INTRODUCTION:

Rheumatoid arthritis (RA), cutaneous lupus erythematosus, and multisystem autoimmune lupus are examples of autoimmune diseases that develop when the body's own tissues are mistakenly attacked by the immune system, resulting in chronic inflammation, discomfort, and sometimes organ damage. About 1% of people worldwide suffer from RA, which is mainly characterized by persistent inflammation of synovial joints that leads to gradual joint degradation and a lower quality of life.

Similar to this, immune-mediated damage to different organs or skin occurs in systemic and cutaneous types of lupus, resulting in complicated and frequently incapacitating symptoms.

Conventional treatments, such as biologics and disease-modifying antirheumatic medications (DMARDs), are useful in treating these conditions, but they frequently have serious side effects and are expensive. As a result, herbal therapy is becoming more and more popular as a complementary or alternative form of treatment. Ayurveda and other traditional therapeutic systems place a strong emphasis on a comprehensive strategy that addresses the root causes of immunological dysfunction. Antioxidant, immunomodulatory, and anti-inflammatory medicinal herbs show promise in the treatment of lupus-related disorders, including autoimmune joint inflammation. The purpose of this review is to investigate these advantages and assess the potential integration of herbal therapies into existing therapeutic approaches.

T-cell suppression, lymphocyte proliferation, mast-cell histamine release, macrophage oxidative activity via chemiluminescence, and dihydroorotate dehydrogenase inhibition linked to pyrimidine production are among the in vitro methods used to evaluate immunomodulatory effects. Plaque-forming cell assays are frequently used to assess B-cell responses. In vivo research uses models related to inflammatory and autoimmune disorders, such as collagen-induced and adjuvant-induced arthritis, hypersensitivity reactions, and autoimmune diseases, such as myocarditis, thyroiditis, and experimental allergic encephalomyelitis. Models of allograft rejection, graft-versus-host disease, and antibody-mediated conditions, including myasthenia gravis and glomerulonephritis, provide further information that helps assess immunological pathways and possible treatments.

Pathophysiology:

Joint inflammation resulting from autoimmune issues is a complex condition marked by an unregulated immune response, environmental influences, and genetic predispositions. The main factor causing inflammation of the synovial membrane is the infiltration of lymphocytes into the joint area. This inflammatory response is intensified by these immune cells releasing pro-inflammatory substances such as interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha), leading to damage in bone and cartilage. Genetic factors, such as the presence of the human leukocyte antigen DR4 (HLA-DR4), significantly enhance the risk of developing this condition. Furthermore, the improper activation and regulation of T and B lymphocytes intensify the autoimmune response.

Systemic autoimmune lupus is a complex ailment of the immune system, recognized by the existence of self-reactive antibodies that target cellular and cytoplasmic elements. This condition results in widespread immune complex buildup and subsequent inflammation, impacting various body systems such as the skin, connective tissues, kidneys, and brain. The ongoing inflammatory condition, attributed to disordered responses from B and T cells, leads to tissue damage and reduces organ functionality.

A specific type of lupus known as cutaneous lupus erythematosus primarily affects the skin, marked by durable inflammatory lesions that may cause scarring. The underlying processes involve immune-mediated damage restricted to the skin, where autoantibodies and immune complexes accumulate, resulting in localized inflammation and harm. Generally, cutaneous lupus erythematosus does not impact systemic organs, although some individuals may later develop systemic multisystem autoimmune lupus¹.

Medicinal plants are acknowledged as significant sources of bioactive compounds that may possess anti-rheumatoid arthritis effects is shown in Fig. 1. These substances, which include flavonoids, terpenes, alkaloids, and polyphenols, provide advantages through a number of pathways, such as reducing oxidative stress, inhibiting pro-inflammatory cytokines, and modifying immune system functions².

Figure 1: Graphical representation of plant used in autoimmune joint inflammation²

1. Mechanisms of Action:

The immune-modulating characteristics of the mentioned Ayurvedic plants are primarily due to their ability to harmonize immune responses, lessen inflammation, and detoxify the body. They operate across various facets of the immune system, strengthening the body's innate defenses while preventing overreaction of the immunological system that can lead to autoimmune diseases.

The previously discussed medicinal plants impact autoimmune joint inflammation through several avenues. 1. Inhibition of Pro-Inflammatory Cytokines Numerous plant-derived substances diminish the synthesis of pro-inflammatory signaling molecules like tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6), which play pivotal roles in the progression and manifestation of rheumatoid arthritis (RA).

2. Antioxidant Activity:

The development of autoimmune joint inflammation is significantly influenced by oxidative stress. The antioxidant qualities of these botanical species help to counteract free radicals, which aids in reducing inflammation while safeguarding against damage to tissues.

3. Regulation of the Immune System:

These herbal plants can contribute to re-establishing immune balance and reducing autoimmunity by modulating the activities of immune cells, particularly T and B lymphocytes³.

IMMUNOSUPPRESSIVE HERBS:

The Asian plant Tripterygium wilfordii, known for its immunosuppressive glycosides, has proved to be effective in treating lupus, often surpassing the benefits of prednisone. Nevertheless, long-term use can lead to negative effects such as kidney problems, reduced bone density, and reproductive issues, highlighting the importance of careful monitoring.

Research has also examined the ability of Artemisia apiacea and Artemisia annua to inhibit immune responses. While further studies are needed to validate these results, initial investigations in China suggest that these herbs might aid in lupus treatment.

Phytoestrogens:

The Impact of Estrogen on Multisystem Autoimmune Lupus:

Women are significantly more affected by multisystem autoimmune lupus, leading to investigations into estrogen's role in the disease's development. This has sparked increased interest in phytoestrogens as potential treatments for managing systemic lupus erythematosus (SLE) due to their resemblance to estrogen.

The Role of Coumestrol in Treating Lupus Nephritis:

Coumestrol, a specific form of phytoestrogen, has shown promise in lowering autoantibody levels and urinary protein concentrations in lupus-affected mice, indicating its potential as a treatment for lupus nephritis. However, some herbs containing phytoestrogens, like Medicago sativa (alfalfa), should be avoided by lupus patients due to canavanine, a substance that might trigger multisystem autoimmune lupus in vulnerable individuals⁴.

Immunomodulatory Plants:

Traditional medicinal practices have been utilized for many years to address various health issues. Approximately 80% of the global population depends on traditional medicine, as per the World Health Organization (WHO). Among nearly 121 drugs frequently prescribed in the United States, around 90 derive from natural sources, mainly plants. For individuals with rheumatoid arthritis (RA), herbal treatments could present a viable option for relief, potentially aiding in symptom management and addressing limitations of conventional medical therapies^5,6 are shown Fig. 2.

Zingiber officinale:

Ginger, scientifically referred to as Zingiber officinale, belongs to the Zingiberaceae family and has been used for culinary and medicinal applications for numerous years. The rhizomes of Zingiber officinale encompass a multitude of bioactive substances, including diarylheptanoids, gingerols, and shogaols. These substances contribute to the plant's ability to treat a number of ailments, including constipation, asthma, elevated blood sugar, strokes, and rheumatoid arthritis (RA)^7-12. Ginger has garnered significant attention for its effects in alleviating pain and inflammation associated with RA. Studies, including those led by Kiuchi et al., have shown that ginger contains ingredients that prevent the production of important inflammatory substances like prostaglandins and leukotrienes^13-18. In particular, diarylheptanoids, especially those with a catechol group, inhibit the function of 5-lipoxygenase, which further reduces inflammation^19-24. Additionally, the compound yakuchinone A also inhibits the formation of prostaglandins^25-28.

Research conducted on rats indicates that high doses of Zingiber officinale extract significantly lower the levels of prostaglandin E2 (PGE2), leading to decreased inflammation^29-34. Each year, around 100,000 tons of ginger are harvested, with 80% originating from China^35-38. Zingiber officinale has become an important natural treatment in both mainstream and alternative medicine, possibly acting as an additional or alternative therapy to conventional methods for autoimmune joint inflammation^39-43.

Aloe barbadensis:

Bioactive substances such anthraquinones, cinnamic acid, and anthranilic acid are responsible for the medicinal value of Aloe barbadensis, often known as aloe vera, which is grown extensively in Europe and some regions of India. Its anti-inflammatory, antibacterial, and laxative properties have led to its traditional use for skin conditions and detoxification. Aloe vera's anthraquinone component is largely responsible for its anti-arthritic properties. Topical aloe vera extract dramatically decreased inflammation and arthritic symptoms in Sprague Dawley rats with adjuvant-induced arthritis^44-46.

Withania somnifera:

Withania somnifera, also known as ashwagandha, grows well in India's arid regions and is utilized extensively in Ayurvedic and Unani medicine. Alkaloids (withanine, somniferine, tropine), steroidal lactones, and acyl glucosides like sitoindoside-7 and sitoindoside-8 are primarily responsible for its therapeutic action. Originally used as an aphrodisiac and liver tonic, it is currently used to treat neurological problems, dementia, ulcers, asthma, and insomnia. Its advantages in treating anxiety, inflammation, and Parkinson's disease are supported by both clinical and animal research. Additionally, new data points to improvements in anemia, arthritis, weariness, and stress as well as possible anti-tumor properties. In rat models of adjuvant-induced arthritis, powdered root shows notable anti-arthritic efficacy^47,48.

Black pepper:

Black pepper, which originates from South India, is also cultivated in nations such as Sri Lanka, Malaysia, Indonesia, and Brazil, although India holds the title of the largest global producer. The alkaloid piperine, volatile oils, spicy resins, piperidine, and starch are among the bioactive components that make up piper, also referred to as black pepper. It is highly esteemed for its stimulating, digestive, gas-relieving, and aromatic qualities. Studies suggest that Piper enhances the uptake of numerous medications and increases the production of gastric fluids. The principal element of black pepper, piperine, is celebrated for its health advantages. In experiments involving rats that had acute arthritis triggered by carrageenan, the administration of piperine at dosages of 20 and 100 mg/kg/day over a period of eight days significantly alleviated the symptoms associated with arthritis^49,50.

Cissampelos pareira:

The flowering plant Cissampelos pareira Linn. is abundant in alkaloids., flavonoids, and saponins. This species displays a variety of medicinal effects, such as antihistamine, antimicrobial, antioxidant, antispasmodic, liver protective, diuretic, blood pressure-lowering, muscle relaxant, uterine relaxant, antiseptic, aphrodisiac, anti-inflammatory, pain-relieving, anti-hemorrhagic, heart-strengthening, sweat-inducing, expectorant, fever-reducing, tonic properties, and stimulant effects. Traditionally, the roots of this plant have been used to treat asthma, heart ailments, coughs, and urinary issues such as cystitis (inflammation of the bladder), dysentery (inflammation of the intestines), diarrhea, dropsy (swelling due to fluid retention), and dyspepsia (indigestion). The leaves are notably recognized for their anti-inflammatory properties. An ethanolic extract derived from the roots of Cissampelos pareira has shown significant potential in managing pain, diarrhea, and arthritis. Animal research has indicated that this extract has strong protective effects against arthritis caused by complete Freund's adjuvant, underlining its possible use in treating inflammatory disorders^51,52.

Arctium lappa:

Arctium lappa L., often called burdock, has been employed in traditional healing practices to manage autoimmune joint swelling, persistent inflammatory bowel issues, and different inflammatory ailments. The lignan arctigenin, which is an important bioactive substance, is present in the seeds of Arctium lappa. As rheumatoid arthritis advances, macrophages release nitric oxide (NO) and pro-inflammatory cytokines, making inflammation worse. Research indicates that both arctigenin and its glycoside, arctiin, possess properties that can reduce inflammation by decreasing NO levels and inhibiting several interleukins, including tumor necrosis factor alpha (TNFa), interleukin-1 beta (IL-1b), interleukin-6 (IL-6), interleukin-4 (IL-4), and interleukin-5 (IL-5). This outcome occurs by blocking the production of inducible nitric oxide synthase (iNOS). The anti-inflammatory and anti-arthritic impacts of arctigenin are believed to stem from its ability to inhibit signaling from nuclear factor kappa B (NF-κB) and the activation of mitogen-activated protein kinase (MAPK). MAPKs play an essential role in the progression of rheumatoid arthritis since they manage the release of inflammatory mediators. Furthermore, arctigenin also inhibits cyclooxygenase-2 (COX-2), an enzyme involved in creating prostaglandin E2 (PGE2). By targeting the MAPK pathways, arctigenin reduces the levels of TNFa and IL-1b within the synovial tissues and monocytes of individuals with arthritis^53,54.

Artemisia absinthium:

Artemisia absinthium L., widely known as wormwood and part of the Asteraceae family, has been applied in traditional Persian remedies for its effectiveness in addressing inflammation, rheumatic ailments, and nerve pain. Scoparone, an essential active ingredient also present in Artemisia capillaris Thunb, considerably lessens inflammation triggered by macrophages stimulated with lipopolysaccharide (LPS) and interferon-gamma (IFN-γ). This effect is accomplished by diminishing the release of prostaglandin E2 (PGE2) and nitric oxide (NO), with the reduction of NO taking place via the inhibition of inducible nitric oxide synthase (iNOS). Moreover, scoparone is crucial in lowering inflammatory mediators by blocking the production of cyclooxygenase-2 (COX-2). The nuclear signaling pathways associated with autoimmune joint inflammation regulate COX-2 expression along with cytokines such as interleukin-1 beta (IL-1b), tumor necrosis factor alpha (TNF-α), interleukin-8 (IL-8), and interleukin-6 (IL-6). Research has demonstrated that the aerial parts of Artemisia sylvatica Maxim. and Artemisia douglasiana Besser can inhibit signaling through nuclear factor kappa B (NF-κB), which aids in reducing rheumatoid arthritis symptoms. Phytochemical analyses have revealed a range of compounds in various Artemisia species, such as Esculetin, Scopoletin, Scopolin, Dehydroleucodine, Moxartenolide, Arteminolides, Artemisolide, 3-Methoxytanapartholide, and Deacetyllaurenobiolide. These compounds are key contributors to their anti-arthritis and anti-inflammatory effects^55-60.

Cassia angustifolia:

Senna, known scientifically as Cassia angustifolia M. Vahl and classified under the leguminoseae family, is an important traditional remedy for various symptoms associated with autoimmune joint inflammation. Nonetheless, scientific studies validating its efficacy for treating rheumatic conditions are limited. In contrast, the leaves of Cassia alata L. have shown potential in reducing inflammation, preventing cartilage damage, and decreasing the infiltration of white blood cells in the synovial fluid of rat knee joints, in addition to addressing other complications related to rheumatoid arthritis. Citron, scientifically referred to as Citrus medica L. in the Rutaceae family, is a plant that is widely grown, with its peel, leaves, and roots often utilized in traditional medicine across Asia, especially in India and Iran. This herbal remedy has been employed for many years to treat conditions like rheumatism, hepatitis, and arthritis. Studies have indicated that Citrus medica possesses properties that decrease oxidation and reduce inflammation. Additionally, the peels of Citrus medica along with those of Citrus unshiu (Swingle) Marcow fruits have shown effectiveness in managing inflammatory diseases, particularly arthritis^61,62.

Abutilon indicum:

Research indicates that Abutilon indicum Linn., part of the Malvaceae family, improves immune reactions, affecting both humoral and cellular immunity. It plays a role in altering serum immunoglobulin levels and enhances results in tests like indirect hemagglutination that are indicative of humoral immunity. Moreover, Abutilon indicum significantly enhances cellular immunity by encouraging neutrophil attachment and improving carbon clearance^63-66.

Adhatoda vasica:

The alcoholic extract from Adhatoda vasica Nees, which belongs to the Acanthaceae family, has been found to reduce neutrophil counts, leading to lowered phagocytic activity. It also exhibits inhibitory effects on the protease of the human immunodeficiency virus (HIV), diminishes T lymphocyte functionality, and reduces reactions related to delayed-type hypersensitivity. The aqueous extract from Acacia catechu, within the Leguminosae family, influences humoral immunity by altering serum immunoglobulin levels and the results of indirect hemagglutination tests. Furthermore, it modifies aspects of cell-mediated immunity by alleviating cyclophosphamide-induced neutropenia while encouraging neutrophil adhesion and improving carbon clearance^67-70.

Achillea millefolium:

Research involving mice has identified that a compound obtained from Achillea millefolium C. Koch (Compositae) significantly enhances both humoral and cellular immune functions. Water extract given at a dosage of 100 mg/kg effectively boosts responses related to delayed-type hypersensitivity. Additionally, this plant extract demonstrates a stimulating effect on immune function that is proportional to the dose given, as shown in the hemagglutination assay^71,72.

Actinidia macrosperma:

Actinidia macrosperma (Actinidiaceae) serves as an immunomodulator by encouraging the proliferation of lymphocytes and enhancing the activity of NK cells. This influence on the immune system aids in activating defenses and strengthening overall immune esponses^73,74.

Allium hirtifolium:

The hydroalcoholic extract taken from Allium hirtifolium Boiss. (Alliaceae) leads to an increase in footpad thickness due to its immunomodulatory effects. Studies suggest that this extract significantly enhances footpad thickness, indicating potential immunomodulatory properties^75,76.

Andrographis paniculata:

The primary ingredient found in Andrographis paniculata Nees (Acanthaceae), known as andrographolide, has been identified as effective in reducing TNF-α levels while significantly boosting together "antigen-specific" as well as "antigen-nonspecific" immunological reactions in mice. Moreover, it has proven effective against various harmful pathogens and possible cancer-causing agents^77,78.

Asparagus racemosus:

The water extract from Asparagus racemosus Willd. has been found to notably raise the levels of CD3(+) (Cluster of Differentiation 3) as well as CD4/CD8(+) (Clusters of Differentiation 4 and 8) markers. This indicates its involvement in activating T-cells. Furthermore, increased antibody levels and enhanced delayed-type hypersensitivity (DTH) responses have been noted, reflecting improved activation of lymphocytes^79,80.

Boswellia serrata:

Boswellia serrata, commonly referred to as Indian frankincense, is rich in boswellic acids, which assist in enhancing joint flexibility among individuals with autoimmune joint inflammation by blocking 5-lipoxygenase. This action helps prevent cartilage degradation and reduces pro-inflammatory leukotrienes. Additionally, it promotes lymphocyte growth, thereby boosting immune functions. These properties highlight its potential effectiveness as a treatment for RA⁸¹.

Chlorophytum borivilianum:

Chlorophytum borivilianum, part of the Liliaceae family, shows promising abilities to influence the body's defense mechanisms. In vivo trials have shown increased phagocytic activity, better adherence of neutrophils, and enhanced delayed-type hypersensitivity (DTH) following treatments with its extracts, as demonstrated by the carbon clearance technique. These findings emphasize its significant potential as a modulator of the body’s defenses⁸².

Cissampelos pareira:

Research on Cissampelos pareira Linn. from the Menispermiaceae family indicates that it influences serum immunoglobulin levels and works effectively in the indirect hemagglutination assay, suggesting it enhances both humoral and cell-mediated immune responses. This highlights its possible contribution to the modulation of the body's defenses⁸³.

Citrus natsudai:

Citrus natsudai Hayata, belonging to the Rutaceae family, exhibits strong immunostimulatory effects, such as increasing lymphocyte proliferation and activating key cytokines like Tumor Necrosis Factor-alpha (TNF-α) and Interferon-beta (INF-β). These findings indicate its influence on immune reactions⁸⁴.

Cleome gynandra:

Cleome gynandra Linn., part of the Capparaceae family, promotes delayed-type hypersensitivity (DTH) and enhances phagocytic functionality, thereby bolstering both humoral and cell-mediated immune responses. These effects underline its potential role as an immunomodulatory substance⁸⁵.

Cordia superb:

Cordia superba Cham. and Cordia rufescens A. DC (Boraginaceae family) methanolic extracts display significant immune-modulating abilities by activating lipopolysaccharide, interferon-gamma (IFN-γ), and nitric oxide (NO). These results support its effectiveness in modulating immune reactions⁸⁶.

Curcuma longa:

Curcumin, a significant bioactive substance with potent anti-inflammatory and antioxidant properties, is found in Curcuma longa L., or turmeric. Curcumin mainly lowers inflammatory cytokines by blocking important signaling pathways like NF-κB and JAK-STAT. According to clinical research, curcumin can reduce autoimmune joint inflammation symptoms, especially when used with conventional treatments. Curcumin consistently inhibits NF-κB activation and dramatically reduces pro-inflammatory markers, such as MCP-1, TNF-α, IL-6, and TGF-β,” according to data from 117 randomized controlled trials⁸⁷.

Glycyrrhiza glabra:

Glycyrrhizin, a crucial substance with anti-inflammatory and immune-boosting properties, is found in Glycyrrhiza glabra L. (Licorice/Yastimadhu). In addition to increasing corticosteroid activity and reducing their adverse effects in autoimmune joint inflammation, glycyrrhizin also lowers reactive oxygen species and inhibits pro-inflammatory enzymes. By encouraging the synthesis of IL-12 in dendritic cells and raising maturation markers including CD40, CD86, and MHC-II, it modifies immunological function. Glycyrrhizin also raises IFN-γ and IL-10 while lowering IL-4. Combining licorice extract with zinc has also shown improved immunomodulatory benefits⁸⁸.

Gymnema sylvestre:

The water-soluble extract from Gymnema sylvestre R.Br. (Asclepiadaceae) has demonstrated significant immune-modulating effects in various in vitro studies, as noted by several researchers. It was found to promote the movement, phagocytic activity, and chemotactic response of neutrophils⁸⁸.

Hibiscus rosa-sinensis:

Hibiscus rosa-sinensis Linn. (Malvaceae) has been demonstrated to improve both humoral and cell-mediated immunological reactions. Research reveals that it boosts phagocytosis and heightens the delayed-type hypersensitivity (DTH) response⁸⁸.

Hyptis suaveolens:

Hyptis suaveolens (L.) Poit. (Lamiaceae) has been shown to hinder both humoral and cell-mediated immune functions. Studies highlight this immunosuppressive characteristic using the indirect hemagglutination test⁸⁹.

Lagenaria siceraria:

The ethanolic extract of Lagenaria siceraria Mol. (Cucurbitaceae) has exhibited immune-stimulating effects both in laboratory settings and in live subjects, reflected by an increased delayed-type hypersensitivity (DTH) response⁸⁹.

Morus alba:

According to several studies, the methanolic extract of Morus alba Linn. (Moraceae) has an effect on humoral and cell-mediated immunity. Results from the indirect hemagglutination assay, serum immunoglobulin measurements, and lethality tests in mice indicate that it has an effect on humoral immunity, and it has an effect on cell-mediated immunity by significantly enhancing neutrophil adhesion, speeding up carbon clearance, and reducing cyclophosphamide-induced neutropenia⁹⁰.

Murraya koenigii:

The methanolic extract of Murraya koenigii (L.) Spreng. (Rutaceae) exhibited immunostimulatory properties together in vitro and in vivo tests; peritoneal macrophages gathered from mice showed a significant rise in nitric oxide (NO), and the culture supernatants indicated enhanced macrophage phagocytic activity, resulting in a higher phagocytic index due to the swift clearance of carbon particles from the bloodstream⁹¹.

Nyctanthes arbortristis:

Nyctanthes arbortristis L. (Oleaceae) seems to boost the immune reaction, impacting both humoral and cell-mediated immunities. This was illustrated by alterations in serum immunoglobulin levels as well as findings from the indirect hemagglutination assay⁹².

Ocimum sanctum:

When reacting to sheep red blood cells (SRBCs), the hydroalcoholic extracts of Ocimum sanctum Linn. (Labiateae) heightened the delayed type hypersensitivity (DTH) reaction. The alcoholic extract was more effective in triggering the DTH response compared to the aqueous version. Both extracts showed a moderate stimulating effect on humoral immunity⁹³.

Emblica officinalis:

Amalaki (Emblica officinalis), high in vitamin C, serves as a powerful antioxidant that strengthens immune performance and protects cells from oxidative harm. It is also recognized for its anti-inflammatory properties. Research on Bagg albino c mice demonstrated that Phyllanthus emblica enhances antibody-dependent cellular cytotoxic activity and improves the effectiveness of natural killer (NK) cells. Findings suggest that Emblica officinalis enhances macrophage phagocytic capability and supports both humoral and cell-mediated immune responses⁹⁴.

Terminalia arjuna:

Research indicates that Terminalia arjuna Roxb. (Combretaceae) boosts antibody titer against sheep red blood cells (SRBC), suggesting its role as an immunomodulator by activating the secondary immune response. However, it showed no significant effect on modulating the primary immune response⁹⁵.

Terminalia chebula:

An aqueous extract derived from dried fruits of Terminalia chebula Retz. (Haritaki) has been shown to augment the humoral antibody titer and delayed-type hypersensitivity (DTH) response in mice. Additionally, another investigation reported an increase in the proportion of CD4+ cells (Cluster of Differentiation 4), a decrease in interleukin-4 (IL-4), accompanied by an elevation in interferon-gamma (IFN-γ), a T-helper 1 (Th1) cytokine. Research demonstrates that this extract also enhanced the DTH response, macrophage phagocytosis, and lymphocyte proliferation⁹⁶.

Tinospora cordifolia:

Tinospora cordifolia Miers. (Guduchi) is prized for its detoxifying and immunomodulatory qualities. Without influencing humoral or cell-mediated immunity, it improves immunological protection by stimulating phagocytosis and blocking C3 convertase in the traditional complement pathway. It has been demonstrated that T. cordifolia aqueous extracts influence immune cell activation, mitogenic responses, and cytokine production. Additionally, studies show elevated levels of interleukin-6 (IL-6), which promote B-cell maturation, cytotoxic T-cell activation, and inflammatory response⁹⁷.

Centella asiatica:

Centella asiatica (gotu kola) is yet another herb noted for its immunomodulatory effects. Clinical trials involving individuals with systemic lupus erythematosus (SLE) have shown enhancements in symptoms with the administration of standardized extracts of gotu kola, highlighting its potential as a safe and effective option for treatment⁹⁸.

Boerhavia diffusa:

Punarnava (Boerhavia diffusa) is recognized for its ability to promote urination and cleanse the body. It is also employed to alleviate inflammation and autoimmune disorders, and it aids in bolstering the body's defense mechanisms⁹⁹.

Figure 2: Few medicinal plants used in autoimmune joint inflammation¹⁰⁶

CONCLUSION:

Because of their various anti-inflammatory, antioxidant, and immunomodulatory properties, medicinal flora offers a useful supplemental strategy for treating autoimmune joint problems. Although rheumatoid arthritis (RA) has shown promising benefits, further research is needed to fully confirm its therapeutic potential and incorporate it into routine clinical practice. Similarly, herbal treatments with immune-modulating and anti-inflammatory properties have demonstrated promising results in reducing symptoms in cutaneous lupus erythematosus and multisystem autoimmune lupus, where traditional therapeutic options remain limited. Nevertheless, comprehensive human clinical trials are still required to verify their efficacy and safety. By addressing underlying imbalances like impeded Agni and Ama buildup, Ayurvedic herbal medicine also has potential as an adjuvant therapy, supporting general health and systemic harmony. In order to clarify mechanisms and demonstrate clinical efficacy, integrating Ayurvedic principles with contemporary medical care requires ongoing research. Effective commercial formulations have emerged in India as a result of growing interest in herbal treatments for RA, offering more therapeutic options that may have fewer side effects than traditional medications.

ACKNOWLEDGEMENT:

We would like to express our gratitude to the School of Pharmacy, Indrashil University, Rajpur, Kadi, for their assistance and resources in the creation of this review article. Their supportive academic environment was essential to the successful completion of this review article.

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Received on 20.11.2025 Revised on 26.12.2025

Accepted on 29.01.2026 Published on 21.04.2026

Available online from April 24, 2026

Res. J. Pharmacognosy and Phytochem. 2026; 18(2):189-200.

DOI: 10.52711/0975-4385.2026.00026

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

Sr. No.	Formulation Name	Use	Company Name
1	Baidyanath Rheumartho Gold Plus	CompanyBaidyanath Rheumartho Gold Plus	Baidyanath
2	Himalaya Rumalaya Forte tablet	Rheumatoid arthritis and osteoarthritis	Himalaya wellness company
3.	Dabur's Rheumatil Tablet	Joint pain	Dabur India Limited.
4.	Divya orthogrit tablet	Arthritis, old arthritis, sprain	Patanjali Ayurved Ltd
5.	GO365 Nutra Tablet	Joint pain, stiffness, and swelling	Charak Pharma Pvt Ltd.
6.	Sandhivati Capsules	Joint pain, muscular and arthritic pain	Dr Vaidya Company
7.	Mahoyograj guggul	Reduces inflammation and stiffness	Dr Vaidya Company
8.	maharasnadi kwatha	Anti-inflammatory action	Dr Vaidya Company
9.	Dr. Ortho Ayurvedic Capsule i	Joint discomforts	Divisa Store
10.	Vita Green Shallak	Reduces swelling as well as stiffness	Green Cross Health Innovation
11.	Rheumizap Tablet	Eases joint inflammation, pain and prevent joint damage	Zealous Health Pvt Ltd
12	Artho Sure Capsules	Joint pain relief	Kapiva Adret Retail Pvt. Ltd.

Patent ID	Primary Composition	Target Application	Extraction/Preparation Method	Efficacy or Key Results
EP2175871B1	Withania somnifera, Tribulus terrestris, Phyllanthus emblica, Boswellia serrata, Zingiber officinale, Tinospora cordifolia	Rheumatic and musculoskeletal disorders (RMSDs)	Water extraction, drying, milling, and sieving to create powdered or paste formulations	Demonstrated analgesic and anti-inflammatory effects; reduced glycosaminoglycan and aggrecan release by up to 40%
KR102576779B1	Centella asiatica (Asiaticoside enriched)	Inflammatory conditions, neurodegenerative diseases, skincare	Hydroponic cultivation under controlled conditions; ethanol extraction	Enhanced asiaticoside content; superior anti-inflammatory and antioxidant efficacy
US11903991	Details truncated in the provided document, focused on bioactive components	Not fully detailed in extracted content	Not fully detailed in extracted content	Not fully detailed in extracted content
US20120082739A1	Turmeric, Boswellia, Ginger, Holy Basil, Rosemary, White Willow, Alpha-Lipoic Acid	Pain management (topical and oral), Anti-inflammatory	Natural extracts reduce pain with fewer side effects compared to conventional drugs.	US20120082739A1
US20190175678A1	Boswellia serrata extract (AKBA enriched), non-acidic resin extract (BNRE)	Anti-inflammatory, Arthritis, Asthma, and other inflammatory conditions	Synergistic combination improves efficacy in reducing inflammation compared to individual components.	US20190175678A1