Therapeutic potential of Kalyanaka Ghrita (polyherbal-medicated Ghrita) in purview of Alzheimer’s disease: A literary review

Yashika Singh; Amzad Ansari; Vidhu Singh; Saroj Parhate; Rajendra Prasad Sharma; Thakur Rakesh Singh

doi:10.4103/jdras.jdras_164_22

REVIEW ARTICLE

Year : 2023 | Volume : 8 | Issue : 3 | Page : 201-212

Therapeutic potential of Kalyanaka Ghrita (polyherbal-medicated Ghrita) in purview of Alzheimer’s disease: A literary review

Yashika Singh¹, Amzad Ansari², Vidhu Singh¹, Saroj Parhate³, Rajendra Prasad Sharma¹, Thakur Rakesh Singh¹
¹ Department of Rasa Shastra and Bhaishajya Kalpana, National Institute of Ayurveda, Jaipur, Rajasthan, India
² Medical Officer, Uttar Pradesh, India
³ Department of Rasa Shastra and Bhaishajya Kalpana, Government Ayurvedic College, Raipur, Chattisgarh, India

Date of Submission	24-Nov-2022
Date of Acceptance	16-Mar-2023
Date of Web Publication	16-Aug-2023

Correspondence Address:
Dr. Yashika Singh
Department of Rasa Shastra and Bhaishajya Kalpana, National Institute of Ayurveda, Jaipur 302002, Rajasthan
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jdras.jdras_164_22

Abstract

Kalyanaka Ghrita (KG) is a polyherbal-medicated Ghrita that is in practice since Vedic times in the traditional system of Indian medicine. Recently, KG was enlisted under the National List of Essential Ayush Medicines, published by the Ministry of Ayush, Government of India, January 2022. Hence, the question always strikes the mind to perceive the historical evolution of KG from the Vedic period to recent times. An extensive literature survey was conducted to search the references of KG in the available Ayurvedic databases to analyze the difference in their herbal ingredients, dose, and therapeutic indications. Total 16 formulations were identified under the name of KG in authoritative textbooks of Ayurveda, with surprisingly similar herbal ingredients and numerous therapeutic indications.

Keywords: Alzheimer’s disease, Ayurveda, CNS disorders, Kalyanaka Ghrita, Rasayana

How to cite this article:
Singh Y, Ansari A, Singh V, Parhate S, Sharma RP, Singh TR. Therapeutic potential of Kalyanaka Ghrita (polyherbal-medicated Ghrita) in purview of Alzheimer’s disease: A literary review. J Drug Res Ayurvedic Sci 2023;8:201-12

How to cite this URL:
Singh Y, Ansari A, Singh V, Parhate S, Sharma RP, Singh TR. Therapeutic potential of Kalyanaka Ghrita (polyherbal-medicated Ghrita) in purview of Alzheimer’s disease: A literary review. J Drug Res Ayurvedic Sci [serial online] 2023 [cited 2023 Sep 23];8:201-12. Available from: http://www.jdrasccras.com/text.asp?2023/8/3/201/383697

Introduction

According to the World Health Organization (WHO), traditional medicines are sum total of knowledge, skills, and practices based on theories, beliefs, and experiences primeval to contrasting cultures, whether explicable or not, used for the maintenance of health as well as prevention, diagnosis, and treatment of physical and mental illness.^[1] Indian system of medicine, that is, Ayurveda includes all medicines intended for internal or external use for the diagnosis, treatment, mitigation, or prevention of disease or disorder in human beings or animals, and manufactured in accordance with the formulae described in the authoritative books of Ayurveda specified in First Schedule of Drugs and Cosmetics Act, 1940.^[2] Successful treatment of any disease requires four fundamental components in Ayurvedic science, namely, physician, drug, attendant, and patient, if endowed with adequate qualities, leads to alleviation of disease. The drug (Dravya) stands second among the four fundamental components of treatment.^[3] Ideal raw drug selection, adequate proportion of raw drugs, ideal manufacturing method, and calculated dose fixation are also required for preparation of any specific formulation.

Kalyanaka Ghrita (KG)^[4] is a medicinal preparation of herbs with Goghrita as primary constituent. KG is a compound herbal oleaginous formulation prepared by infusing active phytoconstituents of 28 different specified herbs in Goghrita, following the principles of Sneha Kalpana. Literal meaning of the word Kalyanaka is “Auspicious.” KG is therapeutically indicated in a wide range of diseases such as Pandu (anemia), Unmada (psychosis), Apasmara (epilepsy), Kasa (cough), Kandu (itching), Visha (poison), Prameha (diabetes), Jwara (fever), Daurbalya (weakness), and Smriti Daurbalya (loss of memory), Shosha (phthisis), and Bandhyatva (infertile).

The first classical mention of KG is found in Charaka Samhita and later on followed in various other scheduled books of Drugs and Cosmetics Act, 1940, well familiar in treating conditions of psychosomatic origin. KG consists of 28 different herbs and Goghrita, prepared by following the principles of Sneha Kalpana. KG is a clinically proven^[5] and widely used formulation in Ayurvedic clinics for the management of mental disorders occurring in every age group.

Disease prevalence

US Centre for Disease Control and Prevention and UN Aging Program have estimated that number of Alzheimer’s disease (AD) incidences above 65 years of age in the world is expected to increase from 420 million in 2000 to nearly 1 billion by 2030, with the proportion of older people being increased from 7% to 12%.^[6] Upto 75% of all dementia cases are of AD.^[7]

AD is defined as neurodegenerative disease which is characterized by neurotic plaques and neurofibrillary tangles from amyloid-β peptide, a build-up in the medial temporal lobe and neocortical areas of brain^[8] which is characterized by a preclinical phase, lasting for years, during which progressive neurodegeneration in the brain occurs before typical clinical symptoms become detectable.^[9] Presently, all approved treatments for AD are symptomatic which aim to improve cognitive and behavioral symptoms without altering the principal course of disease.^[10] Since 2003, the US Food and Drug Administration has not approved any newer therapies for AD and also newer therapies for disease modification of any adult-onset neurodegenerative disorder are not yet approved.^[11]

The clinical features of AD are comparable with Unmada (psychosis) in Ayurveda, Indian System of Medicine, primarily focuses on old age-related neurodegenerative disorders. It represents a broad class of psychological disorders with disturbance in Manas (mental functioning), Samjna (perceptions), Buddhi (application of the acquired knowledge), Smriti (memory), Jnana (experiences), Sheela (conditioned activities), Bhakti (emotional adhesions), Cheshta (behavior), and Achara (sociocultural activities).^[12]

In this review, we have aimed to compile and summarize the scattered information about KG in Ayurvedic databases and provide scientific evidences for efficacy of individual plant ingredients of KG. Major findings from the literature review of KG concerning the contents, dose, therapeutic indications, and probable mode of action of KG in special reference to psychosomatic disorders are summarized in this review, so that the data retrieved in this review can be helpful to plan further research work.

Materials and Methods

Data for literature review was collected through Samhitas (classical texts), Nighantus (lexicons), Ayurvedic Formulary of India (AFI), and Ayurvedic Pharmacopoeia of India (API). The contemporary review was done from modern textbooks and peer-reviewed scientific research journals on PubMed, Scopus, Elsevier, and other relevant databases. Further, each ingredient was evaluated for their Ayurvedic property (pharmacodynamic attributes) related to the probable mode of action in AD.

Results

KG is a compound herbal oleaginous formulation containing 28 herbs and Goghrita prepared by following the principles of Sneha Kalpana [Table 1]. The method of preparation of KG is well explained in API. The therapeutic dose of KG is mentioned as 12 g/day advised with warm milk or warm water as adjuvant.^[13]

Table 1: Pharmacodynamic attributes of Kalyanaka Ghrita

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The Rasa (taste), Guna (attribute), Veerya (potency), Vipaka (biotransform), and Doshaghnata (effect on Doshas) of KG are well depicted in [Table 1]. Out of 28 herbs in KG, there is a predominance of Tikta (bitter), Madhura (sweet), Katu (pungent), and Kashaya (astringent) Rasa, whereas Amla Rasa (sour taste) was found in very minor percentage. However, Lavana Rasa (salt) was absent in all herbs of KG [Figure 1]. Among Guna (attribute) of KG herbs, majority herbs are Laghu (easy to digest), Ruksha (dry), Snigdha (unctous), Tikshna (strong), and Guru (heavy to digest) in nature [Figure 2]. In terms of Veerya (potency) of herbs of KG majority are Ushna Veerya (hot potency) [Figure 3]. The overall Vipaka (biotransformative phase of Rasa) of KG herbs is majorly Katu (pungent) and Madhura (sweet) in Vipaka (biotransformative phase of Rasa). However, only one herb is found to be Amla (sour) Vipaka (biotransformative phase of Rasa) in nature [Figure 4].

Figure 1: Predominance of Rasa (taste) in herbal ingredients of Kalyanaka Ghrita

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Figure 2: Predominance of Guna (property) in herbal ingredients of Kalyanaka Ghrita

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Figure 3: Predominance of Veerya (potency) in herbal ingredients of Kalyanaka Ghrita

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Figure 4: Predominance of Vipaka (biotransformation) in herbal ingredients of Kalyanaka Ghrita

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Upon reviewing the literature, it was found that KG appeared in total of 16 authoritative textbooks of Ayurveda ranging from Bower's manuscript and Charaka Samhita to the Sushruta Samhita, as well as more recent publications such as API and AFI by the Ministry of Ayush, Government of India [Table 3]. Predominantly, same herbs were found in all the formulations of KG with multisystem therapeutic indications such as Apasmara (epilepsy), Jwara (fever), Vatarakta (gout), Unmada (psychosis), Kasa (cough), Mandagni (poor digestive power), Mutrakrichha (dysuria), Visarpa (erysipelas), Kandu (itching), Pandu (anemia), Prameha (diabetes), Visha (poison consumption), oligospermia, low-intelligence quotient, stuttering, Bandhyatva (infertility). It bestows strength, longevity, complexion, nourishment, and Punsavana Karma (male progeny promoter) [Table 2].

Table 3: Historical glimpse of Kalyanaka Ghrita

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Table 2: Pharmacological action of herbal ingredients of Kalyanaka Ghrita

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The individual herbs of KG exhibit nootropic, rejuvenator, anxiolytic, neuroleptic, anticonvulsant, antidepressant, anxiolytic, adaptogenic, and sedative effects [Table 2]. Individual herbs mentioned in KG are used as Rasayana (rejuvenator) at many places in scholarly textbooks of Ayurveda, and they have also been mentioned in various other formulations as ingredients as well.

Discussion

There is an urgent need for disease-modifying treatment that may prevent or slow down the rate of disease progression, but unfortunately for AD, none are currently available. The history of pharmaceutical development for AD has been plagued by an endless parade of mid-to-late-stage clinical trial failures. Nonetheless, significant treads have been made in recent years in understanding key aspects of pathobiology of AD. Though the therapeutic aspects have faced struggles and also many pharmaceutical companies have chosen to abandon their AD drug development divisions, novel therapeutic strategies are still being actively developed and tested.^[14]

Numerous herbs and Ayurvedic formulations have been used to treat neurodegenerative disorders such as Epilepsy, AD, and their associated symptoms. A number of formulations are mentioned in Ayurvedic classics that are useful for limiting the prognosis and treating pathologies in neurodegenerative disorders such as AD and epilepsy. Considering multiherbal ingredients and Goghrita with diversified therapeutic activities of KG may have an upper hand against the conventional drugs used for neurodegenerative disorders.

Unmada (psychosis), a broader term, represents different classes of mental ailments in Ayurvedic science. Numerous mental disorders with different clinical presentations are generally, characterized by a series of a combination of abnormal perceptions, emotions, thoughts, behavior, and relationships with others.^[15]Goghrita has a property of Sanskaranuvartana (potentiation), which means that the above-mentioned properties of all active phytoconstituents of drugs will be carried forward by Goghrita. All such unique qualities such as Rasayana (rejuvenator) and other pharmacological properties of the formulation make it a promising drug for management of neurodegenerative disorders. Sneha Kalpana is pharmaceutical process to prepare oleaginous medicaments from contents like Kalka (herbal paste), Kwatha (decoction), or Drava Dravya (any other liquid such as milk, self-expressed juices, meat juice, etc.) taken in a specific proportion, by subjecting them to graduated heating pattern and for specific duration to fulfill the chief desired parameters, according to the need of therapeutics. Here, the main principle is to transfer active phytoconstituents of herbs in lipid and water as per solubility.^[16]

Goghrita has properties such as Ojovardhaka (immunity booster) and Rasayana (rejuvenator) which suggest that it enhances longevity and quality of life. Rasayana Dravya (rejuvenator drugs) help tissue functioning at optimal level and keep the body in a younger phase by delaying the process of aging and improving the quality of life.^[17] Milk fat is a complex form of lipids prevalent in nature. Goghrita is processed milk fat and basically known as anhydrous milk fat or clarified butter fat mainly composed of glycerides, and other minor constituents are free fatty acids, phospholipids, sterols, sterol esters, carbonyls, hydrocarbons, and carotenoids fat-soluble vitamins.^[18]

The distribution of drug inside blood is influenced by lipid solubility, ionization, and differences in osmolarity inside blood movement. Distribution of lipid-soluble drugs into intra- and extracellular spaces is quick. The drugs that are rapidly absorbed from the gut due to their lipid solubility are known to readily diffuse into cerebrospinal fluid and brain. Due to lipid nature of cell membranes, Goghrita based formulations facilitate passive diffusion of lipid-soluble drugs, nonionized nature of fat-soluble drugs, help in attaining the highest concentration of drug inside cell.^[19] The blood–brain barrier penetrability increases in the absorption and transportation of essential phytoconstituents to the target site. The molecular structure of blood–brain barrier is responsible for this absorption and transportation. The lipophilic nature of membrane separating the central nervous system (CNS) tissue and circulating blood selectively permits the passage of lipids and lipid-soluble drugs across it. Therefore, any drug given in form of Goghrita will not only be processed and absorbed fast but also be able to reach some of the most hard-to-reach areas of the body like CNS. This clarifies the better efficacy of various psychotropic drugs given in the form of Goghrita for CNS disorders.^[20]

Probable mode of action of KG can be evaluated on the basis of Rasa Panchaka (Ayurvedic pharmacodynamic attributes) of KG [Table 1]. Drugs of KG represent a varied picture; majority of these drugs have Kashaya (astrigent), Katu (pungent) and Tikta Rasa (bitter taste), Laghu (lightness) and Ruksha Guna (dryness property), Katu Vipaka (pungent biotransformation), and Ushna Virya (hot potency) all of which influences Sadhaka Pitta in the body. Ushna Virya (hot potency) is Kapha-Vata Dosha Shamaka and due to these properties, Tamas (delusion) and Rajas Gunas (passion attribute), psychological counterparts might be controlled, thus Satva Guna (purity attribute) taking an upper hand may affect Medha (intelligence). The most important cause of Unmada (psychosis) is described as Heena Satva (timid personality). They will be low in Ojas (mentally weak). This depletion can be compensated by Ghrita. Vata Dosha is the controller of the mind.^[21] and Medha (intelligence) is the property of Pitta Dosha.^[22] So, normalcy of Pitta and Vata are major concerns in the treatment of psychiatric illnesses like Unmada (psychosis) which can be counteracted by the Vatapittahara property of Goghrita.

Reviewing upon the pharmacological properties of individual herbs of KG [Table 2], it can be suggested that these groups of herbs when infused with Goghrita through Sneha Kalpana process potentiate Goghrita by addition of active pharmaceutical constituents such as mesuaferrol, lupeol, ursolic acid, and other active phytoconstituents which enhances the pharmacological actions of KG on the nervous system, cardiovascular system, immune system, renal system, and various other systems of the body. Previous in-vivo and in-vitro studies on individual herb of KG have also proved their efficacy as antioxidant, adaptogenic, anti-inflammatory, nootropic activities, and various other activities [Table 2]. These activities are relatable with therapeutic indications of KG mentioned in Ayurvedic databases [Table 3]. Probably, a combination of properties of all these herbs synergistically works on multiple systems of body and becomes responsible for neuroprotective activity and its efficacy in neurodegenerative disorders like AD and Dementia.

In-vivo study conducted by Diddi et al.^[23] to assess ameliorative effect of KG in β-amyloid induced memory impairment in Wistar rats showed that KG significantly improved cognition and memory and increased brain-derived neurotrophic factor and antioxidant status in Aβ_1–42-induced rats. It also reduced brain acetylcholinesterase, oxidative stress, and inflammatory cytokines and prevented neuronal damage. The findings of the study suggest that KG has neuroprotective potential and along with its nootropic property could be a promising therapy for neurodegenerative diseases like AD. Another study was also conducted on Drosophila model of Huntington’s and AD by Sharma et al.^[24] which proved KG to exert more Aβ suppressing pathological effects in comparison to Saraswata Ghrita.

Safety pharmacological studies using core battery tests of preclinical CNS safety pharmacology as assessed by Diddi et al. confirm safety profile of KG and it was found to be devoid of proarrhythmic risk. The respiratory safety profile of KG was validated in respiratory parameters using whole-body plethysmography. According to the findings of this study, KG is a safer medicine that has no CNS, cardiovascular, or respiratory side effects after 28 days of dosage.^[25]

Data from previous preclinical and clinical studies for evaluation of the efficacy of KG also suggest that therapeutically judicious administration of KG significantly reduces the probability of incidences for neurodegenerative disorders such as AD and associated dementia by reducing the number of years lived with diseases.

Conclusion

Based upon the current available databases KG is found effective in disorders such as anemia, epilepsy, psychosis, obsessive–compulsive disorder, fever, dementia, AD, depression, and other. It has Rasayana (rejuvenator) properties due to the presence of Ghrita and its herbal ingredients. Overall, KG appears to be an effective medicine provided it is administered judiciously. Regular consumption of KG has the potential to enervate the progression of neurodegenerative disorders such as AD by exhibiting a nootropic effect and enhancing neuroprotection. Hence, KG improves the quality of life by minimizing the clinical features of diseases and could be promising insinuating treatment modality for neurodegenerative diseases like AD.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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