Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by inflammation and destructive changes in bone and cartilage of multiple joints (Smolen et al., 2022). The RA disease is widely distributed globally with a prevalence of 0.5–2.0% and is believed to affect up to 0.75% of the Indian population (Myasoedova et al., 2020). The etiology of RA has not been fully elucidated till now, however, it is presumed that the interaction between multiple factors like environmental, gender, genetics, and others were associated with the development of RA in patients (Janakiraman et al., 2018, Wu et al., 2022). No complete cure for RA is known where the main aim of the treatment is to provide symptomatic relief which includes decreasing joint pain and inflammation, maximising joint function, and preventing joint destruction. In the modern/allopathic system of medicine, multiple treatment approaches are being employed which mostly include the use of non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease-modifying anti-rheumatic drugs (DMARDs) (Anita et al., 2021). Despite the availability of many types of drugs in modern medicine, their severe adverse reactions with long-term use and high cost limit their usage and impediment in effectively controlling RA. Moreover, it has been reported that about 30–40% of patients with RA fail to respond to conventional therapies. These have led to a shift to many suitable alternatives that include the usage of natural products which offer promising alternatives and adjuncts for treatment of the disease (Moudgil and Venkatesha, 2022). A multidisciplinary approach for the treatment of RA among different forms of medicine including that of the Unani system of medicine (USM) may be of great help. The USM is a type of complementary and alternative medicine that has a rich treasure of therapeutically active herbal-based products and many other options available with extensive patient-beneficial clinical experience on many diseases including that of RA.

In USM the clinical findings of RA closely resemble the findings of Waja al mafasil (rheumatoid arthritis) and is known as such. The Waja al mafasil is extensively explained in Unani medicine with its line of treatment (Arzani, 1931, Ibn Sīnā, 2007, Majusi, 2010, Khatoon et al., 2023). There are so many single and compound Unani herbal formulations mentioned in classical texts that have been used for the treatment of Waja al mafasil by eminent Unani Physicians for ages. These Unani herbal formulations need validation on systemic scientific parameters to generate data regarding their safety, efficacy, and mode of action. One of the Unani formulations named ‘Hudar’ is present in various forms as ‘capsule Hudar’, ‘Habb-e-Hudar’, ‘Qurs-e-Hudar’ mentioned to be useful for the treatment of Waja al mafasil (rheumatoid arthritis). This Unani formulation is composed of two herbs Azaraqi mudabbar (Strychnos nux-vomica L.) and Zanjabeel (Zingiber officinale Rosc.). This Unani herbal formulation has been well received by patients and has been standardised for its quality control (Anonymous, 2001, Shamsi et al., 2010, Akbar et al., 2010). Moreover, the Cap. Hudar has been granted a patent by the National Research Development Corporation (NRDC) with patent no. 250700 dated January 27, 2013 to our parent organisation i.e., Central Council of Research in Unani Medicine, Government of India. Nevertheless, to our best knowledge, no mechanistic study has been reported on the effect of Qurs-e-Hudar on biomarkers in patients with RA. In RA, biomarkers may play an important role in guiding the clinical and therapeutic management and assessing treatment responses to know the possible mechanism of action (Atzeni et al., 2017). For the present study, the candidate biomarkers previously reported to be related to RA disease activity or underlying process were identified through a review of many scientific articles and other authentic sources (Aletaha et al., 2010, Robinson et al., 2013, Centola et al., 2013). Given the importance of drugs being used in USM for RA and the lack of systemic studies on their effect on blood-based markers, we perform the present clinical study. The primary aim of this study was to evaluate and compare the various blood-based biomarkers in RA patients and reference populations as controls. Subsequently, patients with RA were treated with the Unani herbal formulation Qurs-e-Hudar, and efficacy, safety, and effect on these blood-based biomarkers of given Unani test formulation were evaluated for the first time.