Sanoon : A Specialized Dosage form for Dental Diseases in Traditional Persian Medicine

Oral diseases such as tooth loss, periodontal disease, dental caries, oral mucosal lesions and oropharyngeal cancers are chief communal health troubles in the worldwide. Dental caries, as a type of dental diseases, affects 60–90% of school-aged children and the common of adults in the majority industrialized countries. Sanoon is a pharmaceutical dosage form designed for treatment of oral cavity diseasesin the traditional Persian medicine that contains all kinds of mono component or multi component dosage forms with the ability of gum tonic that is finely powdered and used by sprinkling or rubbing it to the gum and dental surfaces. The purpose of the present study is to discuss about different formulation of sanoon dosage form in traditional medicine and find confirmation of their effectiveness in the treatment of dental .


INTRODUCTION
Oral diseases such as dental caries, periodontal disease, tooth loss, oral mucosal lesions and oropharyngeal cancers are major public health problems in the worldwide 1 .Despite low mortality of dental diseases, these disorders impact considerably on general health and quality of life.Teeth have important role in eating ability, primary digestion the food, speech, facial appearance and self confidence 2 .Dental caries, as a kind of dental diseases, affects 60-90% of school-aged children and the majority of adults in most industrialized countries 1 .Dental diseases impose economic burden to health care services.In some countries, the cost of treatment of dental caries is about 5 to 10 % of its total health budget 2 .
From ancient times the mankind has used materials found in nature as a remedy for his various diseases 3 .Afterwards the application of herbal, mineral and animal parts for making medicaments improved impressively in major traditional medicines: Chinese, Ayurveda and Persian [4][5] .Among these medical systems Traditional Persian Medicine (TPM) is one of the richest and oldest systems with various medical and pharmaceutical manuscripts [6][7] .Medieval Persian physicians and philosophers had described anatomy of the oral structure including mouth and tongue, tooth and gingiva and lips and related diseases and their treatments comprehensively 8 .A brief search in TPM literatures shows more than one hundred dosage forms, including some specialized ones like Sanoon [6][7] .Sanoon is a pharmaceutical dosage form designed for treatment of oral cavity diseases, particularly dental problems in TPM.It contains all kinds of mono component or multi component dosage forms with the ability of gum tonic that is finely powdered and used by sprinkling or rubbing it to the gum and dental surfaces 7 -10 .and alternative to conventional treatment.

METHOD
In this study, first we searched TPM books or pharmaceutical manuscripts of Persian scientist during 9th to 18th century AD such as Al-Abniyah an haqaiq al-adviyah, the Canon (Qanun-fi-tebb) , Makhzan-al-Aadvia, Tuhfatul-mumenin, main Qarabadin books of Traditional Persian Medicine for finding different dosage forms used in treatment of oral cavity diseases.In this preliminary study, we found out that sanoon is the most exclusive dosage forms in treatment of dental diseases.In the second part of this study, different types of sanoon were derived from Qarabadins books such as Canon of Medicine, Qarabadin Kabir, Qarabadin Shafahi, Qarabadin Ghaderi, Qarabadin Salehi, Tuhfatulmumenin.Qarabadins books are the main Traditional Persian pharmacological (TPP) text books that explain the preparation procedures, components and indications of compound drugs.All herbs used in these manuscripts with their indications and the processes of the preparation were extracted.Then the most repetitive plants were derived and listed.Afterwards we matched listed medicinal plant names with scientific names.At last these plants were screened in electronic databases including Google scholar, Scopus, PubMed to find possible evidence of their efficacy in the treatment of dental diseases in Modern medicine.The positive findings have been shown in the result section.Because medicinal plants used individually in a form of sanoon,in this part of the study, these herbs with their nature and indications were also derived from Makhzan-al-Aadvia, Al-Abniyah an haqaiq aladviyah, Tuhfatul-mumenin,Qanun fi-tebb, Al-Havi.

RESULT
Some types of oral dosage forms suggested in Traditional Persian Pharmacological text books for treatment of oral cavity disorders.The most common dosage forms included; oral fumigation(Bakhoor), gurgle(Gharghareh), mouthwash(Mazmazeh), tooth powder(Sanoon), oral dusting powder(Zaroor) and oral cooling(Barood).Sanoon, tooth powder, is a specific dosage form for dental diseases that rubbed on the teeth and gingiva.Sanoon was used in the form of powder.For preparing Sanoon, medicinal herbs that are used in this dosage form need to be dried and then usually grinded.According to the indications, the particles of the powder may be very fine or coarse.For example, in strengthener Sanoon, used plants must be grinded finely as possible.In return, particle of polisher Sanoon should be coarse and incomplete powdered.In this formulation, salt were parched and added to the powder.Brushing teeth is necessary before using Sanoon and stomach must be empty.For applying Sanoon,first wet the index finger with water, then put the finger into the tooth powder and rub it on the teeth and gum twice a day.During the usage of Sanoon, Keep the mouth open and rub it sequentially.Wait an hour until saliva be removed.Sanoon as a specific dosage form was administered for dental diseases like toothache and inflammation, loose teeth, discoloration of the teeth, aphthous, halitosis, carious teeth, oral sores, gingival sores and gingival health.The shelf life of Sanoon was 1-6 month.Table 1 shows medicinal plants were used individually in TPP as Sanoon with their scientific names, traditional names, nature, indications and parts used.Nature is the predominant quality 10 .Few formulations of Sanoon dosage forms that were used in TPP have been shown in Table 2. Formulation names, indications, ingredients, scientific names of plant drugs and preparation procedures are also indicated in Table 2.

Punica granatum
Equeous and ethanolic extracts of peel and seed of pomegranatum have demonstrated anticandidial effects and equeous extract has been more effective than ethanolic extract 13 .In another study it has been found that gel content pomegranatum seeds was as effective as chlorhexidine gel in prevention plaqe formation 14 and this can be linked to antibacterial and antiinflammatory activity of pome granatum 15 .Equeous and ethanolic extract of pomegranatum is also effective in decreasing the entiretime of recurrent aphtus and this effect likely connectes to phenolic component 16 .Mouthrinsing content chamomile and pomegranatum extract have an important role in gingival bleeding reduction 17 .

Terminalia chebula
The fruits of terminalia chebula are used in Iranian traditional oral dosage forms.studieshave demonstrated that mouthrinsing content terminalia chebula are effective in reduction microbial plaques, gingival inflammation and nutrilizing salivary PH 18 .Nayak et al approved a reduction of 35-48% at salivary streptococos mutans content forming units at 60 minute after rinsing with ethanolic extract of terminalia chebula and streptococos mutans counts were low up to 6 hours post rinsing.(Terminalia 19).The result of in vivo comparative study of Emblica officinalis and Terminalia chebula extract with chlorhexidine as an anti carries agent ,showed that the equeous herbal extract of Terminalia chebula and Emblica officinalis were more effective than chlorhexidine mouth wash,but with less time of action than chlorhexidine.(terminalia 20).

Tamarix gallica
The fruits of this tree are used in the formulation of mouth and teeth Iranian traditional dosage forms.One species of Tamarix (Tamarix boveana) has shown anti oxidant and free radical scavenging activity.(Tamarix 21).another species(tamarix aphylla)has antimicrobial potential of alkaloids and flavenoids extracted .(tamarix4).it has also shown anti inflammatory and analgesic effects(Tamarix 23 ).

Cyperus lungus
The rhizomes of Cyperus lungus are used in Iranian traditional medicine.Sesquiterpenoids extracted from a species of Cyperus(Cyperus rotundus)have shown anti hepatit B virus activity 24 .In an in vitro syudy methanolic extract of cyperus longus acts as analgesic substance 18 .

Peganum harmala
Peganum harmala seeds, known as espand in Persian, are used in several sanoon formulations with different purposes such as dental and gum restoration, oral cavity disinfection, teeth whitening and aphthous stomatitis treatment 26 .The alkaloids constitute main phytochemicals of Peganum harmala seeds, specially harmaline and harmine which are toxic in nature. 27The alkaloids are the origin of espand's antibacterial [28][29] antifungal, 20 antiparasidal 30 and insecticidal 27 activities.In one study the extract of its β-carboline alkaloids and chiefly harmine showed significant inhibitory effects against Proteus vulgaris, Bacillus subtilis and Candida albicans 28 In another study Staphylococcus aureus, Saccharomyces cerievisae and E. coli were much sensitive than other microorganisms to ethanolic extract of alkaloids. 29Ethyl acetate extract of espand seeds exhibited significant analgesic and antiinflammatory effects in compare with aspirin and diclofenac as standards in rats. 31The anti-oxidant properties of Peganum harmala seeds, extracted with ethanolic, hydro-alcoholic and aqueous solvents, were determined by DPPH free radical scavenging method. 32

Quercus Spp
Galls of Quercus spp.are kind of abnormal plant growth on leaves caused by certain insects.4] gall (Afes) is used in sanoon formulation for treatment of weak gums and aphthous stomatitis 7 because of its high tannin content nutgall shows antibacterial, antiviral, antifungal, larvicidal, antioxidant and hepatoprotective affects.9] Also the effectiveness of its ethanolic extract against a wide range of important bacteria has been studied. 30Quercus infectoria nutgall extracts and fractions could properly control the Culex pipiens larvae 31 and fabrics treated with oak gall extracts showed high anticandidal effects. 324] Besides, because of potent antioxidant and antiinflamatory effects of oak gall extracts they can be potentially used as hepatoprotective compounds [35][36] .

Piper nigrum L
Fruits of black pepper have been used in sanoon formulations to fortify gum and teeth and modulate toothache.(Ref)Alkaloids, glycosides, terpenoids, steroids, flavonoids, tannins and saponins are phytochemical contents of P. nigrum fruits.The ethanolic extract of P. nigrum fruits was examined against several common microorganisms which cause infections in oral cavity.The results demonstrated high antimicrobial effects of extract against Enterococcus faecalis, Lactobacillus acidophilus , Candida albicans and Candida tropicalis compared to chlorhexidine as standard. 37The anti-inflammatory properties of piperine, the main alkaloid of P. nigrum, investigated using carrageen-induced rat paw edema method.The prostaglandin release inhibition occured by administering 5 and 10 mg/kg of piperine to rats following by 1% of carrageenan. 38further studies showed antipyretic activity of piperin in rats. 39In addition, decreasing oxidative stress to the cells induced by a high-fat diet approved the anti-oxidant ability of piperine alkaloid. 40

Rhus coriaria
Rhus coriaria with common name of sumac has been used in TPM for treatment of gums weakness, aphthous stomatitis and toothache.(Ref)Many phytochemicals such as tannins, (iso)flavonoids, terpenoids, etc are reported in sumac fruits. 41The antimicrobial effects of Rhus coriaria water extract on food borne pathogens has been shown.Among these gram positive and gram negative bacterial strains, Bacillus species were most susceptible. 42In other study its water extract possessed antibacterial activity against five common oral bacteria including four streptococcus species and E. faecalis.Besides, the extract inhibited the formation of bacterial biofilm on orthodontic wire. 43Several phytochemicals showing antifungal activity are identified from ethanolic extract of sumac seeds. 44The phenolic content of sumac comprising anthocyanins and hydrolysable tannins causes it to show strong antioxidant activity. 45In one animal study rats with periodontitis were subjected to systemic administration of ethanolic extract of Rhus coriaria and reduction in alveolar bone loss by affecting receptor activator of nuclear factorkappa B ligand(RANKL)/ osteoprotegerin(OPG) balance, total oxidant status(TOS) and oxidative stress index(OSI) levels were reported. 46

Syzygium aromaticum (Eugeniacaryophyllata Thunb)
S. aromaticum with traditional name of gharanfol has been used in TPM for treatment of mental , respiratory, gastro intestinal,urinary tract disease, gums and dental weakness, halitosis.Saponins, tannins, phenols, cardiac glycoside, Anthracene, flavonoids and alkaloids are the main phytochemical compounds of Z. aromaticum flower.The antimicrobial effects of clove flower (Syzygium aromaticum) bud on dental pathogens has been shown in some studies [47][48] .Aqueous extract of Cloves flower (S. aromaticum) has antimicrobial effect on gram positive,gram negative bacteria and fungi including Staphylocococcus epidermis, Escherichia coli, Proteus mirabilis, Klebsiella pnuemoniae, Aspergillus niger, Candida albicans, Rhizopus oryzae [47][48][49] .In other study,its aqueous extract had antimicrobial activity against some standard strains of food-borne pathogen bacteria(S.aureus, S. typhimurium and E. coli and normal ûora S. epidermidis and L. Plantarum) 50 .Other study revealed that Eugenia essential oil possessed an excellent antibacterial activity against oral streptococci including the cariogenic bacteria as well as an excellent antifungal activity 51 .In an in vitro study, the antioxidant activity of water and ethanol extracts of clove (Eugenia carophyllata) buds and lavender (Lavandula stoechas L.) against various antioxidant systems has been shown and compered 52 .Based on data obtained from other in vitro study, clove essential oil and its two active principle(eugenol and eugenylacetate) may positively affect the dental erosion process of apple juice through distinct mechanisms.In this study, clove-oil-treated teeth showed decreased decalcification with respect to control 53 .In an in vivo study,Eugenia caryophyllata powder had anesthetic effect on a kind of fish (Huso Huso ) 54 .Anti-inflammatory effects of eugenol nanoemulsion were shown in an animal model study.In this study, O/W nanoemulsion of eugenol was used in rats for the evaluation of antiinflammatory effects as a topical delivery system 55.

Anacyclus pyrethrum
The root of Anacyclus Pyrethrum has therapeutic effects.The compounds of this plant are Pyrethrine, resinous, pelletonin, tannin, gum, potassium sulfate and carbonate, potassium chloride,calcium phosphate, and carbonate.This plant has been used for treatment of neurologic, respiratory,dental , periodontal and gingival diseases, Stuttering and toothache in TPM  . In anin vitro study, methanolic extract of Anacyclus Pyrethrum root produced little antibacterial effect against Staphylococcus aureus and Streptococcus sanguis 57 .

Rosa damascena
This plant has several compounds such as ter-penes, glycosides, flavonoids, and anthocyanins.The therapeutic uses of R. damascena in TPM include the treatment of abdominal, heart and lung diseases, menstrual bleeding, gums and dental weakness, halitosis , digestive problems the reduction of inflammation, coughing, thirst and wound healing  .. In some animal Model studies, analgesic and antiinflammatory effects of Rosa damascena hydroalcoholic extract has been shown [58][59] .The effectiveness of mouthwash containing. Rosa amascena extract in the treatment of 50 patiant suffering recurrent aphthous stomatitis(comparing to the placebo) has been shown in a randomized, double-blinded, placebo-controlled clinical trial study 60 .According to an in vitro study,the ethyl alcohol and acetone water extracts of R. damascene had antimicrobial effects against P.aueroginosa, C.albicans and E.coli.Among these microorganism, Pseudomonas.aueroginosawas the most susceptible 61 .

CONCLUSION
Dental diseases are one of the major public health problems in the worldwide.Traditional Medical literature reviews shows that oral and dental health are important because there are separate chapters in the main TPM textbook about oral and dental care.This paper showed that sanoon is a specific dosage forms for the treatment of dental diseases with different type of medicinal plants in TPM and the general survey of pharmacological effects of these medicinal plants ( Punica granatum, Terminalia chebula, Tamarix gallica, Cyperus lungus, Quercus Spp, Piper nigrum L, Peganum harmala, Syzygium aromaticum(Eugenia caryophyllata Thunb) ,Rhus coriaria, Anacyclus pyrethrum ,Rosa damascene ) used in the multiple formulations of sanoon mentioned that these plants have different medicinal properties like antibacterial, antiviral, antifungal, antioxidant, gingival inflammation activity anti-inflammatory, antipyretic, analgesic, prevention plaqe, gingival bleeding reduction, anti aphtus and reduction microbial plaques.There fore,modern investigations confirmed the efficacy of some plants which have been traditionally used in Sanoon.Based on the results of the present study and according to the pharmacological characteristics of Sanoon, this dosage form may be useful in the treatment of dental diseases due to easier,specific and efficient delivary of drugs to the oral cavity by lower systemic side effects.We suggest making different Sanoon with efficient medicinal herbs to improve oral and dental health and eventually public health in the community.