INTRODUCTION:

Rheumatoid arthritis (RA) is a systemic, chronic and inflammatory autoimmune disorder that has affected an approximate of 1-2% of adult population worldwide, in which the females are more affected than males (1, 3, 4, 11). The manifestations of RA include inflammation in the joint synovial tissue, cartilage destruction, bone erosion, vasculitis, eye inflammation, cardio-pulmonary disease, pulmonary fibrosis and amyloidosis. As it is an autoimmune disorder which means that any unwanted trigger in the form of a foreign body, chemical or environmental factor, causes mistakenly damage of healthy tissues by a person’s own immune system. In this condition, whenever a person is exposed to a specific ‘trigger’, the immune system components starts damaging the healthy joint tissues. Therefore, the thin joint tissue lining having few blood vessels supply gets thickened due to the accumulation of white blood cells.

This inappropriate immune response activates the various factors of white blood cells including different types of cytokines and other inflammation mediators. According to researches, cytokines like Tumor Necrosis Factor- alpha (TNF-alpha), Interleukin-1 (IL- 1), Interleukin- beta (IL- beta), Interleukin-6 (IL-6), Interleukin-17 (IL-17), Interleukin-18 (IL-18) and receptor activator of nuclear factor kappa-B ligand (RANKL) are involved in case of moderate to chronic arthritic problems. Inflammatory response is initiated due to the activation of T cells, chemokines, adhesion molecules angiogenetic cytokines, growth factors and colony stimulating factors, as well as cyclooxygenase (COX) and lipoxygenase (LOX) (2, 3, 4, 10).

Generally, RA shows mild to moderate stages in the patient. But, with the rapid progress in inflammatory symptoms and irreversible tissue destruction in the joints, it can convert into the chronic state of arthritis, due to the severe effects of rheumatoid factors or HLADR4. In RA, joint damage in initiates due to the activation of cytokines by stimulating synovial macrophages, fibroblasts and chondrocytes in the nearby articular cartilage. There is secretion of some enzymes that are capable in degrading preoteoglycans and collagen, which results in the destruction of joint tissue. Due to the release of inflammatory factors and cytokines inside the joint blood vessels, start in the proliferation and spreading of synovial tissues, which is then called as pannus. Next stage is fibrosis, in which loss of joint mobility begins, which is known as ankylosis. Later, as a result of this, synovial membrane became thick and cartilages eroded; causes swelling in the joints and pain while movement. In the novel research, it has been found that the development of RA is due to the effect of gastrointestinal (GI) tract bacteria cell wall components can induce arthritis.

Components like lipopolysaccharide toxins, peptidoglycan-polysaccharide complex were able to contribute in the development and exacerbation of autoimmune disorders including arthritis in a suitable rat model (2, 3, 10). As RA has become major problem of the old age person, there is a need to find out the suitable and efficient medicines to overcome this problem. Some non-biological compounds like methotrexate and tofacitinib have shown anti-rheumatic activities, according the research. But, besides, it, there are high levels of risk and side effects have seen in the patient including increase in the levels of serum creatinine, serious infections, etc. Therefore, proper management of RA has become a challenge to researchers as well as physicians. With the traditional uses of biological compounds, produced by herbs, it has been cleared that there is a possibility in the successful treatment of all types of arthritis without any adverse effect or side effect by reducing the future risk of arthritis. Hence, in this work, we have done a reviewed study which focuses on the benefits of herbal medicines to establish a successful and efficient treatment of arthritis (6, 7, 11).

Herbs Used in the Treatment of Rheumatoid Arthritis:

Herbal products has got a potential in reducing the adverse effects of various ailment, hence it has various traditional uses in the treatment of different diseases. There are certain secondary metabolites that show pharmacological effect against various diseases. These are alkaloids, flavonoids, tannins and phenolic compounds. Researchers have reported the medicinal impact during the analytical study performed for the treatment of diseases, from their organic extracts, for example, ethanolic, acetonic or methanolic extracts, in specific concentrations. With the hike in the cases of rheumatoid arthritis, the studies have become more focused for curing this major problem. Researchers have got success in finding the herbal medicine, which is able to reduce the symptoms of rheumatoid arthritis as well as risk of developing this disorder (1, 8, 9). Some herbal medicinal plants used to treat RA are described below:

Aloe barbadensis:

It is commonly known as aloe vera in India, found in regions of Europe as well as north-west Himalayas in India. It produces acid compounds like anthraquinone, anthracene, cinnamic acid and anthranilic acid. According to the researches, anthraquinone has showed anti-inflammatory activities against arthritis. It also contains sterols like β-sitosterol and lupeol. β-sitosterol also shows anti-inflammatory activity and beside it, it behaves as an anti-cholesterol agent. On, the other hand, lupeol acts as an analgesic and anti-microbial agent. Anthranilic acid and anthraquinone both have potential against arthritic and articular rheumatic problem. Both of them block the biosynthetic activity of bradykinin which is able to develop pain and inflammation in arthritic patients (4, 5).

Ficus bengalensis:

It is a large and extensive growing tree which is commonly known as Banyan tree in the regions of India. According to the researches, it contains flavonoids, tannins, saponions and steroids that are able to behave as an anti-rheumatic agent as well as capable in improving the immune activities. These activities were observed in the methanolic extract of the bark of banyan tree (8, 4).

Bosewellia serrata:

It is commonly known as shallaki or salai guggal. It is majorly found in the regions of Bihar, Madhya Pradesh and Gujarat in India as well as regions of Northern America and Middle-east. It contains β – boswellic acid in gummy-oleo resins (strips of Bosewellia bark), which has anti-inflammatory, anti-arthritic and anti-atherosclerotic activities. It is capable of deactivation in pro-inflammatory factors i.e. cytokines and other immune factors. Therefore, it has been used as an ayurvedic medicine as well as a potential cure for arthritis since historic period (4, 5, 9).

Withania somnifera:

Common name of this plant is Ashwagandha, also known as Indian ginseng. Since ancient times, it has been used for medicinal purposes in Ayurveda and Unani. The growth and development of this plant require sub-tropical regions in India, mainly Punjab, Rajasthan, Uttar Pradesh, Gujarat, Madhya Pradesh and Maharashtra. Its pharmacological activity has been observed due to the presence of alkaloids and steroidal lactones. Withanine, pseudo-withanine, tropine, pseudo-tropine, somniferine, somnine are the types alkaloids found in Ashwagandha. Researchers have reported the anti-inflammatory effect of root extracts which was equivalent with the effect of 5mg/kg of hydrocorticone sodium succinate. Research has also showed that the oral administration of root powder of Ashwagandha is effective in reducing arthritic problems (4, 5).

Zingiber officinale:

It is the most useful herb, which is generally known as ginger. It is cultivated in the regions of South-east Asia mainly Caribbean island, India, Africa, Australia, Mauritius and Taiwan. It is rich in starch, fat, fibre, volatile oil, inorganic material and residual moisture. The ginger oil has monoterpine, hydrocarbons, sesquiterpene hydrocarbons, oxygenated mono and sesquiterpenes in which sesquiterpene lactones has anti-inflammatory property. In the arthritic patients, ginger has been reported to have positive effect in reducing pain and swelling (4, 5).

Camellia sinensis:

It is native in China, South and South-east Asia including tropical and sub-tropical regions of the world, with the common name Green tea, green tea extract, Chinese tea. Its pharmacologically active components are polyphenols, catechins and flavonols. This plant has showed the effect in reducing the risk of collagen-induced arthritis in the model of rats, by decrease in the serum levels of tumors necrosis factor-α (TNF-α), PGE2, Interleukin- 1 β and Interleukin-6 as well as reduced level of inflammatory cytokines, γ-interferon and COX-2 (4, 5).

Curcuma longa:

Indian saffron or turmeric is cultivated in the various regions of the world including India, Indonesia, China, Sri Lanka, Jamaica, Peru, for its rhizome. Components like volatile oil, resins, starch grains and curcuminoids (yellow colored substance) are found in C. longa. Curcuminoids is also known as curcumin, a natural component which is found in turmeric rhizomes, has anti-inflammatory properties. It has been reported that low doses of purified curcuminoids (4mg total curcuminoids/kg/d) posses inhibitory effect against joint inflammation in the cases of both acute and chronic arthritis. Therefore, it has been considered as an effective anti-inflammatory, analgesic and anti-arthritic agent since traditional period (4, 5, 9).

Boerhaavia diffusa:

It is commonly known as Punarnava, distributed worldwide in the regions of Australia, China, Sudan, Egypt, South Africa, USA, Sri Lanka, Pakistan and Middle-east. Phytochemical molecules like alkaloids, glycosides, steroids, flavonoids and triterpenpoids are present in it. Punarnava plant shows anti-inflammatory activity which works in cases of arthritis (7).

Terminalia chebula:

It is also known as Haritaki which is widely distributed in the regions of India, Pakistan, Nepal and South China. It is one of the components of Triphala Churna. Biologically active compounds like tannins, alkaloids, flavonoids, terpenoids, steroids, saponins, proteins and carbohydrates are present in it. According to researches, it has been proved that this herbal drug has anti-arthritic activity by following Freund’s adjuvant arthritic model (4, 7).

Smilax officinalis:

Sarasparilla, common name of S. officinal is, cultivated in the areas of South America, Jamaica, the Caribbean Mexico and West Indies. Aqueous extract of this has been proven to have anti-inflammatory and analgesic property. Besides it, this plant has proven its anti-arthritic property in the Freund’s adjuvant model (7).

Table 1: Ayurvedic herbal remedies with their possible outcomes during the RA treatment⁵

S. No.	Ayurvedic herbal formulas	Results of the study
1	Dasmularista, Pippatyasava and Vettumarangutika	The results suggested that the combination of the 3 formulas was effective in the stage of RA
2	Zingiber officinale	Majority of patients experienced some level of relief from pain and swelling (28 with RA, 18 with OA and 10 with muscular discomfort)
3	Zingiber officinale –Tinospora cordifolia (decoction)	Reduced pain and swelling (RA patients)
4	RasonadiKvatha (a decoction of Zingiber officinale, Allium sativam and Vitex negundo)	RA patients showed significant improvement in pain, swelling, tenderness and restriction of affected joints
5	Tinospora cordifolia and Balsamodendrom mukul	Improvement in signs and symptoms of RA
6	Tinospora cordifolia and Alpinia officinarum	Improvement in signs and symptoms of RA
7	Vatagajanankusa Rasa and Maharasnadi Kwatha	Reduced pain and swelling of RA patients
8	Vatari Guggul (Bhasajya Ratnavali) and Maharasnadi Kavatha	A significant improvement in pain and a decrease in ESR level of RA patients
9	Withania somnifera, Boswellia serrata, Curcuma longa and a zinc complex	The herbo-mineral formulation produced a drop in the severity of disability score of OA patient
10	Withania somnifera	Improvement in signs and symptoms of RA in 76 % patients

Table 2: List of Common Anti-arthritic Herbs and their pharmacologically active part used in the treatment of Arthritis⁸

S.No	Botanical name	Family	Part used	Extract used	Model Used
1	Aristolochia bracteata	Aristolochiaceae	Whole plant	Petroleum ether, chloroform and methanol	FCA
2	Asystasia dalzelliana	Acanthaceae	Leaves	Ethanolic	FCA
3	Abrus precatorius Linn	Leguminosae	Red and White Seeds	Ethanol	FCA
4	Butea monosperma L	Fabaceae	-	Petroleum ether	FCA
5	Bauhinia variegate	Caesalpiniaceae	Stem	Ethanol	CFA
6	Borassus flabellifer L	Arecaceae	Male flowers (inflorescences)	Ethanolic	FCA
7	Capparis spinosa L	Capparidaceae	Fruit	Ethanol:Water	AIA
8	Capparis erythrocarpos	Capparaceae	Roots	Ethanolic	FCA
9	Cassia uniflora Mill	Caesalpiniaceae	Leaves	Petroleum ether, ethyl acetate, methanolic	CFA
10	Cissampelos pareira	Menispermaceae	Roots	Aqueous ethanolic	CFA
11	Cleome gynandra L	Capparidaceae	Leaves	Ethanolic	AIA
12	Cocculus hirsutus	Menispermaceae	Leaves	Ethanolic	FCA, FIA
13	Costus speciosus	Costaceae	Aerial part	Methanolic	FCA
14	Elaeocarpus sphaericus	Elaeocarpaceae	Fruit	Ethanolic	FCA
15	Ficus bengalensis	Moraceae	Stem bark	Methanolic	FCA, FIA, AIA
16	Glycosmis pentaphylla	Rutaceae	Stem bark	Ethanolic	FCA
17	Glycyrrhiza glabra	Leguminosae	Rhizomes	Methanolic	CFA
18	Hybanthus enneaspermus	Violaceae	Whole plant	Alcoholic and aqueous	FCA
19	Harpagophytum procumbens	Pedaliaceae	Roots	Ethanol	FCA
20	Justicia gendarussa Burm F	Acanthaceae	Leaves	Ethanolic	FCA, CIA

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

CONCLUSION:

India has a vast variety of flora across the different regions of the country which require variable climatic and weather condition to grow. Besides it, these herbs have their own significance in the treatment of various human as well as animal diseases since the ancient times. Rheumatoid arthritis, one of the types of arthritic disorder, has become a common major problem among human, especially after the age of forty. But with the reviewed study, we can conclude that this disorder can also be cured successfully with the help of suitable herbal treatment, without any side effect or adverse effect on the body; reduction in joint pain and swelling.

REFERENCES:

1. Singh Vishwabhan, Patel Harsh, Suvagiya Vishal, Singh Kailash (2011). Some Traditionally Used Anti-Arthritic Herbs A Review. International Research Journal of Pharmacy. 43-45:2(11).

2. Kou Katayama, Takeo Matsuno, Takaki Waritani, Kuniaki Terato, Hiroshi Shionoya (2011). Supplemental Treatment of Rheumatoid Arthritis with Natural Milk Antibodies against Enteromicrobes and their Toxins: Results of an Open-Labelled Pilot Study. Nutrition Journal. 10:2.

3. Melainie Cameron, Joel J. Gagnier, Christine V. Little, Tessa J. Parsons, Anette Blümle and Sigrun Chrubasik (2009). Evidence of Effectiveness of Herbal Medicinal Products in the Treatment of Arthritis; Part 2: Rheumatoid Arthritis. Phytotherapy Research. 1647-1662:23.

4. Amandeep Kaur, Parminder Nain, Jaspreet Nain (2012). Herbal Plants Used in the Treatment of Rheumatoid Arthritis: A Review. International Journal of Pharmacy and Pharmaceutical Sciences. 44-57:4(4).

5. A. Subramoniam, V. Madhavachandran and A. Gangaprasad (2013). Medicinal Plants in the Treatment of Arthritis. Annals of Phytomedicine. 3-36:2(1).

6. Gary J Macfarlane, Ashraf El-Metwally, Howard Bird. Complementary and alternative medicines for the treatment of rheumatoid arthritis, osteoarthritis and fibromyalgia. A report by Arthritis Research UK. 3300/CAM-REP/12-1. ISBN 978-1-901815-13-9.

7. Dhaval Patel, Ginpreet Kaur, Mrunal Ghag Sawant and Pradeep Deshmukh (2013). Herbal Medicine- A Natural Cure to Arthritis. International Journal of Natural Products and Resources. 27-35:4(1).

8. Dixit K. Praveen, Mittal Suchita (2013). Herbal Sources of Anti-Arthritic Potential: A Comprehensive Review. International Journal of Pharmaceutical and Biomedical Research. 88-92: 4(2).

9. Chandini Ravikumar (2014). Herbal Remedy for Rheumatoid Arthritis. Journal of Pharmaceutical Sciences and Research. 310-312:6(9).

10. Clinical Guidelines for the Diagnosis and Management of Early Rheumatoid Arthritis (2009). National Health and Medical Research Council.

11. Eun Bong Lee, Roy Fleischmann, Stephen Hall, Bethanie Wilkinson, John D. Bradley, David Gruben, Tamas Koncz, Sriram Krishnaswami, Gene V. Wallenstein, Chuanbo Zang, Samuel H. Zwillich, and Ronald F. Van Vollenhoven, For the Oral Start Investigators (2014). Tofacitinib versus Methotrexate in Rheumatoid Arthritis. The New England Journal of Medicine. 2377-2386: 370.

Received on 15.10.2015 Modified on 04.11.2015

Res. J. Pharmacognosy & Phytochem. 8(1): Jan.- Mar. 2016; Page 37-40

DOI: 10.5958/0975-4385.2016.00008.X