help the body’s defence systems by scavenging reactive oxygen species (ROS) and boosting the activity of antioxidant enzymes including superoxide dismutase and catalase. This capacity to combat oxidative damage shields cells and tissues against premature aging and degenerative changes, especially in the brain, where oxidative stress is a major contributor to cognitive decline (Kim et al. 2020). Furthermore, the anti-inflammatory properties of Shatavari’s flavonoids are crucial in treating chronic inflammation-related illnesses. These chemicals prevent the synthesis of pro-inflammatory cytokines, including TNF-α, IL-1, and IL-6, as well as enzymes like COX. Flavonoids aid in relieving symptoms in disorders such as arthritis, asthma, and inflammatory bowel disease, as well as neuroinflammatory diseases such as multiple sclerosis and Alzheimer’s (Banik et al. 2020). Shatavari’s flavonoids also have neuroprotective properties, making them very important in the context of cognitive health. These substances help prevent neuronal damage and degeneration in the brain by lowering oxidative stress and inflammation, especially in regions critical for memory and learning, such as the hippocampus. This neuroprotective activity is important in the treatment of Alzheimer’s disease, as oxidative damage and inflammation cause gradual loss of brain function (Akhtar et al. 2024). Furthermore, flavonoids such as kaempferol have been proven to improve synaptic plasticity, which is the capacity of synapses to grow or decrease over time, a process essential for learning and memory (Silva dos Santos, et al. 2021). The flavonoids present in Shatavari are pivotal in supporting its wide range of therapeutic effects. Their antioxidant, anti-inflammatory, and neuroprotective properties make them especially beneficial for managing age-related cognitive decline, and chronic inflammatory conditions. The inclusion of flavonoids such as kaempferol, quercetin, and rutin elevates Shatavari’s value as a therapeutic plant in both traditional and contemporary healthcare systems. These components provide a natural, plant-based alternative to synthetic medications with fewer side effects, making Shatavari a viable choice for the treatment and prevention of a variety of health conditions.

Alkaloids

The alkaloids in Shatavari enhance its medicinal properties, especially the support of the neurological system. These chemicals often exhibit analgesic and sedative properties, making the plant beneficial for alleviating stress and soothing the mind. Alkaloids may potentially enhance Shatavari’s antibacterial and antifungal characteristics, aiding in the prevention of infections (Akhtara 2022). Alkaloids are a broad class of naturally occurring chemical compounds that are generally nitrogenous and have important pharmacological characteristics. Alkaloids have a function in the therapeutic actions of Asparagus racemosus (Shatavari), albeit they are less prominent than other bioactive chemicals such as saponins and polyphenols. Despite this, the alkaloids present in Shatavari have a variety of therapeutic characteristics, including neuroprotective, adaptogenic, and immunomodulatory (Akhtar et al. 2024). These bioactive alkaloids, although not as well investigated as other families of chemicals, have significant therapeutic potential and are essential to Shatavari’s holistic approach to addressing a variety of health issues. The alkaloids in Shatavari are thought to be principally responsible for some of its adaptogenic and neuroprotective properties (Singh, et al. 2023). Adaptogens are compounds that assist the body withstand physical, chemical, and biological stresses by regulating numerous physiological systems, including the adrenal glands, which generate stress hormones such as cortisol (Winston and Adaptogens 2019). Shatavari’s alkaloids may affect the hypothalamic–pituitary–adrenal (HPA) axis, increasing the body’s capacity to adapt to stress and general resilience (Majumdar et al. 2021). Shatavari’s alkaloids promote mental and physical well-being by regulating stress hormones and stabilizing the body’s stress response, making them useful for disorders such as chronic stress, anxiety, and exhaustion (Sharma et al. 2021). In terms of neuroprotection, Shatavari’s alkaloids have been demonstrated to improve brain health by regulating neurotransmitter systems and lowering oxidative damage in the central nervous system. These chemicals may assist in protecting neurones against neurodegeneration, making them potentially effective in the treatment of cognitive illnesses including Alzheimer’s and Parkinson’s (Akhtara 2022). Shatavari alkaloids contribute to the general maintenance of cognitive function by lowering free radical accumulation and inflammation inside the brain, perhaps slowing the advancement of neurodegenerative illnesses. Shatavari’s alkaloids also help to promote immunomodulatory effects. They improve immune function by increasing the activity of numerous immune cells, such as macrophages and natural killer (NK) cells, which improve the body’s capacity to fight infections and disorders (Tiwari et al. 2018). Despite these promising effects, Shatavari alkaloids have not been investigated as extensively as other bioactive components in the plant, and additional study is required to fully understand their modes of action and therapeutic potential. However, available information shows that these alkaloids contribute to Shatavari’s general health advantages by protecting the brain, increasing the body’s stress resistance, and improving immunological function. Shatavari’s alkaloids have important medicinal effects that supplement the activities of the plant’s other bioactive ingredients. These alkaloids contribute to Shatavari’s adaptogenic, neuroprotective, and immunomodulatory properties, making it an effective herb for treating a wide range of health issues. Though further study is required to isolate and characterize the individual alkaloids found in Shatavari, their importance in improving general health and supporting the body’s natural healing processes is evident, making Shatavari a versatile and effective medicinal plant.

Saponins (steroidal saponins)

Steroidal saponins are the primary bioactive compounds in Asparagus racemosus (Shatavari), contributing to the plant’s enormous medicinal potential. These chemicals have a diverse set of pharmacological activities, including neuroprotection, anti-inflammatory effects, adaptogenic activity, immunological modulation, and antioxidants. Shatavari’s estrogenic characteristics make it especially useful for controlling hormonal imbalances and promoting reproductive health (Pandey et al. 2023). Shatavari’s steroidal saponins provide a natural, adaptable answer to a variety of health issues, making it a good choice for the treatment of neurodegenerative illnesses, stress-related disorders, and hormonal imbalances. Steroidal saponins are distinguished by a steroid nucleus (usually a 27-carbon structure) with sugar moieties added at certain locations. The steroidal backbone comprises four fused rings (A, B, C, and D rings), and the sugar component varies in size and composition, although it commonly contains glucose, rhamnose, and arabinose. The sugar component of saponin is responsible for its solubility in water and plays an important role in its biological actions. Meanwhile, the steroidal portion is responsible for its capacity to interact with cell membranes and different receptors in the body. Shatavari saponins are primarily steroidal, which distinguishes them from other saponins that may contain a triterpenoid structure (Bharati and Kumar 2019). The principal steroidal saponins in Shatavari are Asparagoside, Racemoside, and Shatavarins (Shatavarin I, II, III, and IV) (Pandey et al. 2023). Saponins are generally known for their poor bioavailability due to their complex glycosidic structure, which limits their absorption in the gut. However, recent studies suggest that the bioavailability of steroidal saponins from Shatavari can be enhanced through various formulation techniques, such as using nanoencapsulation or combining them with other compounds that increase their solubility (Akhtar et al. 2024). Steroidal saponins from Shatavari are generally considered safe when consumed in recommended doses. However, as with all bioactive compounds, excessive consumption can lead to side effects (Akhtara 2022). The steroidal saponins in Shatavari, notably asparagoside and shatavarins, have been demonstrated to have neuroprotective properties by lowering oxidative stress and inflammation in the brain (Thakkur et al. 2023). These substances assist in regulating the activity of enzymes that generate free radicals, so shielding neurons from harm. This is especially significant in neurodegenerative diseases such as AD, where oxidative stress plays a crucial role in neuronal destruction (Bharati and Kumar 2019). In animal models, steroidal saponins have been found to prevent neuronal mortality in areas of the brain such as the hippocampus, which is important for learning and memory (Sun et al. 2015). As a result, Shatavari may be a viable option for treating cognitive deterioration. Shatavari’s steroidal saponins suppress pro-inflammatory cytokines, including TNF-α and IL-6, reducing inflammation. These saponins inhibit the activity of cyclooxygenase (COX) enzymes and diminish the formation of nitric oxide (NO), which may contribute to inflammation (Tiwari et al. 2018). Shatavari’s anti-inflammatory activity makes it useful in treating neuroinflammatory diseases such as multiple sclerosis and Alzheimer’s (Chaudhry 2021). Saponins in Shatavari have adaptogenic properties, meaning they help the body adapt to stress by regulating the hypothalamic–pituitary–adrenal (HPA) axis, which controls the release of stress hormones like cortisol. Shatavari promotes good stress management by regulating cortisol levels. Shatavari’s adaptogenic characteristics help to boost endurance, stress resistance, and general health (Ray et al. 2021). Steroidal saponins affect the central nervous system (CNS), lowering anxiety and improving mood. Steroidal saponins in Shatavari have minor estrogen-like action, making them useful for hormonal imbalances (Singh, et al. 2023). The steroidal saponins in Shatavari act as potent antioxidants, scavenging free radicals and reducing oxidative damage to cells and tissues. They help in the upregulation of antioxidant enzymes like superoxide dismutase (SOD) and catalase. The antioxidant action of steroidal saponins protects against cellular damage caused by oxidative stress, which is a contributing factor in aging and various neurodegenerative disorders (Akhtara 2022).

Vitamins

Asparagus racemosus (Shatavari) is a popular plant in traditional medicine, notably in Ayurvedic treatments, where it is prized for its adaptogenic and rejuvenating effects. Shatavari has a high concentration of various vital vitamins, which contribute to its numerous health advantages (Singh et al. 2018). Shatavari contains vitamin A in the form of carotenoids such as beta-carotene, which is essential for eyesight, immunological function, and skin health. It is essential for maintaining good eyesight, particularly in low-light circumstances, and it helps the immune system by increasing the generation of white blood cells. It also promotes healthy epithelial tissues and assists in cell differentiation and proliferation (Deshmukh et al. 2019). Vitamin C, also known as ascorbic acid, is another key vitamin contained in Shatavari (Singh et al. 2018). It acts as a powerful antioxidant, protecting cells from oxidative stress. It boosts immunological function, stimulates collagen production for healthy skin, blood vessels, and bones, and speeds up wound healing by promoting tissue repair (Singla et al. 2014). Shatavari also contains vitamin E, a fat-soluble antioxidant that helps protect cellular membranes from oxidative damage. It improves cardiovascular health by limiting oxidative damage to cholesterol, lowers the risk of atherosclerosis, and boosts immunological function by activating T cells (Kant et al. 2015).

Minerals

Asparagus racemosus (Shatavari) includes important minerals including zinc, calcium, magnesium, and phosphorus. These minerals have critical roles in supporting different physiological systems and considerably improve the herb’s medicinal benefits, notably in reproductive health, bone health, and overall vitality. Zinc, an essential trace mineral, regulates enzyme activity, immunological function, and protein synthesis. Zinc in Shatavari improves the herb’s adaptogenic effects and aids immunological regulation. It promotes cell development and hormone production, which helps to keep the reproductive system healthy. Zinc also has antioxidant properties that protect against oxidative stress and inflammation while encouraging skin regeneration and wound healing. This mineral is crucial for skin health and is often featured in Shatavari-based products. Its significance in immune response and antioxidant defence supports Shatavari’s therapeutic benefits in a variety of health disorders (Agrawal and Pandey 2022). Calcium, another important mineral in Shatavari, aids bone health, muscular function, and nerve signaling. Shatavari’s calcium content promotes reproductive health, especially in women, by controlling hormones and preserving bone integrity. As calcium levels normally fall with age, Shatavari helps to prevent disorders like osteoporosis by preserving bone density. Furthermore, calcium is required for muscular contraction and cellular signaling, which is useful for treating muscle imbalances or stress. Shatavari’s calcium content, therefore, has an important role in preserving bone health, particularly in women (Kohli et al. 2023). Magnesium is an essential element that participates in over 300 metabolic activities, including energy generation, muscular function, and nervous system control. It works along with calcium to improve bone health and muscular relaxation. Magnesium also has a soothing impact on the neurological system, reducing tension and anxiety, which may be connected to hormone imbalances. Magnesium controls the menstrual cycle and relieves PMS symptoms. Its capacity to alleviate stress and promote hormonal balance contributes to Shatavari’s adaptogenic qualities (Bopana and Saxena 2007). Phosphorus is required for several metabolic tasks, including bone and tooth production. It interacts with calcium to maintain healthy skeletal structure and cellular function by constituting part of the backbone of DNA and RNA. In Shatavari, phosphorus helps with cellular metabolism, energy generation, and reproductive health. It also helps to maintain pH balance and promotes muscle and nerve function. Phosphorus boosts Shatavari’s overall therapeutic effects, including its reproductive and bone health advantages (Kohli et al. 2023).

Essential oils

Essential oils found in Shatavari may offer promising neuroprotective benefits in the context of AD, primarily through their antioxidant and anti-inflammatory properties, which are critical in combating AD pathological hallmarks such as amyloid-beta plaques and tau tangles (Akhtara 2022). Essential oils, which are volatile chemicals derived from plant materials, have been shown to impact a variety of physiological processes. Shatavari essential oils include a variety of bioactive chemicals, including thymol, eugenol, borneol, hexanal, myrtanol, furfural, pinocarveol, camphor, decanoic acid, 2-ethylhexanol, undecanoic acid, perillaldehyde, 6,10,14-trimethyl pentadecanone, 4-[1-hydroxyethyl] benzaldehyde, and [E]−4-hexadecen-6-yne, which have been reported for their potential to treat neurological problems (Singh et al. 2018). Although Shatavari is not as well known for its essential oil content as some other medicinal plants, new research suggests that its essential oils may help to reduce oxidative stress, neuroinflammation, and neuronal degeneration associated with AD (Kaur 2017). Essential oils in Shatavari may influence AD by reducing oxidative stress. ROS-induced oxidative damage is a crucial factor in the development and progression of AD, leading to neuronal death and cognitive loss. Bioactive compounds found in essential oils have been demonstrated in studies to be powerful antioxidants. These compounds scavenge free radicals and lower lipid peroxidation in the brain, therefore, protecting neurons from oxidative injury (Benny and Thomas 2019). Eugenol found in essential oils has been shown to have neuroprotective benefits in animal models of AD by lowering oxidative stress and enhancing cognitive performance (Goyal et al. 2023). In addition to antioxidant action, Shatavari essential oils may have anti-inflammatory actions, which is another important feature of AD pathophysiology. Chronic neuroinflammation has been linked to the evolution of AD by magnifying the damage produced by amyloid-beta plaques and tau tangles. Essential oils having anti-inflammatory properties, such as borneol and eugenol, can influence inflammatory pathways in the brain. These drugs inhibit the activation of microglia and astrocytes, which are responsible for neuroinflammation in AD, possibly lowering the neuroinflammatory response and decreasing disease development (Liang et al. 2023). Furthermore, essential oils may affect acetylcholine (ACh) function, a neurotransmitter that is required for memory and learning, both of which are compromised in AD. Shatavari essential oils, which include bioactive compounds, may have a role in modifying acetylcholinesterase (AChE) activity. The enzyme AChE degrades acetylcholine, and inhibiting it is a significant treatment target in AD. Essential oils suppress AChE activity, boosting acetylcholine levels in the brain and enhancing cognitive performance (Maggio et al. 2016). Shatavari’s essential oils are a viable possibility for future research into AD due to their antioxidant and anti-inflammatory actions, as well as their capacity to modify cholinergic function (Benny and Thomas 2019). Future research is required to evaluate these benefits in clinical settings; however, the present data highlight the potential significance of Shatavari essential oils in reducing some of the critical variables leading to Alzheimer’s pathogenesis.

Mechanisms of Shatavari in Alzheimer’s disease

Antioxidant effects

Alzheimer’s disease (AD) is a progressive neurological condition marked by cognitive deterioration and memory impairment (Rayathala et al. 2022). Oxidative stress is a primary factor in its pathogenesis, resulting in neuronal damage (Bai et al. 2022). Shatavari (Asparagus racemosus), recognized for its abundant antioxidant properties, has potential strategies for alleviating the course of AD (Kohli et al. 2023). Oxidative stress arises from a disparity between the generation of reactive oxygen species (ROS) and the organism’s capacity to mitigate them (Bai et al. 2022). In AD, ROS impairs cellular structures such as lipids, proteins, and DNA in neurons, leading to the production of amyloid-beta (Aβ) plaques, hyperphosphorylation of tau proteins, mitochondrial dysfunction, and neuronal apoptosis (Bhatt et al. 2021). Shatavari’s saponins, flavonoids, and polyphenols collaborate to eliminate free radicals and mitigate oxidative stress. These antioxidant properties mitigate cellular damage induced by aging, environmental pollutants, and metabolic activities. Consistent intake of Shatavari promotes skin health, mitigates the aging process, and reduces the likelihood of chronic illnesses, including cancer and neurological disorders (Akhtar et al. 2024). Its antioxidant characteristics safeguard the gastrointestinal system, facilitating the management of ulcers, indigestion, and irritable bowel syndrome (IBS) (Bachynski and Cure 2024). Shatavari is abundant in bioactive chemicals that counteract ROS and avert oxidative damage, particularly in brain tissues, which are particularly vulnerable owing to their elevated oxygen demand and lipid composition (Kohli et al. 2023). Its antioxidants safeguard neuronal cell membranes by inhibiting lipid peroxidation, protein oxidation, and mitochondrial dysfunction, which are essential factors in neuronal damage in AD (Akhtara 2022). It inhibits protein oxidation by safeguarding enzymes and structural proteins in neurons, hence preserving cellular integrity. Antioxidants such as saponins and polyphenols safeguard mitochondria, facilitating continuous energy generation and diminishing apoptotic pathways (Ashraf et al. 2024). Shatavari directly neutralizes ROS such as hydroxyl radicals, superoxide anions, and hydrogen peroxide, therefore, mitigating oxidative damage to neurons (Kohli et al. 2023). Metals such as iron and copper facilitate the generation of ROS via the Fenton reaction (Yu and Kuzyakov 2021). The chelation activity of Shatavarins slows this process, hence reducing oxidative stress. Shatavari enhances the expression of antioxidant enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase, therefore, fortifying the brain’s inherent defensive systems (Veena 2010).

Anti-inflammatory effects

Chronic neuroinflammation is a defining characteristic of AD and facilitates its progression. Neuroinflammatory reactions are mostly initiated by microglial cell activation and the secretion of pro-inflammatory cytokines, which intensify neuronal injury (Rodríguez-Gómez et al. 2020). Shatavari (Asparagus racemosus) demonstrates considerable anti-inflammatory properties that alleviate these processes (Mittal and Dixit 2013). Microglia are the intrinsic immune cells of the central nervous system (CNS). Although they provide a protective function by eliminating amyloid-beta (Aβ) plaques and detritus, their prolonged activation results in excessive inflammation and neuronal injury in AD (Fareed et al. 2022). In AD, microglia are continuously activated by amyloid-beta plaques, secreting pro-inflammatory cytokines, ROS, and nitric oxide (NO). This fosters a deleterious environment for neurons and accelerates the development of AD pathology (Cai et al. 2022). The bioactive components in Shatavari inhibit pro-inflammatory cytokines, hence reducing inflammation in the body. It has been shown to diminish inflammation in illnesses such as arthritis, gastritis, and asthma. It facilitates tissue repair, assisting in the healing of ulcers and lesions, particularly within the digestive and respiratory systems (Singh et al. 2018). Shatavari comprises saponins, flavonoids, and polyphenols that regulate microglial activity, inhibiting their hyperactivation in response to Aβ deposits. Shatavari alters the microglial equilibrium towards the M2 phenotype, reducing neurotoxicity and enhancing neuroprotection (Liu et al. 2024). The bioactive components of Shatavari block NF-κB activation, hence reducing inflammation. NF-κB is a crucial transcription factor that stimulates microglial activation and the production of inflammatory genes (Bijarnia, et al. 2025). Shatavari mitigates TLR4-mediated inflammatory responses in the central nervous system. TLR4 represents a significant route in microglial activation (Jyotsana et al. 2023). The saponins and polyphenols in Shatavari diminish the synthesis of TNF-α, IL-1β, and IL-6, thus mitigating inflammation and its subsequent impacts on brain health. Compounds such as flavonoids increase the synthesis of anti-inflammatory cytokines, including interleukin-10 (IL-10), which mitigates inflammation and facilitates tissue healing (Kaur et al. 2017). The mitogen-activated protein kinase (MAPK) pathway modulates cytokine synthesis in microglia. The bioactive components of Shatavari block this pathway, hence diminishing inflammatory reactions. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is a key modulator of cytokine signaling. Shatavari regulates this route to reestablish cytokine equilibrium in the central nervous system (Sharma et al. 2023). In AD, astrocytes, a distinct category of glial cells, become activated and release pro-inflammatory mediators. Shatavari inhibits astrocyte activation, hence averting severe inflammation. Amyloid-beta plaques directly activate inflammatory pathways in the brain. The flavonoids and polyphenols in Shatavari suppress the Aβ-induced activation of microglia and astrocytes, hence reducing neuroinflammation (Gupta and Kale 2023). The excessive generation of nitric oxide by activated microglia leads to neurotoxicity. The bioactive components of Shatavari inhibit inducible nitric oxide synthase (iNOS), hence decreasing nitric oxide levels and mitigating inflammation (Kumar et al. 2020).

Anticholinesterase effects

Cholinesterase inhibition is a crucial therapeutic approach for treating AD, designed to enhance memory and cognitive function by elevating the brain’s acetylcholine (ACh) levels (Marucci et al. 2021). Shatavari (Asparagus racemosus), recognized for its neuroprotective effects, has bioactive substances that may affect cholinesterase activity and improve cholinergic neurotransmission (Majumdar et al. 2021). ACh is a neurotransmitter essential for cognition, memory retention, and attentional processes. It enables communication among neurons, especially in brain areas such as the hippocampus and cerebral cortex, which are crucial for cognitive functions (Marucci et al. 2021). In AD, acetylcholine levels are markedly diminished owing to the degeneration of cholinergic neurons in the basal forebrain (Baker-Nigh et al. 2015). Elevated activity of enzymes such as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) degrades acetylcholine (ACh) (Villeda-González et al. 2024). This results in compromised neurotransmission, leading to memory impairment and cognitive deterioration. AChE is the principal enzyme that hydrolyzes ACh into acetate and choline, therefore, stopping its activity in the synaptic cleft (Baker-Nigh et al. 2015). Shatavari has bioactive components, including saponins, flavonoids, vitamins, minerals, and polyphenols, which may impede cholinesterase activity, hence facilitating acetylcholine-mediated neurotransmission (Singh et al. 2018). Shatavari interacts with AChE and BChE, limiting their enzymatic activity and maintaining ACh levels (Gupta and Kale 2023). Flavonoids, such as quercetin and rutin found in Shatavari, are effective natural cholinesterase inhibitors. These components function by attaching to the active site of cholinesterase, inhibiting the degradation of acetylcholine (Singh et al. 2018). Polyphenolic components in Shatavari demonstrate antioxidant properties that complement cholinesterase inhibition by mitigating oxidative stress, which would otherwise aggravate cholinergic dysfunction. Bioactive components of Shatavari block the active site of cholinesterase enzymes, either competitively or non-competitively, hence obstructing the breakdown of acetylcholine. This improves synaptic transmission and postpones cognitive deterioration (Baker-Nigh et al. 2015). The antioxidant and anti-inflammatory properties of Shatavari mitigate neurotoxicity, safeguarding cholinergic neurons from degeneration. This indirectly facilitates the continuous generation and release of acetylcholine. Besides protecting acetylcholine, Shatavari influences other neurotransmitter systems (e.g., GABA and dopamine), offering a comprehensive strategy for cognitive improvement. Shatavari also enhanced synaptic plasticity, essential for learning and memory development (Gupta and Kale 2023). Synaptic plasticity is the brain’s ability to reinforce or weaken networks between neurons (synapses) in response to activity (Singh et al. 2024; Rai et al. 2024). Oxidative damage intensifies cholinergic dysfunction in AD. The antioxidants in Shatavari inhibit oxidative alterations of cholinesterase enzymes and preserve their functional integrity (Singh et al. 2023). Chronic inflammation disrupts cholinergic signaling. Shatavari’s anti-inflammatory characteristics inhibit cytokine release, safeguarding cholinergic pathways. Shatavari stimulates neurogenesis and increases synaptic integrity, hence bolstering cognitive performance (Singh et al. 2023).

Neuroprotective effects

Shatavari, a medicinal plant prevalent in Ayurvedic medicine, is attracting interest for its neuroprotective properties (Majumdar et al. 2021). Amyloid-beta (Aβ) plaques are characteristic indicators of neurodegenerative diseases such as AD. Their accumulation is neurotoxic, resulting in oxidative stress, inflammation, and neuronal apoptosis (Yu et al. 2021). Shatavari has bioactive constituents, including saponins, alkaloids, and flavonoids, that have antioxidant and anti-inflammatory effects. These chemicals may impede Aβ aggregation by scavenging ROS that facilitate Aβ aggregation (Akhtar et al. 2024). Regulating mechanisms associated with amyloid precursor protein (APP) processing to diminish Aβ production. Hyperphosphorylated tau proteins aggregate into neurofibrillary tangles (NFTs), leading to neuronal impairment in AD (Westfall and Pratap 2017). The antioxidant properties of Shatavari mitigate oxidative damage to kinases and phosphatases that govern tau phosphorylation. By ensuring optimal enzyme activity, it inhibits excessive phosphorylation of tau proteins. It minimizes the development of NFTs while maintaining neuronal integrity (Vineetha et al. 2024). Shatavari promotes neurogenesis, the generation of new neurons, which is crucial for cognitive resilience and recovery after brain damage. Shatavari activates BDNF and nerve growth factor (NGF) pathways that facilitate neuronal survival, differentiation, and growth (Gupta and Kale 2023). It mitigates oxidative stress and safeguards neural stem cells against oxidative harm, hence facilitating the appropriate proliferation and differentiation of new neurons. The phytoestrogens in Shatavari may replicate estrogen, exerting a neuroprotective effect, especially in postmenopausal women experiencing decreased estrogen levels (Per 2013).

Adaptogenic and stress-relieving effects

Shatavari is esteemed as an adaptogen, facilitating the body’s adaptation to physical, emotional, and environmental stressors. It functions by altering the hypothalamic–pituitary–adrenal (HPA) axis, which is essential for regulating stress reactions. It modulates cortisol levels, equilibrates hormonal processes, and amplifies energy levels, making it an exceptional herb for alleviating tiredness and stress-related diseases. Shatavari aids in hormonal equilibrium in women throughout menstruation, pregnancy, and menopause by enhancing estrogenic activity (Singh et al. 2023). Shatavari’s adaptogenic and stress-relieving properties, especially its modulation of the HPA axis, establish it as a significant herbal treatment for alleviating the detrimental impacts of chronic stress (Singh et al. 2023). By lowering cortisol levels, mitigating oxidative stress, and facilitating neurogenesis, it offers a protective barrier against neurodegenerative diseases associated with HPA axis dysfunction. Shatavari is classified as an adaptogen, signifying its role in aiding the body to adjust to physical, emotional, and environmental stimuli while preserving homeostasis. This is especially pertinent for stress-related disorders and their association with neurodegeneration (Kurdukar and Jogdand 2021). The HPA axis serves as the primary regulating mechanism for the stress response. The process involves the hypothalamus, which secretes corticotropin-releasing hormone (CRH); the pituitary gland, which releases adrenocorticotropic hormone (ACTH) in reaction to CRH; and the adrenal glands, which produce cortisol, the principal stress hormone (Herman et al. 2016). Chronic stress results in dysregulation of the HPA axis, marked by sustained cortisol increase, excessive production of CRH and ACTH, and disruption of the negative feedback loop. Shatavari comprises steroidal saponins, notably shatavarins, which have adaptogenic characteristics (Bharati and Kumar 2019). Its adaptogenic characteristics render it a natural anxiolytic, alleviating anxiety and sadness while enhancing general resilience (Wyk 2019). These compounds facilitate the regulation of cortisol secretion by augmenting the feedback mechanisms of the HPA axis and regulating cortisol levels, thus reducing the excessive activation of stress reactions. Chronic stress induces oxidative damage and inflammation, exacerbating dysfunction of the HPA axis. Shatavari’s powerful antioxidant properties counteract ROS, hence reducing oxidative stress (Pandey et al. 2024). Its anti-inflammatory properties reduce the synthesis of pro-inflammatory cytokines, including IL-6 and TNF-α, which may disrupt HPA axis functionality and harm neurons. Shatavari enhances brain health by facilitating neuroprotective processes via the overexpression of neurotrophic factors such as BDNF, which mitigates the adverse effects of stress on hippocampal neurons and optimizes mitochondrial function, hence maintaining cellular energy availability under stress situations (Gupta and Kale 2023).

Advantages of Asparagus racemosus over other medicinal plants and allopathic treatments

Asparagus racemosus has several advantages over other medicinal plants and allopathic treatments reported in previous studies (Rahman and Husen 2022). Asparagus racemosus has multi-targeted action that targets many pathways implicated in neurodegeneration, including oxidative stress, neuroinflammation, and amyloid-beta aggregation, which may provide a more comprehensive approach than many traditional therapies (Rasheed et al. 2023). Adaptogenic properties of Asparagus racemosus help lessen stress-induced neurotoxicity, which is something that allopathic therapies usually do not address, by regulating the hypothalamic–pituitary–adrenal (HPA) axis (Rahman and Husen 2022). According to its traditional usage in Ayurvedic medicine, Asparagus racemosus has a lower profile of adverse effects than many allopathic medications, which often result in cardiovascular or gastrointestinal problems (Akhtar et al. 2024). Its bioactive ingredients preserve neural integrity and encourage neurogenesis, offering a possible benefit over therapies that mostly target symptom relief (Singh, et al. 2023). Asparagus racemosus is a flexible adjunct therapy that is used in conjunction with other therapies to enhance their effectiveness without running the risk of serious interactions (Rahman and Husen 2022).

Preclinical and clinical evidence on Shatavari in AD

Asparagus racemosus (Shatavari) is a prominent plant in Ayurvedic medicine recognized for its many medicinal advantages, including possible neuroprotective effects. Although investigations on Shatavari’s efficacy in AD are nascent, both preclinical and clinical data suggest its potential as a natural complement or substitute for standard AD therapies. This is a review of the preclinical and clinical data that supports its neuroprotective properties in AD.

Preclinical evidence

Preclinical studies, mainly involving animal models and in vitro experiments, have demonstrated that Shatavari exhibits multiple mechanisms that may aid in safeguarding against or potentially reversing the pathological characteristics of AD, including amyloid-beta (Aβ) aggregation, tau hyperphosphorylation, oxidative stress, and inflammation (Raut et al. 2024). In vitro research suggests that Shatavari may impede the aggregation of Aβ, a protein that forms plaques in the brains of individuals with AD (Akhtara 2022). Aβ plaques are significantly neurotoxic and have a role in the neurodegenerative mechanisms seen in AD. A study demonstrated that components in Shatavari may impede amyloid aggregation by interfering with the fibrillization of Aβ. The tau protein aggregates into neurofibrillary tangles (NFTs) in AD, disrupting neuronal function and facilitating neurodegeneration (Majumder and George 2023). Preclinical investigations indicate that Shatavari may modulate the kinases and phosphatases involved in tau phosphorylation, hence inhibiting tau hyperphosphorylation and the development of neurofibrillary tangles (NFTs) (Gupta and Kale 2023). The antioxidant properties of Shatavari may significantly modulate oxidative stress pathways, hence affecting tau phosphorylation. A primary factor in neurodegeneration in AD is oxidative stress, which inflicts damage on neurons and hastens disease development (Shukla et al. 2012). Animal models of AD have shown that Shatavari supplementation reduces lipid peroxidation, reinstates antioxidant enzyme function (including superoxide dismutase and catalase), and safeguards against brain injury (Kaur et al. 2017). Chronic inflammation is a defining characteristic of AD. In vivo, Shatavari has anti-inflammatory characteristics by decreasing the levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, which are heightened in the brains of AD patients (Saggam et al. 2022). In animal models, Shatavari treatment has shown the ability to diminish microglial activity, an indicator of neuroinflammation, and to modify the inflammatory response, possibly mitigating neuronal damage (Singh et al. 2023). Shatavari has shown the ability to increase neurogenesis (the generation of new neurons), notably inside the hippocampus, a brain area critical for memory and cognitive function (Shukla et al. 2012). This characteristic is advantageous in the setting of AD since neurogenesis is often compromised in people with the condition. In mouse models of AD, Shatavari has facilitated the proliferation and differentiation of neural stem cells into functioning neurons, potentially enhancing cognitive function (Akhtar et al. 2024). Preclinical investigations indicate that Shatavari may augment synaptic plasticity and facilitate synaptic repair (O’Leary et al. 2024). The herb’s neuroprotective properties seem to maintain synaptic integrity and neuronal transmission, essential for memory and learning in AD. Asparagus racemosus root extract at 100 mg/kg, orally for 1 week shows a neuroprotective effect on scopolamine-induced AD in mice model. It improves memory impairment and reduces neuronal death in hippocampus areas, indicating its promising effects on AD (Jagdish and Maheep 2021). The several reported preclinical studies on rats and mice are given following in Table 1. The ethanolic extract of Asparagus racemosus (EEAR) roots at 100 and 200 mg/kg shows neuroprotective effects against ethanol-induced cognitive impairment and oxidative stress in Swiss albino male rats. EEAR significantly enhanced memory and learning, and reduced lipid peroxidation (TBARS) and acetylcholinesterase (AChE) activity, demonstrating oxidative stress protection. These findings suggest using EEAR as a natural nootropic drug to treat neurodegenerative diseases like Alzheimer’s (Uddin, et al. 2016). Asparagus racemosus (AR) extract (18 mg/kg) for 2 weeks shows neuroprotective effects on kainic acid (KA)-induced excitotoxicity in mice. KA (0.25 μg in a volume of 0.5 μl) was administered into the hippocampus and striatum to cause neuronal injury. AR reduces oxidative stress and neuronal damage by increasing GPx activity, GSH content, and decreased lipid peroxidation and protein carbonyl levels (Parihar and Hemnani 2004). Asparagus racemosus (AR) root extract (100 and 1000 mg/kg) reversed memory impairments with enhanced cognitive performance and preserved neurons after 90 days of administration in ovariectomized (OVX) rats, which are a model for menopause-induced cognitive deterioration. It also significantly protects against memory impairment and improves neuronal viability in the hippocampus and medial prefrontal cortex (mPFC), possibly offering an alternative to estrogen replacement treatment (Lalert et al. 2013). AR at 200 mg/kg, oral improves memory and cognitive function of 7 days therapy in mice model. The neuroprotective effects of AR were linked to enhanced AChE activity in the hippocampus, notably in the CA1 region emphasizing their cholinergic, antioxidant, and neuroprotective properties (Sharma et al. 2010). AR was also studied for its nootropic and anti-amnesic activities in rats utilizing the Morris Water Maze (MWM) and Elevated Plus Maze (EPM) models. Rats were given AR (50, 100, and 200 mg/kg, p.o.) for 7 days. The MWM test revealed a substantial reduction in escape latency, suggesting increased learning and memory. In the EPM test, AR reversed the increased transfer latency generated by scopolamine (1 mg/kg) and sodium nitrite (NaNO2, 25 mg/kg), indicating anti-amnesic properties. AR also suppressed acetylcholinesterase activity in brain areas such as the prefrontal cortex, hippocampus, and hypothalamus in a dose-dependent manner, indicating that its nootropic and anti-amnesic actions may be mediated via cholinergic system enhancement (Ojha et al. 2010).

Table 1.

Preclinical studies on rats and mice

Drug name	Animals, dose, route, and duration	Inducing drug/target site	Drug effectiveness	Targets/mechanism	References
Methanolic extract of Asparagus racemosus	Adult male Swiss albino mice; 100 mg/kg, oral, for 7 days	Scopolamine (1 mg/kg, I.P.; hippocampal neurons	↓ neuronal mortality in hippocampal CA1, CA3 and DG areas, ↑ memory performance, and showed neuroprotective effects	Phytoestrogenic, estrogen modulation, ↓ oxidative stress, anti-apoptotic, cytokines control; protects neurons, increases neurogenesis, and synaptic plasticity	Jagdish and Maheep (2021)
Ethanolic extract of Asparagus racemosus (EEAR)	Swiss albino male rats; 100 and 200 mg/kg, oral for 21 days	Ethanol (4.5 g/kg, s.c.)-induced cognitive impairment and oxidative stress; hippocampus and cortical areas	EEAR ↑ cognitive performance by EPM, PA, NOR and MWM tests. ↓ oxidative stress and AChE activity	EEAR ↓ TBARS levels, suggesting less oxidative stress. It also inhibited AChE activity, which ↑ ACh levels and improved memory. EEAR also ↑ learning, memory retention and recall through nootropic properties	Uddin, et al. (2016)
Asparagus racemosus (AR) extract	Swiss albino mice; 18 mg/kg, oral mixed with food daily for 2 weeks preceding kainic acid (KA) injection	KA (0.25 mg in 0.5 ml) was injected into the hippocampus and striatum (excitotoxicity model)	↓ Oxidative stress and neuroprotection against KA-induced excitotoxicity. ↑ GPx and GSH levels; ↓ lipid peroxidation and protein carbonyl	GPx activity, GSH levels, lipid peroxidation, and protein carbonyls. The AR extract boosts cellular defences to reduce oxidative stress, preserve neurons, and restore antioxidant enzyme activity	Parihar and Hemnani (2004)
Asparagus racemosus (AR) root extract	Adult female Wistar rats; 100 or 1000 mg/kg/day, oral for 90 days	Ovariectomy (OVX), target: cognitive decline, neuronal viability	The innovative object recognition test confirmed that AR root extract ↑ cognitive function. ↓ Neuron loss in the hippocampus and mPFC	Phytoestrogenic effects, acting on estrogen receptors (ER-α/ER-β), neuroprotective effects, and anti-inflammatory effects	Lalert et al. (2013)
Methanolic extract of the A. racemosus (MAR)	Inbred Charles Foster male albino rats; 50, 100, 200 mg/kg, p.o., for 7 days	Scopolamine (1 mg/kg) and sodium nitrite (NaNO2, 25 mg/kg)	MAR ↓ MWM escape delay, indicating a nootropic effect. Anti-amnesic effects shown by its restoration of scopolamine and NaNO2-induced EPM memory deficits	MAR ↑ cholinergic activity by suppressing AChE in the prefrontal cortex, hippocampus, and hypothalamus. The anti-amnesic benefits are most likely attributed to higher ACh levels and better cognitive function	Ojha et al. (2010)

Clinical evidence

Despite promising preclinical findings, clinical research on Shatavari on AD is limited. However, several studies indicate its possible advantages for neurodegenerative disorders, such as AD. A clinical experiment examined the effects of Shatavari on individuals experiencing age-related cognitive deterioration. The research, although not mainly focused on Alzheimer’s, demonstrated cognitive enhancements in those administered Shatavari extract. The findings indicated that Shatavari may assist in enhancing cognitive function in persons with moderate cognitive impairment (MCI), a precursor to AD (Wele and Gadgil 2021). In therapeutic environments, Shatavari is often used with other Ayurvedic herbs (such as Brahmi, Ashwagandha, and Turmeric) in polyherbal formulations aimed at promoting cognitive function and mitigating neurodegeneration (Chaudhry 2021). Numerous small-scale clinical investigations and anecdotal data indicate that these formulations may boost cognitive performance, alleviate anxiety, and improve general brain function in senior adults; however, more rigorous clinical trials are necessary to produce definitive proof for AD (Bhattacharjee et al. 2020). Shatavari comprises phytoestrogens that have structural similarities to the hormone estrogen. Estrogen has neuroprotective properties, especially in women, with its reduction following menopause associated with a heightened risk of AD. A study indicates that Shatavari’s phytoestrogenic properties may alleviate hormonal imbalances, diminish oxidative stress, and maybe safeguard against cognitive decline linked to AD (Pandey et al. 2018).

Limitations and challenges

Despite the encouraging preclinical and anecdotal data endorsing the neuroprotective properties of Asparagus racemosus (Shatavari) in AD, several substantial limitations and hurdles must be resolved before its acceptance as a conventional therapeutic alternative (Patwardhan 2007).

Insufficient comprehensive clinical evidence

Although preclinical research in animals has shown the possible neuroprotective properties of Shatavari, clinical trials with human participants remain limited and mostly inconclusive. Several limited research and pilot trials indicate potential cognitive advantages of Shatavari; however, these investigations lack the breadth necessary to provide conclusive proof (Sulekha 2022). The majority of existing human research is small-scale trials with restricted sample numbers, limiting the ability to extrapolate the findings to broader groups. Numerous trials have been of short duration, limiting the assessment of the long-term effectiveness and safety of Shatavari in AD. Certain clinical studies fail to include appropriate control groups, complicating the differentiation of Shatavari’s effects from other variables. Large-scale, well-designed, randomized controlled trials (RCTs) are necessary for Shatavari to be recognized as an effective therapy for Alzheimer’s. These studies must concentrate on the long-term effects of Shatavari on cognitive decline, memory, and neurodegenerative indicators (O’Leary et al. 2021; Gudise et al. 2024).

Variability in bioavailability and standardization of herbal extracts

A significant issue associated with herbal remedies such as Shatavari is the inconsistency in the bioavailability of its active constituents. The medicinal benefits of Shatavari are mostly ascribed to its saponins, flavonoids, alkaloids, and steroidal components; however, these substances may exhibit suboptimal absorption in the gastrointestinal system (Kumar et al. 2010). The active constituents of Shatavari may not be well assimilated by the body, hence constraining their efficacy in traversing the blood–brain barrier (BBB) to provide neuroprotective benefits. The bioavailability of Shatavari is subject to variability due to individual variances in metabolism, gastrointestinal health, and enzyme activity, which may affect its therapeutic efficacy (Saravanabhava 2018). Herbal products such as teas, powders, or capsules may exhibit inconsistent bioavailability, and several formulations may not be suited for absorption. Standardization of dosages across various extract kinds is essential to guarantee uniform outcomes in clinical environments. The quality of Shatavari products exhibits considerable variation across producers (Greed et al. 2025). The portion of the plant used (e.g., root vs entire plant), preparation procedures, and extraction processes might affect the concentration of active chemicals. The lack of defined dosages for Shatavari complicates the comparison of outcomes between research and therapeutic applications. Standardized extracts are crucial for guaranteeing uniform treatment outcomes and reducing variability (Rahman and Husen 2022).

Safety issues and possible adverse effects of prolonged use

Although Shatavari has been historically used for several health issues, there is less scientific evidence on its long-term safety, especially concerning AD and its interactions with other medications or therapies (Vishnupriya 2018). Shatavari may interact with certain drugs, including those prescribed for hypertension, diabetes, or hormone replacement treatment. The herb’s phytoestrogenic characteristics may interact with estrogen-sensitive diseases, perhaps influencing hormone-dependent malignancies or hormone therapy. Shatavari is recognized for its immune-modulating properties, which may be unsuitable for those with autoimmune disorders or those undergoing immunosuppressive treatment. The aged demographic, particularly those with AD, may be more susceptible to side effects or undesirable interactions (Savitha 2017). Further investigation is required to determine appropriate doses, long-term safety profiles, and monitoring techniques for geriatric individuals. Certain people may have digestive discomfort, including bloating, diarrhea, or nausea, after consuming Shatavari. Shatavari has phytoestrogens, which may be advantageous for menopausal women; nevertheless, their estrogenic properties may be inappropriate for persons with certain illnesses such as estrogen-sensitive breast cancer, ovarian cancer, or endometriosis (Akhtar et al. 2024).

Necessity for additional research and investigation

Although current research has proposed many neuroprotective mechanisms of Shatavari in AD, such as diminishing oxidative stress, regulating neuroinflammation, and promoting neurogenesis, the precise pathways underlying these benefits remain largely unexplored. Comprehensive molecular and mechanistic investigations are required to elucidate the interaction of Shatavari with cellular pathways implicated in Alzheimer’s pathogenesis (Kaur et al. 2023). The potential significance of Shatavari as a supplementary therapy to standard Alzheimer’s therapies, such as acetylcholinesterase inhibitors or NMDA antagonists, remains little investigated. Research into the synergistic benefits of Shatavari in conjunction with conventional pharmaceutical therapies for Alzheimer’s might be beneficial. The efficacy of Shatavari in decelerating or reversing disease development in Alzheimer’s has not been definitively shown via clinical research (Saroya and Reverse 2018). Future research should examine its effects on the long-term trajectory of Alzheimer’s, specifically investigating its potential to avert cognitive decline, enhance neuroplasticity, and safeguard against neurodegeneration over time (Singh et al. 2018).

Future directions

Future investigations on Asparagus racemosus (Shatavari) should concentrate on three pivotal domains: elucidating intricate neuroprotective mechanisms, standardizing extracts and formulating advanced nanoformulations to improve bioavailability, and executing comprehensive clinical trials to ascertain efficacy and safety. Addressing these areas would reconcile ancient knowledge with contemporary scientific confirmation, facilitating Shatavari’s emergence as a credible treatment alternative for controlling AD. Comprehending the molecular mechanisms by which Shatavari exerts its effects is crucial for determining its involvement in Alzheimer’s treatment. Investigations should explore its capacity to control amyloid-beta aggregation, diminish tau hyperphosphorylation, alleviate oxidative stress, and curtail neuroinflammation. Furthermore, research on its effects on synaptic repair, neurogenesis, and hormone regulation will provide an extensive understanding of its neuroprotective processes. Sophisticated in vitro and in vivo models, together with state-of-the-art tools in epigenetics and genomics, will be crucial in elucidating these pathways. The heterogeneity in herbal extract composition presents a considerable hurdle to repeatability and medicinal use. The standardization of Shatavari extracts to guarantee uniform quantities of bioactive components, including saponins and flavonoids, is crucial. Furthermore, improving the bioavailability of these medicines using sophisticated delivery mechanisms, including nanoparticles, liposomal encapsulations, and nanoemulsions, will optimize their therapeutic effectiveness. Optimizing dosage and including bio-enhancers such as piperine will enhance its pharmacological profile and promote efficient transport to the brain. Stringent clinical studies are fundamental to determining the safety and effectiveness of Shatavari in AD. Extensive, randomized controlled trials (RCTs) need to assess its cognitive, functional, and biomarker effects in heterogeneous patient groups at different stages of AD. Extended studies are necessary to evaluate its safety, tolerability, and side effects. In addition, investigating Shatavari as a supplementary therapy in conjunction with conventional Alzheimer’s therapies may uncover synergistic advantages, while preventative research in at-risk groups might determine its efficacy in postponing disease development. Integrating ancient Ayurvedic principles with contemporary scientific approaches is essential to verify Shatavari as a viable therapy option for AD. This necessitates multidisciplinary cooperation among pharmacologists, neuroscientists, doctors, and specialists in herbal medicine. By overcoming current restrictions and constraints, future research may fully realize the therapeutic potential of Asparagus racemosus, providing fresh optimism in the battle against AD.

Conclusion

The investigation of Asparagus racemosus (Shatavari) as a neuroprotective agent in Alzheimer’s disease (AD) underscores its potential as a viable treatment option. Preclinical research indicates that Shatavari has modes of action that address critical pathogenic characteristics of AD, including amyloid-beta aggregation, tau hyperphosphorylation, oxidative stress, and neuroinflammation. Its capacity to facilitate synapse repair, neurogenesis, and hormonal equilibrium further emphasizes its significance in tackling the complex nature of Alzheimer’s. Despite these encouraging discoveries, substantial gaps persist in the translation of preclinical studies into clinical applications. To fully realize Shatavari’s therapeutic potential, it is essential to comprehensively address the absence of rigorous human studies, the heterogeneity in herbal extract composition, and the obstacles related to bioavailability. The standardization of extracts, the formation of sophisticated delivery methods, and the implementation of meticulously prepared clinical studies are essential subsequent phases in this process.

Author contributions

MN: collating the data and preparation of the drafts; MAK: data mining and suggesting the layout of the figures. AKN, FJA and SP: designing of the structure of the manuscript and proof reading.

Funding

The study was funded by the Indian Council of Medical Research, New Delhi, under reference number 45/61/2020-NANO/BMS.

Availability of data and materials

The raw data generated during this study can be requested from the corresponding author upon reasonable request.

Declarations

Conflict of interest

On behalf of all the authors, the corresponding author states that there is no conflict of interest. The authors have no relevant financial or non-financial interests to disclose.

Consent to participate

Not applicable.

Consent for publication

All the authors of this study provide their consent for publication.