Avicenna's Canon of Medicine: a review of analgesics and anti-inflammatory substances.

Naturally occurring substances mentioned in medieval medical literatures currently have, and will continue to have, a crucial place in drug discovery. Avicenna was a Persian physician who is known as the most influential medical writers in the Middle ages. Avicenna`s Canon of Medicine, the most famous books in the history of medicine, presents a clear and organized summary of all the medical knowledge of the time, including a long list of drugs. Several hundred substances and receipts from different sources are mentioned for treatment of different illnesses in this book. The aim of the present study was to provide a descriptive review of all anti-inflammatory and analgesic drugs presented in this comprehensive encyclopedia of medicine. Data for this review were provided by searches of different sections of this book. Long lists of anti-inflammatory and analgesic substances used in the treatment of various diseases are provided. The efficacy of some of these drugs, such as opium, willow oil, curcuma, and garlic, was investigated by modern medicine; pointed to their potent anti-inflammatory and analgesic properties. This review will help further research into the clinical benefits of new drugs for treatment of inflammatory diseases and pain.

Introduction

Abu Ali al-Ḥusain Ebn Abdullah Ebn Sina (980 –1037 AD), known in the West as Avicenna, was a Persian physician who is known as the most influential medical writers in the medieval period. Between the thirteenth to the seventeenth centuries, Avicenna held a high place in Western medical studies, ranking as an acknowledged supremacy. His works had a crucial impact on the modern medicine and at some universities continued to be used for teaching up to the nineteenth century (Brentjes, 1980 ▶; Weisser, 2011 ▶).

About 100 dissertations were written by Avicenna. Among them, Qanoon-fel-teb (The Canon), originally written in the Arabic, is an immeasurable encyclopedia of medicine that represents all the medical sciences of the time. The Canon was translated into several languages, including Latin, Persian, English, Indian, Chinese, Hebrew, German, and French (Hakim Syed Zillur Rahman, 2004 ▶; Weisser, 2011 ▶). The Canon, translated first into Latin (Canon medicinae) by Gerard of Cremona, was the main medical textbook in several universities in Europe between 11th to 17th centuries (Moosavi, 2009 ▶). Sir William Osler, one of the four founding professors of Johns Hopkins Hospital, noted the Canon as "the most famous medical textbook ever written; a medical bible for a longer time than any other work" (Osler, 1972 ▶).

Avicenna (1988) ▶ divided the Canon into five books:

1. The first book describes different scope of medicine, the elements, the temperaments, the humors, physiological and anatomical principles, and general therapeutic procedures.

2. The second book explains several plant-, animal-, and mineral-derived drugs, in alphabetical order, with an essay on their properties and side-effects.

3. The third book describes an organ-based classification of the diagnosis and treatment of different diseases.

4. The fourth book defines general medical problems that affect the whole body, such as obesity, poisonous bites, and fever.

5. The fifth book contains numerous compound receipts.

Eight hundred drugs and 650 recipes of different compounds from various sources are listed in the Canon, with extensive comments on the effectiveness of each drug or recipe (Danielle, 2008 ▶). Several clinical and experimental studies support the use of some traditional Persian medicines noted by Avicenna in the Canon for the treatment of different diseases. However, most medicinal substances prescribed by Avicenna remain largely unexamined (Gorji, 2003 ▶). The anti-inflammatory and analgesic medicaments are a heterogeneous group of substances, which share definite remedial actions and side effects. The search for new pharmacologically active anti-inflammatory and analgesic drugs offered by medieval medical literatures has led to the discovery of some clinically useful drugs. These compounds, during the last two centuries, have played a crucial role as effective remedies of various human diseases as well as in understanding of basic pathophysiology of some diseases (Gorji and Khaleghi Ghadiri, 2001 ▶; Gorji and Khaleghi Ghadiri, 2002 ▶; Khaleghi Ghadiri and Gorji, 2004 ▶; Vakili and Gorji, 2007 ▶; Bayan et al., 2013 ▶). Despite progress in the development of therapy in recent years, effective and potent anti-inflammatory and analgesic drugs are still required for the treatment of different diseases. The aim of the present study was to provide a descriptive review of all anti-inflammatory and analgesic drugs noted in the Canon of Avicenna. Data for this review were provided by searches of different sections of this book translated in Persian (Avicenna, 1988 ▶). It is hoped that this manuscript will help further research into the clinical benefits of these compounds for treatment of inflammatory diseases.

Anti-inflammatory and analgesic drugs

Avicenna (1988) ▶ describes the signs and symptoms (pain, swelling, redness, fever, impaired functions, etc.) of different inflammatory diseases (such as pneumonia, rhinitis, otitis, dermatitis, etc.) and their treatment with several substances with different modes of action. These drugs were advised to use as prophylactic or therapeutic. Many of these drugs were prescribed for different inflammatory disease, although some of those were advised for a certain disorder. The strategies for treatment of pain and inflammation were divided into the measures of acute and chronic diseases.

Furthermore, these drugs were classified for treatment of mild, moderate, or severe conditions in each disorder. It is also noted that some of these drugs in certain conditions act as anti-inflammatory of analgesic drugs, in other condition my provoke pain or inflammation. The anti-inflammatory and analgesic drugs listed in the Canon include plants, animal products, and minerals. Avicenna emphasized the importance of the dose and the route of administration and defined a schedule for drug application. Drugs were also taken via skin, oral, nasal, or rectal routes as well as by inhalation (Table).

Table

Anti-inflammatory and analgesic substances used in medieval Persia by Avicenna and noted in The Canon. AI (Anti-inflammatory); AG (Analgesic).

Latin Name	Common Name	Effect	Administratin	Diseases
Acorus calamus	Sweet flag	AGAI	OralLocally	SciaticaHeadacheToothachePneumopleuritisMastitisFever
Acorus calamus	Sweet flag	AG	OralLocally	Muscle painSciaticaColic Uterine painFeverPneumonia
Adiantum capillus-veneris	Maidenhair	AI	Locally	General edema
Allium ascalonicum	Shallot	AGAI	OralLocally	HeadacheArthritisOtitis
Allium sativum	Garlic	AGAI	OralLocally	Acute Inflammation Chronic and Malignant WoundsArthritis and GoutSciaticaCommon coldHeadacheEaracheSevere Eye PainAcute Cough Lung disease with hematemesisGastroenteritisLiver diseases
Almond oleum	Almond oil	AGAI	Locally	Rhinitis
Alsidium Helminthocorton	Corsican	AG	OralLocally	Intestinal ulcer Uterine and cervical pain
Althaea officinalis	Marshmallow	AGAI	LocallyOral	DermatitisArthralgia SciaticaEaracheToothacheChronic fever
Anacyclus pyrethrum	Pellitory	AG	OralLocally	Dermatitis Tongue swellingHeadacheEncephalitisEaracheToothache
Anemon cronaria	Anemone	AG	OralLocally	ArthritisNeuralgia
Pimpinella anisum	Aniseed	AGAI	OralLocally	EnteritisOrchitisSores in noseTooth pain
Anethum graveolens	Dill	AGAI	OralLocally	Chronic skin woundsArthritis and Gout
Apium graveolens	Wild celery	AGAI	LocallyOral	OrchitisInflammation of the oral CavityHeadache
Aquilaria malaccensis	Aloes	AGAI	OralLocally	Toothache
Artemisia absinthium	wormwood	AGAI	OralLocallyInhalation	OtitisChronic ophthalmitisChronic fever
Artopa belladona	Nightshade	AG	Locally	General painGastroenteritis
Asarum europaeum	Cabaret	AGAI	OralLocally	Sciatica Chronic ophthalmitisFever
Asparagus officinalis	Asparagus	AGAI	OralLocally	Abdominal pain
Asphodelus ramosus	Asphodel	AGAI	Locally	DermatitisPurulent otitis Gastritis
Avenae fatua	Oat	AI	OralLocally	Scalp inflammationEczemaEarache
Bambagia	Cotton plant	AGAI	OralLocally	EaracheSore ThroatCoughChest painToothache
Berberis vulgaris	Barberry	AIAG	Locally	Arthritis
Boswellia serrata	Frankincense	AIAG	OralLocally	Scalp inflammation ArthritisGout
Brassica oleracea	Cabbage	AIAG	OralLocally	Dermatitis such as herpesToothacheCoughBronchitis and shortness of BreathChest infectionsEye painDropsy and edemaAnal fissure
Brassica Spp.	Mustard	AG	Locally	Joint and muscle pain
Cannabis Sativa	Hemp	AI	Locally	OphthalmitisGeneral edema Infectious woundsGoutUterine pain
Carthamus Tinctorius	Safflower	AG	OralLocally	Muscle pain Headache Toothache and dental caries Chronic earacheChronic cough and bronchitis Purulent wounds
Carum carvi	Caraway	AIAG	OralLocally	Edema ArthralgiaMuscle discomfortArthralgiaScalp inflammation
Cheese	-	AG	OralLocally	PleuritisGastrointestinal discomfort
Cassia fistula	Golden shower	AIAG	OralLocally	General edema EaracheScalp inflammationJoint and bone painEye wounds Gastritis
Castor oleum	Castor oil	AI	OralLocally	Scalp inflammationChronic headache
Centaurea cyanus	Cornflo-wer	AIAG	Oral	Colic
Chrysanthemum parthenium	Feverfew	AG	Locally	Sciatica
Cicer arietinum	Chana	AIAG	Locally	Eye swellingHoarsenessBronchitis and coughStomach pain and gastric ulcerUterine pain and infectionIntestinal ulcerGastroenteritisColic
Cichorium intybus	Chicory	AIAG	OralLocally	Gum diseaseGastritisHeadachesEaracheEye swellingIntestinal ulcer
Cicuta maculata	Hemlock	AIAG	OralLocally	Malignant and purulent WoundsRhinitisChronic headacheToothacheOphthalmitis
Cocos nucifera	Coconut	AIAG	OralLocally	Neck painGastrointestinal ulcerUterine and gum discomfort
Colchicum autumnale	Meadow saffron	AIAG	OralLocally	Purulent dermatitis Burn Chronic woundsSciaticaArthralgiaToothacheHeadache
Commiphera myrrha	Myrrh	AIAG	Locally	Arthralgia
Commiphora gileadensis	Balsam of mecca	AIAG	OralLocallyInhalation	PleuritisHeadacheGastritisBronchitisKidney painHemorrhoid
Convolvulus scammonia	scammony	AIAG	Oral	Gastroenteritis
Coriandrum sativum	Coriander	AIAG	OralLocally	Muscle weakness ArtralgiaHeadachePurulent otitisBleeding gums and gingivitisGastroenteritisHemorrhoid
Corylus aveilana	Common hazel	AIAG	OralLocally	General edemaHerpesAccidental injuriesMuscle painHiccupsGastritisChronic fever
Crocus sativus	Saffron	AIAG	OralLocally	Acute edema and abscessBone fracturesJoint and tendon painHeadacheOral diseases Diphtheria
Cucurbita pepo	Pumpkin	AIAG	Oral	Genitourinary pain
Cupressus sempervirens	pencil pine	AIAG	Locally	Chronic woundsArthralgia Gout
Curcuma longa	Curcuma	AIAG	OralLocally	DermatitisPain in the mouth and gumScalp wounds
Cyclamen coum	Sowbread	AG	Locally	Chronic toothache
Cymbopagon schoenantus	Sweet rush	AIAG	OralLocally	Muscle painMetritisCervicitis
Cynara cardunculus	Artichoke	AIAG	OralLocallyInhalation	HeadacheColicSciaticaArthralgiaBronchitis
Dausus carota	Carrot	AG	OralLocally	Kidney and uterine pain Fever
Elettaria cardamomum	Cardamom	AIAG	OralLocally	Sciatica
Chees Ferment	-	AIAG	Oral Locally	OtitisCystitisGastritisColic Fissure anal
Faba vulgaris	Broad bean	AG	OralLocally	DiphtheriaOphthalmitisOtitisAbscessGastrointestinal painArthritis
Ferula assafoetida	Stinking gum	AI	Oral	Fever
Ferula gumosa	Galbanum	AIAG	OralLocally	HeadacheGastroenteritis
Ficus carica	Comm-on fig tree	AIAG	Oral	Malignant and purulent WoundsStomatitisTooth PainGastroenteritis
Foeniculum vulgare	Fennel	AIAG	Oral	StomatitisOtitis Gastritis
Flores acacia	Acacia	AIAG	OralLocallyInhalation	ArthritisChronic eye disease
Fraxinus excelsior	Ash tree	AIAG	Locally	Gout ArthritisEarache
Fumaria perriflora	Fineleaf fumitory	AG	Locally	Back painToothacheGingivitis
Gentiana lutea	Gentian	AI	Locally	Abdominal pain
Glycyrrhiza glabra	Liquorice	AIAG	OralLocally	Skin wounds ScabiesArthralgiaBack painChronic headache
Hedera helix	Ivy	AIAG	OralLocally	Skin infectionsEaracheScalp inflammation
Helleborus niger	Christmas rose	AIAG	Locally	TonsillitisArthritis GoutLiver pain
Hordeum vulgare	Barley	AI	Oral	Fever
Hyssopus officinalis	Hysso	AG	Locally	Eye swellingOtitisUterine diseases
Illicium verum	Anise	AIAG	OralLocallyInhalation	Dizziness OtitisHeadacheChronic ophthalmitis Chronic fever
Iris florentina	Iris	AIAG	OralLocally	ToothacheJoint contortion
Jasminum officinale	White jasmin	AIAG	Locally	Painful skin diseaseAcute mastitis (in pregnancy)EaracheOphthalmitisEye tumorUterine painGastroenteritisPainful sores in the anal area
Juglans regia	Walnut	AG	Oral	Cervical painGeneral pain
Lactuca sativa	Lettuce	AIAG	OralLocally	General edemaJoint complaints and gout SciaticaStomatitisUterine pain
Lantago psyllium	Flea wort	AI	Locally	Gingivitis
Laureo oleum	Laurel oil	AI	Locally	Joint diseases and goutOphthalmitisNeck painSore throat
Lavendula stoechas	Spanish lavender	AIAG	Locally	ArthritisAnal fissure
Lawsonia intermis	Henna	AIAG	OralLocally	AbscessPurulent scalp inflammationPurulent rashesSciaticaBronchitis
Leidium sativum	Garden cress	AIAG	OralLocally	Gastrointestinal infections OsteitisPurulent otitisToothacheIntestinal ulcerHemorrhoids
Lens culinaris	Lentil	AI	Oral	Intestinal pain
Lignum vite	GrapeTree	AIAG	OralLocally	Earache Headache
Lilium candidum	Iris	AIAG	OralLocally	Eye infectionsSore throatPyelonephritisCystitisChronic fever
Malus orientalis	Apple	AIAG	OralLocally	Acute general edemaMuscle painAbscessOtitisGeneral painMalignant purulent wounds ToothacheChronic cough and pneumoniaAbdominal painGastroenteritis
Marrubium vulgare	Marrubium	AG	OralLocally	SciaticaArthritisGoutOtitisMouth wound GastroenteritisColic
Matricaria Spp	Camomile	AIAG	OralLocally	ToothacheMuscle tightness
Meliloto officinalis	Field melilot	AIAG	OralLocally	OtitisHeadacheEye swelling
Mentha piperata	Pepper mint	AIAG	LocallyOral	Purulent skin wounds PneumoniaMastitis
Mentha pulegium	Penny royal	AIAG	OralLocally	ArthralgiaPurulentMalignant sore
Morus alba	White mulberry	AIAG	OralLocally	Abscesses and rashHerpes Purulent dermattisSciaticaMalignant soreToothacheSore throatChest pain Chronic cough
Myristica fragrans	Nutmeg	AI	OralLocally	ArthritisEpilepsyGoutHeadacheToothacheCystitisGastrointestinal painCerebraleKidney painArthralgia
M yrtus communis	Myrtle	AIAG	OralLocallyInhalation	TestitisHeadacheArthritisOtitisChronic eye diseaseGingivitis CystitisUrinary tract infectionHemorrhoid
Narcissus pseudonarcissus	Lent lily	AIAG	OralLocally	HeadacheHardness tongueEaracheMastitis
Nerium oleander	Rosebay	AI	OralLocally	Acute inflammatoryCervical pain
Nigella sativa	Black cumin	AIAG	OralLocally	ArthralgiaEaracheAbdominal painHemorrhoidsAnal fissuresSores in the genital area
Ocimum basilicum	Basil	AIAG	OralLocally	Kidney-bladder painAbscessHeadacheToothacheGastritisHepatitisMenstrual painUterine painArthralgiaIntestinal ulcerOphthalmitis
Olea europaea	Olive	AIAG	Locally	GoutAcute ophthalmitisChronic swelling of the diaphragmLiver diseaseUterine painKidney pain
Oleum lilia	Lilies oil	AI	Locally	EaracheHeadacheTinnitusKidney painBladder painUterine discomfort
Onosma echioides	Hairy onosam	AG	OralLocally	StomachacheLumbar painLiver pain
Opoponax gummi	Opopana-ax Gum	AG	Locally	PainSciatic pain
Orchis maculata	Spotted orchis	AG	OralLocally	Skin diseasesHerpesSkin indurationCornsArthritis Tinnitus and hearing lossHeadachesEye diseasesCystitisGastroenteritis
Origanum majorana	Marjoram	AIAG	OralLocally	Dermatitis HeadachesOphthalmitisLung diseases such as bronchitis and chronic coughUterine painChronic fever ToothacheGingivitisOtitis
Origanum vulgare	Wild marjoram	AIAG	OralLocally	ToothacheSwelling of the spleen
Oxalis crenata	Sorrel	AIAG	OralLocally	ArthralgiaPurulent lung diseasesBlood spitting and coughing
Paeonia officinalis	Common peony	AIAG	OralLocally	ToothacheFlatulenceAbdominal pain and fever
Papaver somniferum	Opium poppy	AIAG	OralLocally	ArthralgiaSciaticaGoutMuscle pain and nerve injuryOtitisBlepharitisUrogenital painAbdominal painUterine painColic Postoperative painChronic pain
Papavero rosolaccio	Red poppy	AIAG	Locally	DermatitisEaracheEye painUterine painOrchitis
Parce carduus	Thistle	AIAG	Oral	Chronic uterine/cervical pain
Pastinaca sativa	Pastinace	AIAG	OralLocally	HeadacheStomatitisOphthalmitisDermatitis Fever
Phonix dactylifera	Date	AIAG	Locally	OphthalmitisToothache
Pinus grana	Pine seeds	AIAG	OralLocally	AbscessDental cariesToothacheSpleen diseasesUterine disorders
Pinus nuces	Pine cone	AG	Locally	Back muscles vertebrae pain
Pinus silvestris	Pine	AG	Oral	ArthralgiaNerve painBack painMuscle complaintsAbdominal pain and colic
Pinus sylvestris	Scots pine	AIAG	OralLocally	PleuritiHepatitisSplenitisGastroenteric complainJoint and bone painOphthalmitis
Piper nigrum	Black pepper	AIAG	OralLocally	Chronic earache
Pistacia vera	Pistachio	AG	OralLocally	Dermatitis Eliminates the feverHeadache
Plantago major	Way-bread	AIAG	Locally	Bone fractureGoutArthralgia
Platanus orientale	Oriental plane	AIAG	Locally	Knee pain Back painToothacheGeneral hard edema
Polygonum amphibium	Water knotweed	AIAG	Locally	Lumbar pain
Polypodium vulgare	Adders-fern	AIAG	OralLocally	TonsillitisOtitisArthritisOphthalmitisMastitisChronic cough
Populiferve	Poplar	AIAG	OralLocally	Headache
Portulaca oleracea	Common purslane	AIAG	OralLocally	HeadacheArthritisTestitis
Pruntus domestica	Plum	AIAG	Oral	Spleen painGeneral inflammation
Pterocarpus santalinus	Sandal wood	AIAG	Locally	Tooth painChronic coughLiver pain
Punica granatum	Pomegranate	AG	Oral	Gastroenteritis (particularly in children)Cervical discomfortArthralgiaBack painHeadachesEaracheColic DermatitisOphthalmitis Ocular diseases
Raphanus sativus	Radish	AIAG	Oral	Hepatitis
Recinus	Castrol oil	AI	Locally	General edemaPurulent skin woundsImpetigo
Rhabarber rhaponticum	Rheum	AIAG	OralLocally	GastritisGonorrheaChronic fever
Rhus coriaria	Sicilian sumac	AIAG	Oral	GastritisSpleen painMetritisKidney pain
Rosa gallica	Red rose	AIAG	Oral	EdemaToothacheEaracheBreast diseaseBronchitisCough
Rosam	Rose oil	AIAG	Locally	Sciatica and back pain ToothacheHeadache
Rubus sectio	Bramble	AI	OralLocally	ArthritisGoutAcute ophthalmitisMastitisColitis
Saccharum officinalis	Sugar cane	AIAG	OralLocally	GastritisHepatitisMetritis
Salix	Willow	AIAG	OralLocally	OsteitisHeadacheOphthalmitisOrbital Injury Liver disorders and jaundiceDysmenorrhea
Seasam indicum	Sesame	AG	Locally	Chronic ocular diseaseEaracheHemorrhoid
Semecarpod oriente	Marsh nut	AIAG	Locally	ColicArthralgia
Sesamum indicum	Sesame	AIAG	OralLocally	Chronic and malignant sore BurnToothacheEaracheMastitis
Styrax officinalis	Styrax tree	AIAG	OralLocally	Malignant tumorsAcute earacheToothacheRashOphthalmitisBronchitisKidney and bladder painIntestinal ulcerHemorrhoidsFever
Sulfur	Sulfur	AIAG	OralLocally	OrchitisOphthalmitisColic
Tamarindus indica	Tamarind	AI	OralLocally	DermatitisAcute wounds stomach painGastroenteritis
Tamarix gallica	Tamarisk	AG	Locally	Acute edemaHeadaches with fever Stomatitis
Taraxacum officinale	Dandelion	AIAG	Locally	AbscessArthralgia Deep wound Bone woundDermatitisHeadachePurulent ear infectionsInjury of the orbits
Taxus baccate	Yew tree	AI	OralLocally	Sciatic painArthritis and goutDental pain and dental caries HeadachesEar Diseases Gum bleeding and gingivitis
Tragopogon pratensis	Meadow salsify	AIAG	Locally	Wounds and nerve damageMuscleachesGastroenteritis
Trigonella foenum-graecum	Alhova	AIAG	OralLocally	Sciatic painArthralgia
Tropaeolum majus	Monks cress	AIAG	OralLocally	Sore throatArthralgia
Urtica dioica	Nettle	AIAG	OralLocally	GoutHeadacheOtitisOphthalmitisDiarrheaColicChronic pain
Valeriana officinalis	Valerian	AIAG	OralLocally	HeadacheInflammation of the penis Ophthalmitis
Verbascum thapsiforme	Mullein	AIAG	Locally	RhinitisSinusitisOtitisOrchitisOphthalmitis
Vicia sativa	Tare	AG	Locally	BurnArthralgiaHeadacheUterine pain
Vinegar	-	AGAI	OralLocally	Herpes Purulent skin woundsGoutHeadacheGingivitis
Viola odorata	Sweet violet	AIAG	Locally	HeadacheCold
Vitex agnus-castus	Chasteberry	AG	OralLocally	PainColic
Vitis vinifera	Grape vine	AG	OralLocally	GasteritisUterine painAbdominal painKidney and bladder pain
Zingiber officinale	Ginger	AIAG	OralLocally	HeadacheGeneral pain

Some of the medicaments suggested by Avicenna for treatment of inflammation and pain are well-recognized dugs in modern medicine. Many of these compounds are under experimental or clinical investigations for their probable therapeutic effects. However, most of these drugs remain largely unexamined.

Well recognized anti-inflammatory and analgesic drugs

Papaver somniferum

Opium (Papaver somniferum) was advised for treatment of arthralgia, sciatica, gout, muscle pain and nerve injury, otitis, blepharitis, urogenital pain, abdominal pain, uterine pain, colic, postoperative pain, and chronic pain in the Canon. In 1680, Sydenham was noted opium: "Among the remedies which it has pleased Almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium" (Yaksh and Wallace, 2011 ▶).

Administration of opiate in Europe increased rapidly in the 18th century (Miller and Tran, 2000 ▶). Opium and its derivatives have been used as the most widely analgesics for severe pain since the early 1800s (Hamilton and Baskett, 2000 ▶). Nowadays, application of several opioids is considered effective for the treatment of various forms of headaches (Gorji and Khaleghi Ghadiri 2001 ▶), postoperative pain (Hamilton and Baskett, 2000 ▶), neuropathic pain (Berrios et al., 2008 ▶), and different chronic pain syndromes (Vallejo et al., 2011 ▶). Opium also plays a crucial role in our understanding of basic mechanism of pain (Lipman, 1990 ▶).

Salix spp.

In the Canon, administration of willow oil (Salix spp.) was recommended for treatment of headache, osteitis, ophthalmitis, orbital injury, liver disorders and jaundice, and dysmenorrhea. In the first half of the 19th century salicin, the principal active constituent of willow oil was extracted from the willow bark and later salicylic acid was obtained. Today, the synthetically produced preparations of salicylic acid are well-known analgesic, anti-inflammatory and antipyretic drug (Amann and Peskar, 2002 ▶).

Acetylsalicylic acid is recommended as an analgesic and prophylactic in different types of headaches [4], and alleviates dysmenorrhea (Pendergrass et al., 1985 ▶). Furthermore, it has been suggested that regular aspirin use (more than 15 times per month) may be associated with a lower prevalence of non-alcoholic fatty liver disease among men and older patients (Shen et al., 2014 ▶).

Curcuma longa

Curcuma (Curcuma longa) is advised for treatment of different inflammatory diseases and pain in the Canon. Promising effects of curcuma have been reported in patients with various pro-inflammatory diseases, including oncologic disorders, cardiovascular disease, rheumatologic diseases, chronic anterior uveitis, gastrointestinal inflammatory diseases (Crohn's disease, ulcerative proctitis and colitis, irritable bowel disease, pancreatitis, gastric inflammation as well as ulcer, and cholecystitis), lupus nephritis, ischemic brain injuries, and acquired immunodeficiency syndrome (Gupta et al., 2013 ▶; Tamaddonfard, 2013 ▶; Arshami et al., 2013 ▶; Ghosh et al., 2014 ▶).

Cannabis sativa

Cannabis (Cannabis sativa) was prescribed for the alleviation of severe headache as well as treatment for degenerative bone and joint diseases, ophthalmitis, general edema, infectious wounds, gout, and uterine pain. The major active component of cannabis, tetrahydrocannabinols, in addition to other constituents of cannabis has been shown to possess anti-nociceptive properties (Wilson and Nicoll, 2002 ▶).

Cannabinoids alleviate pain by the activation of a brainstem circuit that is required for opioid-mediated analgesia, and modulate basal nociceptive thresholds through the activation of the rostral ventromedial medulla [8]. It has been suggested that cannabinoids may act as an analgesic in migraine pain by inhibition of spreading depression phenomenon (Kazemi et al., 2012 ▶). Different constituents of cannabis have been suggested to be useful in the treatment of intervertebral disc degeneration (Silveira et al., 2014 ▶), endometriosis (Sanchez et al., 2012 ▶), and breast cancer (Behrend, 2013 ▶). Cannabis has been suggested to be used to treat patients with cancer who do not adequately treated with other analgesics and anti-emetics (Nauck et al., 2004 ▶).

Allium sativum

Garlic (Allium sativum) was recommended by Avicenna in his book for treatment of acute inflammation, chronic and malignant wounds, arthritis and gout, sciatica, common cold, headache, earache, severe eye pain, acute cough, lung disease with hematemesis, gastroenteritis, and liver diseases. Anti-inflammatory effect is a well-known property of this plant. Garlic and its bioactive components protect the hepatocytes from several toxic agents and act as antimicrobial, antifungal, and antiviral substances (Bayan et al., 2014 ▶). Diallyl disulfide, a major organosulfur compound in garlic oil, has been shown to a useful substance in treatment of respiratory inflammation (Shin et al., 2013 ▶). Administration of garlic have been suggested for treatment of common cold (Allan and Arroll, 2014 ▶), arterial occlusive disease (Jepson et al., 2013 ▶), migraine headache (Roussos and Hirsch, 2014 ▶; Marschollek et al., 2014 ▶), and prevention of different tumors (Bayan et al., 2014 ▶).

Medicaments under investigation for their probable anti-inflammatory and analgesic effects

Matricaria chamomilla

Avicenna advised to use chamomile (Matricaria chamomilla) for treatment of headache, edema, conjunctivitis, jaundice, chronic fever, lithiasis, amenorrhea, toothache, and muscle tightness. Chamomile is recommended to relieve itching and inflammation and facilitate healing of peristomal skin lesions in patients undergone the gastrointestinal or urinary surgeries (Charousaei et al., 2011 ▶).

The fluid extract from chamomile reduced pain of aphthous ulcers in patients suffering from recurrent aphthous stomatitis (Ramos-e-Silva et al., 2006 ▶). It is hypothesized that chamomile flavonoids and polyphenols due to its anti-inflammatory properties via the inhibition of pro-inflammatory biomarkers in macrophages, inhibition of endogenous prostaglandin E2 levels, and reduction of nitric oxide values may alleviate migraine pain (Zargaran et al., 2014 ▶). Chamomile modulates phase I and phase II drug metabolizing enzymes in the liver (Maliakal and Wanwimolruk, 2001 ▶), improves endometrial tissue arrangements (Farideh et al., 2010 ▶), and alleviate pain and edema present in various inflammatory conditions (Tomić et al., 2014 ▶) in animal experiments. The anti-inflammatory effect of chamomile is suggested to be mainly due its essential oils, such as bisabololand, chamazulene and matricin, possibly via inhibition of histamine release and the production of prostaglandin (Safayhi et al., 1994 ▶; Miller et al., 1996 ▶; Srivastava et al., 2010 ▶).

Malus orientalis

Apple (Malus orientalis) is advised for treatment of acute general edema, muscle pain, abscess, otitis, purulent wounds, toothache, chronic cough and pneumonia, abdominal pain, and intestinal inflammation as well as for prevention of headache by Avicenna. The apple contains polyphenols with a large variability in their structures, which are stored in vacuoles and chromoplasts (Francini and Sebastiani, 2013 ▶). Antioxidant reactions of phytochemicals inhibit the oxidation of harmful substances and act as radical catcher. Reactive oxygen species are noxious in a large amount and cause cell damage by reaction with lipids, proteins and deoxyribonucleic acid (Mladenka et al., 2010 ▶). Secondary plant metabolites and polyphenols have anti-inflammatory, anti-carcinogenic, anti-microbial, anti-oxidant, and anti-thrombotic effects (Scalbert et al., 2005 ▶; Jelodarian et al., 2013 ▶). Apple polysaccharide extract is suggested to prevent colitis-associated colon cancer via the inhibition of TLR4/MD2-mediated signaling and the inhibition of NF-κB-mediated inflammatory signaling pathways (Zhang et al., 2015 ▶). Apple flavonols in combination with fish oil inhibited the production of pro-inflammatory mediators and significantly improved blood lipid profiles in rats with diet-induced hyperlipidemia and lipopolysaccharide-induced acute inflammation (Sekhon-Loodu et al., 2014 ▶).

High-flavonoid apple was associated with decreases in the transcription levels of inflammation-linked genes for interleukin-2 receptor, chemokine receptor 2, chemokine ligand 10, and chemokine receptor 10 as well as in production of prostaglandin E2 (Espley et al., 2014 ▶).

Boswellia serrata

In medieval Persian, frankincense (Boswellia serrata) was advised for treatment of abscess, wounds and malignant tumors, skin rashes, dermatitis, nausea and vomiting, gastrointestinal inflammation, and arthritis. Several experimental studies have shown that frankincense possesses anti-inflammatory, analgesic, antimicrobial, hepatoactive, and anti-proliferative effect (Abdel-Tawab et al., 2011 ▶).

The resinous part of Boswellia serrata possesses several anti-inflammatory substances, including mono-, di-, tri-, tetra-, and four major pentacyclic triterpenic acids (Siddiqui, 2011 ▶). Oral administration of Boswellia serrata gum resin extract significantly reduced the levels of several inflammatory mediators (interleukins 1β and 6, tumor necrosis factor-α, Interferon gamma, and prostaglandin E2), and increased interleukin-10.

The protective effect of frankincense against rheumatoid arthritis is suggested evident due to the decrease in arthritis scoring and bone histology in a collagen induced arthritis model in rats (Umar et al., 2014 ▶). Aflapin, a novel Boswellia-derived anti-inflammatory product, significantly inhibited interleukins 1β-induced death of human primary chondrocytes and improves production of glycosaminoglycan in human chondrocytes (Sengupta et al., 2011 ▶).

Cinnamomum camphora

Camphor (Cinnamomum camphora) is advised for treatment of headache and arthralgia as well as against inflammation in different organs. Camphor inhibited heat-sensitive transient receptor potential vanilloid subtype 1 (TRPV1) and several other related channels, which may underlie the analgesic effects of camphor (Xu et al., 2005 ▶). Camphor activated cultured primary keratinocytes (contained heat-activated receptors), and this effect was abolished in TRPV3 null mice (Moqrich et al., 2005 ▶).

Phytochemical investigation of Myrrh (Commiphera myrrha) has resulted in identification of more than 300 secondary metabolites which have exhibited a wide-range of pharmacological properties that are effective in treatment of inflammatory and infection diseases.

The bioactive steroids guggulsterones have been suggested as a potent inhibitory component on tumor cells and inflammation (Shen et al., 2012 ▶). Lavender (Lavendula stoechas) is believed to have a variety of therapeutic and curative properties in the Canon. In a placebo-controlled clinical trial, inhalation of lavender oil was suggested as an effective and safe treatment in acute management of migraine attacks (Sasannejad et al., 2012 ▶). Lavender inhibited some inflammatory processes, such as lipopolysaccharide-induced inflammatory reaction (Koulivand et al., 2013 ▶).

Ethanolic and aqueous extracts of saffron (Crocus sativus), another analgesic and anti-inflammatory drug mentioned in the Canon, have been suggested as a useful substances in treatment of different kinds of neuropathic pain and acetaminophen toxicity (Amin and Hosseinzadeh, 2012 ▶; Omidi et al., 2014 ▶.

Several strategies have been used for development of new drugs. One of these strategies is the use, development and improvement of existing medicines, like natural healing substances, which have been used long to treat the illnesses in traditional medicine. Although some of anti-inflammatory and analgesic substances advised by Avicenna in the Canon are used by modern medicine, the exact mechanism of their action as well as biochemical and pharmacological values needs more investigations. Several other drugs are still unexamined, which have the potential for further investigations and discovery of new drugs against inflammatory diseases and pain.