INTRODUCTION:

Traditional and folklore medicines play an important role in healthcare. There exist a plethora of knowledge and benefits of herbal drugs in our ancient literature of ayurvedic and unani medicine. Medicinal plants and their optional secondary metabolites are increasingly used in the treatment of many diseases. According to World Health Organization (WHO) about 80% of the population in developed countries relies mostly on traditional medicine for their primary healthcare. The search for herbal remedies is growing which can be accounted for its effectiveness, minimal side effect and relatively low cost of the herbal drugs. Complementary, alternative and traditional medicines are the pivotal source of herbal medication guidance, but surely modern medicine must prove these guidelines through scientific methods before using them in practice.

In this review, we have endeavored to assess the plants and the most clinical evidence of their anti-inflammatory and anti arthritic effects.¹

Inflammation is a severe response by living tissue to any kind of injury. There can be four primary indicators of inflammation: pain, redness, heat or warmness and swelling. Inflammation is either acute or chronic inflammation. Acute inflammation may be initial response of the body to harmful stimuli. In chronic inflammation, the inflammatory response is out of proportion resulting in damage to the body². Cyclooxygenase (COX) is the key enzymes in the synthesis of prostaglandins, prostacyclins and thromboxanes which are involved in inflammation, pain and platelet aggregation.³ Steroidal and non-steroidal anti-inflammatory drugs (SAIDs and NSAIDs, respectively) are currently the most widely used drugs in the treatment of acute inflammatory disorders, despite their renal and gastric negative secondary effects.³ these drugs block COX-1 and COX-2 enzymes activity. COX enzymes assist with prostaglandins production. NSAIDs, steroidal anti-inflammatory drugs are being used till now, as a resulting term uses of these drugs cause adverse side effects, like gastric lessions, cardiovascular, renal failure and gastrointestinal damage.⁴

Rheumatoid arthritis (RA) is an autoimmune disease in which there is joint inflammation, synovial proliferation and destruction of articular cartilage. It is one of the most common autoimmune diseases which is chronic, progressive and systemic inflammatory disorder affecting the synovial joints and typically leads to symmetrical arthritis causing joint damage, which has accountability for the deformity and disability. It is the most common cause of physical disability in developed countries and the prevalence ranges from 0.3% and 1.50% with a female:male ratio of 3:1.⁵ There is no known cure for RA but several drugs such as anti-inflammatory and DMARDS are used in mono or combination therapies to inhibit the disease process. However, prolonged use of these drugs is associated with deterious side effects like gastric ulceration, hemorrhage, anemia and kidney dysfunction.⁶ Thus, researchers have been directed towards the use of biologics and plant derived drugs in the treatment of disease and to overcome the serious drawbacks. Hence, there is an urgent need to find safer compounds for the management of inflammation and RA. Thus, Revival with herbal and and other complementary therapies in the management of chronic diseases (RA and other inflammatory diseases are well documented.⁷

Anti inflammatory and Antiarthritic Plants:

Aloe emodin:

Aloe emodin is an anthraquinone and a variety of emodin present in aloe latex, an exudate isolated from aloe plants. Aloe emodin is traditionally used as an anti inflammatory agent. Aloe emodin shows in vitro anti-inflammatory activity due to inhibition of inducible nitric oxide (iNO) and prostaglandin E_2,via its action on murine macrophages.⁸The potential immunosuppressive mechanism of emodin may be due to the suppression of lymphocyte proliferation and influence of cytokines. The anti inflammatory activity of Aloe emodin was studied in carageenan rat induced paw oedema and the study shows that aloe emodin showed significant (P < 0.001) reduced paw edema at 50 and 75mg/kg. Study of ant arthritic activity was carried out by Complete Freund’s adjuvant induced arthritis model and it showed significant (P<0.001) decrease in injected and non injected paw volume. Aloe emodin exhibited better antiarthritic activity than the standard diclofenac. It is known that aloe emodin inhibits dose dependently inducible nitric oxide synthase (iNO) and nitric oxide (NO) production. In particular, aloe emodin was an effective inhibitor of inflammatory responses, and its activity was similar to that of potent flavanols. Several publications also reported the therapeutic possibility of Aloe emodin as well in neurodegenerative conditions.⁹

Cassia fistula:

Cassia fistula linn from Fabaceae family is a flowering plant which is considered as an herbal medicine for the treatment of various diseases. It is also known as Golden shower has therapeutic importance in healthcare since ancient times. In Ayurvedic medicine the golden shower tree is known as Aragvadha “disease killer”.¹⁰ Methanols extract of Cassia fistula leaves were tested for anti-inflammatory activity as compared with phenylbutazone, using carrageenan, histamine and dextran induced paw edema in rats. The relative percentage of inflammatory inhibition by Cassia fistula extract was maximum at 800 mg/kg against all inflammatory mediators, with a maximum edema inhibition of 34.6 percent at 4h after administration of the inflammatory agent as compared with phenylbutazone at 35.6 percent inhibition at 4 h after injection of carrageenin.¹¹Anti arthritic effect of methanolic and anthraquinone extract of Cassia fistula were evaluated in Complete Freund’s Adjuvant (CFA) induced murine model of RA. The result showed a significant with a p-value<0.05 and about 36-50% lesser ankle swelling and reduction in rheumatoid factor by 62.5% and 87.5% as compared to that of the deceased control in a dose dependent manner (500mg>250mg/kg) for both methanolic and anthraquinone extract of Cassia fistula. Cassia fistula due to its anti-inflammatory and anti- oxidant properties it can be used in RA treatment.¹²

Costus speciosus:

Costus speciosus Koen. (Keu, Crape ginger) belonging to the family Costaceae is an Indian ornamental plant, which has been widely used in several indigenous medicinal formulations. C. speciosus plant extracts were tested for its anti inflammatory and anti arthritic activity. Anti inflammatory property of the ethanolic extract of the rhizome of Costus speciosus was studied in Carrageenan rat induced paw edema. Significant anti inflammatory effect was found against carrageenan induced edema formation in rats at doses of 400 and 800mg/kg.¹³ The therapeutic potential of the plant as an anti-arthritic agent were tested against Freund’s complete adjuvant (FCA) induced arthritis. For the evaluation of antiarthritic activity the methanolic extract of the aerial parts of Costus speciosus were used in experimental animals. After 21 days the methanolic extract of CS in doses of 400 and 800mg/kg showed significant (P<0.05) protection against increased paw thickness. CS showed dose dependent action in all experimental animals and thereby indicating that CS has significant anti arthritic properties.¹⁴

Curcuma longa:

Oxidative stress has been implicated in many chronic diseases, and its pathological processes are closely related to those of inflammation, in that one can be easily induced by another. In fact, it is known that inflammatory cells liberate a number of reactive species at the site of inflammation leading to oxidative stress, which demonstrates the relationship between oxidative stress and inflammation.¹⁵Tumor necrosis factor alpha (TNF-alpha is a major mediator of inflammation in most diseases, and this effect is regulator by the activation of a transcription factor, nuclear factor (NF)-kB. Whereas TNF-alpha is said to be the most potent NF-kB activator, the expression of TNF-alpha is also regulated by NF-Kb. Curcumin has been shown to block NF-kB activation increased by several different inflammatory stimuli. Curumin has also been shown to suppress inflammation through many different mechanisms beyond the scope of this review, there by supporting its mechanism of action as a potential anti-inflammatory agent.¹⁶ One such disease associated with inflammation, both chronic and acute, is osteoarthritis.^17,18 This systematic review and meta-analysis provided scientific evidence that 8-12 weeks of standardize turmeric extract (typically 1000mg/day of curcumin) treatment can reduce arthritics symptoms (mainly pain and inflammation-related symptoms)and result in similar improvements in the symptoms as ibuprofen and diclofenac sodium. Therefore, turmeric extracts and curcumin can be recommended for alleviating the symptoms of arthritics.¹⁹

Hibiscus rosa-sinensis:

It belongs to malvaceae family and the extract of metanolic hibiscus rosa-sinensis leaves (250 and 500 mg/kg body weight orally) was used carrageenan and dexran induced rat paw edema anti-inflammatory model. Indomethacine was used as standard drug which showed significant anti-inflammatory activity. The inhibition of edema by 17.12% and 16.46 % with 250mg/kg, 45.35%, and 44.51% with 500mg/kg body weight after 3h with carrageenin dextran respectively. The plant extract at the dose level of 250 and 500mg/kg body weight by oral route exhibited significant (P<0.001) anti-inflammatory activities against all the agents used.²⁰Anti arthritic activity of hydroalcoholic extract of Hibiscus rosa sinensis (HRS) was tested against Freund’s complete adjuvant (FCA) induced arthritis in rats. The HRS significantly reduces the paw volume and arthritic index. From this study it is evident that HRS possesses antiarthritic activity which may be due to its anti-inflammatory and antioxidant activity.²¹

Harpagophytum procumbens:

Extract of Harpagophytum procumbens (Devil’s claw) has become the research as a potential therapeutic agent in the treatment of rheumatic arthritis and NSAIDs. Many studies evaluated the anti-inflammatory effects of Harpagophytum procumbens with inconsistent and contradictory results. The aim of this study was to investigate the Harpagophytum procumbens on both acute and chronic inflammatory processes in rats and responses in mice. The acute model of inflammation includes carrageenan induced rat back-paw edema test.²² The chronic models of inflammation include Complete Freund’s adjuvant-induced arthritis and cotton pellet-induced granuloma test.^23,24,25,26 None of NSAIDs was ideal in controlling the signs and symptoms of inflammation joint diseases. It can concluded that Harpagophytum procumbens is a herbal agent having reasonable anti-inflammatory effect compared to indomethacin and the findings of the present work justified the use of this plant in the treatment of rheumatism.

Lawsonia innermis:

Lawsonia innermis Linn belonging to family Lythraceae commonly known as Henna/Mehandi in India. It is a much branched glabrous shrub or small tree, cultivated for its leaves although stem bark, roots, flowers and seeds have also been used in traditional medicines. Lawsonia inenrmis plant have traditional claim for use in anti inflammatory and arthritic disorder. Anti inflammatory activity was studied using an ethanolic extract of L.innermis in carrageenan rat induced paw edema. The extracts (100 and 200mg/kg) showed the maximum inhibition of 39.49% and 55.98% with carrageenan induced paw edema. L. innermis may be used for therapeutic purposes mainly in the prevention of oxidative damage that occurs during inflammation.²⁷Anti arthritic activity of hydroalcoholic extract of Lawsonia innermis is done by Freund’s adjuvant induced arthritis model and formaldehyde induced arthritis model. HAELI (200 and 400mg/kg) shows significant inhibition of paw diameter on day 14^thand day 21^st with P<0.01. Anti arthritic effect of Lawsonia innermis extract may be through maintenance of synovial membrane and thereby inhibiting cytokines and leucotriene infiltration inhibition.²⁸

Moringa oliefera:

The plant Moringa oliefera Lam from family Moringaceae is well known for its various medicinal properties and a common ingredient of many polyherbal formulations for a variety of claims. Different parts of Moringa oliefera were traditionally used for the treatment of wide variety of ailments like arthritis and joint pain.²⁹The anti-inflammatory activity of aqueous and ethanolic extracts of leaves of M.oliefera against carrageenan induced paw edema in albino rats. Two extracts shows maximum action in which the aqueous extract showed significant P<0.01 edema suppression similar to that of ibuprofen. Ethanolic extract also shows similar anti inflammatory action.³⁰Inorder to evaluate the anti arthritic activity ethanolic extract of leaves of Moringa oliefera were used against Complete Freund’s adjuvant (CFA) induced arthritis in rats was used as a disease model. A significant decrease in arthritic index (p<0.01) was recorded in groups that were given Moringa extract. The animal group that was given Moringa extract at dose of 250mg/kg body weight showed better arthritic index. The study revealed that Moringa extract has a considerable effect in preventing development or ameliorate arthritis disease severity. Since Moringa leaves being the most abundant plant part suitable for commercial mass production of botanical medicinal properties.³¹

Oenothera biennis:

Evening primrose oil in patients with Rheumatoid arthritis. Forty patients with rheumatoid arthritis and upper gastrointestinal lesions due to non-steroidal anti-inflammatory drugs entered a prospective 6-month double-blind placebo controlled study of dietary supplementation with gamma-linolenic acid 540mg/day. Nineteen patients received active therapy (as evening primrose 6g/day) and 21 received placebo (oliveoil6g/day). Other results showed a significant reduction in morning stiffness with gamma-linolenic acid at 3 months and reduction in pain and articular index at 6 months with olive oil. Whilst gamma- linolenic acid may produce mild improvement in rheumatoid arthritis, olive oil may itself have unrecognized benefits.³²And also treat the anti-inflammatory activity in Type 2 Diabetic patients. The significant reduction in serum MDA and TNF-alpha levels after three months of combining evening primrose oil supplement to the conventional metformin therapy at the onset of diagnosis. It can be concluded that early intervention with natural oil rich in gamma linolenic acid, which anti-inflammatory with traditional hypoglycemic drugs can improve therapeutic benefits.³³

Zingiber officinale:

Fresh ginger into two wide range catagories, that is volatiles and non-volatiles. Ginger has staring potential for treating a number of aliments including degenerative disorders of arthritis, rheumatism and also anti inflammatory activity.³⁴oral administration of Z.officinale extract has shown different and inconsistent effects, depending on the quality of consumption. Although administration of squeezed ginger extract to mice one time or twice has elevated the tumor necrosis factor-alpha (TNF-alpha) in peritoneal cells, long term consumption of the extract has increased the serum corticosterone level and has reduced proinflammatory mediators.³⁵Ginger powder has had ameliorative effect in musculoskeletal and rheumatism patients through inhibiting cyclooxygenase and lipooxygenase pathway in synovial fluid.³⁶

The Important anti inflammatory bioactive isolated markers from various plant species was depicted in Table. No 1.

CONCLUSION:

Indian sub continent is a rich source of plant and animal wealth which is due to the varied geographical and agro climate regions. It is a well-known fact that traditional system of medicines always played an important role in meeting health care needs. Inflammatory diseases stand as one of the foremost health problems worldwide, which is the leading cause of disability in the western and developing countries. Therapies in case of western medicines are often limited in efficacy, carry the risk of adverse effects and also too costly especially in case of developing countries. Therefore, treating inflammatory diseases with plant derived compounds which are accessible and do not require laborious pharmaceutical synthesis. The given plant provides essential compounds with active principles, having no or minimum side effects and may be useful for disease control. From the above review it should be manifest that there are many medicinal plants which exert anti inflammatory and anti arthritic activity at a particular dose. From this we can conclude that isolation of lead compound from plants can be used for the better treatment of various inflammatory diseases.

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Received on 07.01.2021 Modified on 17.05.2021

Res. J. Pharmacognosy and Phytochem. 2023; 15(3):220-224.

DOI: 10.52711/0975-4385.2023.00034