Plants having Anti-arthritic and Immunomodulator Potentials: An Review


Rupesh Pandey1, Priyanka Upadhayay1, Shiv Shankar  Shukla2*

1Research Scholar, Pacific University, Udaipur, Rajasthan

2Columbia Institute of Pharmacy, Tekari, Raipur  C.G.

*Corresponding Author E-mail:



Many allopathic drugs reported to be used for the treatment of inflammatory disorders are of least interest now a days due to their potential side effects and serious adverse effects and as they are found to be highly unsafe for human assistance. Herbals containing anti-inflammatory activity (AIA) are topics of immense interest due to the absence of several problems in them, which are associated with synthetic preparations. The primary objective of this review is to provide a deep overview of the recently explored anti-inflammatory agents belonging to various classes of phytoconstituents like alkaloids, glycosides, terpenoids, steroids, polyphenolic compounds, and also the compounds isolated from plants of marine origin, algae and fungi. Also, it enlists a distended view on potential interactions between herbals and synthetic preparations, related adverse effects and clinical trials done on herbals for exploring their AIA.


KEYWORDS:  Alkaloids, anti-inflammatory agents,   glycosides, herbals, immunomodulation.




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



Botanical name Family Part used


Parts and Extract used

Chemical constituent

Model used

Ref no.


Abrus precatorius Linn


Red and White Seeds Ethanol

flavones luteolin, abrectorin, orientin, isoorientin and desmethoxycentaureidin 7-0-rutinoside




Asystasia dalzelliana


Leaves Ethanolic

Steroids, flavanoid, alkaloids, tannins




Aristolochia bracteata


Whole plant Petroleum ether, chloroform and methanol

Aristrolochic acid, alkaloids, flavanoids.





Butea monosperma. L


Whole plant, Petroleum ether

Gallic acid,   pyrocatechin




Bauhinia variegate


Stem Ethanol

flavanoid, alkaloids




Borassus flabellifer L


Male flowers (inflorescences) Ethanolic

Steroids, saponins, borassosides.




Capparis spinosa L


Fruit Ethanol: Water

Flazin, Guanosine, Capparine,




Capparis erythrocarpos


Roots Ethanolic

Proteins, poly phenols




Cassia uniflora Mill


Leaves Petroleum ether, ethyl acetate, methanolic

Proteins, poly phenols, alpha galactosidase




Cissampelos pareira


Roots Aqueous ethanolic

Alkaloids, flavanoids




Cleome gynandra L


Leaves Ethanolic

Alkaloids, carotinoids, flavanoids, phytates, saponins,tannins




Cocculus hirsutus


Leaves Ethanolic

Alkaloids, carotinoids, flavanoids, phytates, saponins,tannins




Costus speciosus


Aerial part Methanolic

Diosgenin, succinic acid




Elaeocarpus sphaericus


Fruit Ethanolic

Alkaloids, carbohydrates, glycosides




Ficus bengalensis


Stem bark Methanolic

Alkaloids, glycosides




Glycosmis pentaphylla


Stem bark Ethanolic

Alkaloids, flavanoids




Glycyrrhiza glabra


Rhizomes Methanolic

Alkaloids, glycosides




Harpagophytum procumbens


Roots Ethanol

Alkaloids, glycosides




Hybanthus enneaspermus


Whole plant Alcoholic and aqueous

Alkaloids, carbohydrates, glycosides,




Justicia gendarussa Burm F


Leaves Ethanolic

Alkaloids, glycosides




Lawsonia innermis


Leaves Hydroalcoholic

Alkaloids, carbohydrates, glycosides, phytosterols, Saponins, tannins, proteins, flavanoids




 Merremia emarginata Burm.F


Whole plant Ethanolic

Alkaloids, carbohydrates, glycosides,




Machilus macrantha


Bark Petroleum ether, alkaloidal fraction, acetone extracts

Alkaloids, carbohydrates, glycosides,




Merremia tridentata (L.) Hall. F


Whole plant Ethanol

Ergosie alkaloids, pyrrolidine alkaloids




Piper longum


Fruit Aqueous

Alkaloids, steroids, tannins,




Pongamia pinnata


Leaves Methanolic

Alkaloids, steroids, tannins, flavanoids and glycosides




Phyllanthus amarus



alkaloids, glycosides, flavanoids,




Punica granatum Linn


Seeds Ethanolic

flavanoids, phenolic compounds




Pistia stratiotes


Leaves Aqueous and ethanolic

Alkaloids, glycosides,steroi ds, polysaccarides




Premna serratifolia Linn


Wood Ethanol

Alkaloids, steroids, tannins, flavanoids and glycosides




Randia dumetorum


Fruit Methanolic

alkaloids, glycosides, flavanoids,




Ricinus communis


Leaves Hydroalcoholic

Alkaloids, glycosides, steroids




Syzygium cumini


Seeds Methanolic

Alkaloids, glycosides, steroids, polysaccarides




Strychnos potatorum Linn


Seeds Aqueous

Saponin glycosides, Bsitosterol, carbohydrates




Sida rhombifolia


Aerial part Ethanol and aqueous

Alkaloids, glycosides, steroids




Tamarindus indica Linn


Seeds Alcoholic and aqueous

 alkaloids, glycosides, flavanoids, phenolic compounds




Tinospora cordifolia Willd


Leaves Ethanol

Alkaloids, glycosides, steroids, polysaccarides




Vernonia anthelmintica


Seeds Ethanolic

Sterols, sequiterpene lactones, flavones




Vitex negundo Linn


Leaves Ethanolic

Carbohydrates, sterols, alkaloids, glycosides, flavanoids, phenolic compounds




Wedelia calendulacea L


Leaves Methanol

flavanoids, phenolic compounds



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.  



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

Accepted on 14.03.2017           © RJPT All right reserved

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

DOI: 10.5958/0974-360X.2017.00222.0