Herbal Medicinal Oils in Traditional Persian Medicine

Azadeh Hamedi1, Mohammad M. Zarshenas2, 3*, Maryam Sohrabpour2, Arman Zargaran4 1- Department of Pharmacognosy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran 2- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran 3- Department of Traditional Pharmacy, School of Pharmacy and Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran 4- Research Office for the History of Persian Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

Author for correspondence:

Mohammad M. Zarshenas Department of Traditional Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran Po Box: 71345-1583 Fax: +987112424126 E-mail: zarm@sums.ac.ir

Abstract Ethnopharmacological relevance Contribution of ethnopharmacological knowledge in Iran has a backbone of more than 3000 years of Persian medical experiences. Accordingly, considering traditional medical knowledge, based on historical manuscripts and evidences can help to find Iranian ethnopharmacological roots based on traditional concepts, more classified. Aim of the study One of the most famous herbal dosage forms aiming to achieve therapeutic purposes is in the form of herbal oils. Therefore current study has been carried out to bring together common oils, preparation methods and related therapeutic approaches mentioned during ancient and medieval Persia as well as related current pharmacological findings. Materials and Methods Information on of oils, preparation methods and related clinical administration was obtained from documents of ancient Persia and selected manuscripts of Persian medicine during 10 th to 18th century AD. Moreover, current investigations on these plants, regarding to their mentioned usage has been carried out by search on Pubmed, Scopus and Google scholar data bases. Results Using medicinal oils had a root dated back to ancient era in Iran. Furthermore, in medieval period, fifty one different simple medicinal plant oils of 31 families along with specific preparation method were found and identified from Persian pharmaceutical manuscripts. Flower, fruits and leaves were the most applied parts for preparation. In oil-bearing plant part, direct compression or distillation was applied; while others were subjected to vehicles

like sesame, olive or almond oils in order to prepare the related oil. Herbal oils were used via topical, oral, and even nasal routes as ways of clinical approaches. Meanwhile, most herbal oils were used for gastrointestinal, musculoskeletal and nervous system ailments. According to current investigations, most related proven effects of cited medicinal plants were anti inflammatory and analgesic properties. Conclusions As herbal oils are still applicable in traditional medicinal plants markets, preparation of medicinal oil and those applications can be considered as a simple formulation having desirable clinical approaches. Beside historical clarification, present study can provide a data list on clinical approaches of herbal oils and thus might lead to perform further clinical trials. Key words: Ancient Persia, Medieval Persia, Medicinal oil, Herbal oil

Introduction Since antiquity, one of the most ancient dosage forms of natural medicines was herbal formulation (Kasthuri, et al., 2010). Since the dawn of civilization As long as the civilization began, medical treatment employs induces the use of herbal, animal and mineral medicaments (Rezaeizadeh, et al, 2009), while the fundamental elements for remedies in traditional medical systems were medicinal herbs (Gurav, et al., 2011). These medicines have been applied either individually or in combination with other natural medicaments to prepare a practical form for treatment (Wadud, et al., 2007). Many traditional systems of medicine have presented herbs and those combinations in ancient formulations such as pills, powders, decocted, etc (Kiyohara, et al., 2004). Remained m Medical and pharmaceutical manuscripts authored by medieval Persian practitioners, which are not only an accumulation of all the existing information of other traditional medical systems, but also a great collection of their own ingenious studies (Khaleghi Ghadiri and Gorji, 2004), provided a vast field mentioning medicinal herbs formulations. In fact, pioneers of medieval practitioners namely Rhazes (865925 AD) and Avicenna (9801037 AD) created Persian golden epochs of medical sciences throughout the history. This golden age was from 8th to 17th centuries (West, 2008; Zargaran, et al., 2012a). Most of current ethnopharmacological knowledge in Iran was derived from historical manuscripts. A remained group of traditional practitioners who worked with medicinal plants and traditional concepts are Attars in Iran. Mostly it is a familiar job and the traditional knowledge was transferred cross generations to reach to current era (Yesilada, 2005; Naghibi, et al., 2005). In this regard, considering traditional knowledge of medicine, based on historical manuscripts and evidences can help to find Iranian ethno pharmacological roots based on traditional concepts, more classified. Manuscripts of medicine and pharmacy in Persia encompass various pharmaceutical dosage forms from medieval Persian medicine. One of the most famous forms of application,

aiming to achieve therapeutic purposes via topical or systemic route of administration is the series of medicinal oils, derived and prepared from plenty of herbal medicines (Avicenna, 1988; Heravi, 1765). Formulation and preparation of herbal oils were described under a subject namely Adhaan or Dohn. The subject can be found in a series of Persian traditional pharmaceutical manuscripts, Qarabadin. Qarabadin (pharmacopeia) books were defined as medical formularies texts on drug compounding, recipes and indications (Levey, 1966). Medicinal oils are ignored and not much investigated in contemporary medicine. However application of herbal oils as fixed or volatile, as well as herbal extracts for medical purposes dates back to long time ago(how long ago, give a time reference) and may have originated from ancient medical cultures namely Chinese, Indian and Egyptians (Shikov, et al., 2009). Herbal oil can easily be prepared and lead us to a new and practical opportunity to take the advantages for the therapeutic interventions. Therefore, current this study has been carried out to bring together common medicinal oils from traditional manuscripts of Persian medicine and also to derive the preparation methods considered for the dosage form along with reported therapeutic approaches.

Method of the survey The employed research method of this manuscript is primarily based on the investigation of the remaining manuscripts of Persian medicine during 10 th to 18th century AD, involving the medical and pharmaceutical text books of this era. In this survey, selected manuscripts are Canon of Medicine (Ibn sina, 1025), book of Qarabadin-e-azam (Azamkhan, 1853), Qarabadin-e-ghaderi (Arzani, 1714), Qarabadin-e-kabir (Aghili, 1772), Qarabadin-esalehi (Heravi, 1765) and Tohfat ol Moemenin (Tonekaboni, 2007). It should be noted that

these texts are defined as main references for PhD traditional pharmacy program in Iran (Program Book of Ph. D Degree in Traditional Persian Pharmacy, 2007). In these references, sections giving information about the medicinal oils, preparation and their administration were studied and the related data were collected, categorized and analyzed. A short study on some examples of using medicinal oils from ancient Persia was also done. The scientific names of the main components of medicinal oils were then authenticated by use of botanical textbooks such as "Dictionary of Medicinal Plants", "Popular Medicinal Plants of Iran", "Pharmacographia Indica" and "Indian Medicinal Plants" (Soltani, 2004; Amin, 2005; Dymook, et al., 1893; Khare, 2007). Also an additive research on current pharmacological effects of the mentioned medicinal herbs was carried out by search on Pubmed, Scopus and Google scholar data bases in order to find the relation between traditional knowledge and current findings. (not quite sure what you mean, are you researching the additives to these herb/oils etc, or is this extra research in this area?)

Results Some examples of using medicinal oils from Ancient Persia Medical and pharmaceutical uses of oils in Persia dates back to the ancient times. The Ancient Persia, as the history of Persia from the beginning up to 637AD (Wiesehfer, 2006) (entrance of Islam to Iran), encompasses three large dynasties, Achaemenid (550-330 BC), Parthian (247 BC-224 AD) and Sassanid (224-637AD). The recorded evidences from these empires are much more than the others (Zargaran, et al., 2012b). There is scant information about the medical and pharmaceutical evidences of these epochs. Of most

important documents, Bondahesh, a Sassanid Pahlavi manuscript, divided all plants to 11 th groups, where the oily herbs are of those, and denoted that each plant with oily seed is called oily plant (Dadegi, 2006). Examples of those herbs which are mentioned in the Bondahesh are Olive oil, (Olea europea L.), Castor oil (Ricinus communis L.) and Hemp (Cannabis sativa L.) (Dadegi, 2006; Biruni, 2004). Remains of the tools for oil extraction from oily seed, dating back to the Sassanid period, was found in Bishapur (Fig. 1), an ancient city located in the Fars province of Iran. Design on stone showing Stone carvings show a man with an oil jar in one hand and a towel in the other hand (Fig. 2) exists in Persepolis (Achaemenid capital, 500 BC). The figure may represent that oils were used widely in cosmetics the common use of oils in cosmetics, especially as demulcent agents after bath in ancient Persia (Mohagheghzadeh, et al., 2011). Animal oils were also used as the base for topical preparations. In the formulation of hand and face cream, related to 330 BC, saffron (Crocus sativus L.) and labdanum oil (Cistus ladanifer L.) where devised made to be to be applied (Gershevich, 2006). Extraction of oil soluble ingredients of medicinal plants in common oils was also reported from the ancient documents. Lily oil was an oily topical analgesic medicine derived by the above method (Adhami, 2007).

Medicinal oil, Preparation and Formulations from Medieval Persia Persian medieval scholars believed that the use of the medicinal oil dosage form is attributed to Pythagoras and Socrates and then transferred later to other scholars and physicians (Tonekaboni, 2007). In Persian medicine, practitioners used the term dohn or the plural

term adhaan in the description of medicinal oils and also meticulously explained the remarks details of preparation methods and application aspects of the formula. Generally, medicinal oil was a pharmaceutical dosage form divided to two main groups. In the first group the oil was directly extracted from the herb (via direct compression of the oil-bearing plant components or distillation of aromatic plants parts); and in the second one group possibly obtained indirectly by frequent extraction of a plants crude parts to prepare vegetable oils (Mikaili, et al., 2012). In this the latter group, soft and fragrant aerial parts such as flowers, leaves, or fleshy fruit were soaked in an oily vehicle (including, but not limited to, almond, sesame and olive oils using traditional methods of preparation) under then exposed to the sun exposure or external an heat source for several days (Avicenna, 1025; Heravi, 1765). The process was then repeated by replacing the spent parts with fresh ones until the base had taken on the color and smell of consumed herbal parts (Maceration in heated oil) (Heravi, 1765). The method is somewhat similar to what is called enfleurage today (Eltz, et al., 2007). However in the enfleurage process, animal fat is applied. The above process was often spoken as the method of Greek practitioners (Heravi, 1765). Today, the method is introduced as an oil infusion which is the result of steeping plant parts having desired chemical compounds or flavors in an oily solvent. On the other hand, rigid botanical parts such as roots and barks were decocted in water (aqueous extraction). In this type of oil preparation, the resulting extract was then boiled in an oily vehicle until the water disappeared and the oil remained (Boiling and evaporating method) (Tonekaboni, 2007). Persian practitioners applied special methods for plants spectacular products such as gums. Of those, the procedure for gummy derivatives such as Frankincense is also considerable. In that method, the gum was thoroughly dispensed in oil, in a glass container. Then the container was being hung suspended in the boiling water until the gum was fully dissolved in the oil (Boiling water bath) (Heravi, 1765). The oil of

aromatic gum resins like such as myrrh was said to be extracted via distillation method (Aghili, 1772). According to the above mentioned, around one hundred different medicinal oils prepared by the applied method of preparation and clinical administrations were derived from considered pharmaceutical manuscripts of Traditional Persian Medicine (TPM). Among those, common formulations of popular medicinal plants in the form of simple oil or oil form prepared by use of one certain herb are listed in Table 1 (Avicenna, 1024; Aghili 1772; Arzani, 1861; Heravi, 1765; Tonekaboni, 2007). Also, specific part (do you mean specifically), the

method of preparation and traditional literatures which the formulation was mentioned in, was added to the table. On the other hand, clinical uses of herbal oils and diseases which were remarked said to be curesd by are listed in table 2. Furthermore, research regarding to current medical knowledge and related to traditional application of oils and their active components is cited in Table 2. Beside simple oils, compound medicinal oils of herbal medicaments have also been noted in Persian pharmaceutical manuscripts. The aims of this devising (what does this mean??) can be within reduction of unwanted effect or potency, reinforcement of the efficacy, blocking out the unsavory taste, achieving the multiple therapeutic purposes or even modification of some undesirable effects related to the main ingredients, using accompanying medicinal herbs (Aghili, 1772).

Discussion and Conclusion

Medicinal oils (Adhaan) are of traditional dosage forms leaning on the experiences of medical practitioners for thousand years of antiquity. Herbal oils were prepared for various ailments in medieval epochs. Nowadays, many of these formulations are used as ethnomedical preparations by traditional practitioners in Iran (Mikaili, et al. 2012). In theAt first glance it seems that herbal medicinal oils are limited to essential oil and fixed oil, types , and are directly separated from the oil bearing parts of the plant. Definitely hHerbal oils are not limited to these two groups. The enfleurage method or oil infusion which is now still applicable can be introduced as a traditional preparation method for herbal oils. Actually In fact, oil infusion is can be a simple means of extracting oil soluble ingredients from plant parts. Out of 31 families, the most common medicinal plants used to prepare oils were belonged to Apiaceae (6 cases) and Asteraceae (5 cases) (Fig. 3). Also, the most parts used used parts of a plant to derive the oil were leafves, fruits and flowers (Fig. 4). Among two main groups of preparation methods, medicinal oils directly extracted from the herbs and indirectly by frequent extraction of plants crude parts in an oily vehicle, "distillation" for the first group and "maceration in heated oil" as well as "boiling and evaporating" for the second ones were most common methods (Fig. 5). These medicinal oils were used via topical, oral, and even nasal routes as way of clinical approachedeliverys. Administration of oils through these routes seems to be purposely and targeted for absorption into the body. Oils for gastrointestinal, respiratory, as well as urinary and reproductive interventions have being used orally, while nasal route was considered for those affecting on central nerves system. On the other hand, topical forms with the most application were generally subjected for nervousneuropathic, musculoskeletal and integumentary approaches.

The most mentioned usage for medicinal oils in traditional Persian medicine was for gastrointestinal (GI) system (Fig. 6). Some of traditional applications reported in Persian literatures may have corresponding to the current investigations. Apparently, analgesic and anti inflammatory effects were the most related pharmacological effect regarding in relation to the modern medicine (table 2). In this regard, mentioned oils and their usages in traditional Persian medicine can be good candidates for further investigations to find new herbal drugs. It should be noted that the only directly related pharmacological effect that can be matched to reported properties, is the application of essential oil. Hence application of clove oil and damask rose oil as an analgesic agent (Daniel et al., 2009; Hajhashemi et al., 2010), cinnamon oil with carminative and antimicrobial properties (Bouhdid et al., 2010; Harries et al., 1977) as well as the sedative effect of bitter orange (Carvalho-Freitas and Costa, 2002) can be a proof for traditional reported effects. On the other hand, clinical reports for traditional medicinal oils which were obtained via direct compression have similarities to those of modern medicine. In this regard, the antiinflammatory and neuroprotective effect of terebinth oil (Giner-Larza, et al., 2002; Orhan et al., 2012), antiepileptogenic and neuroprotective properties of black cumin oil (Kanter et al., 2006) as well as xanthine oxidase inhibitory of almond oil polyphenols (Chen and Blumberg, 2008) can be considerable evidences for traditional applications. Overall, for these types of herbal oil the medieval dosage form is the same as herbs metabolites. Oils made via infusion of desirable parts of the herb in an oil base (maceration in heated oil) were also popular for Persian practitioners. Apparently in this method, ingredients which may have affinity to the oil phase would be extracted into the oil. In this procedure, oil can act as a nonpolar solvent. This kind of oil is now considered in aromatherapy as it contains

concentrated herb essence (Johns, 2010). Medieval practitioners used this method for soft parts of medicinal plants. Sixteen cited oils in this study found to be prepared via this method. We did not find any clinical work on these types of oils, but on applied herbs relevant to the traditional reports. The procedure of oil infusion or macerated oil dosage form can be considered as a newly rediscovered field particularly for aromatherapy. As it mentioned in prior section, a group of traditional oils were also made up of boiling and evaporating method (Tonekaboni, 2007). It is an old and also invasive method for preparing such a dosage form. In this method, chemical constituents in the aqueous phase would be trapped in the oil phase after evaporation of aqueous phase. But obviously large parts of heat sensitive components extracted in aqueous phase may be decomposedbreakdown by overheating. As this method is not well accepted in current medicine, we found no credible evidence indicating the use of these types of dosage form in contemporary science. But for most constitutive herbs, relative effects were found according to current pharmacology. Regarding to Table 2, herbs of this oily dosage form possess pharmacological effects similar to the medieval reports. It should be remarked that current works were mostly done on ethanolic, methanolic and aqueous extracts. In this type the herbal hydrophilic ingredients were initially extracted in water before boiling along with the oily fraction. Comparing to the respective scientific data on ethanolic, methanolic and aqueous extracts of related plants (Table 2), it may come to mind that the medieval method can be considerable (do you mean viable methods?). For some cited oils with the preparation method of oil infusion (Maceration in heated oil), we derived clinical works which were done on aqueous extracted fractions. Aqueous fractions certainly have no similar constitutes comparing to those which would extracted in

oil infusion process. In contrast, organic extractions with nonpolar solvents may extract similar components. But regardless of the type of extraction, we preferred to gather those pharmacological effects related to the herbs of this category too. Despite of some advantages such as ease of administration or rapid absorption by massaging, herbal oils may be less applicable as a pharmaceutical dosage form in todays medicine. This fact may be due to the complications in industrial preparation and standardization of such a natural formulation. Furthermore development of new topical dosage forms such as semisolid formulations perhaps, is another reason for abandoning the oils. Although tracks of this form are observed in todays herbal therapy, much information on various medicinal herbs in oil formulas are still remained unstudied from traditional systems of medicine. A number of herbal oils directing certain clinical approaches can be found by searching through medical and pharmaceutical manuscripts of traditional systems. The oil form of natural medicaments can be considered as a simple dosage form having desirable clinical application. Beside historical clarification, presentthis study can provide a list of data on clinical remedies based on centuries of experience and thus might lead to perform further clinical trials.

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