Osteoarthritis: Insights into Diagnosis, Pathophysiology, Therapeutic Avenues, and the Potential of Natural Extracts

Abstract

Osteoarthritis (OA) stands as a prevalent and progressively debilitating clinical condition globally, impacting joint structures and leading to their gradual deterioration through inflammatory mechanisms. While both non-modifiable and modifiable factors contribute to its onset, numerous aspects of OA pathophysiology remain elusive despite considerable research strides. Presently, diagnosis heavily relies on clinician expertise and meticulous differential diagnosis to exclude other joint-affecting conditions. Therapeutic approaches for OA predominantly focus on patient education for self-management alongside tailored exercise regimens, often complemented by various pharmacological interventions primarily targeting pain alleviation. However, pharmacological treatments typically exhibit short-term efficacy and local and/or systemic side effects, with prosthetic surgery being the ultimate resolution in severe cases. Thus, exploring the potential integration or substitution of conventional drug therapies with natural compounds and extracts emerges as a promising frontier in enhancing OA management. These alternatives offer improved safety profiles and possess the potential to target specific dysregulated pathways implicated in OA pathogenesis, thereby presenting a holistic approach to address the condition's complexities.

Keywords: Boswellia serrata; Glycine soja; Harpagophytum procumbens; Matricaria chamomilla; Zingiber; aescin; bromelain; curcumin; devil’s claw; natural extracts; osteoarthritis; quercetin.

Figure 1

Schematic representation of the pathological mechanisms in osteoarthritis (OA) highlighting the complex interplay among bone, cartilage, and synovial tissues [126]. The diagram illustrates how prolonged mechanical stress, wear, and trauma lead to the secretion of extracellular matrix (ECM) by cartilage cells. Key enzymes involved in ECM remodeling—such as MMPs, ADAMTSs, plasmin, plasminogen activator, and TIMPs—are shown to have disrupted activity, contributing to excessive cartilage catabolism. The role of interleukins, TGF-β, and BMP-2 in cartilage morphology, tissue homeostasis, and metabolism is depicted alongside the suppression of TIMPs. The feedback loop of MMP activation, TNF-α, and interleukin synthesis by synovial tissues and chondrocytes fosters a sustained inflammatory cascade. This leads to the release of NO and prostaglandin E2, proliferation of chondrocytes, and deposition of collagen type X, which undergoes calcification, exacerbating OA pathology. BMP-2: bone morphogenetic protein 2; PA: plasminogen activator; MMP: matrix metalloproteinase; TGF-β: transforming growth factor beta; TIMP: tissue inhibitor of metalloproteinase; TNF-α: tumor necrosis factor alpha; NO: nitric oxide; PGE2: Prostaglandin E2; IL-1: Interleukin-1; IL-8: Interleukin-8.