Can Ashwagandha Leaf be Replaced with its Root in Therapeutics? A Review through Published Literature

Introduction: Ashwagandha ( Withania somnifera Linn. Dunal) is an important and frequently used herb in Ayurvedic therapeutics. Its numerous parts, including flowers, leaves and roots, are said to have wide range of health-encouraging properties. Although Ashwagandha’ s root have been used traditionally, it necessitates sacrificing the whole plant. So, there is a need to explore bio-activities in other parts of the plant. Ashwagandha leaf is traditionally used as an ethnomedicine in various regions of India. Leaves of Ashwagandha are least considered in the classical literature and hardly there are references for their therapeutic utilities. Considering this, it has been planned to gather evidences against the therapeutic efficacies of Ashwagandha leaf. Materials and Methods: PubMed indexed articles published till 12 th September 2022 were reviewed using the search strategy " Ashwagandha ", “ Withania somnifera ”, “ Ashwagandha AND leaf”, “Withania AND leaf”. Results: Searching by using the keyword “ Ashwagandha AND leaf” yielded 252 results, while the search "Withania AND leaf" resulted in 245 results. Out of these 245/252; the free full texts were only 42 that have been considered in this review. The plant leaf is extensively used in folklore practice for various disease conditions. The leaf is preferred using both internal and external routes. Pre-clinical, clinical studies have been established diversified therapeutic benefits of Ashwagandha leaf. Conclusion: Ashwagandha leaf studies shows numerous bioactive compounds as present in its root. It can become a lead for the anticancer, neurodegenerative, anti-microbial and anti-inflammatory purpose and can be used as widely as its roots.


INTRODUCTION
For numerous concerns, traditional medicines have gained more popularity in the present era.Traditional medicines are widely accessible, relatively safe and have high level of public trust, thus World Health Organization (WHO) also supports, recommends and promotes it in national health programs.People in South-East Asia nations and other parts of world have employed traditional medical systems for healthcare for generation and industrial production is also environmentally friendly. [1]urveda, the Indian traditional medicine is a science developed by the experiences and wisdom of Indian ancestors.Ayurveda has given exigent contribution in global health care.The potential of Ayurveda in providing primary health care has received global attention leading to its globalization at a fast pace.To sustain the present momentum and to meet the ensuing globalization, it is necessary to have a strong institutional framework with the capacity to generate the resources in a sustainable and economical manner.
Ayurveda uses natural resources in therapeutics after converting them into formulations.Researches and reviews published in recent years on Ayurveda formulations have helped in creating a conceptual interface between Ayurveda and Modern Science.][5][6][7] Ashwagandha (Withania somnifera Linn.Dunal), one such important and frequently used herb in Ayurvedic therapeutics.Its numerous parts, including flowers, leaves and roots, are said to have wide range of health-encouraging properties.Ashwagandha is trusted to enhance the body's resilience to stress so, it works as a powerful adaptogen.Ashwagandha works on following body systems -(i) the nervous system, by improving functions of brain and memory, (ii) the reproductive system by maintaining a healthy sexual and reproductive balance, (iii) improve the cell-mediated immunity and boost the body's resistance to illness and (iv) acts as anticancer, anti-inflammatory anti-arthritic agent.Preliminary investigations suggested that, constituents of Ashwagandha offer a range of therapeutic effects with slight or no associated toxicity.These results are quite positive, so this plant should further researched in order to confirm the findings and elucidate additional possible therapeutics effects.The available information supports the therapeutic values of Ashwagandha as a promising Rasayana (regenerative tonic), due to its diversified pharmacological actions. [8,9]though Ashwagandha's root have been used traditionally, it necessitates sacrificing the whole plant.So, there is a need to explore bio-activities in other parts of the plant.The leaves of Ashwagandha are least considered in the classical literature and hardly there are references for their therapeutic utilities.However, there are works that have generated evidence against the use of Ashwagandha leaf in different pathological conditions.Chemical constituents identified in Withania somnifera leaf are given in Table 1.Considering this, it has been planned to compile available information on the therapeutic efficacies of Ashwagandha leaf.

MATERIALS AND METHODS
PubMed indexed articles published till 12 th September 2022 were reviewed using the search strategy "Ashwagandha", "Withania somnifera", "Ashwagandha AND leaf ", "Withania AND leaf ".In addition, information on folklore claims against the use of Ashwagandha leaf in different pathologies was also compiled.

RESULTS
Withania somnifera is the most widely distributed species in the genus.Thus the search was limited to Withania somnifera.Searching by using the keyword "Withania somnifera" yielded 1413 results and the search using the keyword "Ashwagandha" yielded 1503 results.When the search was narrowed down to "Ashwagandha AND leaf ", the results were reduced to 252, while the search "Withania AND leaf " resulted in 245 results.Out of these 245/252; the free full texts were only 42 that have been considered in this review as enlisted in Table 2.The remaining articles were related to phytochemical analysis etc. that are not compiled in this attempt.
Although Ashwagandha leaf is traditionally used as an ethnomedicine in various regions of India as enlisted in Table 3 and Figure 1.But, there is no direct reference towards its use as a medicine in the classical literature, except in a couple of references for its recommendation as a topical medicament.2]

DISCUSSION
In Ayurveda, the root of Ashwagandha is used in most of formulations as a medicine.References against the use of Ashwagandha leaf as medicine in classical texts of Ayurveda are rare, however, the leaves are extensively used in folklore practices that can be witnessed at Table 4. Its use is even observed in traditional practices in various parts of Pakistan and Bangladesh. [10]e warm leaf is advised to be tied over the inflamed joints for managing pain.Topical application of leaf to counter manifestations associated with inflammation is also observed
ASH-WEX and FIV -suppress the proliferation and migration of activated microglia.ASH-WEX and FIV were screened and found to possess Withaferin A and Withanone as active phytochemicals.
FIV seems to contain more quantity of Wit A and Withanone than ASH-WEX.Thus, FIV is higher effective than the ASH-WEX in the current results. [64] Parkinson's disease Leaf extract (A-Extract)

PD model mouse (Male Swiss albino mice)
Treatment with A-Extract significantly improved the levels of Glutathione and Glutathione peroxidase in the Parkinson's mouse brain.
The extract could be a potential drug in treating oxidative damage and physiological abnormalities in PD.
[65]  Oral [29]  in the practice.Using pastes, decoctions, and ashes as dusting powders is in practice to manage wounds, bed sores, and other skin lesions.

Activity
Oral administration of leaf infusion is said to be beneficial in the management of diabetes.Chewing fresh leaves is believed to be useful in controlling obesity and improving memory.The decoction made out of the leaves is said to be useful in the management of productive cough, and asthma.It is even said to be beneficial in the management of tuberculosis.In the management of psychological stress, insomnia and anxiety also the leaf and it's different dosage forms were used.

Place and
A number of chemical constituents have been identified in leaves that may be beneficial as anti-cancerous, anti-bacterial, anti-inflammatory, neuro-protective, and immuno-stimulatory agents.Experimental studies have established neuro-protective activity (against Glioblastoma, Neuroblastoma, Parkinsonism), anti-cancer activity of leaf extract.The aqueous extracts are reported to be beneficial in lead induced toxicity.The extracts are also found to be useful as Anti-malarial, Anti-inflammatory, Antioxidant, Anti-bacterial, Hypo-glycemic, Hypo-lipidemic and Anti-diabetic agents.Standardized dried aqueous extracts were found to improve psychomotor and cognitive performance in a multi-dose, double-blind, crossover, placebo-controlled study suggesting an effective supplemental therapy for illnesses linked to cognitive impairment.These studies infer that Ashwagandha leaf has a great potential in therapeutics and can be explored in wider studies.

CONCLUSION
Though folklore practices are observed against the use of leaves in varied pathologies, the actual role in the maintenance of health, specifically with regard to protecting against various chronic, non-communicable diseases are not established systematically.This review highlights the potential health benefits of easily available plant part.Further, the studies on Ashwagandha leaf reported much similar bioactive compounds as present in roots, inferring the possibility of using leaf in place of root.

Table 4 : Use of Ashwagandha leaf in folklore practices. Figure
1: Ethnomedicinal uses of Ashwagandha leaf in India.