## 1 Introduction  
Osteoarthritis (OA) is a lingering joint illness accompanied by inflammation of the synovium and cartilage degeneration, causing physical disability in the elderly. Functional foods and medicines have been commonly utilized to care for OA, but pharmacological treatment of OA has limited effects [1; 2]. Non-steroidal anti-inflammatory drugs (NSAIDs) are usually utilized for reducing inflammation and pain in OA. However, a long-time consumption of NSAIDs adversely affects the gastrointestinal and cardiovascular systems [3; 4]. To this day, the etiology of OA is not obvious, and no effectual therapeutic treatment has been developed for OA. Therefore, safer and more effective novel agents are needed for the treatment of OA [1].  
The extracellular matrix (ECM) is mostly an organization of type I and II collagen, and aggrecan, which are the main constituents of ordinary cartilage that support the arthroidial cartilage to adapt to biomechanical forces during joint activity [5]. ECM is created and retained by the chondrocytes and is controlled by SOX9, which encodes the main transcription factor for ECM homeostasis [6,7]. Many studies have shown that inflammatory reactions generally play an enormous role in the OA and contributes to chondrocyte movement and phenotype and ECM degradation [7, 8, 9]. Overexpression of pro-inflammatory cytokines like IL-1\(\beta\) and IL-6 are implicated in the etiology of OA by upregulating the matrix metalloproteinases (MMPs) and triggering ECM collapse. In particular, IL-1\(\beta\) exerts inflammatory reactions by considerably upregulating the production of pro-inflammatory factors, and catabolic factors, for example, leukotriene B\({}_{4}\) (LTB\({}_{4}\)), nitric oxide (NO), and MMPs to degrade the ECM [10, 11, 12].  
MAPK mechanisms have been revealed to play an apparent part in terms of OA biology such as matrix composition and homeostasis of cartilage [13,14]. Additionally, NF-\(\kappa\)B mechanisms are a core controller of pro-inflammatory and catabolic factor production. When the NF-\(\kappa\)B mechanisms are activated, NF-\(\kappa\)B p65 is phosphorylated in the cytoplasm and ultimately translocated to the nucleus [15,16]. Practically, transitions in these mechanisms have been identified to play a crucial role in articular chondrocyte function as well as form part of OA etiology and illness progression [17].  
The fruit of _Terminalia chebula_ Retz. (Fam. Combretaceae) has been widely utilized in Ayurvedic, Iranian medicine, and Unani as a treatment for diverse diseases such as asthma, bleeding piles, sore throat, vomiting, and gout [18, 19, 20]. Moreover, _T. chebula_ has been widely known to exhibit antioxidant effects by inhibiting ROS and NO production [21, 22, 23, 24]. Clinical research has also proven that oxidative stress and inflammation contribute to OA, low back pain (LBP), and motor-related joint discomfort. The _T. chebula_ fruit exhibits antioxidant efficacy and downregulates inflammatory cytokines; however, its therapeutic effects warrant further investigation [25, 26, 27, 28, 29].  
Meanwhile, recent preclinical and clinical studies have revealed that the standardized aqueous extract of _T. chebula_ fruit (AyuFlex(r)) could markedly suppress OA progression [25, 30, 31, 32, 33, 34, 35]. However, the underlying mechanism, the anti-arthritic effect of AyuFlex(r), remains obscure. Therefore, in our study, we devised experiments to clarify the effectiveness and applications of AyuFlex(r), and to evaluate the protective effectiveness of arthroidial cartilage in IL-1\(\beta\)-treated chondrocytes and MIA-incurred OA in a rat model.