INTRODUCTION:

Arthritis is inflammation of one or more of your joints. The main symptoms of arthritis are joint pain and stiffness, which typically worsen with age. The most common types of arthritis are osteoarthritis and rheumatoid arthritis. The major complaint by individuals who have arthritis is joint pain. Pain is often a constant and may be localized to the joint affected. The pain from arthritis is due to inflammation that occurs around the joint, damage to the joint from disease, daily wear and tear of joint, muscle strains caused by forceful movements against stiff painful joints and fatigue.

Allopathic medications have been prescribed to alleviate symptoms of this disease which results into associated side effects like heart attack, stroke, stomach ulcers, bleeding from the digestive tract, and kidney damage etc [1]. Hence the use of herbal medicine is becoming popular due to toxicity and side effects of allopathic medicines. The plant, as one of the important sources, still maintains its original place in the treatment of various diseases, including arthritis, with minimum side effects. Considerable studies have been carried out on ethno medicinal plants; however, only few indigenous medicinal plants have attracted the interest of scientists, to investigate them as a remedy for arthritis.

Role of Immunostimulants or immunomodulators

Drugs which enhance immune responses and can be used for the prevention or cure of some infective conditions and also in the management of arthritis [2].

Immune Mechanism

Basically there are two different types of lymphoid cells, T and B cells which mediate ‘cellular’ and ‘serologic’ or ‘humoral’ immunity, respectively. Both these types of cells are present in the circulating blood and in peripheral lymphoid tissues[3]. The recognition of the antigen by the T cells leads to proliferation of these cells, infiltration of immune cells at the site of action and cellular immunity.These reactions may be manifested as Delayed type Hypersensitivity, tissue graft rejection [3]. The other limb of immune system involving B cells is responsible for the genesis of specific antibodies immunoglobulins (IgA, IgD, IgE, IgM). The recognition of antigen (Ag) by the B cells leads to proliferation of these cells, conversion to plasma cells and generation of specific antibodies (Ab). The specific Ab binds with the specific antigen leading to its inactivation or even phagocytosis. Phagocytic Activity by Nitroblue tetrazolium dye reduction assay, Lymphocyte Proliferation by mitogen.

Immune Deficiency

Immune system protects against invading microorganisms, toxins and foreign cells. Immunodeficiency areas like Digeorge’s syndrome due to lack of T cells (deficient cellular immunity), agammaglobinaemia due to lack of B cells (deficient humoral immunity) and Severe combined immunodeficiency disease (SCID) is due to adenosine deaminase deficiency causing death to T and B cells. AIDS is due to infection with HIV which causes depletion of CD4+ T helper cells .

Mechanisms of Immunomodulation

Drugs may modulate immune mechanism by either suppressing or by stimulating one or more of the following steps

1. Antigen recognition and Phagocytosis

2. Lymphocyte proliferation/differentiation

3. Synthesis of antibodies

4. Antigen-antibody interaction

5. Release of mediators due to immune response

6. Modification of target tissue response/target effecter organ

7. Complement system

List of herbal sources of anti-arthritic activity

S.No	Botanical name Family Part used	Family	Parts and Extract used	Chemical constituent	Model used	Ref no.
1.	Abrus precatorius Linn	Leguminosae	Red and White Seeds Ethanol	flavones luteolin, abrectorin, orientin, isoorientin and desmethoxycentaureidin 7-0-rutinoside	FCA	[4]
2.	Asystasia dalzelliana	Acanthaceae	Leaves Ethanolic	Steroids, flavanoid, alkaloids, tannins	FCA	[5]
3.	Aristolochia bracteata	Aristolochiaceae	Whole plant Petroleum ether, chloroform and methanol	Aristrolochic acid, alkaloids, flavanoids.	FCA	[6]
4.	Butea monosperma. L	Fabaceae	Whole plant, Petroleum ether	Gallic acid, pyrocatechin	FCA	[7]
5.	Bauhinia variegate	Caesalpiniaceae	Stem Ethanol	flavanoid, alkaloids	CFA	[8]
6.	Borassus flabellifer L	Arecaceae	Male flowers (inflorescences) Ethanolic	Steroids, saponins, borassosides.	FCA	[9]
7.	Capparis spinosa L	Capparidaceae	Fruit Ethanol: Water	Flazin, Guanosine, Capparine,	AIA	[10]
8.	Capparis erythrocarpos	Capparaceae	Roots Ethanolic	Proteins, poly phenols	FCA	[11]
9.	Cassia uniflora Mill	Caesalpiniaceae	Leaves Petroleum ether, ethyl acetate, methanolic	Proteins, poly phenols, alpha galactosidase	CFA	[12]
10.	Cissampelos pareira	Menispermaceae	Roots Aqueous ethanolic	Alkaloids, flavanoids	CFA	[13]
11.	Cleome gynandra L	Capparidaceae	Leaves Ethanolic	Alkaloids, carotinoids, flavanoids, phytates, saponins,tannins	AIA	[14]
12.	Cocculus hirsutus	Menispermaceae	Leaves Ethanolic	Alkaloids, carotinoids, flavanoids, phytates, saponins,tannins	FCA, FIA	[15]
13.	Costus speciosus	Costaceae	Aerial part Methanolic	Diosgenin, succinic acid	FCA	[16]
14.	Elaeocarpus sphaericus	Elaeocarpaceae	Fruit Ethanolic	Alkaloids, carbohydrates, glycosides	FCA	[17]
15.	Ficus bengalensis	Moraceae	Stem bark Methanolic	Alkaloids, glycosides	FCA, FIA, AIA	[18]
16.	Glycosmis pentaphylla	Rutaceae	Stem bark Ethanolic	Alkaloids, flavanoids	FCA	[19]
17.	Glycyrrhiza glabra	Leguminosae	Rhizomes Methanolic	Alkaloids, glycosides	CFA	[20]
18.	Harpagophytum procumbens	Pedaliaceae	Roots Ethanol	Alkaloids, glycosides	FCA	[21]
19.	Hybanthus enneaspermus	Violaceae	Whole plant Alcoholic and aqueous	Alkaloids, carbohydrates, glycosides,	FCA	[22]
20.	Justicia gendarussa Burm F	Acanthaceae	Leaves Ethanolic	Alkaloids, glycosides	FCA, CIA	[23]
21.	Lawsonia innermis	Lythraceae	Leaves Hydroalcoholic	Alkaloids, carbohydrates, glycosides, phytosterols, Saponins, tannins, proteins, flavanoids	FCA, FIA	[24]
22.	Merremia emarginata Burm.F	Convolvulaceae	Whole plant Ethanolic	Alkaloids, carbohydrates, glycosides,	FCA	[25]
23.	Machilus macrantha	Lauraceae	Bark Petroleum ether, alkaloidal fraction, acetone extracts	Alkaloids, carbohydrates, glycosides,	FCA	[26]
24.	Merremia tridentata (L.) Hall. F	Convolvulaceae	Whole plant Ethanol	Ergosie alkaloids, pyrrolidine alkaloids	CFA	[27]
25.	Piper longum	Piperaceae	Fruit Aqueous	Alkaloids, steroids, tannins,	FCA	[28]
26.	Pongamia pinnata	Fabaceae	Leaves Methanolic	Alkaloids, steroids, tannins, flavanoids and glycosides	FCA	[29]
27.	Phyllanthus amarus	Euphorbiaceae	Aqueous	alkaloids, glycosides, flavanoids,	FCA	[30]
28.	Punica granatum Linn	Punicaceae	Seeds Ethanolic	flavanoids, phenolic compounds	FCA	[31]
29.	Pistia stratiotes	Araceae	Leaves Aqueous and ethanolic	Alkaloids, glycosides,steroi ds, polysaccarides	AIA	[32]
30.	Premna serratifolia Linn	Verbenaceae	Wood Ethanol	Alkaloids, steroids, tannins, flavanoids and glycosides	AIA	[33]
31.	Randia dumetorum	Rubiaceae	Fruit Methanolic	alkaloids, glycosides, flavanoids,	FCA	[34]
32.	Ricinus communis	Euphorbiaceae	Leaves Hydroalcoholic	Alkaloids, glycosides, steroids	FCA	[35]
33.	Syzygium cumini	Myrtaceae	Seeds Methanolic	Alkaloids, glycosides, steroids, polysaccarides	FCA	[36]
34.	Strychnos potatorum Linn	Loganiaceae	Seeds Aqueous	Saponin glycosides, Bsitosterol, carbohydrates	FCA	[37]
35.	Sida rhombifolia	Malvaceae	Aerial part Ethanol and aqueous	Alkaloids, glycosides, steroids	AIA	[38]
36.	Tamarindus indica Linn	Ceasalpiniaceae	Seeds Alcoholic and aqueous	alkaloids, glycosides, flavanoids, phenolic compounds	FCA	[39]
37.	Tinospora cordifolia Willd	Menispermaceae	Leaves Ethanol	Alkaloids, glycosides, steroids, polysaccarides	FCA	[40]
38.	Vernonia anthelmintica	Asteraceae	Seeds Ethanolic	Sterols, sequiterpene lactones, flavones	FCA	[41]
39.	Vitex negundo Linn	Verbenaceae	Leaves Ethanolic	Carbohydrates, sterols, alkaloids, glycosides, flavanoids, phenolic compounds	FCA	[42]
40.	Wedelia calendulacea L	Asteraceae	Leaves Methanol	flavanoids, phenolic compounds	CFA	[43]

FCA- Freund’s Complete Adjuvant induced arthritis, AIA- Adjuvant induced arthritis, CIA- Collagen induced arthritis, FIA- Formalin induced arthritis, AIA- Agar induced arthritis, CFA- Complete Freund’s Adjuvant induced arthritis

Chemical Constituent

Wide ranges of phytoconstituents were responsible for anti-arthritic activity includes alkaloids, glycosides, tannins, phenolics, anthocyanins, sterols, triterpenoids etc . These phytoconstituents present in plant exert desired pharmacological effect on body and thus act as natural anti-arthritic agents.

Various animal models for anti arthritic activity

Collagen type ii induced arthritis in rats

Collagen-induced arthritis (CIA) is among the most widely used animal models of RA. CIA is genetically controlled by Class II major histocompatibility complex (MHC) molecules. CIA an excellent model for studying the mechanisms underlying immune responses to an auto antigen potentially involved in human disease. Collagen arthritis can be induced readily in many strains of rats by immunizing them with heterogonous or homologous native type II collagen emulsified in incomplete Freund's adjuvant. This disease, which is characterized by the development of both cellular and humoral immune response to type II collagen, can be passively transferred by sensitized spleen and lymph node cells as well as IgG antibodies to type II collagen. These findings are consistent with the proposal that collagen arthritis is the relt of immunologic hypersensitivity to type II collagen. In a recent report, showed that rats with adjuvant arthritis exhibited both humoral and cellular sensitivities to homologous type II collagen. When introduced into the dermis, CII is immediately captured by antigen-presenting cells (APCs).Disease involves activation of both T and B cells that are antigen-specific and auto reactive. T cell and T cell-derived cytokines promote differentiation and activation of macrophages, osteoclasts and fibroblast, leading to an aggressive erosive arthritis[44].

Complete Freund's adjuvant induce arthritis in rat

Freund's complete adjuvant induced arthritis in rat model which is the best and most widely used experimental model for arthritis with clinical and laboratory features which closely mimic the clinical features of human rheumatoid disease. This model is sensitive to anti inflammatory and immune inhibiting medicines and considers being relevant for the study of phathophysiological and pharmacological control of inflammation process as well as for the evaluation of anti nociceptive potential of drugs[45,46].

Cartilage oligomeric matrix protein (COMP) induced arthritis

Immunization with COMP in IFA induces severe arthritis in susceptible rat strains, such as DA and LEW. Although the peripheral joint arthritis clinically resembles RA, COMP-induced arthritis, however, does not result in the permanent destruction of joints. Disease development appears to be dependent on an immune response to autologous COMP and not on cross-reactivity to other cartilage rat collagens [47,48,49].

Carrageen induce paw odema

Carrageen an (CRR), a sulphated polysaccharide, is often used in pain models. CRR produces acute and chronic inflammatory responses. The acute response appears to be similar to rheumatoid arthritic lesions, which are characterized by sustained cellular emigration[50,51]. Hydrolyzed carrageen an induce ileocecal inflammation by inhibiting deoxyribonucleic acid synthesis it also effects on chromium release, and cell morphology retarded cell growth and eventually caused cell death.

Monosodium urate crystal-induced arthritis

Unmetabolised product of purine are deposited as uric acid in synovial tissue joint which evoke activation of kinin leukotriene B4, Accumulation of neutrophil granulocytes characterized by intermittent attack of Acute Arthritis or Gout. On this this principle are injected interadermaly at knee joint produce arthritis[52]. The importance of urate in gout and the deposition of sodium urate in gouty tophi is well known. By Injecting 20 mg sodium urate crystal suspensions in their own knee joint 12. They experienced severe pain and prostration which resembled an acute gouty attack[53].

Proteoglycan-induced Arthritis

Proteoglycan (PG) aggrecan, a major macromolecular component of cartilage, is highly immunogenic; it induces arthritis in genetically susceptible BALE/c mice. PGcore protein-speciWc synthetic peptides to prime and hyper-immunize BALB/c mice[54].

Expected outcome of researched work

The proposed research work is thought to be a step towards providing directions for further research for better treatment with least toxicities for arthritis disease.

CONCLUSION:

Arthritis is an auto immune disorder characterized by pain, swelling and stiffness. Its prevalence depends upon age. It occurs more frequently in women than in men. It is an inflammation of synovial joint due to immuno mediated response. The high incidences of anti-CII antibodies and CII-specific T cells indicate that CII is one of the major auto antigens of human RA. In this way, the higher prevalence's of CII-specific antibodies and T cells noted during the early phase of RA indicate that CII-specific immunity plays an important role in the initiation of inflammation in the articular joints. So, collagen type-II is best model for evaluation of anti-arthritic drugs compare to other models.

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Received on 17.01.2017 Modified on 24.02.2017

Research J. Pharm. and Tech. 2017; 10(4): 1252-1256.

DOI: 10.5958/0974-360X.2017.00222.0