Phytotherapeutic Approaches to Rheumatoid Arthritis: A Comprehensive Review of Medicinal Plants with Anti-Rheumatic Potential

Rheumatoid arthritis (RA) is a chronic inflammatory joint disorder with an autoimmune origin, primarily marked by the presence of autoantibodies such as rheumatoid factor (RF), which targets immunoglobulin G, and anti-citrullinated protein antibodies (ACPAs). If not adequately managed, RA can lead to progressive joint deterioration, physical disability the onset of comorbidities and decreased quality of life1. Cardiovascular disease (CVD), infections, depression, gastrointestinal disorders, and cancer (particularly lymphoma and lymphoproliferative diseases, lung cancer, and melanoma) are among the possible comorbidities2,3. The global frequency of RA in adults is between 0.5% and 1%. According to survey, the frequency in North America and Europe might be higher than in Asia. Whether this regional variation results from genetic, environmental, or study design variations is unknown4,5. Among the risk factors for RA are neuroendocrine, hormonal, reproductive, epigenetic, and genetic variables. Environmental risk factors include smoking and other airborne exposures; microbiota and infectious agents, diet, and socioeconomic factors 6.

Pathophysiology of Rheumatoid Arthritis

Tolerance to self is broken when an antigen-presenting cell presents an autoantigen (for example, following citrullination) or a foreign peptide (for example, a bacterial or viral peptide that cross-reacts with an autoantigen) to a naive T cell via a major histocompatibility complex (MHC) class II molecule (carrying the shared epitope), supported by costimulatory molecules. Activated T cells differentiate into TH1, TH17, or T follicular helper (Tfh) cells and release lymphokines that can aid B cells and activate macrophages. After differentiating into a plasma cell, the B cell releases these autoantibodies, such as those directed against citrullinated proteins7.8.

Figure No. 1. Pathogenic Aspects of Rheumatoid Arthritis. - APC, Antigen presenting cell; IL, Interleukins; RF, Rheumatoid factor; ACPA, Anti-citrullinated peptide antibody; TNF, Tissue necrosis factor; MMP, Matrix metalloproteinase; RANKL, receptor activator of nuclear factor κB ligand.

In the synovium, autoantibodies attach to their corresponding autoantigens to form immune complexes where the autoantigens have collected. Via their Fc component, the immune complexes stimulate additional B cells to produce anti-IgG antibodies (rheumatoid factor), which grow the immune complexes and may enhance complement activation. The immune complexes can attach to macrophages and other cells through Fc and complement receptors, causing them to release proinflammatory cytokines and other inflammatory mediators like TNF and IL-6. Additionally, macrophages can be activated by lymphokines derived from activated T cells, such as IL-17 or interferon (IFN)-γ10. In the presence of proinflammatory cytokines, fibroblasts that express receptor activator of nuclear factor κB ligand (RANKL) can stimulate macrophages to differentiate via preosteoclasts into osteoclasts that resorb bone from the synovial, exostal site; this process begins at the cartilage-bone junction. Additionally, these cytokines trigger chondrocytes to release cartilage-degrading enzymes (Figure 1)7.9. For centuries, Indigenous culture has long used medicinal plants for therapeutic purposes, relying on traditional knowledge developed through trial and error over centuries. Modern pharmaceuticals, although effective, often focus on isolated active compounds with specific mechanisms, which not fully address the multifaceted nature of disease such as RA, Cancer, diabetes and autoimmune disorders. While the plant kingdom continues to serve as an important source for chemical entities supporting drug discovery, the rich traditions of herbal medicine developed by trial and error on human subjects over thousands of years contain invaluable biomedical information just waiting to be uncovered using modern scientific approaches. This review summarizes the therapeutic potential of medicinal plants in RA management.

1. Jatropha Curcas  

The study involved extracting the Jatropha curcas flowers with various solvents, with the ethanolic extract showing the highest antioxidant activity and phytochemical content, including alkaloids, flavonoids, terpenoids, and phenols. The anti-arthritic potential of Jatropha curcas ethanolic extract (JCEE), focusing primarily on the ethanolic extract due to its superior antioxidant properties. The study begins with phytochemical screening of the flower extracts obtained using petroleum ether, ethanol, and water as solvents. The ethanolic extract was found to contain significant amounts of alkaloids, flavonoids, terpenoids, phenols, carbohydrates, and glycosides, whereas the aqueous extract contained most of these except glycosides. The petroleum ether extract showed fewer phytochemicals, mainly alkaloids.  Quantitative analysis revealed that the ethanolic extract had a total phenolic content of 121.02 mg gallic acid equivalents per gram (GAE/g) and a total flavonoid content of 301.34 mg rutin equivalents per gram (RE/g), which were notably higher than the aqueous extract (63.16 mg GAE/g phenols and 104.41 mg RE/g flavonoids). These bioactive compounds are well-known for their antioxidant and anti-inflammatory effects, which are crucial in combating rheumatoid arthritis.  The antioxidant activity was evaluated using multiple in-vitro assays including DPPH radical scavenging, superoxide dismutase (SOD) activity, and reducing power assays. The ethanolic extract exhibited moderate free radical scavenging activity with IC50 values of 118.20 µg/ml for DPPH and 167.50 µg/ml for superoxide radicals, compared to ascorbic acid standards at 26.08 µg/ml and 36.27 µg/ml respectively. The reducing power of the ethanolic extract also increased in a dose-dependent manner, indicating its potential to neutralize oxidative stress.  LD50 (lethal dose 50), as obtained from acute oral toxicity study was 2000 mg/kg b. w. Therefore, in the current investigation, ethanolic medication extract dosages of 200 mg (low) and 400 mg (high) were chosen to assess their anti-arthritic effectiveness.

Figure 1: Jjatropha Curcas

Experimental Groups

Four groups of six animals each were formed using a random number generator (n=6). Total duration of study is 28^th day.

Giving the extracts to the animal 30 minutes before administering Freund’s adjuvant and continuing until the 28th day. On days 0^th, 7^th, 14^th, 21^st, and 28^th, the size of each paw was measured using electronic digital callipers. Blood samples were taken from the retro-orbital plexus after 28 days and analysed for total leukocyte counts (TLC), differential leukocyte counts, and other factors (DLC).  Both doses significantly reduced paw swelling over 28 days compared to the arthritic control group, with the higher dose showing greater efficacy. On day 28, paw volume measurements for the treated groups were 1.65±0.02 ml and 1.33±0.03 ml for the low and high doses respectively, versus 0.61±0.04 ml for the standard drug indomethacin.  Additionally, haematological parameters such as total leukocyte count and differential leukocyte count were improved, indicating reduced systemic inflammation. The study concludes that the ethanolic extract of Jatropha curcas flowers possesses potent antioxidant and anti-arthritic activities, likely attributable to its rich phytochemical composition. This supports the traditional use of the plant in managing inflammatory conditions and highlights its potential as a source for developing safer anti-arthritic therapies²⁷.

2. Mesua ferrea Linn

 In the Indian traditional medical system, Mesua ferrea Linn. seeds are used to cure inflammatory and painful disorders such as arthritis, wound healing, antimicrobials, and skin diseases28. According to reports, the plant possesses a number of biological properties, including antibacterial, analgesic, CNS depressive, and antidote29. The presence of active ingredients such fixed oil and xanthones may be the cause of Mesua ferrea seeds' antiarthritic action, as demonstrated by the findings of the other studies. In this study, Mesua ferrea Linn seeds were extracted using petroleum ether, ethyl acetate, and alcohol. According to phytochemical analysis, extracts from Mesua ferrea show the presence of proteins, carbohydrates, tannins, phenolic compounds, lipids and oils, and coumarin glycoside. At a level of 5000 mg/kg, the studied extracts showed no toxicity or death in any of the groups. 300 and 500 mg/kg were therefore administered as therapeutic doses. Wistar albino rats were used to test the anti-arthritic efficacy using a model of arthritis caused by formaldehyde and complete Freund's adjuvant (CFA). After formaldehyde and CFA induction, paw volume measurements were made on the fourth, eighth, fourteenth, and twenty-first days.

Experimental Groups

The rats were randomly divided into nine groups. Each treatment group contained six Wistar rats. Total duration of study is 14 days.

Figure 2: Mesua ferrea Linn

Formaldehyde Induced Arthritis: The evaluation conducted on the 10th day revealed that, in comparison to the arthritis control group, treatment with both doses of all Mesua ferrea extracts considerably decreased the edema in the injected (left) hind paw at a dose of 300 mg/kg. The percentage inhibition of paw edema on the 10th day was 60.69, 59.69, and 53.46 for lower doses of pet ether, ethyl acetate, and alcoholic extracts, and 59.69, 58.62, and 52.66 for higher doses. On the 10th day, animals treated with Diclofenac Sodium (DCS) demonstrated a paw edema inhibition of 63.19%.

CFA- induced arthritis model: The extracts were administered for 14 days at doses of 300 and 500 mg/kg p.o. and DCS (13.5 mg/kg p.o.). When CFA was injected, arthritis developed. Each rat's left hind limb was injected with 100µl of CFA containing heat-killed and dried Mycobacterium tuberculosis (strain H37Ra, ATCC-25177) on the 0th day. It is assumed that the late-phase arthritis and flare in the injected foot are immunologic processes, while the initial reaction of edema and soft-tissue thickening at the depot site in this animal is due to the irritating effect of the adjuvant. Moreover, In addition, the lower dose of the petroleum ether extract of Mesua ferrea showed greater effectiveness than DCS. Except for the group treated with alcohol, both the DCS and Mesua ferrea extract groups exhibited a recovery in body weight compared to the control group. According to one study, weight loss during inflammation may result from impaired nutrient absorption in the intestines, and administering anti-inflammatory agents can help restore normal absorption³⁰. The observed recovery in body weight among rats treated with Mesua ferrea and DCS may be attributed to enhanced nutrient absorption in the intestines and a decrease in the discomfort associated with severe arthritic conditions. Previous studies have noted a moderate elevation in white blood cell (WBC) counts during arthritis, likely due to interleukin-1β (IL-1β) driven increases in colony-stimulating factors. Findings from the current research suggest that both Mesua ferrea and DCS contribute to the normalization of WBC levels. Furthermore, common haematological disruptions associated with arthritis such as reduced haemoglobin (Hb) levels and elevated erythrocyte sedimentation rate (ESR) were significantly corrected by treatments involving Mesua ferrea extracts and DCS, with the exception of the alcohol-based extract. The decline in Hb levels during arthritic states is believed to stem from lower erythropoietin production, diminished bone marrow responsiveness, and increased premature red blood cell breakdown. Similarly, the rise in ESR is commonly linked to heightened synthesis of inflammatory plasma proteins like fibrinogen and globulin, which serve as markers of active yet often non-specific disease activity³¹. This research confirms the traditional application of Mesua ferrea seeds for alleviating pain and managing arthritis-related disorders. Evidence from previous studies suggests that their therapeutic potential against arthritis may be linked to naturally occurring compounds such as fixed oils and xanthones³².

3. Pergularia daemia

Pergularia daemia Forsk., a perennial twining herb widely distributed in southern India, has long been used in traditional medicine. The aerial parts of the plant have been employed for their anthelmintic, antiseptic, and antivenom properties, as well as in the treatment of gastric ulcers and reproductive health concerns, including uterine and menstrual disorders. The leaves are traditionally used to manage a range of conditions such as anaemia, leprosy, arthritis, haemorrhoids, amenorrhea, dysmenorrhea, infantile diarrhoea, general body pain, asthma, bronchitis, and pertussis. In folk medicine, a leaf extract of P. daemia combined with lime or ginger is commonly used to alleviate rheumatic symptoms³³.  The current investigation assessed the anti-arthritic efficacy of the methanolic extract of P. daemia (PDME) using a complete Freund’s adjuvant (CFA)-induced arthritis model in rats. No mortality or adverse physiological or behavioural effects were observed in the PDME-treated groups, indicating a favourable safety profile. Liquid chromatography–mass spectrometry (LC–MS) analysis of the extract revealed the presence of several bioactive flavonoids, including formononetin, quercetin, chrysoeriol, taxifolin, and naringenin. These compounds are well-documented for their anti-inflammatory and immunomodulatory properties, and are likely contributors to the observed anti-arthritic effects of P. daemia.

Experimental groups

The rats were randomly assigned to five groups, each consisting of six animals, and the study was conducted over a period of 35 days.

Figure 3 :Pergularia daemia

On day 0, experimental arthritis was induced by administering 0.1 mL of Complete Freund’s Adjuvant (CFA) into the right hind paw of each rat. 14 days following induction, therapeutic interventions commenced with oral administration of Pergularia daemia methanolic extract (PDME) and the reference drug, diclofenac sodium, continuing from day 15 through day 35. Paw volume was recorded prior to CFA administration and again post-treatment to assess inflammatory changes. On 36^th day, animals were anesthetized for radiographic evaluation of the hind limbs, after which they were euthanized to facilitate the collection of blood samples for biochemical analysis. Joint tissues from the hind limbs were preserved for histopathological examination. CFA-induced arthritic rats exhibited a marked decline in body weight compared to healthy controls, a typical manifestation of systemic inflammatory response. Treatment with PDME resulted in notable recovery of body weight and a reduction in paw edema, indicating a therapeutic effect. Furthermore, CFA administration led to a significant increase in paw thickness, which was markedly attenuated in rats receiving PDME at both 250 mg/kg and 500 mg/kg body weight doses, as compared to the arthritic control group. Serum biochemical analyses revealed that PDME administration significantly lowered levels of rheumatoid factor (RF) and C-reactive protein (CRP), biomarkers associated with systemic inflammation and autoimmune activity. These reductions suggest the anti-inflammatory and immunomodulatory potential of the extract. Additionally, the erythrocyte sedimentation rate (ESR), another key indicator of inflammation, was also significantly decreased in both PDME- and diclofenac-treated rats, in contrast to untreated arthritic animals. Ultrasonographic and histopathological evaluations further confirmed the therapeutic efficacy of PDME, demonstrating evidence of cartilage repair and bone regeneration in the affected joints. These collective findings support the conclusion that methanolic extract of P. daemia exerts significant protective and restorative effects in CFA-induced arthritis, thereby validating its potential as an anti-arthritic agent³⁴.

4. Wedelia calendulacea L.

Wedelia calendulacea L., commonly found as a wild-growing herb across various regions of India, particularly thrives in cool and humid environments. This species has been traditionally recognized for its diverse pharmacological activities, including immunostimulatory³⁵, antibacterial36, wound-healing, and anticancer properties³⁷. Recent investigations have expanded its therapeutic scope by examining its potential in the treatment of rheumatoid arthritis and related cardiovascular complications. This study specifically aimed to assess the protective effects of W. calendulacea against methotrexate-induced endothelial damage in a rat model of arthritis induced by Complete Freund’s Adjuvant (CFA). Additionally, the extract was evaluated for its ability to enhance the anti-arthritic efficacy of methotrexate through possible synergistic mechanisms. For the preparation of the extract, 250 grams of air-dried and coarsely powdered leaves were subjected to Soxhlet extraction using methanol as the solvent for a continuous cycle of 24 hours. The methanolic extract was then concentrated and used for pharmacological evaluation. Acute toxicity studies were conducted in accordance with the guidelines set by the Organisation for Economic Co-operation and Development (OECD), employing mice of both sexes weighing between 20–30 grams. The highest non-lethal dose for the methanolic (MeOH) extract was determined to be 5000 mg/kg body weight. Based on this finding, 1/10^th  of the maximum tolerated dose 500 mg/kg was selected as the standard effective dose for therapeutic studies. To investigate dose-dependent anti-arthritic effects, three dosage levels of the extract (250 mg/kg, 500 mg/kg, and 750 mg/kg body weight) were administered. These doses were evaluated in a CFA-induced arthritic model to determine the extract’s efficacy across a range of concentrations.

Experimental Group

Animals were randomly grouped into seven groups. Each group having 6 animals.

Figure 4: Wedelia calendulacea L.

On the first day of the study, all experimental animals except those assigned to the normal control group received a subplantar injection of 0.1 mL of Complete Freund’s Adjuvant (CFA) into the left hind paw to induce arthritis. The CFA formulation consisted of Mycobacterium butyricum (6 mg/mL), suspended in heavy paraffin oil and thoroughly homogenized using a mortar and pestle to ensure a uniform emulsion. Following CFA administration, no therapeutic intervention was provided for a period of 12 days, allowing for the full development of arthritic symptoms. On day 12, animals were fasted for approximately 16 to 20 hours prior to blood collection. The serum samples obtained were used to assess various biochemical markers. Based on both morphological and biochemical evaluations, animals were then randomized into treatment groups to ensure uniformity across study arms. Therapeutic interventions commenced on day 13 and continued until day 28. The severity of arthritis and related secondary lesions was assessed post-treatment using a combination of physiological, biochemical, and histopathological evaluations. The study also focused on the in vivo antioxidant potential of the test compounds. Antioxidant activity was determined through the measurement of superoxide dismutase (SOD), catalase, and lipid peroxidation levels (quantified by malondialdehyde, MDA, content). Arthritic rats (Group II) displayed a significant reduction in SOD and catalase levels, alongside a marked increase in MDA, indicating oxidative stress. Methotrexate treatment alone did not produce a statistically significant improvement in these oxidative stress markers. In contrast, administration of Wedelia calendulacea at varying dosages led to a significant increase in SOD and catalase activity and a notable reduction in lipid peroxidation. Moreover, co-administration of W. calendulacea with methotrexate yielded more pronounced antioxidant effects, further enhancing the biochemical profile. The arthritis index peaked on day 12 across all arthritic groups and showed a significant decline by days 18 and 28 in animals receiving treatment. Persistent hind paw swelling was observed in the CFA-only group throughout the study duration. However, treatment with the methanolic extract of W. calendulacea resulted in dose-dependent inhibition of paw edema: 78.81% at 250 mg/kg, 84.74% at 500 mg/kg, and 70.33% at 750 mg/kg. Methotrexate alone (1 mg/kg, orally) achieved a 92.79% reduction in paw edema. Notably, the combined treatment of methotrexate with W. calendulacea (500 mg/kg) exhibited the highest reduction at 93.58%, indicating a synergistic interaction. Hematological assessments revealed that CFA-induced arthritis significantly reduced hemoglobin (Hb) and red blood cell (RBC) counts while elevating white blood cell (WBC) counts, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), homocysteine, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-1 (IL-1). Treatment with W. calendulacea, both alone and in combination with methotrexate, normalized these parameters, underscoring its anti-inflammatory and immunomodulatory potential. The combination therapy was particularly effective in reversing disease-induced alterations, surpassing the effects observed with monotherapy. No significant deviations in physiological or biochemical parameters were noted in the control or drug control groups, confirming the safety of the interventions. Vascular reactivity studies using aortic strip preparations from arthritic animals demonstrated impaired relaxation responses to peroxynitrite (ONOO?) and acetylcholine (ACh), suggesting the presence of endothelial dysfunction associated with the arthritic condition. Treatment with W. calendulacea significantly improved both ONOO?- and ACh-induced relaxation responses, while methotrexate enhanced only the ONOO?-mediated pathway, without a statistically significant effect on ACh response. Collectively, these findings highlight the potential of Wedelia calendulacea as a promising candidate for the development of new anti-arthritic and cardioprotective therapies, either as a stand-alone treatment or in combination with existing standard pharmaceuticals such as methotrexate³⁸.

5. Cissus Quadrangularis

Cissus quadrangularis has been extensively studied for its diverse pharmacological properties, including anti-osteoporotic, analgesic, anticancer, and antibacterial activities39,40. Phytochemical investigations of the plant’s stem have revealed its potential to enhance bone mineralization, supporting its traditional use in promoting skeletal health41.  In the current investigation, the anti-arthritic efficacy of the active fraction of Cissus quadrangularis (AFCQ), isolated from the acetone extract of the stem, was evaluated using an in vivo model of arthritis induced by Complete Freund’s Adjuvant (CFA) in Wistar rats. Inflammatory responses were assessed through carrageenan-induced paw edema, and changes in hematological and biochemical parameters were systematically analyzed.

Figure 5: Cissus quadrangularis

The stems of C. quadrangularis were first dried, powdered, and sequentially extracted using a Soxhlet apparatus with solvents of increasing polarity. Among the obtained extracts, the acetone fraction exhibited the highest inhibitory activity against pro-inflammatory enzymes such as cyclooxygenase (COX) and lipoxygenase (LOX), identifying it as a promising candidate for further study. Consequently, this fraction underwent additional purification through adsorption column chromatography, leading to the isolation of the bioactive compound referred to as AFCQ. To determine the safety profile, acute oral toxicity testing was conducted in accordance with regulatory guidelines, revealing a median lethal dose (LD??) of 1000 mg/kg body weight for AFCQ. Based on standard toxicological practices, 1/10^th of the LD?? - equivalent to 100 mg/kg body weight was chosen as the effective dose for pharmacological evaluation. For comparison, two standard drugs were included in the study: celecoxib, a selective COX-2 inhibitor and representative NSAID, at a dose of 50 mg/kg body weight, and methotrexate, a well-established DMARD, administered at 0.3 mg/kg body weight. This experimental setup enabled a comparative analysis of AFCQ’s therapeutic performance against standard anti-inflammatory agents, while also providing insights into its mechanism of action through modulation of inflammatory mediators and restoration of altered biochemical markers in the context of CFA-induced arthritis.

Experimental groups

The experimental animals were divided into five group’s containing six rats in each group.

One hour after the administration of carrageenan, paw volume in the experimental animals was measured using the plethysmography method to assess acute inflammation. Following the induction of arthritis using Complete Freund’s Adjuvant (CFA), treatments with the active fraction of Cissus quadrangularis (AFCQ) and standard reference drugs began on day 14. Paw volume in all experimental groups was recorded at multiple time points specifically on days 0, 4, 7, 14, 21, 25, and 28 using a plethysmometer to monitor inflammation progression and therapeutic response over time. On day 29, the animals underwent radiographic (X-ray) examination to evaluate bone and joint structural changes. Subsequently, the animals were euthanized, and tissue samples were collected for comprehensive hematological, biochemical, and histopathological analyses. Notably, AFCQ administered at 100 mg/kg demonstrated a superior inhibitory effect on paw edema compared to both celecoxib (50 mg/kg) and methotrexate (0.3 mg/kg), indicating a robust anti-inflammatory potential. In CFA-induced arthritic rats, a marked reduction in red blood cell (RBC) count and hemoglobin (Hb) levels was observed, along with elevated white blood cell (WBC) count and erythrocyte sedimentation rate (ESR) typical indicators of systemic inflammation. Treatment with AFCQ, as well as the standard drugs, significantly mitigated these hematological disturbances, restoring them toward values observed in non-arthritic control animals. Biochemical evaluations revealed that arthritic animals experienced significant reductions in total serum protein, albumin levels, and albumin/globulin (A/G) ratio, alongside elevations in globulin, C-reactive protein (CRP), and blood glucose levels. Oral administration of AFCQ, celecoxib, and methotrexate was effective in reversing or compensating for these alterations, suggesting a systemic anti-inflammatory and homeostatic effect. Ceruloplasmin, a copper-binding plasma protein critical for iron metabolism and oxidative balance, also served as an inflammatory marker in this study. Elevated levels of copper and iron in the serum of CFA-treated rats reflected hepatic stress and systemic inflammation. These elevations were significantly reduced following treatment with AFCQ and standard drugs, indicating normalization of hepatic function and a reduction in oxidative damage. Histopathological analysis of the proximal tibiotarsal joint in arthritic rats revealed classic signs of rheumatoid pathology, including severe edema, cartilage degeneration with partial erosion, bone marrow destruction, and intense infiltration of inflammatory exudates into the articular space. In contrast, joint sections from AFCQ-treated animals displayed notable improvements in structural integrity and inflammatory reduction. Radiographic analysis further supported the protective effects of AFCQ. Treatment over a 14-day period resulted in a visible reduction in soft tissue swelling and preservation of bone architecture, with decreased evidence of bone dissolution when compared to untreated arthritic animals. Taken together, these findings strongly suggest that Cissus quadrangularis, particularly its acetone-derived active fraction (AFCQ), exerts potent anti-inflammatory and anti-arthritic effects. These therapeutic benefits are likely attributable to the presence of phenolic compounds and other bioactive constituents within the extract, which contribute to its ability to modulate inflammatory mediators and protect against joint and systemic damage42.

6. Cleistopholis Patens

Cleistopholis patens has been traditionally utilized in ethnomedicine for the management of various ailments, including fungal infections, rheumatoid arthritis, and cardiovascular conditions. The present study aimed to assess the anti-arthritic efficacy of ethanol and aqueous extracts derived from the stem bark of Cleistopholis patens (SBCP) using the Complete Freund’s Adjuvant (CFA)-induced arthritis model in Wistar rats. Prior to initiating therapeutic evaluation, both extracts underwent acute oral toxicity testing in Wistar albino rats, conducted in accordance with established toxicological protocols. The animals were monitored for 24 hours post-administration to observe any signs of toxicity or mortality. No adverse effects or fatalities were recorded at doses up to 5000 mg/kg body weight, confirming the extracts' safety profile. Based on these findings, three dosages 400 mg/kg, 600 mg/kg, and 800 mg/kg were selected for the study to investigate the dose-dependent anti-arthritic effects of the SBCP extracts in vivo

Experimental Groups

A total 135 Wistar albino rats divided into nine groups of 15 rats each were used. Total duration of study is 31 day

Figure 6: Cleistopholis patens