The Journal of Phytopharmacology 2015; 4(6): 311-318

Online at: www.phytopharmajournal.com

Review Article Rheumatoid arthritis and herbal drugs: A review

ISSN 2230-480X
JPHYTO 2015; 4(6): 311-318 Jyoti B. Wadekar*, Ramesh L. Sawant, Unnati B. Patel
November- December
2015, All rights reserved ABSTRACT

Rheumatoid Arthritis (RA) is a chronic autoimmune disease of unknown aetiology that affects 0.5% of the
population and can result in disability owing to joint destruction, characterized by joint synovial inflammation
Jyoti B. Wadekar and progressive cartilage and bone destruction resulting in gradual immobility. The greatest disadvantage in
Department of Pharmacognosy, the presently available potent synthetic drugs lies in their toxicity and reappearance of symptoms after
Pad. Dr. Vithalrao Vikhe Patil discontinuation. With limitations of existing drug molecules herbal drugs are gaining interest among RA
Foundations College of Pharmacy, patients. Medicinal plants are plants containing inherent active ingredients used to cure disease or relieve
Vilad Ghat, Post MIDC, symptoms of arthritis. The aim of this review is to update information on RA including causes, epidemiology,
Ahmednagar, Maharashtra- prevalence, symptoms and diagnosis, classification, medications, toxicities of allopathic anti-rheumatic drugs
414111, India and importance of herbal drugs for the management of RA. The present review also focuses on the medicinal
plants that interact with the mediators of inflammation and are used in the treatment of rheumatoid arthritis
Ramesh L. Sawant
Department of Pharmaceutical
(RA).
Chemistry and PG Studies, Pad.
Dr. Vithalrao Vikhe Patil Keywords: Rheumatoid Arthritis, causes, medications, classification, medicinal plants.
Foundations College of Pharmacy,
Vilad Ghat, Post MIDC,
Ahmednagar, Maharashtra-
414111, India INTRODUCTION
Arthritis, generally inflammation of joints is a one of the oldest known diseases occurring almost in all
Unnati B. Patel
Department of Pharmaceutical age groups. In India, more than about 20% of total population is suffering from arthritis [1]. Rheumatoid
Chemistry and PG Studies, Pad. Arthritis (RA) is a chronic autoimmune disease of unknown aetiology, characterized by joint synovial
Dr. Vithalrao Vikhe Patil inflammation and progressive cartilage and bone destruction resulting in gradual immobility [2].
Foundations College of Pharmacy,
Vilad Ghat, Post MIDC, It was first found in early Native American population several thousand years ago but might have
Ahmednagar, Maharashtra- appeared in Europe after 17th century [3]. Pro-inflammatory cytokines such as tumor necrosis factor-
414111, India (TNF-), interleukin (IL)-1, and IL-6 are important mediators of the disease perpetuation [4]. The
arthritis usually begins in the small joints of the hands and the feet, spreading later to the larger joints,
the inflamed joint lining or synovial extends and then erodes the articular cartilage and bone, causing
joint deformity and progressive physical disability. Extra-articular features include nodules, pericarditis,
pulmonary fibrosis, peripheral neuropathy and amyloidosis [5].

Causes

Arthritis involves the breakdown of cartilage. Cartilage normally protects a joint, allowing it to move
smoothly [6]. The process produces an inflammatory response of the synovial (sinusitis) secondary to
hyperplasia of synovial cells, excess synovial fluid, and the development of panes in the synovial. The
pathology of the disease process often leads to the destruction of articular cartilage and alkalosis of the
joints. Rheumatoid arthritis can also produce diffuse inflammation in the lungs, pericardium, pleura, and
sclera, and also nodular lesions, most common in subcutaneous tissue. Although the cause of rheumatoid
arthritis is unknown, autoimmunity plays a pivotal role in both its chronicity and progression, and RA is
considered a systemic autoimmune disease.

Epidemiology

About 1% of the world's population is afflicted by rheumatoid arthritis, women three times more often
than men [7]. Arthritis represents one of the most prevalent chronic health problems and is a leading
cause of disability. Arthritis affected 43 million U.S. adults in 2002 and by the year 2020, this number is
Correspondence: expected to reach 60 million [8]. It is up to three times more common in smokers than non-smokers,
Prof. Jyoti B. Wadekar particularly in men, heavy smokers, and those who are rheumatoid factor positive. A study in 2010 found
Department of Pharmacognosy, that those who drank modest amounts of alcohol regularly were four times less likely to get rheumatoid
Pad. Dr. Vithalrao Vikhe Patil arthritis than those who never drank [9].
Foundations College of Pharmacy,
Vilad Ghat, Post MIDC, Prevalence of RA
Ahmednagar, Maharashtra-414111,
India RA is strongly associated with the inherited tissue type Major histocompatibility complex

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(MHC) antigen HLA-DR4 (most specifically DR0401 and 0404) is most often worst in the morning. It may last one to two hours (or
hence family history is an important risk factor. The risk of first even the whole day). Stiffness for a long time in the morning is a clue
developing the disease appears to be greatest for women between 40 that one may have RA, since few other arthritic diseases behave this
and 50 years of age, and for men somewhat later [10]. The incidence way [19].
and prevalence of RA generally rises with increasing age until about
age 70, then declines [11-13]. Around twice as many women as men are Other signs and symptoms that can occur in RA include:
affected. The prevalence of RA is generally lower in developing
countries, with few or no cases found in some African surveys [14]. Joint pain and swelling; reduced ability to move the joint; redness of
The prevalence in native American groups can be considerably higher the skin around a joint; warmth around a joint; loss of energy and
[15-17]
. appetite; low fevers; dry eyes and mouth from a related health
problem; Sjogren's syndrome Firm lumps, called rheumatoid nodules,
which grow beneath the skin in places such as the elbow and hands.

Methods to detect RA include clinical assessment, imaging and

laboratory tests. Clinical assessment and opinion is considered the
gold standard [20]. Diagnosis of RA depends on the symptoms and
some blood tests can also help to confirm RA. Telltale signs include:

Anemia (a low red blood cell count); rheumatoid factor (an antibody,
or blood protein, found in about 80% of patients with RA in time, but
in as few as 30% at the start of arthritis); antibodies to cyclic
citrullinated peptides (pieces of proteins), or anti-CCP for short (found
in 60 70% of patients with RA); Elevated erythrocyte sedimentation
rate (a blood test that, in most patients with RA, confirms the amount
of inflammation in the joints).

Figure 1: Comparison of normal joint and joint affected by rheumatoid

X-rays can help in detecting RA, but may not show anything
arthritis abnormal in early arthritis. Even so, these first X-rays may be useful
later to show if the disease is progressing. Often, MRI and ultrasound
scanning are done to help judge the severity of RA. There is no single
Symptoms and diagnosis
test that confirms an RA diagnosis for most patients with this disease.
The pervasive nature of arthritis symptoms and their effect on
physical, social and occupational activities can be discouraging, Medications
resulting in psychological sequelae such as anxiety, depression and
helplessness [18]. Medications may be prescribed along with lifestyle changes. All
medications have risks, some more than others [21-22].
RA can be hard to detect because it may begin with subtle symptoms,
such as achy joints or a little stiffness. The stiffness seen in active RA

Table 1: Medications available for treatment of rheumatoid arthritis

Treatment Drugs
Over The Counter Acetaminophen (Tylenol), Aspirin, ibuprofen, or naproxen
Disease-modifying anti-rheumatic Methotrexate, gold salts, penicillamine, sulfasalazine, and hydroxychloroquine.
drugs (DMARDs) Common combinations of DMARDs include methotrexate hydroxychloroquine,
methotrexate sulfasalazine, sulfasalazine hydroxychloroquine, and methotrexate
hydroxychloroquine sulfasalazine.
Nonsteroidal anti-inflammatory Paracetamol, ibuprofen, naproxen, meloxicam, etodolac, nabumetone, sulindac,
drugs (NSAIDs) tolementin, choline magnesium salicylate, diclofenac, diflusinal, indomethicin,
ketoprofen, oxaprozin, and piroxicam.

Biological agents Tumor necrosis factor alpha (TNF) blockers

-etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), certolizumab
pegol (Cimzia), golimumab (Simponi)
Monoclonal antibodies against B cells rituximab (Rituxan)

Generally, over-the-counter medications are recommended first: stroke, stomach ulcers, bleeding from the digestive tract,
and kidney damage.
Acetaminophen (Tylenol) is usually tried first. It is
advisable not to take more than the recommended dose or Surgery and other treatments
do not take the drug along with a lot of alcohol. Doing so
may damage liver. In some cases, surgery may be done if other treatments have not
Aspirin, ibuprofen, or naproxen are nonsteroidal anti- worked. This may include:
inflammatory drugs (NSAIDs) that can relieve arthritis pain.
However, they have many potential risks, especially if used Arthroplasty to rebuild the joint
for a long time. Potential side effects include heart attack, Joint replacement, such as a total knee joint replacement

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Classification were revised in 1987 by the American College of Rheumatology

(ACR) [24].
Classification criteria for RA were first proposed by the American
Rheumatism Association (ARA) in 1958 [23]. The 1958 ARA criteria

Table 2: The 1987 revised ARA/ACR criteria for the classification of rheumatoid arthritis*

Criterion Short title Definition

1. Morning stiffness Morning stiffness in and around the joints, lasting at least 1 hour before maximal improvement. At
least 3 joints.
2. Arthritis of 3 or Areas simultaneously have had soft tissue swelling or fluid (not bony overgrowth alone) observed
more joint areas by a physician. The 14 possible areas are right or left PIP, MCP, wrist, elbow, knee, ankle, and
MTP joints.
3. Arthritis of hand At least 1 area swollen (as defined above) in a wrist, MCP or PIP joint.
Joints
4. Symmetric Simultaneous involvement of the same joint areas [as defined in (2)] on both sides of the body
Arthritis (bilateral involvement of PIPs, MCPs, or MTPs is acceptable without absolute symmetry).
5. Rheumatoid Subcutaneous nodules, over bony prominences, or extensor in juxtaarticular regions, observed by a
Nodules physician.
6. Serum Demonstration of abnormal amounts of serum rheumatoid factor or any method for which the result
rheumatoid has been positive in <5% of normal control subjects.
factor
7. Radiographic Radiographic changes typical of rheumatoid arthritis on posteroanterior hand and wrist radiographs,
Changes which must include erosions or unequivocal bony decalcification localized in or most marked
adjacent to the involved joints (osteoarthritis changes alone do not qualify).

*For classification purposes, a patient shall be said to have rheumatoid arthritis if he/she has satisfied at least four of these seven criteria. Criteria 1 through 4 must have been present for
at least 6 weeks. Patients with two clinical diagnoses are not excluded.

Need for herbal drugs for the management of RA: look for complementary and alternative medicine (CAM) options in
coping with this debilitating disease.
Conventional treatments for rheumatoid arthritis (RA) present a
number of problems, in terms of both safety and efficacy [25]. Owing
to side effects of synthetic drugs as shown in table 2, many patients

Table 3: Showing toxicities of allopathic anti-rheumatic drugs [26]

Sr. No. Drug Toxicities

1. Methotrexate (DMARDs) Stomatitis, rash, alopecia, infrequent myelosuppression, hepatotoxicity, rare but potentially
life-threatening pulmonary toxicity
2. Oral Gold Salts Diarrhoea
3. Injectable Gold Salts Stomatitis, myelosuppression, rash, thrombocytopenia
4. Cyclosporine Renal impairment, hypertension, gingival overgrowth
5. D-penicillamine Rash, stomatitis, dysgeusia, proteinuria, myelosuppression
6. Nonsteroidal Antiinflammatory Gastrointestinal symptoms (indigestion, ulceration, hemorrhage, stomatitis); renal
Drugs abnormalities; pulmonary neurological abnormalities; abnormalities; dermatologic
abnormalities; hematologic abnormalities; hepatic abnormalities; displacement of protein-
bound drugs; possible systemic complications

Research has indicated that people suffering from chronic pain, as in

RA, and those dissatisfied with current treatment are very likely to
seek alternative treatments, and an estimated 6090% of persons with
arthritis use CAM. With the growing interest in herbal therapies
among persons with rheumatoid arthritis, there exists a need for
investigation into their safety and efficacy [27].

The management of rheumatoid arthritis is a multidisciplinary

approach in order to lessen the pain, reduction of inflammation and
restoration of joints function. In practical terms suppression of
inflammation is the target intensive therapy. Herbal medicines have
become popular for the treatment of rheumatoid arthritis worldwide
recently [28].

Herbal medicinal drugs that interact with the mediators of

inflammation are used in the treatment of rheumatoid arthritis (RA)
which are shown in below listed table:

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Table 3: List of plant species and their families, constituents/isolated compounds, therapeutic uses and parts used in pain-inflammatory disorders including rheumatoid arthritis

Sr. Biological Source Part Used Active Ingredient Therapeutic Uses Extract Reference
No.
1. Annona montana. Leaves, fruit, Cyclomontanins A-D (1- 4), annomuricatin C (5), and Anti-rheumatic, anthelmintic, anticonvulsant, Methanol [29]
(Annonaceae) seeds, bark, (+)-corytuberine antidepressant, antimicrobial, antineoplastic, antiparasitic,
roots antispasmodic, antiviral, astringent, cardiodepressant,
cytostatic, cytotoxic, febrifuge, hypotensive, insecticide,
nervine, pectoral, sedative, stomachic, vasodilator,
vermifuge
2. Abrus precatorius Fresh leaves Triterpenoids (abrusosides A-D) Colds, cough, convulsion, fever, rheumatism, Methanol [30-31]
(Fabaceae/ Leguminosae) conjunctivitis and ulcers by traditional healers
3. Aristolochia Whole plant Ceryl alcohol, -sitosterol, aristolochic acid, Anthelmintic, fever, purgative and painful joints. Petroleum ether, [32]
bracteolata alkaloid, myristic, palmitic, stearic, lignoceric, oleic chloroform and
(Aristolochiaceae) and aristolochic acid, aristolochic acid aristolactam Methanol
a nitrogen containing compound and magnoflorine
4. Alpinia conchigera Griff. Rhizomes Galangoflavonoid, 1S-1-acetoxychavicol acetate, 1- Analgesic and anti-inflammatory Ethanol [33-34]
(Zingiberaceae) acetoxychavicol acetate (galangal acetate), -Sitosterol
diglucoside (AG-7) and -sitsteryl Arabinoside
5. Alchornea cordifolia Leaf Tannins, phenolic acids: gallic acid, ellagic acid, Anti-inflammatory: chancre, yaws wounds, cicatrisation, Aqueous decoction and [35]
(Euphorbiaceae) protocatechic acid, flavonoids: quercetin, hyperin and ulcers, caries, toothache, gum inflammation and methanol extract
guaijaverin and an alkaloid: triisopentenylguanidine conjunctivitis
6. Asparagus racemosus Roots, Leaves, Steroidal glycosides including shatavarins I-IV, Ulcerogenesis, antioxidant, treatment of thirst, fainting, Methanol [36]
(Liliaceae) flowers and diosgenin and various sterols, alkaloid asparagamine A, dyspnoea, and gout
fruits flavonoids: quercitin, rutin and hyperoside, an
isoflavone, and a mucilage
7. Anacardium occidentale Leaves Myricetin, quercetin, kaempferol, apigenin and Diarrhoea, diabetes, swelling, skin diseases, mouth ulcers, Ethanol extract and its [37]
(Anacardiceae) glycosides anti-inflammatory petroleum ether,
solvent ether, ethyl
acetate, butanol and
butanone fraction
8. Azadirachta indica Leaf alkaloids, flavonoids, triterpenoids, phenolic Anti-inflammatory, antipyretic, antimalarial, antitumour, hydro-alcoholic [38-39]
(Meliaceae) compounds, carotenoids, steroids and ketones antiulcer, antidiabetic, antifertility extract, ethyl acetate
and n-butanol fractions
9. Allium cepa (Liliaceae) Bulbs Organic sulfur compounds, including trans-S-(1- Antimicrobial, anti-inflammatory Petroleum ether, [40-42]
propenyl) cysteine sulfoxide, Smethylcysteine methanol and aqueous
sulfoxide, Spropylcysteine sulfoxide and cycloalliin; extracts
flavonoids; phenolic acids; sterols including cholesterol,
stigma sterol, -sitosterol; saponins; sugars and a trace
of volatile oil composed mainly of sulfur compounds,
including dipropyl disulfide, fructans
10. Antrodia cinnamomea (Fungus) Antrocamphin A, ergostane-type triterpenoids and Cancer, inflammatory disorders and antioxidant Methanol extract [43-44]
(Fomitopsidaceae) Fruiting bodies polyacetylenes
11. Butea frondosa (Fabaceae) Roots and Flavanoids, glucosides and lectins Anti-inflammatory Aqueous extract [45-46]
leaves

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12. Barringtonia racemosa Fruits, leaves Diterpenoids and triterpenoids, lycopene, bartogenic Anti-inflammatory, anti-tumor, anti-nociceptive, - Hexane, ethanol and [47]
(Lecythidaceae) acid glucosidase inhibitory, anti-bacterial and anti-fungal methanol, ethyl acetate

13. Boswellia serrata Roxb. Oleogum resin Resin which is pentacyclic triterpenoid in nature in Cancer, inflammation, arthritis, asthma, psoriasis, colitis Petroleum ether [48]
(Burseraceae) which boswellic acids (-boswellic acid, acetyl-- and hyperlipidemia
boswellic acid, keto--boswellic acid and acetyl-11-
keto--boswellic acid)
14. Borassus flabellifer L. Male flowers Alkaloids, terpenoids, Anti-inflammatory, anti-laprotic, diuretic, antiphlogistic, Ethanol [49]
(Arecaceae) (inflorescences) spirostane-type steroid saponins and phenolic stomachic, sedative, laxative, aphrodisiac,
compounds immunosuppressant
15. Aegle marmelos (Rutaceae) Roots, leaves Glycoside, alkaloids, coumarins, fatty acid and sterols, Vata diseases, insomnia, seizures, and hysteria, for Aqueous extract and [50]
and fruits tannins, skimmianine, essential oil (mainly diarrhoea, dysentery, colitis, loss of appetite and alcoholic
caryophyllene, cineole, citral, eugenol), sterols and or abdominal dull pain, anti-inflammatory
triterpenoids, including lupeol, -sitosterol and -
amyrin, flavanoids (mainly rutin) and coumarins,
including aegeline, marmesin and umbelliferone
16. Commiphora mukul Stem Guggulsterones (E- and Z-stereoisomers) and gugulipid Arthritis, obesity, and other disorders Ethyl acetate [51]
(Burseraceae)
17. Calluna vulgaris Aerial parts Kaempferol-3-O--D-galactoside, a common flavonol Anti-inflammatory and antinociceptive, antirheumatic, Ethanolic, chloroform, [52]
(Ericaceae) derivative diuretic, astringent and treatment of urinary infections ethyl acetate, n-butanol
and water, methanol
18. Cistus laurifolius Leaves Favonoids; 3-O-methylquercetin (1), 3,7-O- Inflammatory ailments including rheumatism and renal Ethanol [53]
(Cistaceae) dimethylquercetin (2) and 3,7-O-dimethylkaempferol inflammations
19. Cardiosperum Leaves Saponins, alkaloids, (+)-pinitol, apigenium, luteolin and Anti-inflammatory activity Alcoholic [54]
helicacabum (Sapindaceae) chrysoeriol.
20. Cyperus rotundus Tubers -sitosterol, 1,8-cineole, 4-alpha,5-alpha-oxidoeudesm- Anti-inflammatory, cervical cancer, liver, menstrual Methanol [55]
(Cyperaceae) 11-en-3-alpha-ol, alkaloids, alpha-cyperone, alpha- disorders, menstrual pain, as a digestive stimulant and for
rotunol, beta-cyperone, beta-pinene, beta-rotunol, beta- memory
selinene, calcium, camphene, copaene, cyperene,
cyperenone, cyperol, cyperolone cyperotundone D-
copadiene, D-epoxyguaiene, D-fructose, D-glucose,
flavonoids, gamma-cymene, isocyperol, isokobusone,
kobusone, limonene, linoleic-acid, magnesium,
mnganese, mustakone, myristic-acid, oleanolic-acid,
oleanolic-acid-3-o-neohesperidoside, oleic-acid, P-
cymol, patchoulenone, pectin, polyphenols, rotundene,
rotundenol, rotundone, selinatriene, stearic acid,
sugeonol, sugetriol
21. Cleome rutidosperma Aerial parts Alkaloids, steroids, flavonoids Stimulant, antiscorbutic, anthelmintic, vesicant, 90% [56]
(Capparidaceae) rubifacient, carminative, antiplasmodial, analgesic, Ethanol, petroleum ether,
locomotor, antimicrobial, diuretic, laxative diethyl ether and ethyl
acetate
22. Callophyllum innophyllum Nuts Xanthone dehydrocylogua-nadine, callophllin-B Anti-inflammatory Methanol [57]
(Clusiaceae)
23. Ficus religiosa (Moraceae) Leaves, stem Sterols, glycosides, tannins and amino acids Laxative, diarrhoea, asthma, cough, earache, toothache, Methanol, Aqueous [58]

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bark migraine, gastric problems, haematuria and memory

enhancing activity
24. Justicia gendarussa Leaves Sterols and flavonoids fever, hemiplegia, rheumatism, arthritis, headache, ear Ethanol (95%) [59]
(Acanthaceae) ache, muscle pain, respiratory disorders and digestive
troubles
25. Moringa oleifera Flowers, leaves Nitrile glycosides, niazirin, niazirinin, sterol Anti-arthritic Hydroalcoholic extract [60]
(Moringaceae) components stigmasterol, campisterol
26. Nyctanthes Leaves, stems Nyctanthoside, polysaccharides, iridoid glycosides, Sciatica, arthritis and anti-inflammatory Alcoholic extract [61]
arbortristis henylpropanoid glycoside, -sitosterol, -amyrin,
(Oleaceae) hentri-acontane, benzoic acid, glycosides
27. Premna serratifolia Wood Iridoid glycosides, alkaloids, phenolic compounds and Cardiovascular diseases, skin diseases, inflammatory 90% Ethanol [62]
(Verbenaceae) flavonoids diseases,
arthritis, gonorrhoea, rheumatism, anorexia and jaundice.
28. Pistacia khinjuk Leaf Flavonoid; galloylated compounds, gallic acid, methyl Anti-inflammatory Aqueous methanol [63]
(Anacardiaceae) gallate, quercetin-3-O-?-d-(4)C(1)-galactopyranoside
(hyperin), myricetin-3-O-?-l-(1)C(4)-rhamnopyranoside
(myricitrin), 1,6-digalloyl-?-d-glucose, 1,4-digalloyl-?-
d-glucopyranoside, and 2,3-di-O-galloyl-(?/?)-(4)C(1)-
glucopyranose (nilocitin)
29. Phyllanthus emblica syn. Leaves, bark or Flavonoids, kaempferol, ellagic acid and gallic acid; Hypercholesterolemic, rheumatoid arthritis and Water [64]
Emblica officinalis fruit vitamin C and other antioxidants like emblicanin A, osteoporosis
(Phyllanthaceae) emblicanin B, punigluconin, pedunculagin
30. Rosa multiflora Thunb. Hips Fatty acid, mainly including dodecanoic acid (8.72%), Dietary and medicinal purposes like cold, flu, Ethanol, petroleum ether, [65]
(Rosaceae) hexadecanoic acid (9.24%), pentadecanoic acid inflammation, osteoarthritis, rheumatoid arthritis and ethyl acetate
(1.58%), linoleic acid (26.04%), oleic acid (22.58%) chronic pain
and octadecanoic acid (6.3%)
31. Vitex negundo Roots, bark, C-glycoside, casticin, essential oil, vitamin c, benzoic Antiseptic, ophthalmic, anti-gonorrhoeic, depurative, anti- Ethanol, water [66]
(Verbenaceae) leaves, flowers acid, flavone inflammatory
32. Vernonia Seeds, dried Alkaloids, flavonoids, steroids, triterpenes and Anti-inflammatory, anti-arthritic Ethanol (99.9%) [67]
anthelmintica (Asteraceae) seeds, leaves polyphenols
and
Roots

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CONCLUSION Rheumatism Arthritis & Rheumatism-Arthritis Care & Research 1988;

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HOW TO CITE THIS ARTICLE

Wadekar JB, Sawant RL, Patel UB. Rheumatoid arthritis and herbal drugs: A
review. The Journal of Phytopharmacology 2015;4(6):311-318.

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