AYUHOM

REVIEW ARTICLE
Year
: 2022  |  Volume : 9  |  Issue : 2  |  Page : 67--76

Kaphaketu Rasa as a Potential Anti-Inflammatory Ayurveda Herbo-Mineral Drug: A Scoping Review


Pooja Yadav1, Abhishek Upadhyay2, Sanjay Kumar1,  
1 Department of Rasashastra and Bhaishajya Kalpana, National Institute of Ayurveda, Deemed to be University, Jaipur, Rajasthan, India
2 Department of Kayachikitsa, National Institute of Ayurveda, Deemed to be University, Jaipur, Rajasthan, India

Correspondence Address:
Pooja Yadav
Department of Rasashastra and Bhaishajya Kalpana, National Institute of Ayurveda, Deemed to be University, Jaipur, Rajasthan
India

Abstract

In the present scenario, people are more prone to various diseases due to poor immunity arising due to lifestyle changes, smoking, and air pollution. Poor lifestyle is responsible for Kapha predominant diseases like Kasa, Shwasa, and other metabolic as well as auto-immune disorders. In Ayurvedic pharmaceutics, Kaphaketu Rasa (KKR) consisting of Aconitum chasmanthum Stapf ex Holmes (Vatsanabha), purified Borax (Tankana), Incinerated Conch shell (Shankha Bhasma), Piper longum Linn., and Zingiber officinale Roxb. Has been indicated for Kapha related diseases. Eight varieties by the name of KKR are documented in Ayurvedic texts. To understand the rationale of mentioning these varieties and to explore the potential areas of its usefulness in contemporary clinical conditions, this study was performed. Information regarding this formulation was collected from the major Ayurveda texts as well as electronic sources for available scientific evidence, commercial availability of the formulation was also checked. The available data supports its use as a potent Kapha pacifying formulation whereas scientific evidence supports its action as an anti-inflammatory, analgesic, antipyretic, antispasmodic, anti-allergic as well as mucolytic agent. However, this formulation needs to be studied through animal and clinical studies to understand and explore its mode of action, drug interactions, dose-response relationships, adverse reactions, etc., in different clinical conditions.



How to cite this article:
Yadav P, Upadhyay A, Kumar S. Kaphaketu Rasa as a Potential Anti-Inflammatory Ayurveda Herbo-Mineral Drug: A Scoping Review.AYUHOM 2022;9:67-76


How to cite this URL:
Yadav P, Upadhyay A, Kumar S. Kaphaketu Rasa as a Potential Anti-Inflammatory Ayurveda Herbo-Mineral Drug: A Scoping Review. AYUHOM [serial online] 2022 [cited 2023 Mar 31 ];9:67-76
Available from: http://www.ayuhom.com/text.asp?2022/9/2/67/370088


Full Text



 Introduction



Kaphaketu Rasa (KKR) is a classical Ayurveda (herbo-mineral) Kharaliya (prepared in mortar) formulation. It is indicated in diseases arising due to aggravation of Kapha like Jwara (febrile conditions), Kasa (cough), and Karnaroga (diseases of the ear), etc., Aconitum chasmanthum Stapf ex Holmes, incinerated conch shell (Shankha Bhasma), Borax (Tankana), and Piper longum Linn. (Pippali) are the main ingredients of this formulation. By the name of KKR, eight variant formulations have been mentioned in different texts of Ayurveda. These formulations differ in the ingredients, therapeutic dose, and indications thus changing their efficacy and providing wider options for Ayurveda practitioners to prescribe KKR as per clinical symptoms and severity of the disease. To understand the rationale behind mentioning different varieties of the KKR in Ayurvedic texts and exploring the potential usefulness of this formulation in present-day disease entities, the present review was performed.

Objectives

Present review was performed with following objectives:

Exploring the varieties of KKR mentioned in Ayurveda textsUnderstanding its mode of action and applicability as per Ayurveda conceptsSurvey of commercial availability of different varieties of KKR will be carried outThe potential scope of KKR in present-day clinical conditions will be explored.

 Materials and Methods



Literature regarding KKR was collected from the major texts of Ayurveda listed in Schedule 1 of the Drug and Cosmetic act 1940. The collected material was sorted, analyzed, and presented under relevant headings in the form of text and tables. The online sources such as Google Scholar, PubMed, AYUSH Research Portal, DHARA, Research Gate and other electronic sources were searched using the relevant terms like KKR, Vatsanabha, Aconite, Pippali, P. longum, Piperine, Aconitine, etc.

 Kaphaketu Rasa in Ayurveda Classics and Its Clinical Indications



KKR is a herbo-mineral formulation first described in Rasendra Sar Sangraha (R.S.S.). Ayurvedic Formulary of India (AFI),[1] an official publication of Government of India regarding Ayurvedic formulations also refers to R.S.S. On review of major Ayurveda texts for formulations, 14 types of KKR were found. All these varieties are mentioned under Bharat Bhaishajya Ratnakara and Rasayoga Sagara.[2] On further analysis, excluding the repetition of KKR varieties with common ingredients, total eight varieties with slight variation in composition are documented. The details of eight varieties are given in [Table 1].{Table 1}

 Market Availability



In Ayurvedic texts, 8 varieties of KKR have been described. Commercially available samples of KKR in the market were analyzed for variation in the ingredients. For the market survey, samples of KKR being prepared by major Ayurveda pharmaceutical houses of repute were collected and checked for ingredients. It was found that most of the pharmacies are preparing KKR mentioned in R.S.S.[4] KKR available in the market contains purified Tankana, purified Vatsanabha, Shankha Bhasma, powder of Pippali, and for trituration Ardraka Swarasa is used. No other variety of KKR mentioned in classical texts is commercially being prepared by pharmaceutical companies.

 Pharmaceutical Processing of Kaphaketu Rasa



KKR contains Aconite,[13] a schedule E1 drug with potentially hazardous properties if not used in therapeutic limits after proper processing (shodhana). For making it acceptable and safe for oral administration KKR preparation involves purification (shodhana) of Vatsanabha,[14] Tankana,[15] and Shankha[16] followed by their Marana,[17] and powdering of P. longum and other herbs. All the powdered ingredients are triturated (bhavana) with Ardraka Swarasa (juice of Ginger). The details of pharmaceutical preparation of KKR are elaborated below.

Purification of Aconite (Vatsanabha Shodhana)

For the purification of Aconite, generally, two methods are mentioned in texts; Nimmajana (dipping) and Swedana (steaming) using different media[18] like cow's urine, cow's milk, goat's milk, Triphala kwatha,[19] etc. In process of dipping, raw Vatsanabha is dipped in cow's urine and kept in the sunlight for three days; cow urine being changed daily. After 3 days, Vatsanabha is taken out, washed with warm water, peeled off and dried in the sun. Purified and dried aconite is then powdered and is preserved for further use. While steaming process involves steaming the raw pieces of Vatsanabha using Dola yantra (swing apparatus) for three to 6 h in different media as described above. Purification helps in reducing the percentage of harmful ingredients like aconitine to therapeutic value.[20]

Purification of Conch shell (Shankha Shodhana)

To purify the conch shell there is a provision for steaming it in swing apparatus[21] with sour liquids like Kanji, Nimbu Swarasa (lemon juice), Jayanti swarasa, Tanduliya swarasa, etc.[22] Shankha is steamed (swedana) using either of the media for 4 to 12 h in Dola Yantra (swing apparatus), followed by washing with hot water and drying. Shankha is having the alkaline impurities (Kshariya) thus to neutralise them processing with Amla dravya is mentioned in texts. Also, the corrosive nature helps in loosening the molecular cohesiveness and helps drugs to break into fine particles.[23] Shankha Bhasma purified using lemon juice was found more effective over other purifying media in relieving gastro-oesophageal reflux.[24] Lemon juice also reduces the chances of contamination and the addition of foreign material into the formulation.[25]

Incineration of Conch shell (Shankha marana)

Generally purified Shankha is incinerated on high heat (temperature ≈ 650°C) and then allowed to cool, re-powdered and again incinerated.[17] This process is repeated till the criteria of Bhasma formation are fulfilled.[26] However, AFI has mentioned trituration of purified Shankha using Kumari swarasa (juice of aloe vera).[27] Pellets of purified Shankha are made after triturating with Kumari Swarasa and are incinerated (Gaja Puta) by placing them in earthen vessels. This process is repeated till the Bhasma achieves the Lakshana of Rekhapurantav, and other criteria of Bhasma formation.

Purification of Borax (Tankana Shodhana)

Tankana is purified by process of Nirjalikarana (dehydration) by heating it on medium flame in an iron pan. After dehydration, Tankana become anhydrous and chances of foreign contamination becomes less.

Final step in processing

Pippali, purified Vatsanabha, purified Tankana, and Shankha Bhasma are grinded together in a mortar and triturated with juice of Ginger (Ardraka Swarasa). Tablets of the therapeutic dose is made after giving three Bhavana (trituration) of Ardraka Swarasa.[4] Since Kharaliya rasayana bind various drugs into a single molecular form, so they are more effective in their actions even in the smaller dosage.[28] Bhavana with Swarasa (juice) or Kwatha (decoction) of similar quality (Tulyavirya Dravya) drugs, therapeutic dose decreases whereas the potency of the final drug increases.[29]

 Pharmacological Properties



KKR is a Kapha-Vata pacifying formulation. The ingredients of this formulation majorly act on the Kapha and Vata. This formulation is beneficial in such clinical conditions where Kapha is the dominant factor in the pathogenesis. The pharmacological properties of the ingredients of the KKR are tabulated below [Table 2].{Table 2}

Review of the database regarding KKR didn't yield much information hence the search was modified to information pertaining to its ingredients. The relevant information of the ingredients is presented further in this article.

Vatsanabha (Aconitum chasmanthum)

Vatsanabha,[13] a poisonous drug mentioned in Schedule E1 of the Drug and Cosmetic rule 1945, is Katu (pungent), Tikta, Ashukari (fast acting), Vyvayi (permeation all over body before digestion), Vikasi (distribution all over body without passing through routine digestive process), Ushna, and Teekshna, spreads rapidly in the body with a fast onset of action. Amashaya (seat of Ama i.e., upper part of gastrointestinal tract) is the dominant site of Kapha in the body and is also involved in pathology of Jwara (fever). Weak digestive fire (Mandagni) is responsible for Kapha and Ama production, having the potential to obstruct the micro channels (Srotas) of the body. Chronic obstruction in the channels further aggravates the Vata and disease manifests as Kapha and Vata related signs and symptoms. As the name implies KKR, it abolishes the vitiated Kapha and thus subsides the Vata. Due to its Kapha and Jwara mitigating properties, Vatsanabha is main ingredient of Ayurvedic formulations designed for the treatment of Kapha and febrile conditions. Ayurvedic classics have described methodology for making it useful in therapeutics and studies have shown that these purification procedures reduce the toxic effects of aconite significantly. After therapeutic processing, percentage of ingredients like aconitine decrease to therapeutic value.[20] After purification, the total alkaloid content of toxic substances decreases, while the percentage of less toxic substances such as aconine, hypoaconine, and benzylhypoaconine increase due to the conversion of the toxic aconitine into aconine or hydrolysis of the alkaloids to their respective amino alcohols after the purification process.[56]

Owing to its Vednasthapaka (analgesic) and Shothahara (anti-inflammatory) properties, it has been used in Ayurvedic clinical practice for treating autoimmune, musculoskeletal, respiratory illnesses, and gastrointestinal disorders. Pharmaceutical studies have identified Aconitine, Mesaconitine, etc. As its major alkaloids which have been studied experimentally for different outcomes.[57] Aconitine, a diester alkaloid in mice models has shown antinociception properties. It has been found beneficial in different types of pains including acute, visceral pain and pain arising due to inflammations. These findings render it as a useful therapeutic agent for painful musculoskeletal as well as clinical conditions presenting with the pain of visceral origin.[35] Aconitum alkaloids have also shown metabolism stimulation properties experimentally and could be a possible therapeutic agent in diseases associated with a lower metabolic rate like hypothyroidism.[38] Bulleylaconitine, a diterpenoid alkaloid found in Aconitum chasmanthum, has shown anti-allergic and anti-inflammatory effects in asthma models by reducing the immunoglobulin E (IgE), monocyte chemoattractant protein-1, eosinophil, and lymphocytes which are important inflammatory mediators involved in the pathogenesis of asthma.[37] Aconitum is also a potential therapeutic agent in various arthropathies including autoimmune conditions like rheumatoid arthritis. Interleukin-6 (IL-6) is an important cytokine involved in the pathogenesis of rheumatoid arthritis responsible for joint destruction and other systemic features present in rheumatoid arthritis. Benzoylaconitine, a monoester alkaloid of aconitum has shown its antirheumatic effect by inhibiting IL-6 and IL-8 in experimental models.[58]

Vatsanabha has been traditionally classified as a Svedajanana drug (drugs enhancing sweating). Brown adipose tissue in humans is responsible for thermogenesis and Aconitine, when administered in cold stressed mice has led to an increase in the weight of brown adipose tissue by upregulating the uncoupling protein-1 level which is responsible for its thermogenic effect. The weight of white adipose tissue in these models has reduced, these findings make aconitum a possible therapeutic agent in obesity, fever, and conditions with low basal metabolic rate.[59] The antimicrobial effect of Aconitum has also been explored and its potential inhibitory effect against Staphylococcus aureus has been found.[60]

Tankana (Borax)

Tankana, a salt of tetra boric acid, is an alkaline drug having Ruksha and Ushna properties which is indicated for the treatment of Kapha related disorders like Kasa, Shwasa and Jwara, etc. Due to its Deepana and Pachana properties it works on Agni (digestive fire) hence, is widely prescribed in functional, as well as organic disorders of the gastrointestinal tract. It is also indicated in inflammations associated with the upper and lower respiratory tract.[61]

Tankana is invariably used as an antidote to Aconitum and is found as an ingredient in Ayurvedic formulations containing Aconitum. Its anti-dotal effect was evaluated in Aconitum poisoning and has shown a protective effect against aconitum induced acute and sub-acute as well as cardiac and neuromuscular toxicity.[62]

Borax is having antibacterial and antifungal activities and has been found effective against Escherichia coli, Pseudomonas aeruginosa, S. aureus, Streptococcus pyogenes, Candida albicans, Aspergillus niger and Aspergillus clavatus.[41]

Shankha Bhasma (CaCO3)

Shankha Bhasma is the incinerated conch shell consisting of CaCO3. It's therapeutic indications are indigestion, hyperacidity, bloating, pain abdomen, diarrhoea, etc.[45] Shankha Bhasma is a Kshara (alkali) with Deepana (enhancing digestion) properties.[44] It works at Amashaya (upper part of GIT) and Urah (chest) which are the seat of Kapha, thus helps in improving Agni, relieving Shoola (pain) and Kapha-nissarna (expectoration). With pacification of Kapha, Ama condition which is responsible for underlying inflammation in the body is subdued. Shankha Bhasma consists of calcium carbonate that can crystallize into calcite and aragonite. The calcite decomposes to calcium oxide on exposure to heat during the preparation of Shankha Bhasma. It absorbs water and carbon dioxide to form a mixture of calcium hydroxide and calcium carbonate. Shankha Bhasma is also beneficial in gastro-esophageal reflux, which is a trigger factor[63] for various respiratory symptoms, which can be controlled by its ability to reduce the secretion of gastric juice and pepsin inhibiting properties.[64]

Shankha Bhasma exhibits gastric tissue cytoprotective, antisecretory, and free radical scavenging properties. Shankha Bhasma is a very potent antacid, anti-inflammatory, antispasmodic, and anti-diarrhoeal drug and a good source of organic calcium.[45]

Pippali (Piper longum)

P. longum is a popular herb mainly used in disorders like Agnimandhya (loss of appetite), Ajirna (Indigestion), colic, Kasa (conditions associated with cough), Shwasa, etc. P. longum has been studied extensively and consists of Piperine, Piplartine, piperlongumine, Piperlonguminine, Methyl 3, 4, 5-trimehoxycinnamate as the major constituents.[45]

Piperine, a major active constituent of P. longum possess potent antiallergic properties. It has exhibited a potent anti-allergic effect in allergic rhinitis and asthma experimental models by inhibiting major allergic inflammatory mediators like IgE, IL-6, and IL-1b. Treatment with Piperine in allergic mice models has also shown a reduction in nitric oxide levels which signifies its role in reducing airway inflammation. Petroleum ether extract of P. longum has also exhibited respiratory stimulant action in smaller doses whereas its extract and Piplartine, a constituent has shown cough reflex suppression activity.[50]

P. longum also has anti amoebic activity against Entamoeba histolytica and Caecal amoebiasis. This activity was noted highest at a concentration of 1000 μg/kg/day and cleared all E. histolytica from mice intestines at this concentration.[65]

Piperine has also been evaluated for analgesic and anticonvulsant properties and has exhibited these effects similar to indomethacin, valproic acid, and carbamazepine. At higher doses petroleum extract of P. longum has resulted in convulsion due to medullary stimulant factors. These observations indicate the clinical efficacy of KKR as analgesic in lower doses but simultaneous points to avoid overdosing as higher concentration of such ingredients may result in convulsions. Further, these findings warrant the need of evaluating KKR's safety and efficacy in different convulsive neurological disorders. Apart from these properties, P. longum also possesses anti-hyperglycaemic, anti-lipid peroxidative, and anti-oxidant properties which make it a useful therapeutic agent in a wide range of disorders.[66]

Piplartine a major constituent of P. longum has shown cough suppression activity by suppressing oesophageal ciliary movement in experimental models.[67]

Ardraka (Zingiber officinale)

Zingiber officinale rhizome is used in fresh and dried form. The fresh rhizome is termed Ardraka whereas the dried rhizome is known as Shunthi. It possesses anti-inflammatory, analgesic, anti-allergic, carminative, and antispasmodic properties and is used in many Ayurvedic pharmaceutical preparations as an ingredient. Zingiberol, Zingiberene, Gingerosol, Shoagol, and Gingerol are found as major constituents in Z. officinale.[62] Its anti-inflammatory activity has been attributed to its ability to reduce pro-inflammatory mediators and due to its antioxidant effect. It inhibits macrophages, neutrophils, monocytes, and leukocyte migration to the site of inflammation and thus can limit the extent of tissue damage.[68]

Shunthi is also used in Ayurvedic clinical practice as an anti-inflammatory and for pain management. Zingiberol and dried rhizome ethanol extract have exhibited anti-inflammatory and analgesic activities by acting on the central as well as peripheral pain pathways. They inhibit cyclooxygenase, a major enzyme involved in the formation of prostaglandins.[63]

Juice of Z. officinale is main Anupana (drug delivery agent/adjuvant) of important formulations used for the treatment of respiratory diseases. Shoagol and Gingerol have shown anti-inflammatory action on the generation of cytokines responsible for airway inflammation in ovalbumin-induced asthma mice models. They also suppress mucus production and bronchial hyperresponsiveness. It's constituent (6)- gingerol, (8)- gingerol, and (6)- shoagol has also exhibited bronchial relaxant properties.[69] Zinger and P. longum also exhibit bio-enhancing properties which are useful in reducing the dose as well as the duration of treatment.[70] KKR has also shown anti-histaminic activity[71] and has been found effective in curing Bronchial Asthma[72] and chronic bronchitis.[73]

 Discussion



KKR is a Kapha-Vata pacifying drug, mainly acting on aggravated Kapha. All eight varieties of KKR mentioned in Ayurvedic literature [Table 1], except variety eight are of Kapha-Vata pacifying nature. However, their composition is not uniform which could be due to the fact that, Ayurveda clinicians in ancient times were preparing medicines for their clinical practice on their own by using different combination of ingredients and owing to the Kapha pacifying nature of the drug they have named it so. Depending upon the severity of underlying pathology they might have used this formulation by adding more potent Kapha pacifying ingredients like Piper nigrum, Hartaal, Pushkarmoola, etc. Variety eight mentioned in [Table 1] is metalo-mineral formulation having Rasayana properties which can be used in clinical entities of Kapha origin. However, only variety 1 [Table 1] is cited in Ayurvedic Formulary of India[74] and is also commercially available in market today. Further researches related to different varieties may lead us to the relevance of explaining different varieties of KKR and their clinical significance can also be understood with the help of relevant studies in different diseases.

Ayurveda physiology revolves around Tridosha (three humors) i.e., Vata, Pitta and Kapha. Physiological limits of these humors is observed in the state of health, whereas derangement of any one or combination of these cause diseases. Pathological accumulation of Kapha has the tendency to initiate inflammation in the body.[75] Vitiated Kapha can cause obstruction in channels (Srotorodha) due to Ama (harmful undigested metabolic waste) which on getting chronic may initiate the inflammation at the site of involvement (Sthansanshraya).[76] KKR is Katu (Pungent), Tikta (bitter) rasa dominant formulation having Deepana, Pachana and Soshana properties. KKR, due to its Katu rasa[77] (pungent), Ushna, Tikshna[78] (penetrating), fast acting properties (Vyavayi-Vikasi),[79] has the ability to reduce the aggravated Kapha. Deepana,[80] Pachana,[80] and Shoshana actions of KKR improve the digestive power and help in clearing the obstructed channels (Srotorodha), thus relieving the Kapha associated inflammation. Condition of aggravated Kapha, Agnimandhya (Indigestion), and Ama (undigested food) are observed in Kasa, Amavata, Shotha, etc., and in present-day clinical entities like obstructive airway diseases, obesity, COVID-19 and other autoimmune disorders. Owing to its properties, KKR has been indicated mainly in Kaphaja disorders associated with Shotha (inflammation), Jwara (febrile conditions), Kasa (cough), Karnaroga (disease of ear), Mandagni (reduced metabolism), etc. Although very less scientific data is available related to KKR but evidences of its action as anti-histaminic, anti-asthma and anti-inflammatory activity have been reported in some studies.

The possible mode of action of KKR on the basis of its properties according to fundamentals of Ayurveda is depicted in [Figure 1]. The scientific literature regarding the ingredients of the formulation points towards its potential as an anti-inflammatory, analgesic, antipyretic, anti-allergic Ayurvedic formulation however the scientific data of KKR as a formulation is scarce which warrants the need and scope of exploring this drug in different experimental as well as clinical settings. Scope of pharmacological actions of KKR on the basis of properties of its ingredients have been listed in [Table 3].{Figure 1}{Table 3}

 Conclusion



Out of different varieties of KKR mentioned in Ayurvedic texts, commercially available KKR is of great therapeutic value for Kapha related acute and chronic inflammatory disorders. It has been used traditionally for the management of Kapha related diseases involving respiratory, digestive and musculoskeletal system. On the basis of the scientific evidences presented in this review, it can be hypothesized that KKR has a great scope in Ayurvedic clinical practice as an anti-inflammatory, analgesic, antipyretic, antispasmodic, and anti-allergic drug. However, there is a paucity of clinical data on this formulation. Further well-designed studies are required to explore its mode of action in present day clinical conditions.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1The Ayurvedic Formulary of India. Part 1. Rasayoga: 41. 2nd ed., Sec. 20. Delhi: Ministry of Health and Family Welfare Publications Civil Lines; 2003. p. 715.
2Hariprapannaji VP. Rasayoga Sagara. Dwitiyabhaga. Reprint. Ver. 226-237. Varanasi: Krishnadas Academy; 1998. p. 218.
3Ram Choubey PD. Brihad Rasaraj Sundar. 3rd ed. Varanasi: Chaukambha Orientalia; 2000. p. 292-3.
4Bhatt SG. Rasendra Sara Sangraha. Hindi Commentary by Dr. Indradev Tripathi. Ch. 2, Shloka 30-32. Varanasi: Chaukambha Orientalia; 2018. p. 343-4.
5Das SG. Bhaisajyaratnavali. Hindi Commentary by Shri Kaviraja Ambikadatta Shastri. Ch. 5, Shaloka 860, 861-863. Varanasi: Chaukambha Orientalia; 2018. p. 153.
6Sharma SS. Rasa Tarangini. Hindi Commentary by Dharmanand Shastri. 9th ed., Tarang 24, Shloka 106-109. Delhi: Motilal Banarsidas; 1973. p. 667.
7Dhundhuknath A. Rasendra Chintamani. Hindi Commentary by Sidhinandan Mishra. Ch. 9, Shloka 25-27. Varanasi: Chaukambha Orientalia; 2011.
8Vaidya SD. Rasa Chandanshu. Hindi Commentary by Pro. Ghyanendra Pandey. Paricheda 1. Varanasi: Chaukambha Krishndas Academy; 2010. p. 431-2.
9Bhatt SG. Rasendra Sara Sangraha. Hindi Commentary by Dr. Indradev Tripathi. Ch. 2, Shloka 1. Varanasi: Chaukambha Orientalia; 2018. p. 474.
10Ram Choubey PD. Brihad Rasaraj Sundar. 3rd ed. Varanasi: Chaukambha Orientalia; 2000. p. 428.
11Ram Choubey PD. Brihad Rasaraj Sundar. 3rd ed. Varanasi: Chaukambha Orientalia; 2000. p. 466.
12Das SG. Bhaisajyaratnavali. Hindi Commentary by Shri Kaviraja Ambikadatta Shastri. Parishista 2, Shaloka 12-13. Varanasi: Chaukambha Orientalia; 2018. p. 1239.
13Malik V. Law Relating to Drug and Cosmetics. 26th ed. Schedule E1. Lucknow: EBC Publishing Ltd.; 2018. p. 371.
14Sharma SS. Rasa Tarangini. Hindi Commentary by Dharmanand Shastri. 9th ed. Tarang 24, Shloka 19-22. Delhi: Motilal Banarsidas; 1973. p. 651.
15Sharma SS. Rasa Tarangini. Hindi Commentary by Dharmanand Shastri. 9th ed., Tarang 23, Shloka 77-78. Delhi: Motilal Banarsidas; 1973. p. 318.
16Sharma SS. Rasa Tarangini. Hindi Commentary by Dharmanand Shastri. 9th ed., Tarang 12. Shloka 6-7. Delhi: Motilal Banarsidas; 1973. p. 285-6.
17Sharma SS. Rasa Tarangini. Hindi Commentary by Dharmanand Shastri. 9th ed., Tarang 12, Shloka 17-19. Delhi: Motilal Banarsidas; 1973. p. 287-8.
18Sharma SS. Rasa Tarangini. Hindi Commentary by Dharmanand Shastri. 9th ed., Tarang 24, Shloka 24-25. Delhi: Motilal Banarsidas; 1973. p. 651-2.
19Bhatt SG. Rasendra Sara Sangraha. Hindi Commentary by Dr. Indradev Tripathi. Ch. 1, Shloka 381. Varanasi: Chaukambha Orientalia; 2018. p. 94.
20Ilanchezian R, Roshy Joseph C, Acharya R. Importance of media in Sodhana (Purification/Processing) of poisonous herbal drugs. Anc Sci Life 2010;30:54-7.
21Upadhyay M. Ayurveda Prakasha. Hindi Commentary by Gulrajsharma Mishra. Ch. 2., Shloka 263. Delhi: Chaukhambha Bharati Academy; 2016. p. 323.
22Sharma SS. Rasa Tarangini. Hindi Commentary by Dharmanand Shastri. 9th ed., Tarang 12, Shloka 6-11. Delhi: Motilal Banarsidas; 1973. p. 285-6.
23Sachin A, Baijnath PA, Sandip RB, Dipti AD, Rinku T. Pharmaceutical characterization & pharmacological consideration of Shankha Bhasma: An Ayurvedic formulation. IAMJ 2020;8:3239-45.
24Ranade M, Chary DL. Comparison of two purification products of Shankha Bhasma: A prospective randomized control trial. J Nat Sci Biol Med 2013;4:160-2.
25Savita S, Yadevendra Y, Usha S, Sushma R, Khemchand S. Characterization of conch shell nanoparticles (Shanka Bhasma) synthesized by the classical method. Sch Int J Tradit Complement Med 2020;3:90-9.
26Rasavagbhata A. Rasaratnasamucchaya. Vigyanbodhini Commentary of Datatreya Ananta Kulkarni. Reprint Edition. Ch. 10, Shloka 48-49. New Delhi: Mehechanda Lachamandas Publications; 2007.
27Anonymous. The Ayurvedic Formulary of India. Part 1. 2nd ed. Delhi, India: Department of Indian Systems of Medicine & Homoeopathy, Ministry of Health & Family Welfare, Government of India, The Controller of Publications; 2003. p. 245.
28Bano P, Kshetri DR, Shankar Rao K. Consequence and impact of Bhavana in Ayurvedic pharmaceutics – A conceptual study. Int J Ayu Pharm Chem 2019;10:307-16.
29Agnivesha A. Charaka Samhita of Agnivesha Revised by Charaka & Dridhbala, Vidyotini Hindi Commentary by Pt. Kashinath Shastri & Dr. Gorakhnath Chaturvedi, Kalpa Sthana 12/47. Varansi: Chaukhamba Bharati Academy; Reprint 2001.
30Sharma SS. Rasa Tarangini. Hindi Commentary by Dharmanand Shastri. 9th ed., Tarang 24, Shloka 26-28. Delhi: Motilal Banarsidas; 1973. p. 653.
31Sharma AP. Dravyagguna Vigyana. Ch. 2. Varanasi: Chaukhambha Bharati Academy; 2009. p. 107.
32Sharma SS. Rasa Tarangini. Hindi Commentary by Dharmanand Shastri. 9th ed., Tarang 24, Shloka 27. Delhi: Motilal Banarsidas; 1973. p. 287.
33Sharma SS. Rasa Tarangini. Hindi Commentary by Dharmanand Shastri. 9th ed., Tarang 24, Shloka 28-31. Delhi: Motilal Banarsidas; 1973. p. 653.
34Dubey N, Dubey N, Mehta R, Saluja A. Selective determination of aconitine in polyherbal oils containing aconitum chasmanthum using high-performance thin-layer chromatography. J AOAC Int 2009;92:1617-21.
35Deng J, Han J, Chen J, Zhang Y, Huang Q, Wang Y, et al. Comparison of analgesic activities of aconitine in different mice pain models. PLoS One 2021;16:e0249276.
36Anwar S, Ahmad B, Subhan M, Gul W, Nazar-ul-Islam. Biological and pharmacological properties of aconitum chasmanthum. J Biol Sci 2003;3:989-93.
37Zhan X, Zhang W, Sun T, Feng Y, Xi Y, Jiang Y, et al. Bulleyaconitine A effectively relieves allergic lung inflammation in a murine asthmatic model. Med Sci Monit 2019;25:1656-62.
38Hikino H, Takata H, Konno C. Anabolic principles of aconitum roots. J Ethnopharmacol 1983;7:277-86.
39Sharma SS. Rasa Tarangini. Hindi Commentary by Dharmanand Shastri. 9th ed., Tarang 23, Shloka 79-81. Delhi: Motilal Banarsidas; 1973. p. 319.
40Sharma SS. Rasa Tarangini. Hindi Commentary by Dharmanand Shastri. 9th ed., Tarang 23, Shloka 79. Delhi: Motilal Banarsidas; 1973. p. 319.
41Adhvaryu TR, Patel KS, Kori VK, Rajagopala S, Manjusha R. In-vitro antimicrobial activity of Tankan. EJBPS 2015;2:210-3.
42Sharma SS. Rasa Tarangini. Hindi Commentary by Dharmanand Shastri. 9th ed., Tarang 12, Shloka 20. Delhi: Motilal Banarsidas; 1973. p. 288.
43Ram Choubey PD. Brihad Rasaraj Sundar. 3rd ed. Varanasi: Chaukambha Orientalia; 2000. p. 172.
44Sharma SS. Rasa Tarangini. Hindi Commentary by Dharmanand Shastri. 9th ed., Tarang 12, Shloka 20-21. Delhi: Motilal Banarsidas; 1973. p. 288.
45Vivek T, Kiran V, Khemchand S. Therapeutic indications of Sankha Bhasma: A review. Int Res J Pharm 2017;8.
46Sharma AP. Dravyagguna Vigyana. Ch. 4. Varanasi: Chaukhambha Bharati Academy; 2009. p. 279.
47Bhavamisra S. Bhavprakash Nighantu. Commentary by Pro. Krishnachand Chunekar. Shloka 54. Varanasi: Chaukhambha Bharati Academy; 2020. p. 15.
48Bhavamisra S. Bhavprakash Nighantu. Commentary by Pro. Krishnachand Chunekar. Shloka 54-57. Varanasi: Chaukhambha Bharati Academy; 2020. p. 15.
49Khushbu C, Roshani S, Anar P, Carol M, Mayuree P. Phytochemichal and therapeutic potential of Piper longum Linn a review. Int J Res Ayurveda Pharm 2011;2:157-61.
50Aswar U, Shintre S, Chepurwar S, Aswar M. Antiallergic effect of piperine on ovalbumin induced allergic rhinitis in mice. Pharm Biol 2015;53:1358-66.
51Bhavamisra S. Bhavprakash Nighantu. Commentary by Pro. Krishnachand Chunekar. Shloka 49. Varanasi: Chaukhambha Bharati Academy; 2020. p. 14.
52Bhavamisra S. Bhavprakash Nighantu. Commentary by Pro. Krishnachand Chunekar. Shloka 50. Varanasi: Chaukhambha Bharati Academy; 2020. p. 14.
53Bhavamisra S. Bhavprakash Nighantu. Commentary by Pro. Krishnachand Chunekar. Shloka 51-52. Varanasi: Chaukhambha Bharati Academy; 2020. p. 14.
54Liu Y, Liu J, Zhang Y. Research progress on chemical constituents of Zingiber officinale Roscoe. Biomed Res Int 2019;2019:5370823.
55Ojewole JA. Analgesic, antiinflammatory and hypoglycaemic effects of ethanol extract of Zingiber officinale (Roscoe) Rhizomes (Zingiberaceae) in mice and rats. Phytother Res J 2006;20:764-72.
56Maurya SK, Seth A, Laloo D, Singh NK, Singh Gautam DN, Singh AK. Śodhana: An Ayurvedic process for detoxification and modification of therapeutic activities of poisonous medicinal plants. Anc Sci Life 2015;34:188-97.
57Dubey N, Dubey N, Mehta R, Saluja A. Selective determination of aconitine in polyherbal oils containing aconitum chasmanthum using high-performance thin-layer chromatography. J AOAC 2009;92:1617-21.
58Yu HH, Li M, Li YB, Lei BB, Yuan X, Xing XK, et al. Benzoylaconitine inhibits production of IL-6 and IL-8 via MAPK, Akt, NF-κB signaling in IL-1β-induced human synovial cells. Biol Pharm Bull 2020;43:334-9.
59Makino T, Kato K, Mizukami H. Processed aconite root prevents cold-stress-induced hypothermia and immuno-suppression in mice. Biol Pharm Bull 2009;32:1741-8.
60Shi Y, Liu L, Shao W, Wei T, Lin G. Microcalorimetry studies of the antimicrobial actions of Aconitum alkaloids. J Zhejiang Univ Sci B 2015;16:690-5.
61Sankpal J, Takalikar J. Comperehencive review of Tankana. JAIMS 2018;3:110-5.
62Sarkara PK, Prajapatib PK, Shuklab VJ, Ravishankar B. Evaluation of processed borax as antidote for aconite poisoning. J Ethnopharmacol 2017;205:138-46.
63Matyasova Z, Novotna B, Matulova M, Dolina J, Kroupa R, Láníková Z, et al. The relation of GERD, bronchial asthma and the upper respiratory tract. Vnitr Lek 2005;51:1341-50.
64Sur TK, Pandit S, Sen S, Bhattacharyya D, Debnath PK. Anti-ulcer activity of Shankha Bhasma (Calcined Conch Shell). Explor Anim Med Res 2013;3:48-56.
65Ghoshal S, Lakshmi V. Potential antiamoebic property of the roots of Piper longum Linn. Phytother Res 2002;16:689-91.
66Bikhari IA, Alhumayyd MS, Mahesar AL, Gilani AH. The analgesic and anticonvulsant effects of piperine in mice. J Physiol Pharmacol 2013;64:789-94.
67Zaveri M, Khandhar A, Patel S, Patel A. Review and research chemistery and pharmacology of Piper longum. Int J Pharm Sci Rev Res 2010;5:67-76.
68Ezzata SM, Ezzata MI, Okbaa MM, Menzec ET, Abdel-Naim AB. The hidden mechanism beyond ginger (Zingiber officinale Rosc.) potent in vivo and in vitro anti-inflammatory activity. J Ethnopaharmacol 2017;214:113-23.
69Kim E, Jang S, Yi JK, Kim H, Kwon HJ, Im H, et al. Ginger-derived compounds exert in vivo and in vitro anti-asthmatic effects by inhibiting the T-helper 2 cell-mediated allergic response. J Exp Ther Med 2022;23:49.
70Dudhatra GB, Mody SK, Awale MM, Patel HB, Modi CM, Kumar A, et al. A comprehensive review on pharmacotherapeutics of herbal bioenhancers. ScientificWorldJournal 2012;2012:637953.
71Joshi BB, Agnihotri P, Joshi A, Kulkarni AR. Anti-histaminic activity of Kaphaketu Rasa on Histamin induced bronhcospasm in guinea pigs. Int J New Technol Res 2016;2:73-4.
72Anuroopa HK, Gouda S, Diggavi M. Clinical efficacy of Kapha Ketu Rasa on Tamaka Swasa. J Ayurveda Integr Med Sci 2016;1:10-18. http://dx.doi.org/10.21760/jaims.v1i3.4411.
73Shilpa LS, Prashanth AS. A clinical study on the efficacy of Lavangadi Vati and Kaphaketu Rasa in the management of Kaphaja Kasa w.s.r to chronic bronchitis. J Ayurveda Integr Med Sci 2017;3:38-42.
74Anonymous. The Ayurvedic Formulary of India. Part 1. 2nd ed. Delhi, India: Department of Indian Systems of Medicine & Homoeopathy, Ministry of Health & Family Welfare, Government of India, The Controller of Publications; 2003. p. 669, 20:8.
75Agnivesha A. Sutra sthana. In: Charak Samhita. Hindi Commentary by Pt. Kasinath Sastri. Dr. Gorakhnath Chaturvedi. Part 1. Ch. 18/3. Varanasi: Chaukhambha Bharti Publication; 2013.
76Agnivesha A. Chikitsha sthana. In: Charak Samhita. Hindi Commentary by Pt. Kasinath Sastri. Dr. Gorakhnath Chaturvedi. Part. 1. Ch. 12/8. Varanasi: Chaukhambha Bharti Publication; 2013.
77Agnivesha A. Sutra sthana. In: Charak Samhita. Hindi Commentary by Pt. Kasinath Sastri. Dr. Gorakhnath Chaturvedi. Part 1. Ch. 26/4. Varanasi: Chaukhambha Bharti Publication; 2013.
78Acharya S. Purva khanda. In: Saranadhara Samhita. Dipika Hindi Commentary by Dr. Brahmanand Tripathi. Ch. 4/34. Varanasi: Chaukhambha Surbharti Prakashan; 2017.
79Acharya S. Purva khanda. In: Saranadhara Samhita. Dipika Hindi Commentary by Dr. Brahmanand Tripathi. Ch. 4/19-20. Varanasi: Chaukhambha Surbharti Prakashan; 2017.
80Acharya S. Purva khanda. In: Saranadhara Samhita. Dipika Hindi Commentary by Dr. Brahmanand Tripathi. Ch. 4/1. Varanasi: Chaukhambha Surbharti Prakashan; 2017.