INTRODUCTION:

Rheumatoid arthritis was a complex disease involving many cell types including macrophages, T cells, B cells, fibroblasts, lymphocytes etc. It was a progressive disease of synovial lining of peripheral joints with symmetrical inflammation that tends to potentially deforming poly arthritis and a broad spectrum of extra articular features. Common extra articular symptoms include anemia, muscle wasting, dry eyes etc. The patient experiences a reduced life expectancy due to frequent involvement of many organ systems. Several genes were implicated in vulnerability to RA and severity of disease, together with PTPN22, class II major histocompatibility complex genes and peptidylarginine transferases.

Evidence of serum immunity including high serum levels of auto antibodies such as rheumatoid factors and anticitrullinated peptide could be existed for many years before the onset of clinical arthritis. Cytokine networks involve tumour auto reactive T cells to escape deletion. Immune reactivity can be identified before clinical disease and could be manifested by the production of RFs and anti citrullinated peptide antibodies. When cells were recruited to the synovium, then the interleukin-6, necrosis factor and many other factors involved in disease perpetuation and could be targeted by therapeutic agents.

Bone and cartilage destruction appear to be primarily arbitrated by osteoclasts and fibroblast-like synoviocytes. The roles of small molecule mediators of inflammation (e.g., arachidonic acid metabolites), autoantibodies, cytokines, growth factors, chemokines, adhesion molecules and matrix metalloproteinase (MMPs) had been carefully defined.

ETIOLOGY:

The reasons for rheumatoid arthritis remain unknown but there is evidence that RA is immune mediated. It is possible that many arthritogenic stimuli activate the immune response in susceptible host. Epidemiological studies convey that both environmental and genetic factors cause RA. Although the immune genetics behind RA was incompletely understood, one of the top-studied and possibly most prominent genetic risk factors was class II MHC haplotype of an individual.

PATHOPHYSIOLOGY:

RA is characterized by infiltration of a variety of inflammatory cells into joints. Chronic inflammation characterized by antigen induced activation of lymphocytes which accumulate within joints. TNF and interleukin -1 are released by mast cells, macrophages etc which is linked with pro-inflammatory cytokine network in RA. This mediator causes matrix-degrading activities that eventually cause joint destruction. Sustained inflammation causes hypertrophy of synovium and formation of pannus leading to erosive destruction of cartilage and bone [2, 3].

On exposure to genetic and environmental factors innate immunity causes activation of dendritic cells, macrophages and fibroblast like synoviocytes. This occurs in the synovial region and from there dendritic cells move to the central lymphoid region to present the antigen. Thereby T-cells are activated which in turn cause the activation of B cells. T and B cells migrate to the joints and cause the activation of osteoclasts and other inflammatory cells. These in turn cause the release of proteolytic enzymes causing destruction in target organ. Figure 1 illustrates the pathophysiology of rheumatoid arthritis.

TREATMENT:

The goals of management of RA were to relieved pain, inflammation, prevent joint destruction, improve patient functional ability and maintain a normal lifestyle. The treatment was carried out with the help of vaccines, surgical sympathectomy, fever therapy, gold salt injections, cortisone advent etc. Treatment using biological drugs can be categorized below:

a. Disease modifying antirheumatic drugs:

It includes immunosuppressant drugs like methotrexate, cyclosporine etc and other drugs like sulfasalazine, leflunomide and gold sodium thiomalate.

b. Biologic response modifiers (BRMs):

It includes TNF-α inhibitors like infliximab, adalimumab and IL-1 antagonist like anakinra.

c. Adjuvant drugs including corticosteroids:

These drugs are limited due to life threatening side effects including malignancies, ulcers, bleeding and perforations. In many cases 2 or 3 drugs together should be used which produces potential adverse effects, which may be serious. Due to these limitations use of Complementary and Alternative Medicine (CAM) therapy such as acupuncture and usage of herbal extracts came to existence.

CAM practices were grouped to natural products, mind body medicine and, manipulative and body based practices. Herbal medicine involves the use of a dried or extracted form as therapeutic substances. There was a rich heritage of ethnobotanical usage of herbs by various tribal communities in India. Some of the herbal medicines used for RA are outlined below with their mechanism of actions.

Boswellia:

Plant extract containing oleo-gum resin obtained from the plant Boswellia serrate belonging to the family Bursaraceae was used to treat many diseases including Rheumatoid arthritis. The resin contain volatile oil such as cymene, limonene, terpinolene etc and gum portion is composed of mainly arabinose, xylose and galactose in small amounts. The gummy exudate from the plant is known as guggul [4]. Boswellic acid had specific inhibition of leukotriene synthesis via 5-lipooxygenase and cyclooxygenase activity or by blocking its translocation [5, 6].

Black currant seed oil:

The berries and leaves of the plant Ribes nigrum of family Saxifragaceae are used medicinally for maintaining health and treating several diseases. The oil obtained from these seed oil is a rich source of omega-3 and -6 fatty acids [ALA and GLA respectively]. It helps to maintain joint cell structures and function and possess anti-inflammatory action in the synovial region.

The essential acids ALA and GLA gets converted to prostaglandins in body which regulate the immune system and joint inflammation.GLA directly acts on some inflammatory cells and suppress inflammation [7].

Borage seed oil:

The oil obtained from the seed of Borago officinale belonging to the family Boraginaceae contains tannic acid, oleic acid, palmeitic acid and very high levels of linoleic acid and GLA. GLA was a precursor of prostaglandins which modulate the immune system. GLA might also suppress the inflammatory responses, by directly acting on inflammatory cells (inhibiting LT synthesis) [8].

Capsicum:

Capsicum are the dried ripe fruits of the plant Capsicum annum of Solanaceae family, which contain fixed oil, protein, pigments (capsanthin and carotene) and capsaicin as a volatile pungent principle. Even though capsaicin was thought to have carcinogenic activity it had been used to relieve pain in rheumatism and to treat psoriasis topically. Capsaicin causes depolarization of C-fibre polymodal receptors and release of substance P, which was a neurotransmitter that relayed pain signals to brain. Repeat applications deplete the reserves of substance Pat the afferent neurons leading to pain relief [1, 9].

Turmeric:

It was the dried as well as fresh rhizome of the plant Curcuma longa of Zingiberaceae family that was widely used as spice, coloring and flavoring agent. The active constituent of turmeric is curcumin. It selectively inhibits synthesis of inflammatory PG’s, thromboxane without affecting prostacyclin synthesis. Thus helps in anti-inflammatory activity [6]. It also provides protection against vascular thrombosis. Curcumin also inhibits cox-2 enzyme which is actually a pro-inflammatory substance [10 - 12].

Cats claw:

It is also known as life giving wine of Peru. The plant extract is obtained from the stem and roots of the plant Uncaria tomentosa of family Rubiaceae. The extract contains oxindole alkaloids, tannins, quinovic acid, glycosides, flavonoids and sterols. Pentacyclic oxindole alkaloids possessed anti-inflammatory and immune modulating effects [13]. The anti-inflammatory property resulted from its ability to inhibit TNF-α and to a lesser extent PGE-2 production [12, 14, 15].

Evening primrose oil:

It is also known as King’s cure-all. The extracted oil was rich source of polyunsaturated omega-3 fatty acids (LA and GLA) which could help in the regulation of pain and inflammation. It has been used to alleviate the morning stiffness in rheumatoid arthritis [16, 17].

Fever few:

The plant feverfew is also known as Featherfew. It consist of fresh and dried leaves and also aerial parts of the plant, which contain sesquiterpenes, lactones, chrysanthemin A and B, parthenolide, chrysanthemonin, chrysanthemolide and partholide. The anti-inflammatory activity is due to the inhibition of serotonin and histamine. Both play an important role in pain during rheumatism [18-20].

Flax seed oil:

It is also called as Linseed oil. It consists of the dried ripe seeds of the plant Linum usitatisimum of the family Linaceae and consist of glycerides of palmeitic, stearic, oleic, linoleic, linolenic acids and linamarin. Linseed oil was a rich source of ALA, which gets converted into docosahexanoic acid (DHA) and eicosapentanoic acid (EPA) which in turn gets converted to Prostaglandins (PGs). PGs regulate the immune system and fight joint inflammation [21, 22].

Tripterygium wilfordii:

The whole plant is poisonous except the root pulp which is used medicinally. The active constituents include triptolide (diterpene triepoxide), tripdiolide, triptolidenol, tripchlorolide and 16-hydrotriolide. The main constituent is triptolide which has an immunosuppressive activity and reduce the inflammation of joints by reducing the production of proteins causing inflammation [23].

Ashwagandha:

Withanolides, Withania roots are the other common names. The drug consists of the dried roots and stem bases of the plant Withania somnifera of the family Solanaceae. It contains alkaloids and steroidal lactones. The alkaloids include Withanine (main), Somniferine, Withananine, Pseudowithanine, Tropine, Pseudotropine and Choline. It reduces amplification and propagation of inflammatory response without causing any gastric damage [9, 24].

Willow:

Salix purpurea and other species of the family Salicaceae are the main sources of willow. The main constituent is salicin , a natural source of acetyl salicylic acid (aspirin). Salicin inhibits the production of PGs in the nerves and thus relieves pain and discomfort [25-27].

Ginger:

It consists of the fresh or dried rhizome of the plant Zingier officinal is belonging to the family Zingiberaceae. Ginger oil is constituted of monoterpenes, sesquiterpenes, oxygenated mono and sesquiterpenes and phenyl propanoids. The ginger extract reduces the production several chemical substances which promote joint inflammation [28-30]. Ginger inhibits the production of PGs in the nerves and relieves pain and discomfort

CONCLUSION:

Understanding of the etiology and pathogenesis of RA remains a complex problem, although the level of understanding had progressed considerably in recent years. T cell-dependent and independent processes contributed to disease initiation and perpetuation. It might important to appreciate differences in disease pathogenesis at various stages of process. These hypothesis have revealed many novel therapeutic targets and interventions that might lead to significant clinical benefit. The use of herbal medicines has increased for the past decade. It is safer, tolerant and more efficacious therapeutic approach. The standard drugs used for treatment of RA produce high degree of toxicity. This led to the emergence of herbal medicines. Studies have shown that compounds derived from Solanaceae, Bursaraceae, and Zingiberaceae show anti-inflammatory activity. Hence used in the treatment of RA.

CONFLICT OF INTEREST:

None

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Received on 30.12.2015 Modified on 22.01.2016

Res. J. Pharmacognosy & Phytochem. 8(1): Jan.- Mar. 2016; Page 32-36

DOI: 10.5958/0975-4385.2016.00007.8