Application of herbal rectal suppositories beyond intestinal disorders in Persian medicine

Fatemeh Ebrahimi,Mohammadali Torbati,Zoleikha Khoshbakht,Laleh Khodaie,3＊

1Department of Phytopharmacy,School of Traditional Medicine,Tabriz University of Medical Sciences,Tabriz,Iran.

2Department of Food Science and Technology,Faculty of nutrition,Tabriz University of Medical Sciences,tabriz,Iran.

3Medical Philosophy and History Research Centre,Tabriz University of Medical Sciences,Tabriz,Iran.

Abstract

Background: Herbal rectal suppositories (RSs) were prescribed not only as a drug delivery system but also as a storing method in Persian medicine.According to the record of ancient references,RSs were clinically administered for diarrhea,constipation,colitis,ascites,dysentery and intestinal parasites,sciatic,lower back pain and joint aches,fever,kidney disease and as an aphrodisiac.Objectives:The aim of this study is to categorize and review different types of RSs,their main herbal components and to find evidence to elucidate their clinical administration.Results: In this study,7 manuscripts were studied to extract and categorize 11 types of herbal rectal suppositorie (RS) formulations,their ingredients and therapeutic indications.Furthermore,the Persian and scientific names of 43 herbs and their temperaments were mentioned in this study.Hence,ancient therapeutic indications of herbs used in RS formulations as well as their proven effects have been studied,which makes it possible to compare ancient and proven indications of medicinal plants used as ingredients of RSs.Conclusions:In modern medicine,RSs are mostly used for anorectic disorders.However in traditional Persian medicine,they were commonly used not only for anorectic and intestinal diseases,but also as an aphrodisiac,an agent for healing joint,sciatic pain and lumbago,an anti-fever,and an anti-ascites.Other implications of this study could be producing new insights of utilizing herbal RSs in diseases and disorders beyond anorectic and intestinal disorders.

Keywords:Rectal suppositories,Traditional medicine,Herbs,Medicinal plants,Persia

Background

According to description of the United States Pharmacopeia (USP37 NF32),suppositories are solid dosage forms in which one or more APIs (active pharmaceutical ingredients) are dispersed in a suitable base and molded or formed into suitable shapes for insertion into the rectum to provide both systemic and local effects.They usually melt,soften or dissolve at body temperature.Moreover,they are considered as an appropriate route of administration for drugs which are sensitive to pH,enzymes of stomach or to the environmental conditions.Also,the other reasons to substitute this administration route instead of oral one are: first,not to bypass portal circulation;second,risk of vomiting;third,their usage before surgery;and forth,in uncooperative patients (who makes swallowing impossible) [1,2].Suppository bases typically include cocoa butter,glycerinated gelatin,hydrogenated vegetable oils,mixtures of polyethylene glycols of various molecular weights,and fatty acid esters of polyethylene glycol.The suppository base can have a notable influence on the release of the APIs [3].The first use of RSs has been reported in Egyptian civilization (3150 B.C.) [1,4].Other documents showed its prevalence as a dosage form in traditional Chinese,Persian,and Ayurveda medicines[5-7].

In preceding decades,traditional systems of medicine have attained great popularity among the patients.Success of this system in the treatment of disease owes to consideration,particularly in cases for which conventional medicine has been insufficient [8].The principles of PM (Persian medicine) are based on quadratic elements;four elements that are described by natural philosophy areAir,Fire,Water,andEarth,each of which has its own specific quality,Airis hot and moist,Fireis hot and dry,Wateris cold and moist,andEarthis cold and dry.So,each object in the world has its own specific quality based on its dominant element(s).Beliefs in temperament existed not only in PM but also in many other traditional medical theories.Medicinal plants also adhere to this rule and have their own temperaments.Persian herbal pharmacopeias described the pharmacological effects of the herbs by the aid of their temperaments[9].

The origin of PM dated back before Islamic era(before 637 A.D.) and rose during 9thto 12thcenturies(called as Islamic Golden Age) and continued to the 18thcentury,and after this time it was replaced by the molecular (conventional) paradigm of medicine.During Islamic Golden Age,many manuscripts and books includingQarabadins(Persian pharmacopeias)and medical encyclopedias likeCanon of medicine(written by Avicenna in 1025 A.D.) were written[10-12].When searching these ancient references,we notice that suppositories were described as one of the important dosage forms,not only as a drug delivery system,but also as a method of storing components of medicines.In contrast with modern medicine,which describes suppositories as the rectal ones,in the mentioned manuscripts,suppositories consisted of a variety of types-nasal,vaginal,urethral,rectal (as drug delivery dosage forms) and ophthalmic (as a storing method)suppositories[7,13,14].

To the best of our knowledge,there was not any previous study about RSs,addressed in the Persian manuscripts.Also,due to the emphasis of mentioned manuscripts on the mentioned kind of dosage form,the aims of this study are: first,to review the indications and major herbal components of RSs;second,to investigate the differences between the modern suppositories and the RSs;and third,to search the major herbal components of RSs and their recently confirmed pharmacological evidence to reconcile the effects of the mentioned medicinal plants from the both modern and ancient point of view.

Experimental materials

In this study,some of the most important Persian manuscripts related to the pharmaceutical sciences which were defined asQarabadines,as well asTohfat-ol-MomeninandMakhzan-ol-Adviehwere used.Qarabadinesdiscussed types of the ancient dosage forms used by ancient physicians,their ingredients,procedures of their preparation,administered dosage,their indications and maintenance procedures as well as the best time of their usage and other related issues(Table 1) [13-18].Also,the Persian and scientific names,the used parts of the herbs as well as ancient and confirmed pharmacological evidence of the most used herbs which were frequently utilized in RSs formulations were derived from mentioned ancient manuscripts as well as from electronic databases including Science Direct,PubMed,Scopus and Google Scholar,from September 2016 to May 2017,to accord traditional indications and pharmacological effects of the herbs.The related articles were selected from the mentioned data bases by the aid of key words chosen from mesh: herb,medicinal plants as well as pharmacology and toxicology.To authenticate the scientific names of herbs,botanical textbooks including “A dictionary of Iranian plant names”,“Popular medicinal plants of Iran”and“Identification of medicinal and aromatic plants of Iran” were used[19-21].

Results

Manufacturing process of suppositories

Generally,in order to make applicable suppositories,the first step was making a fine powder from dry ingredients including dried herbs,the animal’s material and the minerals.Then,the ingredients were sieved to achieve suitable particle sizes.As an important point,gums and resins were dissolved in the appropriate solvents.After mixing all ingredients,a binder such as plant extracts,mucilage,honey,oils and tar were needed to stick all particles together.Finally,the products were severely dried and stored in the closed door glass containers to increase their shelf lives as much as possible.The RSs shelf life was claimed to be 5-6 years in cold and up to 1 year in hot regions,respectively[13].

The RSs were described as solid dosage forms in shapes of a little chestnut or a date kernel,which means they had variable sizes.In this case,the size of RSs was dependent on the purpose of their application.The RSs applied to the aphrodisiac purposes were medium sized.Small sized ones were applied in opium containing suppositories to reduce the risk of addiction by the patient.The large sized ones were used in colon targeted types to ensure their maximum efficacy on the site of action [13,14].This part is in contrast with the modern suppositories not exceeding 2-3 centimeters and usually weigh about 2 g each[3].

Herbal components and clinical indications

As mentioned before,the RSs were used both in the local and systemic diseases.Hemorrhoids,anorectic inflammation and lesions,anal fissures,and accidental bowel leakage were some of the important local conditions treated by this kind of dosage form.Also,they were notified as the most beneficial treatment in some of the lower abdominal diseases such as diarrhea,constipation,colitis,ascites,dysentery and intestinal parasites.Further prescription conditions of suppositories were disorders such as sciatic,lower back and joint aches and fever.They were used as an aphrodisiac as well [13-15].Furthermore,RSs were considered as the urgent dosage forms when colorectal system needed a little stimulation to unload its contents and to relieve the existing obstruction.Moreover,they were the first priority in patients who had low physical strength and could not tolerate using enema for the treatment based on PM perspective[13,14].

Table1 Related pharmaceutical manuscripts in Persian medicine

Table2 Some RSs formulations derived from Persian medicine

Ancient Persian pharmacists used several natural resources for their medicaments.To prepare RSs,natural resources including different parts of herbs,their gums and resins,mineral substances such as salt,borax,clay,ferrus sulfate,ferrus oxide and tar,as well as some parts of animal material for instance animal fats and castoreum were applied.However,in most cases,the active ingredients of rectal suppositorie (RS)were herbal components.

Some important and commonly used RSs formulations,their ingredients and indications are represented in Table 2.Moreover,in PM related manuscripts,the term active ingredient was known asAmood,meaning the most important component of the medicament,so other ingredients were mostly added as the excipients to stabilize,maintain and enhance the therapeutic effects of RSs and to deliver them to the xxx site of action [13,14].As it is apparent in Table 3,Amoodherbs in RS formulations are selected.Furthermore,ancient indications as well as confirmed effects ofAmoodherbs are shown in Table 3.

As it can be seen in Figure 1,the usage percent of herbs as RS ingredients for each ailment is shown;among the ailments cured by commonly used herbs to make RSs,joint,sciatic pains and lumbago,obstructive and flatulent colic and hemorrhoid are mostly treated by the listed herbs in Table 3,respectively.Besides,Figure 2 indicates the percentage of the temperaments of the herbs as RS ingredients.Among the commonly used herbs as RSs ingredients,mostly used medicinal plants have hot and dry temperaments (65.11%).The temperaments of the commonly used herbs are hot and dry (65.11%),cold and dry (23.25%),cold and moist(6.97%)and hot and moist(4.65%),successively.

Figure1 The usage percent of herbs as RS ingredients for each ailment

Figure2 The percent of the temperaments of the herbs as RS ingredients

Table3 Commonly used medicinal plants in RSs formulations with their Persian and scientific names,temperaments,used parts,ethno medicinal and approved indications

Irsa Hot and dry Rhizomes -14 Iris pseudoacorus L.Anti-hemorrhoids,relieving sciatic pains,anti-ascites,laxative effect 15 Afsantin Artemisia absinthium L.Hot and dry Root Anthelmintic effect,relieving obstructive colic,anti-hemorrhoids,healing joint pains Anti-inflammatory effect[59]anti-parasites[30]Anti-inflammatory,analgesic and anti-parasitic actions[34]17 Zenian(Nankhah)16 Shooniz Nigella sativa L.Hot and dry Seed Relieving flatulent colic,anti-hemorrhoids,healing joint pains,anthelmintic effect Trachyspermu m ammi(L.)Sprague Hot and dry Seed Relieving flatulent colic,anthelminthic and aphrodisiac effects,anti-ascites Antispasmodic activity,anti-inflammatory,nematicidal and anthelmintic activities[29]Laxative effect[65]19 Khiar chanbar 18 Sabr Aloe vera L.Hot and dry Latex Anthelmintic and laxative effects Cassia fistula L.Hot and wet Fruit Relieving obstructive colic,laxative effect Laxative effect[67]20 Golnar Punica granatum L.Cold and dry Flowers Anti-diarrhea -21 Kondor Boswellia sacra Flueck.Hot and dry Gum-resin Anti-dysentery,healing wound,anti-hemorrhoids and anti-diarrhea Analgesic effect[35]Anti-inflammation[36]23 Halileh Terminalia chebula L.22 Gall(Mazoo)Quercus spp.Cold and dry Fruit＆Gall Anti-hemorrhoids,anti-diarrhea Cold and dry Fruit Anti-ascites,anti-hemorrhoids,anti-diarrhea Anti-diarrheal and anti-inflammatory activities[37,38,50]Anti-diarrhea[51]25 Amoleh Phylantus emblica L.24 Balileh Terminalia bellerica L.Cold and dry Fruit Anti-diarrhea Cold and dry Fruit Aphrodisiac effect,anti-hemorrhoids,anti-diarrhea Anti-diarrhea,anti-dysentery,anti-inflammation[39]26 Khatmi Althaea officinalis L.Cold and wet Flowers Anti-fever,relieving obstructive colic,laxative effect-27 Za’faran Crocus sativus L.Hot and dry Flowers Anti-dysentery,relieving obstructive colic,healing wound Relaxant activity[49]28 Sorenjan Colchicum L.Hot and dry Root Relieving flatulent colic,sciatic＆joint pain Anti-arthritic activity[60]29 Heltit(Anghouze h)Ferula asa foetida L.Hot and dry Oleo-gum-res in Carminative,anthelmintic and aphrodisiac effects,anti-hemorrhoids Antispasmodic,anthelmintic,anti-ulcerogenic,and antiinflammatory activities[31]30 Banafsheh Viola odorata L.Cold and wet Aerial parts Anti-fever,relieving obstructive colic-

RSs,Rectal suppositories;-,Has not been approved.

Considerations

Due to the risk of addiction and impotence,opium containing drugs have been restricted to severe pains.So,when opium is as a component in the combination of a suppository,a string is placed inside it;thus,as soon as pain relieves,the patient pulls out the suppository [22].Applying the suppositories at bedtime and then lying on the back are advised to maximize their effects in the conditions like lower back,sciatic and joint aches.Laxative suppositories as well as the ones specified for colon diseases are mostly made in large sizes,about a middle finger size,for increasing drug delivery to its action site[22].Besides,it is noticed that frequent administration of RSs could lead to hemorrhoids[13].

Discussion

The rectum is an important route of drug administration;firstly,for the medicines which have severe gastrointestinal side effects;secondly,it is suitable for unconscious patients,old people and infants who have problem with swallowing medicines;thirdly,to prevent hepatic enzyme break down;fourthly,for direct and rapid action on the site;fifthly,to promote the evacuation of the bowel;sixthly,to apply as unit dosage forms of the drugs [23].On the other hand,studies have indicated some side effects of non-herbal suppositories;for instance,rectal ulcers associated with the use of non-steroid antiinflammatory drugs caused discontinuation of suppositories [24].Furthermore,some of the suppository bases caused severe mucosal damage accompanied with irritation,ulceration and inflammation [25].Hence,RSs might cause rectal stricture and stenosis [26].So,this study set out with the aim of introducing RSs,their indications in PM and their proved pharmacologic effects in modern medicine.

As it is shown in both Table 2 and 3,the most significant indications of RSs are anthelminthic,anti-hemorrhoid,aphrodisiac,wound healing,carminative,relieving obstructive and flatulent colic,anti-diarrheal,anti-dysentery,healing joint,sciatic pain,and lumbago,anti-fever,laxative and purgative.As it is illustrated in Table 3,commonly used medicinal plants in the RSs formulations,have been shown according to recent studies.

The herbs,mostly applied in RSs formulations as anthelmintic agents,are 8 out of 43,including the seeds and the fruits ofCitrullus colocynthisL.,the roots ofArtemisia absinthiumL.,the latex ofAloe veraL.,the seeds ofNigella sativaL.,the rhizomes ofZingiber officinaleRoscoe.,the gum ofEuphorbia helioscopiaL.,the seeds ofTrachyspermum ammi(L.)Sprague,the oleo-gum resin ofDorema ammoniacumD.Don and the oleo-gum-resin ofFerula asa foetidaL.Among the 8 mentioned medicinal plants,the anthelmintic effects of 3 of them including the latex ofAloe veraL.,the oleo gum resin ofDorema ammoniacumD.Don,and the fruits ofCitrullus colocynthisL.have not been ascertained yet[27-31].

As it is apparent in Table 3,the herbs which have been claimed to be utilized as ingredients of anti-hemorrhoidal RSs in PM manuscripts are 15 out of 43,covering the oleo-gum resin ofFerula gummosaBoiss.,the roots ofCyperus longusL.,the seeds ofLinum usitatissimumL.,the rhizomes ofIris pseudoacorusL.,the seeds ofNigella sativaL.,the gum resin ofBoswellia sacraFlueck.,the fruits and the gall ofQuercusspp.,the fruits ofTerminalia chebulaL.,the fruits ofPhylantus emblicaL.,the oleo-gum resin ofFerula asa foetidaL.,the latex ofPapaver somniferumL.,the fruits ofMyrtus communisL.,the seeds and the leaves ofPlantago majorL.,the fruits and the seeds ofCitrullus colocynthis(L.),Schrad.and the gum ofAcacia nilotica(L.) Delile.Some of which have been studied for their anti-inflammatory,analgesic and anti-ulcer activities[30-44],but the efficacy of them on hemorrhoidal conditions have not been investigated yet.

As it is presented in Table 3,3 out of 43 herbs have been traditionally used as carminative herbs in RS formulations,that including the seeds ofApium graveolenseL.,the oleo gum resin ofFerula asa foetidaL.and the oleo-gum-resin ofCommiphora mukulEngl.In this case,none of them have been investigated for the aforementioned effect.Hence,Table 3 presents the herbs which have been traditionally applied for relieving obstructive and flatulent colic (17 out of 43),containing the rhizomes ofZingiber officinaleRoscoe.,the gum ofEuphorbia helioscopiaL.,the seeds ofRicinus communisL.,the roots ofArtemisia absinthiumL.,the seeds ofNigella sativaL.,the seeds ofTrachyspermum ammi(L.)Sprague.,the fruits ofCassia fistulaL.,the flowers ofAlthaea officinalisL.,the flowers ofCrocus sativusL.,the roots ofColchicumL.,the aerial parts ofViola odorataL.,the fruits and the seeds ofCitrullus colocynthis(L.) Schrad.,the latex ofPapaver somniferumL.,the oleo-gum resin ofCommiphora myrrha(Nees) Engl.,the gum-resin ofFerula persicaWilld.,the leaves and the fruits ofSenna alexandrinaMill.,and the oleo-gum resin ofConvolvulus scammoniaL.Among the mentioned herbs,antispasmodic and relaxant activity of the rhizomes ofZingiber officinaleRoscoe.,the flowers ofCrocus sativusL.,and the seeds ofTrachyspermum ammi(L.)Sprague have been recently revealed[27,29,49].

As it is apparent in Table 3,the seeds ofApium graveolenseL.,the aerial parts ofMalva rotundifoliaL.,the seeds and the leaves ofTrigonella foenum-graecumL.,the seeds ofRicinus communisL.,the rhizomes ofIris pseudoacorusL.,the latex ofAloe veraL.,the fruits ofCassia fistulaL.,the flowers ofAlthaea officinalisL.,the fruits and the seeds ofCitrullus colocynthis(L.) Schrad.,the leaves and the fruits ofSenna alexandrinaMill.,the stem extract ofSacharrum officinarumL.and the oleo-gum resin ofConvolvulus scammoniaL.(12 out of 43) have been traditionally used as the laxative and purgative ingredients in the RS formulations.Likewise the mentioned effects of the latex ofAloe veraL.,the fruits ofCassia fistulaL.,the fruits and the seeds ofCitrullus colocynthis(L.) Schrad.,and the leaves and the fruits ofSenna alexandrinaMill.have been ascertained by the recent researches[43,65-67].

Also,as it is apparent in Table 3,9 out of 43 herbs have been traditionally applied as anti-diarrheal agents by ancient PM pharmacists,including the flowers ofPunica granatumL.,the gum resin ofBoswellia sacraFlueck.,the fruits and the galls ofquercusspp.,the fruits ofTerminalia chebulaL.,Terminalie bellericaL.,Phylantus emblicaL.,the latex ofPapaver somniferumL.,the fruits ofMyrtus communisL.,and the seeds and leaves ofPlantago majorL.The mentioned effect of the fruits ofTerminalia chebulaL.,Terminalie bellericaL.,Phylantus emblicaL.and the latex ofPapaver somniferumL.have been indicated by recent researches[39,50-52].Moreover,Table 3 presents that 8 out of 43 herbs have been traditionally applied as anti-dysentery agents in RSs formulations,covering the aerial parts ofMalva rotundifoliaL.,the flowers ofCrocus sativusL.,the gum-resin ofBoswellia sacraFlueck.,the latex ofPapaver somniferumL.,the seeds and the leaves ofPlantago majorL.,the gum- resin ofCommiphora myrrha(Nees) Engl.,the gum-resin ofFerula persicaWilld.,and the gum ofAcacia nilotica(L.) Delile.At this point,only anti-dysentery activity of the latex ofPapaver somniferumL.has been proved by recent investigations[53].

As it is shown in Table 3,the herbs claimed to be utilized as the ingredients of RSs with the aphrodisiac effects in the PM manuscripts are 8 out of 43,including the roots ofZingiber zerumbet(L.)smith,the roots ofCyperus longusL.,the seeds and the leaves ofTrigonella foenum-graecumL.,the seeds ofTrachyspermum ammi(L.) Sprague,the fruits ofPhylantus emblicaL.,the oleo gum resin ofFerula asa foetidaL.,the stem extract ofSacharrum officinarumL.,the roots ofAnacyclus pyrethrum(L.) Lag.However,among the 8 mentioned medicinal plants,two of them with anthelmintic effects have been indicated by recent researches,including the seeds and the leaves ofTrigonella foenum graecumL.as well as the roots ofAnacyclus pyrethrum(L.)Lag.[46-48].

As it is clear in Table 3,6 out of 43 herbs have been traditionally used as wound healing agents in RS formulations,covering the gum resin ofAstragalus fasciculifoliusBoiss.,Ferula gummosaBoiss.,Boswellia sacraFlueck.,the flowers ofCrocus sativusL.,the oleo- gum-resin ofCommiphora myrrha (Nees)Engl.and the gum ofAcacia nilotica (L.) Delile.Among the 6 herbs,only the gum resin ofAstragalusfasciculifoliusBoiss.and the gum ofAcacia nilotica(L.) Delile have been shown to have wound healing effects by recent researches[44,45].

Likewise,as it is apparent in Table 3,the medicinal plants that have been traditionally used as ingredients of RSs for healing joint,sciatic pain,and lumbago are 19 out of 43 herbs including the oleo-gum resin ofDorema ammoniacumD.Don.,the gum-resin ofFerula gummosaBoiss.,the rhizomes ofZingiber officinaleRoscoe.,the seeds ofApium graveolenseL.,the roots ofZingiber zerumbet(L.) smith.,the gum ofEuphorbia helioscopiaL.,the seeds and the leaves ofTrigonella foenum-graecumL.,the seeds ofRicinus communisL.andLinumusitatissimumL.,the rhizomes ofIris pseudoacorusL.,the roots ofArtemisia absinthiumL.,the seeds ofNigella sativaL.,the roots ofColchicumL.,the seeds and the fruits ofCitrullus colocynthis(L.) Schrad.,the rhizomes ofPolygonatum orientaleDesf.,the oleo gum resin ofCommiphora mukulEngl.,the gum resin ofFerula persicaWilld.,the oleo-gum resin ofConvolvulus scammoniaL.and the roots ofAnacyclus pyrethrum(L.) Lag.Among the mentioned herbs,the oleo-gum-resin ofDorema ammoniacumD.Don.,the gum ofEuphorbia helioscopiaL.,the rhizomes ofIris pseudoacorusL.,the fruits and seeds ofCitrullus colocynthis(L.) Schrad.,the rhizomes ofPolygonatum orientaleDesf.,the oleo-gum-resin ofConvolvulus scammoniaL.,and the roots ofAnacyclus pyrethrum(L.) Lag.have not been researched for their antiarthritic,analgesic or anti-inflammatory effects yet[27,32,33,35,54-64].

As it is indicated in Table 3,the barks ofCinnamomum camphoraL.,the flowers ofAlthaea officinalisL.and the aerial parts ofViola odorataL.(3 out of 43) have been traditionally applied as anti-fever ingredients in RS formulations.None of the aforesaid herbs have been examined for anti-fever activity by recent investigations.

As it is shown in Table 3,the seeds and the leaves ofTrigonella foenum-graecumL.,the seeds ofRicinus communisL.,the rhizomes ofIris pseudoacorusL.,the seeds ofTrachyspermum ammi(L.) Sprague,and the fruits ofTerminalia chebulaL.(5 out of 43)have been traditionally used as anti-ascites by ancient pharmacists.In this regard,the mentioned pharmacological activity of none of the aforesaid herbs has been proved yet.

These facts indicate that,the biological,pharmacological and medical effects of the aforesaid herbs not proven yet could create good fields for future researches.Even though,the RSs might have many effective properties,some factors for quality control of the RSs must be considered.Visual inspection,which could be an evidence of physical or chemical instability,surface texture or form,color and odor of this dosage form,disintegration,the uniformity of mass,and the uniformity of content must be thoroughly considered [3].Although,scientific studies have revealed that the herbs of varying potency,when combined with each other,may theoretically produce a greater result as compared to the individual use of the herb,in the mentioned polyherbal suppositories,drug interactions,side effects,contraindications and accurate dosage of the herbs must be comprehensively studied [68,69].On the whole,due to the anti-inflammatory effects of some ingredients of the RSs as well as unwanted side effects of them,the introduced RSs and the herbs might represent a new,promising and effective dosage forms for some diseases.Moreover,in modern medicine herbal suppositories are mostly used for anorectal disorders[70],but in PM manuscripts they were commonly used not only for anorectal and intestinal diseases but also as an aphrodisiac,an agent for healing joint,sciatic pain and lumbago,an anti-fever,and an anti-ascites.Other implications of this study could be the possibility of utilizing herbal RSs in diseases and disorders beyond anorectal and intestinal ones.

Conclusion

The current study shows the impact of RSs in PM during medieval era.It is important to clarify the history of pharmacy in this region.Also,our comparison between traditional knowledge and current findings indicates that these historical suggestions could be a good candidate to evaluate and perform further investigations for finding new drugs based on old experiences.In fact,herbal RSs have not been thoroughly investigated;indeed,this manuscript guides the interested researchers to continue their researches on this issue.Moreover,validation of the traditional claims and development of safe and effective botanical medicine seems to be necessary.