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Abstract

Osteoarthritis is the most common articular disease worldwide. Nonetheless, common osteoarthritis treatments are either not effective or associated with side effects. Now the materials derived from plants have found a relevant place in drug discovery. Until the mid-18th century, osteoarthritis in all medical schools worldwide had been managed as general arthritis. Avicenna, the famous scholar of Iranian traditional medicine has provided a long list of herbs that have been used traditionally to treat arthritis. To gain this worthy list, we searched his most famous medical masterpiece: Canon of Medicine. Some of these materials are investigated and employed by modern medicine. However, it is difficult to ignore that still more of these naturally occurring materials could be of use in modern medicine not only to prevent osteoarthritis progression but also osteoarthritis management as natural anti-inflammatory drugs.

Keywords

Iranian traditional medicine osteoarthritis pharmacological treatment

Osteoarthritis of joints especially knee is one of the most causes of limited function and pain in older age worldwide.¹ Although the prevalence of this multifactorial etiology disease varies according to its definition, generally it is considered as an increasing affecting disease, likely due to spread of its underlying etiologic factors such as old age, obesity, overweight, knee injury, repetitive use of joint, joint laxity, and muscle weakness.²

Although much progress has been made in the treatment of some arthritis such as osteoarthritis, mostly there are no treatments today available to prevent most of these diseases, or control its underlying causes, but rather treating the symptoms. This unfortunate result comes from this fact that the exact etiologies of these diseases are not known. The present treatments available for osteoarthritis are ineffectual and have long treatment durations and will often cause the patient to drop his or her treatment plan. Pharmaceutical research on traditional herb treatments is demonstrating a great promise for the discovery of new and more effective drugs for this painful and crippling disease in the near future.³ Approximately 80% of the populations in the developing countries are turning to their folk or traditional medicines for treatment and care. Based on recent data, at least 25% of drugs in modern pharmacopoeias are derived from herbs and many other drugs are synthetic analogues made on the prototype compounds taken from herbal remedies. There is a noticeable growing dependency on the usage of the complementary medicinal system for cost reduction and better health care services, which has led governments around the world to pay greater attention to invest in complementary and alternative medicine. The terms alternative/complementary/nonconventional medicine are used as a substitute for traditional medicine in some countries.⁴

The first step to discover these new more effective drugs from the potential plants is collecting the data for their uses in given countries which they are used.⁵

In Iranian traditional medicine several herbal remedies have been recommended that have antiarthritis effect and still may not have been evaluated in modern phytotherapy. This study was designed to review and assess these remedies and their biological mechanisms and efficacy in healing in the modern publications.

Iranian Traditional Medicine

About the relation between modern thought and Avicenna we have to admit that although the achievements of any age may be subject to decay with the lapse of centuries, the ideas that gave rise to them continue living through all cycles. Therefore, to offer a real place for Avicenna in modern thought is not to offer a return, as it were, to old architecture, or the costumes of long ago.⁶ Avicenna (Ibn Sina (/ˌəbneˈsiːnɑː/)) (ad 980-1037), the Chief of Physicians and the pioneer of modern medicine, in his most famous medical masterpiece: Canon of Medicine (Qanun fi al-Teb(/ˌɢɑːˈnuːnfetˈteb/)), which was the main reference source for medical sciences in many Western and medieval Islamic countries from the 13th to the 18th centuries, has divided the skeletal pain into some categories including “vaja-al-zahr,” backache; “vaja-al-khaserah,” flank pain; “vaja-al-warak,” coxalgia; “erghounnesaa,” sciatalgia; “neghres,” arthritis of foot and ankle; and “vaja-al-mafasel,” arthritis of other limbs like knees and hands.

According to Avicenna (Ibn Sina), the subjective reasons of arthritis are the following:

Dystemperament: in whole of the body or in ordering organs

Bad humors

and the objective reasons of arthritis are

Weakness of limb due to dystemperament

Congenital weakness of limb

The main mentioned risk factors for arthritis include catarrh (as seen in the origin of the word: rheumatism that discoveries its theorization, more than some centuries earlier), indigestion, lack of movement or exercise, heavy sex, and drinking of spirits particularly at fasting, amenorrhea, any heavy activity like exercise, sex, or bath right after eating/inadequate digestion/indigestion, constipation, trauma, and insomnia.⁷

Iranian traditional medicine states one of the most important treatment strategies of any disease such as arthritis is removing the causes of disease to reduce inflammation and relieve pain. In this view, there are 3 steps for treating diseases:

Lifestyle and diet modification

Use the medication

Using manual tasks⁸

In his treatise, Ibn Sina discusses at length the mechanism of the plant derivatives recommended for the treating the painful joints. This is easily accessible in the texts of Iranian traditional medicine. Avicennas preference was to treat the cause of joint paint rather than reliving the joint pain by the use of sedatives and analgesics.⁹

The pharmacologic treatment of osteoarthritis in today’s medicine was also used in Iranian traditional medicine, as can be noted in above 3 important steps for managing diseases. The intention of this study is to evaluate the step: pharmacological use.

Materials and Methods

To gain that point and because there is no synonymous for osteoarthritis in Iranian traditional medicine, we have searched Canon of Medicine (Qanun fi al-Teb by Ibn Sina (ad 980-1037)), the major source of Iranian traditional medicine, exact terminology of arthritis in Arabic: “وجع المفاصل “vajae-al-mafasel” “to obtain remedies recommended for arthritis, and then we adapted with the English translation¹⁰ and finally the electronic databases: Google Scholar and PubMed were checked to find any in vitro, in vivo, or clinical evidence for their efficacy and possible mechanisms by undertaking some research into the herb names and terms like arthritis, joint pain, anti-inflammatory, antioxidant, and analgesic.

Results

Listed in Table 1 are herbal remedies with their scientific and common names as well as their family, traditional names, route of administration, and function. The search results for in vitro, in vivo, or clinical evidence are illustrated in Table 2. As you will observe, the majority of the medicinal substances prescribed by the Persian physicians (Table 1) are still unexamined and have not been evaluated in modern phytotherapy (Table 2).

Table 1.

Medicinal Plants Used for the Treatment of Arthritis (Osteoarthritis) in Iranian Traditional Medicine.^7,10

No.	Scientific Name	Common Name	Family	Iranaian Traditional Medicine Name	International Phonetic Alphabet Phonology	Administration	Traditional Effect
1	Aloe barbadensis Miller	Aloe vera	Liliaceae	Sabr	/sæbr/	Oral	Soda purgative
2	Atropa belladonna L	Belladonna	Solanaceae	Yabruj	/jæbruːd͡ʒ/	Topical	Phlegm purgative, narcotic
3	Berberis aristata Dc	Ophthalmic barberry	Berberidaceae	Hudad	/hʊdæd/	Oral	Dissolvent, purgative
4	Brassica oleracea capitola L	Cabbage	Brassicaceae	Karnab	/kærnæb/	Oral and topical	Purgative, analgesic, diuretic
5	Cassia fistula L	Purging cassia	Fabaceae	Khiar shambar	/xiːɑrʃæmbær/	Topical	Dissolvent, purgative
6	Citrullus colocynthis S	Colocyntb	Cucurbilaceae	Hanzal	/hænzæl/	Topical and rectal	Dissolvent, absorbent
7	Cocos nucifera L	Coconut	Arecaceae	Jauz al-hindi	/d͡ʒoʊzʊlhendɪ/	Topical	Tonic, nutritive
8	Colchicum luteum B	Hermodactyle	Liliaceae	Suranjan	/suːrænd͡ʒɑːn/	Topical and oral	Astringent, purgative
9	Convolvulus scammonia L	Scammony	Convolvulaceae	Saqmunia	/sæɢmuːniːʌ/	Topical	Dissolvent, detergent
10	Cornus muscula L	Dog-wood	Cornaceae	Mu	/maʊ/	Oral and topical	Astringent, detergent
11	Croton tiglium L	Croton	Euphorbiceae	Mahudanah	/mɑːhuːdɑːnæ/ /	Oral	Purgative
12	Dryopteris filixmas L	Male fern	Polypodiacea	Darubotaris	/dɑːruːbeʈɑːres/	Oral	Desiccant
13	Embelia ribes Burm F	Embelia	Myrsinaceae	Birank Kabuli	/beræŋkekɑːbʊliː/	Oral	Expels the phlegm of the joint
14	Emblica officinalis G	Emblic myrobalan	Euphorbiaceae	Amlaj	/æmlæd͡ʒ/	Oral	Reduces the heat of blood
15	Ferula assafoetida L	Asafoetida plant	Apiaceae	Anjudhan	/ænd͡ʒedɑːn/	Topical	carminative
16	Ferula galbaniflua B	Opoponax-galbanum	Apiaceae	Jaoshir	/d͡ʒævʃiːər/	Oral and topical	Purgative, detergent, carminative
17	Ferula persica Wild	Sagapanum	Apiaceae	Sakbinaj	/sækbiːnæd͡ʒ/	Topical, rectal, and oral	Carminative, attenuant, detergent
18	Lemna minor L	Duck weed	Araceae	Tahlab	/tæhlæb/	Topical	styptic
19	Lepidium latifolium L	Lepidium	Brassicaceae	Shitaraj	/ʃiːɑːtæræd͡ʒ/	Oral	Carminative desiccant
20	Momordica elaterium L	Squirting cucumber	Cucurbitaceous	Qiththa al-himar	/ɢeθɑːʊlhemɑr/	Rectal and topical	Detergent, attendant
21	Narcissus tazetta L	Narcissus	Amaryllidaceae	Narjis	/nærd͡ʒes/	Topical	detergent, desiccant
22	Papaver somniferum L	Opium poppy	Papaveraceae	khashkhash	/xæʃxɑːʃ/	Topical oral	Narcotic, analgesic
23	Peganum harmala L	Syrian rue	Zygophylaceae	Harrmal	/hærmæl/	Topical	Attenuant
24	Plantago ovata Forsk	Ispaghula	Plantaginaceae	Bazr Qatuna	/bæzreɢætuːnɑː/	Topical	Analgesic
25	Raphanus sativus L	Radish	Cruciferae	Fujl	/fʊd͡ʒl/	Topical and oral	Attenuant
26	Ruta graveolens L	Common rue	Rutaceae	Sadhab	/sʊdɑːb/	Topical and oral	Dissolvent, carminative, vessel cleansing
27	Trigonella corniculata L	Cultivated fenugreek	Fabaceae	Handaquqa	/hændæɢuːɢʌ/	Oral	Desiccant, detergent
28	Verbascum thapsus L	Great Mullien	Scrophulariaceae	Mahizahraj	/mɑːhiːzæhræd͡ʒ/	Oral	Carminative
29	Withania somnifera L	Ashwagandha	Solanaceae	Buzidan	/buːziːdɑːn/	Oral	Attenuant

Table 2.

Evaluation of Some Plants Prescribed by Avicenna as Natural Arthritis (Osteoarthritis) Remedies Using Modern Scientific Methods.

Scientific Name	Modern Biological Activity		References
Well-recognized herbal remedies contributing to development anti-inflammatory and analgesic drugs
Colchicum luteum Baker	Anti-inflammatory	In vitro inflammatory enzymes inhibition activities and reduction of induced edema and arthritis in some experimental models	11 -13
Papaver somniferum Linn	Narcotic	Opioids like codeine and morphine, alone or in combination with other analgesics, in the management of osteoarthritis pain	14 -17
New recognized herbals with potential anti-inflammatory and analgesic properties
Aloe barbadensis Miller	Anti-inflammatory Laxative Antioxidant	Effective on inflammatory skin conditions such as ultraviolet-induced erythema tested in a clinical trial Causing a significant increase in the water content of the rat large intestine In vitro evidence of exhibition weak scavenging activity of hydrogen peroxide	18 18 19
Atropa belladonna Linn	Immunomodulatory Uricosuric	Positive modulatory effect of extracellular matrix formation on early phases of skin wound healing in rats Increase in the fractional excretion of uric acid in subjects with hyperuricemia or gout	20, 21 22
Berberis aristata Dc	Anti-inflammatory	Potent anti-inflammatory activity against endotoxin-induced experimental uveitis in the rabbit and in vitro evidence of its anti–Helicobacter pylori activity	23, 24
Brassica oleracea capitola Linn	Antioxidant	?in vitro evidence of antioxidant activity and free radical scavenging activity	25
Cassia fistula Linn	Antioxidant Anti-inflammatory	Effective in both experimental model and clinical trials	26, 27
Citrullus colocynthis Schrad	Analgesic Antioxidant Anti-inflammatory	Having analgesic and anti-inflammatory activities in experimental animals and effective in antioxidant and free-radical scavenging assays	28
Cocos nucifera Linn	Antioxidant Anti-inflammatory	Inhibition of the cell migration in formalin-injected paws as an inflammation model and effective as antioxidant agent	29
Cornus muscular Linn	Anti-inflammatory Antioxidant	Reduction of serum levels of pro-inflammatory factors in rat models of myocardial ischemia and reperfusion and showing remarkable antioxidant activity in them	30
Croton tiglium Linn	Laxative Pro-inflammatory	Effective on ion transport of the rat intestinal epithelia. Effective as pro-inflammatory agent	31 32
Embelia ribes Burm F	Analgesic Antioxidant	Safe analgesic in toxicity evaluation in laboratory animals Effective in antioxidant defense against free radicals and oxidative stress in some organs of rats	33 34
Emblica officinalis gaertn	Anti-inflammatory Antioxidant	Reduction of inflammation in several experimental models Effective in experimental models of rats	35, 36 37
Ferula assafoetida Linn	Anti-inflammatory Antioxidant	Effective in experimental models Having radical scavenging and antioxidant potential in antioxidant assays	38 39
Ferula galbaniflua Boiss	Anti-inflammatory Antioxidant	Effective at in vivo antioxidant assays and in vitro and in vivo anti-inflammatory studies	40
Ferula persica Wild	Anti-inflammatory Antioxidant	Effective at in vivo antioxidant assays and in vitro and in vivo anti-inflammatory studies	40
Lemna minor Linn	Increases inflammation responses Antifungal	Increase in inflammatory response in mice. Effective in experimental models	41 42
Lepidium latifolium Linn	Antioxidant Diuretic	Having radical scavenging and antioxidant potential in antioxidant assays Increase considerably urinary excretion and slightly ion excretion in a study on rats	43 44, 45
Momordica elaterium Linn	Antioxidant Anti-inflammatory Analgesic	Effective in scavenging free-radicals and inhibiting lipid peroxidation and oxidation anti- Effective in some studies in vitro and in vivo mainly due to inhibition the expression of tumor necrosis factor in lymphocytes and in macrophages The same	46
Narcissus tazetta Linn	Immunomodulatory Antifungal	Inhibition of proliferation of leukemia L1210 cells Active against Candida albicans in experimental models	47 48
Plantago ovata Forsk	Anti-inflammatory Antioxidant	Effective in experimental models due to its polyphenols serving as natural antioxidant and anti-inflammatory	49
Raphanus sativus Linn	Anti-inflammatory Antioxidant	Having anti-inflammatory effects in the rats with all of the histopathological changes due to fat-rich diet Having antioxidant activity in alimentary hyperlipidemia in rats	50 51
Ruta graveolens Linn	Anti-inflammatory Antiarthritic Antioxidant	Decrease the paw edema in carrageenan induced rat paw edema and adjuvant induced arthritis The same Decrease the activities of antioxidant enzymes in experimental rat model	52, 53 53
Trigonella corniculata Linn	Antioxidant	Having anti-radical power in antioxidant and free radical scavenging assays	54
Withania somnifera Linn	Anti-inflammatory Antiarthritic	Reduction in inflammatory changes in adjuvant arthritis. The same	55, 56

Discussion

Iranian traditional medicine, as previously mentioned above, has a wide range of remedies that were presented for the treatment of arthritis. Hermodactyle described under the entry Suranjan in Iranian traditional medicine is the best example of conventional medicine that was inspired by alternative medicine. This plant has been widely used in Iranian traditional medicine as the chief substance of many combination formulations for relieving various types of arthritis, particularly gout.⁷ As recent studies have shown that colchicine could be used not only in gout but also in osteoarthritis treatment,^57
–59 this notable and worthy herb was a key remedy for all types of arthritis in Iranian traditional men.¹⁰ This evidence could be a guide for using other plants listed above recommended for treating arthritis for managing osteoarthritis.

Indeed, Avicenna has considered the inflammation in osteoarthritis similar to inflammation in other forms of arthritis. Until the 18th century, the humoral theory would explain all diseases, and all types of arthritis was known as rheumatism.⁶⁰ According to his teaching, subtyping of arthritis depends on signs and symptoms of arthritis.⁷ For instance, in severe osteoarthritis, the inflammation of joint reaches the state observed in rheumatoid arthritis,⁶¹ and in gout they are categorized and managed similarly. In contemporary era, the main recent observations suggest a strong association between inflammation and the progression of structural changes in osteoarthritis.⁶¹

The other well recognized plant, opium poppy that is known as khashkhash in Iranian traditional medicine, was recommended orally and topically by Ibn Sina as a pain medicine. This plant is the natural source of opioids, which are the gold standard for treating moderate to severe chronic pain. Although the use of opioid therapy to manage patients with chronic noncancer pain is controversial because of the possibility of addiction or abuse,⁶² few studies have evaluated the role of opioids in pain relief of osteoarthritis. There is some evidence that supports the effectiveness of opioids like codeine and morphine, alone or in combination with other analgesics, in the management of osteoarthritis pain, the cardinal feature of this disease.^14

–17

Since many years, it is known that reactive oxygen species play a critical role in inflammatory processes, including varies types of arthritis such as osteoarthritis. The degradation of cartilage, the end point of joint tissue degradation, is the result of the combination of mechanical stress and biochemical factors, predominantly metalloproteinase and reactive oxygen species. Enzymatic and nonenzymatic antioxidants balance the activity of reactive oxygen species mostly by inhibiting oxidative enzymes and scavenging free radicals. So antioxidant therapy strategies have been postulated for the treatment of osteoarthritis.⁶³ As the above data show, most of plants recommended by the venerable master Ibn Sina have antioxidant and/or anti-inflammatory properties. These herbs include aloe,^18,19 ophthalmic barberry,^23,24 cabbage,²⁵ purging cassia,^26,27 colocynth,²⁸ coconut,²⁹ dog-wood,³⁰ embelia,^34,64 emblic myrobalan,^35
–37 asafoetida plant,^38,39 galbanum,⁶⁵ sagapanum,^40,66 lepidium,⁴³ squirting cucumber,⁴⁶ ispaghula,⁴⁹ radish,⁵⁰ common rue,⁶⁷ cultivated fenugreek,⁵⁴ and ashwagandha,^55,68 which could have anti-arthritic effect by their anti-inflammatory and/or antioxidant properties.

Although these herbs have antioxidant and anti-inflammatory properties, In Iranian traditional medicine, properties such as attenuant, purgative, diuretic, and carminative also contribute to the loss of pain in the inflammation of the joints, by removing the humors causing pain. This is in accordance with the logic of the Iranian traditional medicine—“humors doctrine.” However, some plants like colocynth,²⁸ embelia,³³ and squirting cucumber,⁴⁶ analgesic effect has been assayed separately.

Now in modern medicine we know that one of the predisposing factors to osteoarthritis development is renal dysfunction.⁶⁹ There is evidence that glomerular filtration rate correlates inversely with the severity of knee osteoarthritis.⁷⁰ For this reason, many studies have been and are being done to evaluate the effect of renal tonics in the treatment of osteoarthritis.⁷¹ Many of the plants that Avicenna introduced to relieve pain of arthritis have diuretic properties (Table 1). In some plants like lepidium,^44,45 urinary excretion of some unknown pro-inflammatory factors maybe the effective action, as seen in urinary excretion of uric acid in the treatment of gout. The observed uricosuric effect of anticholinergic agents²² can justify the use of belladonna for various arthritis especially those depending on uric acid excretion.

Similarly, one can imagine that some of these compounds with laxative action^18,31 expel the active factors that can cause inflammation of joints. Future research will open the mystery of this story.

A few of these herbs like common rue,⁶⁷ hermodactyle,¹³ and ashwagandha^55,68 have shown different beneficial effects on adjuvant experimentally induced arthritis treatment. Anti-inflammatory action of some plants, like duckweed is also controversial, as it has both antifungal activity,⁴² which can be a sign of a probable anti-inflammatory action⁷² and increasing inflammatory response,⁴¹ or in croton with pro-inflammatory properties and opposite properties like tumor-promoting and antitumor activities.³²

Conclusion

As discussed above, the herbal remedies described for managing all kinds of arthritis, including osteoarthritis, by the Grand Master of medicine Ibn Sina, are mostly supported by modern documents to have anti-arthritic effect to treat and prevent osteoarthritis. Undoubtedly, further research is needed to prove the safety and effectiveness of these herbs to manage osteoarthritic joint pain and inflammation. Hopefully, effective drugs could be made in the future, and this article could be a small step taken in this journey.

Footnotes

Acknowledgments

The inspiration for this article is the result of an ongoing PhD thesis (Anahita Ghourchian, No.: 142) at the School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Author Contributions

All authors discussed the concept of the manuscript. AG and RC drafted the first version. All authors edited and approved the final version of the manuscript.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors wish to acknowledge the financial support (Grant No.: 11672).

Ethical Approval

The study protocol was approved by Ethics Committee of Shahid Beheshti University of Medical Sciences.

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Scientific Evaluation of Pharmacological Treatment of Osteoarthritis in the Canon of Medicine

Abstract

Keywords

Iranian Traditional Medicine

Materials and Methods

Results

Discussion

Conclusion

Footnotes

Acknowledgments

Author Contributions

Declaration of Conflicting Interests

Funding

Ethical Approval

References