REVIEW ARTICLE Basis for the Use of Substitutes for Medicinal Flora and Harmonization of Rational Use: A Critical Appraisal Based on “Kitab al-Abdal”: A Classical Compendium of Unani Medicine Narayanam Srikanth1, Bidhan Mahajon2, Mukesh Chincholikar3, Rakesh Narayanan4, Sridevi Venigalla5, Bhagwan S Sharma6, Shruti Khanduri7, Ashfaque Ahmad8

Abstract​ Background: Non-availability, indefinite identity, and adulteration of medicinal plants are key worrying areas in herbal or natural product-based industry/market. In this regard, the approach of ancient physicians does not seem to be hypothetical or haphazard. They had applied their mind and laid down certain principles and also evolved a methodology to identify and adopt substitutes. Abu Bakr Mohammad Ibn Zakariya al-Razi (Rhazes) (865–925 AD), a leading physician of Unani System of Medicine and Persian scholar of the early Islamic world compiled an exclusive monograph entitled as “Maqala Fi Abdal al-Adwiya al-Mustamala Fi al-Tibb wa al-Ilaj” popularly known as “Kitab al-Abdal” which is the first and foremost unique book on substitutes of Drugs in Unani Medicine. Aims and objective: This review aims to explore the rationality for substitution of the drugs mentioned by Rhazes in view of fundamental principles of Ayurveda. Materials and methods: All the 223 substitutes of 122 original drugs mentioned in the transcript of “Kitab al-Abdal” have been thoroughly scrutinized and categorized accordingly as per the adopted fixed criteria (i.e., Category I: Single substitutes for an original drug, Category II: Double substitutes for an original drug, Category III: Triple substitutes for an original drug, Category IV: Tetrad/four substitutes for an original drug). Any drugs or substitutes, which are not available in Ayurveda texts, were excluded from the analysis. Result and discussion: Analyzed data highlight that about 76% substitutions are having similarity with fundamentals of Ayurveda (Rasapañcaka) and Unani Medicine (Yaksaniyat-e-mizaj). Although the maximum substitutes mentioned in “Kitab al-Abdal” are not practiced or directly mentioned in the texts of Ayurveda as a source of substitute/alternative source of the particular original drug, but the rationales behind the substitution are often similar with the fundamental concept of Ayurveda (Rasapañcaka). The review may serve as ready references for the researcher, physicians, as well as industry of both Ayurveda and Unani system of medicine in order to find the appropriate substitution of a rare raw drug. This may also confess the scope of multidimensional research for harmonization of unique substitution and their inclusion in the National Pharmacopeia. Keywords: Ayurveda, Kitab al-Abadal, Pratinidhi dravya, Rhazes, Substitute, Unani. Journal of Drug Research in Ayurvedic Sciences (2020): 10.5005/jdras-10059-0102

Introduction​ 1–7Central Council for Research in Ayurvedic Sciences, New Delhi, India Eastern medical systems like Ayurveda and Unani Medicine have 8National Institute of Indian Medical Heritage, Central Council for been in existence for centuries. These systems are based on the Research in Ayurvedic Sciences, Hyderabad, Telangana, India holistic and vitalistic concept that the body constitutes of the five Corresponding Author: Bidhan Mahajon, Central Council for Research basic elements (Pañca Mahābhūta) like ether (Ākāśa), air (Vāyu), fire in Ayurvedic Sciences, New Delhi, India, Phone +91 8593038842, (Agni), water (Jala), and earth (Pṛthvī) and an imbalance in these e-mail: [email protected] elements causes diseases (Vyādhi). The concept of cleansing and How to cite this article: Srikanth N, Mahajon B, Chincholikar M, et al. purification of body through various holistic approaches and use Basis for the Use of Substitutes for Medicinal Flora and Harmonization of plant-based natural substances gradually made the popularity of Rational Use: A Critical Appraisal Based on “Kitab al-Abdal”: A of both age old Ayurveda and Unani system of medicine, which is Classical Compendium of Unani Medicine. J Drug Res Ayurvedic Sci 2020;5(2):121–131. also indicated by strong growth in the market for herbal or natural medicines and alternative health care.1,2 Recent data show share Source of support: Nil of the International trade of herbal products and the alternative Conflict of interest: None medicine market in a global economy has been increasing at a rapid rate of approximately 15% annually.3 Around 29,000 herbal substances used by more than 1,000 companies have annual substitutes wherever there was a shortage of raw materials to attain revenues exceeding US$60 billion. This trend is causing scarcity of similar end results in medical practice. One such great physician medicinal plants which has led to apprehension on how to fulfill the was Abu Bakr Mohammad Ibn Zakariya al-Razi, known in the West worldwide demand of these holistic medicines.4–9 The physicians as Rhazes. In the context of scarcity of raw materials, one of his of yore faced the same problems and had applied their mind, greatest contributions was “Maqala Fi Abdal al-Adwiya al-Mustamala laid down certain principles, and evolved methodology to adopt Fi al-Tibb wa al-llaj” popularly known as “Kitab al-Abdal”. This is

© The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons. org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Basis for the Use of Substitutes for Medicinal Flora and Harmonization of Rational Use the oldest existing book pertaining to Unani Medicine on unique substitutes for single or simple drugs. This review critically analyzed the novel substitutes mentioned in “Kitab al-Abdal” in light of Ayurveda fundamental principles.

Abu Bakr Mohammad Ibn Zakariya Al- Razi (865–925 AD) Abu Bakr Mohammad Ibn Zakariya al-Razi, known in the West as Rhazes, was a leading physician of Unani system of medicine. A comprehensive thinker, Razi made fundamental and enduring contributions to various fields, which he recorded in his more than 200 manuscripts. He is particularly remembered for numerous advances in medicine through his observations and discoveries. Influenced by Hippocrates and classical Greek medicine, Al Razi wrote numerous books on a range of medical and scientific subjects. The Al-Mansuri and Al-Hawi, his encyclopedic reviews of medicine, were translated into several languages and became a standard text for Islamic and European medical students for centuries. He was a keen experimenter and observer. As director of a large hospital in Baghdad and physician to the royal court, he engaged in medicine on a practical level and these experiences instil his writings. Ibn Ibn Abī Uṣaybiʿa (d. 1270 AD), has mentioned 220 books by Rhazes in Uyūn ul-Anbāʾ fī Ṭabaqāt al-Aṭibbā, (Urdu translation, CCRUM, New Delhi, 1990 AD, Vol. I, p. 576), Maulana Abdul Salam Nadvi in “Hukma-e-Islam” mentioned 29 important books by Rhazes on medicine which are still available in different libraries. These include Fig. 1: Image courtesy: Central Council for Research in Unani Medicine Al-Ḥāwī fī al-Tibb (Continens Liber), Bar us-Sa’ah (Cure in an Hour), (CCRUM), New Delhi Kitab fi al-Fasd wal-Hijamah (A book on cupping and venesection), Kitab al-Judari wal-Hasbah (A book on the Small-pox and Measles), Kitab al-Tibb al-Rūḥānī (A book on the spiritual medicine), Kitāb • Category I (Single substitute): for one original drug one al-Murshid (The Guide), Kitāb al-Mansuri fī al-Tib (The Book of substitute is mentioned. Medicine for Mansur), Kitāb al-Fakhir fi al-Tib (A proud book on • Category II (Double substitute): for one original drug two medicine), Kalam fil Furuq bain al-Amraz, Kitab At’ima al-Maraza (A substitutes are mentioned. book on the foods for the patients), Kitab Auja al-Mafasil (A book on • Category III (Triple substitute): for one original drug three the arthritis), Kitab al-Qulanj (A book on the colic), Manafi al-Aghzia substitutes are mentioned. wa Daf’e’ Mazarriha, etc., famous texts.10–13 • Category IV (Tetrad substitute): for one original drug four substitutes are mentioned. Kitab Al-Abdal Rationales behind the substitution were critically analyzed for One of the greatest contributions of Rhazes in the area of raw drugs each said categories based on fundamental principles of Unani as was “Maqala Fi Abdal al-Adwiya al-Mustamala Fi al-Tibb wa al-Ilaj” well as Ayurveda system. While critical analysis of data, following popularly known as “Kitab al-Abdal”. This book on substitutes of exclusion criteria were fixed: single drugs contains valuable information on the fundamental principles, uses, dosages, etc., of various substitutes for 122 single • The original drugs, the substitutes, and the drugs not having drugs, in a systematic and concise manner, some of which were correct botanical identities were excluded from the analysis. native to author’s own country, Iran. It is an authentic book which • All original drugs whose corresponding substitutes are not has been mentioned as important treaties in other books also. In practiced in Ayurveda were excluded from the analysis even September 1999, the Central Council for Research in Unani Medicine though the original drugs are practiced in Ayurveda. (CCRUM) translated and edited the manuscript with the help of four • Any substitute/s whose corresponding original drug is not manuscripts retrieved from the Asiatic society Kolkata, Rampur Raza practiced in Ayurveda was also excluded from the analysis even Library, Khuda Baksh Oriental Public Library, Patna, and a private though the substitute/s drug is/are practiced in Ayurveda. 14–18 collection at Aligarh (Fig. 1). Observation of Critical Analysis The present review shows maximum source of drugs mentioned in Materials and Methods​ “Kitab al-Abdal” are from plant origin only; while some of them are In this review, all the 122 original drugs (Pradhāna dravya) and of animal and mineral origin (Fig. 3). While analyzing each category, 223 substitutes (Pratinidhi dravya) mentioned in “Kitab al-Abdal” it was found that maximum 54 original drugs are mentioned in have been thoroughly scrutinized, comparing with their botanical Category I, where 44 drugs are found to be used in Ayurveda names and their descriptions in various classical texts, Nighaṇṭu and (Figs 2 and 4), while in Category II maximum 86 substitutes are published literature of Ayurveda.19,20 For systematic analysis of data, mentioned among these 49 substitutes are used in Ayurveda all the 122 drugs have been divided into four categories as follows: system (Fig. 2). Based on comparative analysis of the data in both

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Fig. 2: Core observation of critical analysis

I–IV) based on number of substitution mentioned for a single original drug (one Pradhāna dravya). Underlying principle of substitution in each category are publicized in Tables 1 to 6. Besides the drugs based on medicinal plants, drugs of animal and mineral origins are also described with their substitutes, some of them are also found to be used in Ayurveda

Discussion​ Unani Principles of Substitution (Abdal-e-Advia) Present review aimed to relate the fundamental principles and parameters were followed while substituting a drug with its other alternatives. Rhazes was very clear in his creation “Kitab al-Abdal” that a substitute (Badal) should only be used when the original drug meant for use is not available. It is clearly stated that no drug can be a complete substitute (Badal) for another drug in all aspects. Also, the drug having the similar property can be a Fig. 3: Distribution of drugs as per source of origin substitute for original drug for the very specific activity only. It is essential that the substituted drug should match the original drug Ayurveda (based on Rasapañcaka) and Unani system (based on in temperament (Yaksaniyat-e-Mizaj), for instances, if a drug is hot Yaksaniyat-e-mizaj), it was observed that in Category I, 17 drugs are and dry in first degree the substitute drug should also be hot and having similarity (Table 1) while 5 are having non-similarity (Table dry in first degree. It is equally important that physician should be 2); in Category II, 13 drugs are having similarity (Table 3) while 5 are clear for which action a given drug is replaced by another because having non-similarity (Table 4); similarly in Category III, 10 drugs are often one drug is substituted by another drug for a specific action having similarity (Table 5) and in Category IV, 5 drugs are having but its other action may be quite different (Tables 1 to 6). There are similarity with Ayurveda and Unani principles (Table 6). The review several instances where drug of one origin though different from also highlights some unique original drugs mentioned in “Kitab other drug of the other origin may replace it, such as animal origin al-Abadal” for which the proper identity is still not established in drug may be replaced by a plant origin drug, substitute for Jund Ayurveda as well as Unani System of Medicine (Tables 7 and 8). The Bedastar (castoreum) is Mirch Siyah (black pepper) half its weight substitutes of many of these drugs are found to be frequently used (Table 7). Similarly, substitute for a plant origin drug could be an in Ayurveda (Fig. 5). animal origin drug, for example, calcinated and washed shell of After critically analyzing the trends of substitution in “Kitab eggs is a substitute for Tarasis (Gummiferrum) (Table 7). One species al-Abdal”, all the drugs are categorized in four categories (Category of a drug could be a substitute for the drug of other species, for

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Fig. 4: Categorization of drugs based on number of substitutes mentioned in “Kitab al-Abdal” for a single original drug (one Pradhāna dravya)

Table 1: Category I: List of drugs mentioned with single substitute in “Kitab al-Abdal”. List of drugs where rationale behind substitutions is closely similar with Ayurveda principle (Rasapañcaka) though not directly mentioned as substitute in Ayurveda texts Annotation Drug name S. no. number (Unani) Botanical name Substitute(s) 1 001 Akitmakit Caesalpinia bonduc (L.) Roxb. (Ayurveda- Fawania (Paeonia officinalis L.) (Udsalība) Latākarañja) 2 006 Ushuq Dorema ammoniacum D.Don (Ayurveda- Wasakh al-Kaur (Artemisia maritima L.) (Ayurveda-Cauhāra) Uṣaka) 3 025 Jauz-Ut-Teeb Myristica fragrans Houtt. (Ayurveda- Sumbul (Valeriana officinalis L.) (Ayurveda-Tagara bheda) Jātīphala) 4 027 Jadwar Delphinium denudatum Wall. Ex Hook.f. & Zarambad (Curcuma zedoaria (Christm.) Roscoe) (Ayurveda- Thomson (Ayurveda-Nirviṣā) Karcūra) 5 046 Hast dahan Aquilaria agallocha Roxb. (Ayurveda- Qantooriyundaqiq (Luffa cylindrica (L.) M.Roem.) (Ayurveda- Aguru) Dhāmārgava) 6 056 Hamama Amomum aromaticum L. (Ayurveda- Waj (Acorus calamus L.) (Ayurveda-Vacā) Sthūla Elā bheda) 7 062 Huzuz Berberis lycium Royle. (Ayurveda- Feelzahraj (Berberis aristata DC.) (Ayurveda-Dāruharidrā) Dāruharidrā bheda) 8 075 Mur Commiphora myrrha (Nees) Eng. Filfilaswad (Piper nigrum L.) (Ayurveda-Marica) (Ayurveda-Bola) 9 082 Salikha Cinnamomum cassia Blume (Ayurveda- Darsini (Cinnamomum zeylanicum Blume) (Ayurveda-Tvak) Tvak bheda) 10 084 Sumbul Valeriana officinalis L. (Ayurveda-Tagara Lazkhir (Cymbopogon schoenanthus (L.) Spreng.) (Ayurveda- bheda) Rohiṣa bheda) 11 087 Suranjan Colchicum luteum Baker (Ayurveda- KorAzraq-Commiphora mukul (Hook. ex Stocks) (Ayurveda- Surañjāna) Guggulu) 12 093 Urooq Curcuma longa L. (Ayurveda-Haridrā) Mamiran (Coptis teeta Wall.) (Ayurveda-Mamīrā) 13 097 Sadawaran/ Cinnamomum zeylanicum Blume Kababa (Piper cubeba L.) (Ayurveda-Kaṅkola) Darsini (Ayurveda-Tvak) 14 103 Sibr Aloe vera (L.) Burm.f. (Ayurveda-Kumārī) Huzaz (Berberis aristata DC.) (Ayurveda-Dāruharidrā) 15 104 Qust Saussurea lappa Clarke (Ayurveda- Akarkara (Anacyclus pyrethrum DC.) (Ayurveda- Kuṣṭha) Ākārakarabha) 16 112 Shaharaj Fumaria parviflora L. (Ayurveda-Parpaṭa) Senna (Cassia angustifolia Vahl.) (Ayurveda-Svarṇapatrī) 17 113 Sheetraj Plumbago zeylanica L. (Ayurveda-Citraka) Fuw (Paeonia officinalis L.) (Udasalība) example, substitutes for Salikha (Cinnamomum cassia Blume) is purification; if margosa flowers are not available Margosa leaves Darsini (Cinnamomum zeylanicum Blume) (Table 1). Sometimes may be used. Hence, from the analysis, it is clear that fundamental part of the same plant serves as substitute, e.g., if a particular techniques for substitution of a drug in “Kitab al-Abadal” are based part of the plant or tree is not available another part of the same on Yaksaniyat-e-Mizaj (similarity in temperament) and Yaksaniyat- plant is used which is common practice as in the case of blood e-Afal (similarity in action) or both. Along with the drugs exhibit

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Table 2: Category I: List of drugs mentioned with single substitute in “Kitab al-Abdal”. List of drugs where rationale behind substitutions is not exactly similar with Ayurveda principle (Rasapañcaka) and also not mentioned as substitute in Ayurveda texts S. no. Annotation number Drug name (Unani) Botanical name Substitute(s) 1 010 Azad Darkhat Melia azedarach L. (Ayurveda- Waraq-e-Shahdanaj (Cannabis sativa L.) (Ayurveda- Mahānimba) Bhaṅgā) 2 013 Aftimoon Cuscuta reflexa Roxb. (Ayurveda- Turbud (Ipomoea turpethum L.) (Ayurveda-Trivṛt) Ākāśavallī) 3 040 Dohn al-ward Rosa damascena Herrm. Dohn al-Banafsaj (Viola odorata L.) (Ayurveda- (Ayurveda-Taruṇī) Banaphśā) 4 042 Dohn al-nilofar Nymphaea alba L. (Ayurveda- Dohn al-Banafsaj (Viola odorata L.) (Ayurveda- Kumuda) Banaphśā) 5 044 Haal Elettaria cardamomum Maton. Kababa (Piper cubeba L.) (Ayurveda-Kaṅkola) (Ayurveda-Elā)

Table 3: Category II: List of drugs mentioned with two substitutes in “Kitab al-Abdal”. List of drugs where rationale behind substitutions is closely similar with Ayurveda principle (Rasapañcaka) though not directly mentioned as substitute in Ayurveda texts Annotation Drug name S. no. number (Unani) Botanical name Substitute(s) 1 008 Abhal Juniperus communis L. (Ayurveda- 1. Saleekha (Cinnamomum cassia Blume) (Ayurveda-Tvak Hapuṣā bheda) 2. Jauz-us-Sarw (Cypress tree) 2 102 Foful Areca catechu L. (Ayurveda-Khadira) 1. Sandalahmar (Pterocarpus santalinus L.) (Ayurveda- Raktacandana) 2. Bazar al-Banj (Khurasāni Ajwāyan)-Hyoscyamus niger L. 3 029 Darsini Cinnamomum zeylanicum Blume 1. Salikha (Cinnamomum cassia Blume) (Ayurveda- (Ayurveda-Tvak) Tvak bheda) 2. Kababa (Piper cubeba L.) (Ayurveda-Kaṅkola) 4 035 Dohn al-khirwa Ricinus communis L. (Ayurveda-Eraṇḍa) 1. Dohn al-Fujul (Raphanus sativus L.) (Ayurveda-Mūlaka) 2. Zeit (Olea europaea L.) (Ayurveda-Jaituna) 5 041 Dibaq Viscum album L. (Ayurveda-Bandāka) 1. Kor (Commiphora mukul Hook.) (Ayurveda-Guggulu) 2. Abhal (Juniperus communis L.) (Ayurveda-Hapuṣā) 6 048 Waj Acorus calamus L. (Ayurveda-Vacā) 1. Kamoon (Cuminum cyminum L.) (Ayurveda-Jīraka) 2. Rewand (Rheum emodi Wall.) (Ayurveda-Revandcini) 7 058 Habb al-baan Moringa oleifera L. (Ayurveda-Śigru) 1. Qushoor-e-salikha (Cinnamomum cassia Blume) (Ayurveda-Tvak bheda) 2. Bisbasa (Myristica fragrans Houtt.) (Ayurveda-Jātīphala) 8 060 Habb al-neel Ipomoea hederacea Jacq. (Ayurveda- 1. Shahm-e-hazal (Citrullus colocynthis L.) (Ayurveda- Kṛṣṇabīja) Indravāruṇī) 2. Mahudana (Euphorbia neriifolia L.) (Ayurveda-Snuhī) 9 083 Sazij Hindi Cinnamomum tamala Nees and Eberm. 1. Talisfar (Taxus baccata L.) (Ayurveda- (Ayurveda-Tamālapatra) Sthauṇeyaka)* 2. Sumbul-ut-teeb (Valeriana officinalis L.) (Ayurveda- Tagara bheda) 10 109 Rewand Rheum emodi Wall. (Ayurveda- 1. Ward (Rosa damascena Herrm.) (Ayurveda- Amlaparṇī) Taruṇī)* 2. Sumbul-ut-teeb (Valeriana officinalis L.) (Ayurveda- Tagara bheda) 11 068 Karkarhan Spilanthes acmella (L.) (Ayurveda- 1. Akarkara (Anacyclus pyrethrum DC.) (Ayurveda- Marahaṭṭikā) Ākārakarabha) 2. Sheetraj (Plumbago zeylanica L.) (Ayurveda-Citraka) 12 071 Labani Liquidambar orientalis Miller. 1. JundBedastar-North American beaver (Castor (Ayurveda-Turuṣka) canadensis) and the European beaver (Castor fiber) 2. Dohn al-Yasmin (Jasminum grandiflorum L.) (Ayurveda- Jātī) 13 118 Khulanjan Alpinia officinarum Hance (Ayurveda- Qurfat al-qaranfal Kulañjana bheda) Substitute-i. Dar-chini (Cinnamomum zeylanicum Blume) (Ayurveda-Tvak) ii. Bazr al-Qareez (The correct identity not known) *Vīrya (potency) is mentioned in Ayurveda as Śīta

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Table 4: Category II: List of drugs mentioned with two substitutes in “Kitab al-Abdal”. List of drugs where rationale behind substitutions is not exactly similar with Ayurveda principle (Rasapañcaka) and also not mentioned as substitute in Ayurveda texts Annotation S. no. number Drug name (Unani) Botanical name Substitute(s) 1 014 Asabe-e-Sufr/Urooq al-Sufr Curcuma longa L. (Ayurveda-Haridrā) 1. HazarJashan (Bryonia alba L.) 2. So’ad (Cyperus rotundus L.) (Ayurveda-Mustā) 2 021 Parsiawashan Adiantum capillus-veneris L. 1. Banafsaj-Viola odorataL. (Ayurveda- (Ayurveda-Haṃsapādī bheda) Banaphśā) 2. Waraq al-Sosan (Iris ensata Thunb) (Ayurveda- Pārasika vacā) 3 032 Difla Nerium oleander L. (Ayurveda- 1. Asabi al-malik (Trigonella uncata Karavīra) Boiss) 2. Warq al-Teen (Ficus carica L.) (Ayurveda-Phalgu) 4 092 Ausaj Rumex vesicarius L. (Ayurveda- 1. Ushna (Parmelia perlata Ach.) (Ayurveda- Cukrikā) Śaileya) 2. Fofil (Areca catechu L.) (Ayurveda-Pūgaphala) 5 115 Tambol Piper betle L. (Ayurveda-Nāgavallī) 1. Aas 2. Warqqaranfal (Syzygium aromaticum L.) (Ayurveda-Lavaṅga)

Table 5: Category III: List of drugs mentioned with three substitutes in “Kitab al-Abdal”. List of drugs where rationale behind substitutions is closely similar with Ayurveda principle (Rasapañcaka) though not directly mentioned as substitute in Ayurveda texts Annotation Drug name S. no. number (Unani) Botanical name Substitute(s) 1 005 Asaroon Asarum europaeum L. (Ayurveda-Taga- 1. Qirdmana (Cardamine pratensis L.) ra pratinidhi) 2. Waj (Acorus calamus L.) (Ayurveda-Vacā) 3. Hamama (Amomum aromaticum L.) (Ayurveda-Sthūla Elā bheda) 2 015 Baladur Semecarpus anacardium L.f. (Ayurveda- 1. Bunduq-Corylusa vellana L. Bhallātaka) 2. Dohn al-Balsan. (Balsamodendrum opobalsamum (L.) Kunth ex DC. Syn. Commiphora gileadensis (L.) C.Chr.) 3. Naftabyaz 3 026 Jintiyana Gentiana lutea L. (Ayurveda- 1. Asal-e-KarafsRoomi (Apium graveolens L.) (Ayurveda-Ajamodā Trāyamāṇā bheda) bheda) 2. Asaroon (Asarum europaeum L.) (Ayurveda-Tagara pratinidhi) 3. QishrAsl al-Kibar (Capparis spinosa L.) (Ayurveda-Hiṃsrā) 4 052 Zafran Crocus sativus L. (Ayurveda-Kuṅkuma) 1. Qust (Saussurea lappa Clarke) (Ayurveda-Kuṣṭha) 2. Sumbul (Valeriana officinalis L.) (Ayurveda-Tagara bheda) 3. Qishr-e-salikha (Cinnamomum cassia Blume) (Ayurveda-Tvak bheda) 5 059 Habb al- Ricinus communis L. (Ayurveda-Eraṇḍa) 1. Lubb al-fistaq (Pistacia vera L.) (Ayurveda-Mukūlaka/abhisuka) khirwa 2. Habb al-fujul (Raphanus sativus L.) (Ayurveda-Mūlaka) 3. Habb al-sanobar (Pinus gerardiana Wall.) (Ayurveda-Nikocaka) 6 074 Lisan-ul- Holarrhena antidysenterica Wall. 1. Jauz (Juglans regia L.) (Ayurveda- asafeer (Ayurveda-Kuṭaja) Akṣoṭa) 2. Tudarisurkh (Cheiranthus cheiri L.) (Ayurveda-Todarī) 3. Bahmansurkh (Centaurea behen DC.) 7 079 Na’na Mentha piperita L. (Ayurveda-Pūtihā 1. Faudanjnahri (Mentha aquatic L.) (Ayurveda- bheda) Pūtihā bheda) 2. Qust (Saussurea lappa Clarke) (Ayurveda-Kuṣṭha) 3. Sumbul (Valeriana officinalis L.) (Ayurveda-Tagara bheda) Contd…

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Contd… Annotation Drug name S. no. number (Unani) Botanical name Substitute(s) 8 098 Fawaina Paeonia officinalis L. (Udsalība) 1. Qishr-e-Rumman (Punica granatum L.) (Ayurveda-Dāḍima) 2. Far al-samoor (Hide of Samoor) 3. Ezamaswaqat al-Ghazlaan (Calf bones of deer) 9 100 Filfilmoya Piper longum L. (Ayurveda-Pippalī) 1. Nar Mushk 2. Suranjan(Colchicum luteum Baker) (Ayurveda-Surañjāna) 3. Qurtum (Carthamus tinctorius L.) (Ayurveda-Kusumbha) 10 107 Qasab Bambusa arundinacea Willd. 1. Tomarhiroon (Phoenix dactylifera L.) (Ayurveda- (Ayurveda-Vaṃśa) Kharjūra) 2. Khatmi (Althaea officinalis L.) (Ayurveda-Khatmī) 3. Hindba (Cichorium intybus L.) (Ayurveda-Kāsanī)

Table 6: Category IV: List of drugs mentioned with four substitutes in “Kitab al-Abdal”. List of drugs where rationale behind substitutions closely similar with Ayurveda principle (Rasapañcaka) though not directly mentioned as substitute in Ayurveda texts Annotation Drug name S. no. number (Unani) Botanical name Substitute(s) 1 030 Dar sheeshan Myrica nagi Thunb. (Ayurveda-Kaṭphala) 1. Yanboot (Ceratonia siliqua L.) 2. Zaraswand (Aristolochia longa L.) 3. Asaroon (Asarum europaeum L.) (Ayurveda-Tagara pratinidhi) 4. Darunaj (Doronicum pardalianches L.) 2 050 Zaranbad Curcuma zedoaria (Christm.) Roscoe 1. Sheetraj (Plumbago zeylanica L.) (Ayurveda- (Ayurveda-Karcūra) Citraka) 2. Darunaj (Doronicum pardalianches L.) 3. Tarkhashqooqbarri (Cichorium intybus L.) (Ayurveda- Kāsanī) 4. Habb al-Utraj (Citrus medica L.) (Ayurveda-Bījapūraka) 3 055 Zarnab Flacourtia cataphracta Roxb. (Ayurveda- 1. Salikha (Cinnamomum cassia Blume) (Ayurveda- Prācīnāmalaka) Tvakbheda) 2. Kababa (Piper cubeba L.) (Ayurveda-Kaṅkola) 3. Darchini (Cinnamomum zeylanicum Blume) (Ayurveda- Tvak) 4. Jauz-ut-teeb (Myristica fragrans Houtt.) (Ayurveda- Jātīphala) 4 119 Khayarshambar Cassia fistula L. (Ayurveda-Āragvadha) 1. Turanjbeen (Alhagi maurorum Medik.) (Ayurveda- Yavāsa) 2. Lahm al-Zabib (Vitis vinifera L.) (Ayurveda-Drākṣā)) 3. Turbud (Ipomoea turpethum L.) (Ayurveda-Trivṛt) 4. Rub al-soos (Glycyrrhiza glabra L.) (Ayurveda- Yaṣṭimadhu) 5 122 Ghariqoon Dorema ammoniacum D.Don 1. Farbiyoon (Euphorbia resinfera Berg.) (Ayurveda-Uṣaka) 2. Turbud (Operculina turpethum (L.) Silva Manso Syn. Ipomoea turpethum (L.) R. Br.) (Ayurveda-Trivṛt) 3. Aftimoon (Cuscuta reflexa Roxb.) (Ayurveda-Ākāśavallī) 4. Khirbaq (Helleborus niger L.) similar therapeutic effects, Yaksaniyat-e-zahiri khususiyat (similarity classics, Acharya Vagbhata first time described the principles of in physical properties/organoleptic characters) is also considered substitution for a Yoga (compound formulation). While preparing as key for substitution (Abdal-e-Advia) in Unani Medicine.18,21,22 the compound formulation if a particular drug is not available, it should be substituted with another available drugs having the yurveda otion of ubstitution bhāva A N S (A similar Rasapañcaka or similar potency for desired actions.23 The pratinidhi dravya) ancient scholars of Ayurveda have emphasized the underlying In Ayurveda, the opinions regarding substitution are vividly found principle behind the substitution should be Guṇātmaka sāmya in the classical texts like Yogratnakar, Bhavprakash, etc. Among the (similarity in Rasapañcaka) and Karmātmaka sāmya (similarity in

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Table 7: Drugs of animal and mineral origin with their substitute Annotation S. no. number Drugs Scientific/English name Description 1 016 Milh-e-Hindi Sodium chloride Has been mentioned as substitute for Basfaij Polypodium vulgare L. 2 023 Jund Bedastar North American beaver (Castor canadensis) and Substitute for Jund Bedastar has been the European beaver (Castor fiber) mentioned as: 1. Filfil (Piper nigrum L.) (Ayurveda-Marica) 2. Waj (Acorus calamus L.) (Ayurveda-Vacā) 3 051 Zoofa-e-Ratab When the sheep herds graze around plants Mukh Saq al-Baqr (Bone marrow of cow) which secrets toxic milk, this milk is deposited in their loins in form of grime. Separated from their wool and cleaned, this is known as Zoofa- e-Ratab. 4 057 Hajar-e- This drug and its substitute belong to mineral According to Bolus Hajar-ul-Fizza is its substitute Faroiya group of drugs and their correct identity is not determined 5 067 Kohl Antimony sulphide Substitute for Kohl written as Nuhas Moharraq (Tamba) 6 072 Lulu Moti/Muktā/Pearl Sadaf resembles Lulu 7 095 Khar al- Pigeon’s feces The drugs 1. Khar al-Hamam (Pigeon’s feces) and 2. Hamam Hilteet (Ferula foetida Regel.) has been mentioned as substitute for Farbiyoon (Euphorbia resinfera Berg.) 8 098 Ezam aswaqat Calf bones of deer The drugs 1. Qishr-e-Rumman (Punica granatum al-Ghazlaan L.), 2. Far al-samoor (Hide of Samoor), and 3. Ezam aswaqat al-Ghazlaan (Calf bones of deer) told as the substitute for Fawaina (Paeonia officinalis L.)

Table 8: List of main drugs described in “Kitab al-Abdal” where the correct botanical or scientific names are not mentioned S. no. Annotation number Drug name (Unani) Description Substitute(s) 1 009 Andahman The botanical identity of this drug is not 1. Teen-e-armani established. It is used in diarrhea and 2. Qishr-e-Rumman-Punica granatum L. dysentery (Ayurveda-Dāḍima) 3. Sandal abyaz-Santalum album L. (Ayurveda-Candana) 2 012 Afzar The botanical identity of this drug is not 1. Kundur-Boswellia serrata Roxb. (Ayurveda- established. Used in mental confusion Śallakī) 2. Bazar al-Raziyanaj-Foeniculum vulgare Mill. (Ayurveda-Miśreyā) 3. Louz Hulu-Prunus amygdalus Batsch (Ayurveda-Vātāda) 3 034 Dawa-al-Qust This a compound formulation which includes Dawa al-Luk several other single drugs, used for liver and stomach diseases 4 077 Mu The botanical identity of this drug is not Zuzateeb (Myristica fragrans Houtt.) established. This is hot and dry, diuretic and (Ayurveda-Jātīphala) emmenagogue, digestive, commonly used in amenorrhea, flatulence and dysuria 5 085 Sarw English name given as Cyprus tree but exact 1. Qishr al-rumman (Qishr-e-Rumman-Punica botanical identity not found, fruits retentive granatumL.) (Ayurveda-Dāḍima) and anthelmintic heals ulcer, tones up liver, 2. Anzaroot (Astragalus sarcocolla Dymock) stomach, spleen. Beneficial in rectal and (Ayurveda-Rudantī bheda) uterine prolapse 6 088 Sadawaran/Saza- A gum found in Bun trees used as cold, 1. Feelzahraj(Berberis aristata DC.) (Ayurveda- waran dry, retentive, checks hemoptysis, useful in Dāruharidrā) menorrhagia and hair fall 2. Asal al-Qasb 7 110 Shabanak The botanical identity of this drug is not Marzanjosh (Origanum vulgare L.) established. This is a hot and dry, useful in infantile epilepsy, good for flatulence, heals wound

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potentially similar. This approach may lead to utility of sustitutes/ alternates sources supported by credible evidence.

Conclusion​ The key of substitution mentioned by Rhazes in “Kitab al-Abadal” are based on the temperament and desired pharmacological action of the drug, which is also established in Ayurveda classics in the term of “Rasapañcaka” (property) and Karma (action). Thus, the review concludes the conceptual key for substitution in both the ancient traditional systems was in a similar way. There are maximum similarities except little dissimilarity, in fundamental constituents of medicinal plants mentioned in Ayurveda and Unani Medicine. Therefore, such unique primitive factors for substitution can be considered for future area of scientific exploration and harmonization. The present review highlights that there is enough scope for research and unification in the area of substitution. The study may provide a greater scope for the physician to Fig. 5: Analysis of substitution trends in “Kitab al-Abdal” based on Ayurveda fundamental principle (Rasapañcaka) utilize herbs that are easily available, cost-effective, and most appropriate for the clinical condition and their inclusion in National Pharmacopeia. Karma, i.e., pharmacological actions) or both. This is also openly stated that a physician (Vaidya) can substitute a particular Dravya References from a yoga (compound formulations) based on the condition of patient (rogi bala), time/season (kāla), or condition of disease 1. Lloyd I. The energetics of health. Chapter 2 Traditional and complementary systems of medicine. Elsevier BV; 2009. pp. 13–27. (specificroga and rogī bala).24 The substitutes or alternative sources DOI: 10.1016/B978-0-443-06955-0.00002-6. of medicinal flora are also expressed on the basis of regional 2. Lloyd I. The changing perspectives of health and medicine from the availability [e.g., in Southern part of India, due to non-availability ancient era to the postmodern era. Energet Health 2009. 1–3. DOI: of the herb, Śaṅkhapuṣpī (Convolvulus pluricaulis Choisy) the 10.1016/b978-0-443-06955-0.00002-6. available plant Aparājitā (Clitoria ternatea L.) is used as the source 3. Newmaster SG, Grguric M, Shanmughanandhan M, et al. DNA of Śaṅkhapuṣpī while in North India Convolvulus pluricaulis Choisy. barcoding detects contamination and substitution in North American is considered as Śaṅkhapuṣpī]. Availability of the plant parts (e.g., herbal products. BMC Med 2013;11:222–235. in Daśamūla group of drugs stem barks of the plants are used in 4. Gutierrez S, Ang-Lee MK, Walker DJ, et al. Assessing subjective and psychomotor effects of the herbal medication valerian in healthy place of root). Seasonal availability [e.g., Rakta Punarnavā (Boerhavia volunteers. Pharmacol Biochem Behav 2004;78(1):57–64. DOI: diffusa L.) can be substituted for Śveta Punarnavā (Trianthema 10.1016/j.pbb.2004.02.011. 25 portulacastrum L.) in case of non-availability]. Likewise, different 5. McCabe S. Complementary herbal and alternative drugs in clinical techniques are adopted in Ayurveda system for the selection of practice. Perspect Psychiatr Care 2002;38(3):98–107. DOI: 10.1111/ Pratinidhi Dravya with rational basis.25–29 j.1744-6163.2002.tb00663.x. 6. De-Smet PAGM. Drug therapy: herbal remedies. N Engl J Med Scope for Harmonization of Substitution 2002;347(25):2046–2056. DOI: 10.1056/NEJMra020398. 7. Khan H. Medicinal plants in light of history: recognized therapeutic From the above discussion, it is very clear that the basis of modality. J Evid Based Complementary Altern Med 2014;19(3):216– substitution mentioned in “Kitab al-Abdal” are also found to be 219. DOI: 10.1177/2156587214533346. supported by various Ayurveda lexicographers (Nighaṇṭukāra). 8. Khan H, Rauf A. Medicinal plants: economic perspective and recent The analysis of review also revealed the same; although few of developments. World Appl Sci J 2014;31:1925–1929. them are found to be different as per Ayurveda principle (Fig. 2). 9. Olsen CS, Finn H. Market efficiency and benefit distribution in medicinal The scholars of both Unani and Ayurveda system of medicine plant markets: empirical evidence from South Asia. Int J Biodivers Sci have kept their views on substitution with the rationality in their Manag 2009;5(2):53–62. DOI: 10.1080/17451590903063129. 10. Rhazes. The spiritual physick of Rhazes. translated by AJ Arberry in own language but logically behind this seems to be quite similar. the Wisdom of the East Series. London: John Murray; 1950. If a substitute is suggested, it should be explained and specified 11. Rhazes (al-Razi). A treatise on the smallpox and measles. translated that particular drug to be a substitute for which disease and which by WA Greenhill. London: Sydenham Society, 1848; rpt. Baltimore: drug (similarity action and similarity in properties). The review Williams & Wilkins; 1939. highlights number of unique substitutes those are not directly 12. Savage-Smith E. Medicine Rashed R, ed. Encyclopedia of the History mentioned as substitutes in Ayurveda texts may be evaluated for of Arabic Science, vol. 3, London and New York: Routledge; 1996. p. bridging the gap. For harmonization of substitute’s, two types of 903–962. research could be undertaken. One is literary research concerning 13. Timkin O. A medieval translation of Rhazes’ clinical observations. Bull Hist Med 1942;12:102–117. fundamental properties of the drug may be compared with each 14. Hitti PK. History of the Arabs from the earliest times to the present. other after a survey of literature in both Ayurveda and Unani system 10th ed., London: Macmillan; 1977. p. 365. of medicine and the detail notes may be prepared in what respect 15. Robinson V. The story of medicine. New York: New Home Library; they are similar. The second is planned clinical research, so that the 1944. explored drugs could be clinically tried on patients and detailed 16. Porter D. Health, civilization, and the state: a history of public health clinical notes may be prepared about in which condition they are from ancient to modern times. New York: Routledge; 1999. p. 25.

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17. Singhal KC, Rahman SZ. Abdal al Advia (substitution of drugs) - a 23. Vagbhata. In: Ashtanga Hridaya, Sutrasthana 15/46. Pt. Hari Sadashiva challenge to Pharmacovigilance (chapter 3) Arunabha R, Kavita G. Shastri Paradakara., editor. Varanasi: Chaukhamba Surbharati Pharmacovigilance: an update. New Delhi: Vallabhbhai Patel Chest Prakashan; 2007. p. 240. Institute; 2004. pp. 22–44. 24. Agnivesha. In: Charaka, Dridhabala, Charakasamhita, Vimana 18. Anonymous, ‘Kitab al-Abadal’(Book on substitutites of Single drugs). Sthana, Rogabhishjitiya Vimanam, 8/149. Vaidya Jadavaji Trikamaji Abadal’ by Abu Bakr Mohammad Ibn Zakariya al-Razi (Rhazes) (865- Acharya., editor. Varanasi: Chaukhamba Surbharati Prakashan; 2005. 925 AD). Central Council for Research in Unani Medicine (CCRUM). p. 249. New Delhi: 1999. 25. Yogratnakara. Purvardha, Abhavavarga/38 Shetty M, Babu S, ed. 1st 19. Sharma SK, Chunekar KC. Medicinal plants used in Ayurveda. ed., Varanasi: Chowkhabha Sanskrit Series; 2005. p. 178. New Delhi: Rashtriya Ayurveda Vidyapeeth (National Academy of 26. Joshi PR, Patel BR, Shukla VJ. An overview of the causes of current Ayurveda) RAV Publications; 1998. practices in pratinidhi dravyas (substitution of drugs) in ayurveda 20. Chunekar KC, Pandey GS. Bhavprakash nighantu, Reprint edition, including newer techniques for their evaluation. Ayu 2012;33(4): Varansi: Chaukhambha Bharati Academy; 1998. 481–485. DOI: 10.4103/0974-8520.110518. 21. Rahman SZ, Khan RA, Latif A. Importance of Pharmacovigilance in 27. Mitra SK, Kannan R. A note on unintentional adulterations in Unani system of medicine. Indian J Pharmacol 2008;40(Suppl1):S17– Ayurvedic herbs. Ethnobotanical Leaflets 2007;11:11–15. S20. 28. Kokate CK, Purohit AP, Gokhele SB, Pharmacognosy. 39 edi., Nirali 22. Amr SS, Tbakhi A. Abu Bakr Muhammad Ibn Zakariya Al Razi (Rhazes): Prakashana, Pune, 2007; pp. 97-98. philosopher, physician and alchemist. Ann Saudi Med 2007;27(4): 29. Saraswathy A. Adulterants and substitutes in Ayurveda. Sachitra 305–307. DOI: 10.5144/0256-4947.2007.305. Ayurved 2001;54(1):63–66.

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