## 1 Introduction
The common treatment options for OA include drugs such as non-steroidal anti-inflammatory drugs, steroids and opioids with their specific side effects. Therefore, in recent years, many research studies focused on natural pharmaceuticals and nutraceuticals which may be explored as alternative options, being effective, safe and cost-efficient, with great potential in the treatment of OA, especially due to their anti-inflammatory and analgesic effects, anti-oxidation, regulation of chondrocyte metabolism and proliferation, and cartilage protection [12; 13; 14; 15; 16]. Traditional Brazilian plants were reviewed by [PERSON] et al., including 24 species with anti-arthritic and anti-osteoarthritis (investigated in preclinical models), and 14 species (in randomized clinical trials), their effects being ascribed to phenolic compounds (such as flavonoids) [17]. Plant-derived polysaccharides have shown great effects in anti-inflammation, anti-oxidation, the regulation of chondrocyte metabolism and proliferation and cartilage protection, demonstrating significant potential in OA treatment. Polysaccharides have been found to reduce the expressions of pro-inflammatory cytokines (such as NF-\(\kappa\)B, IL-1\(\beta\), IL-6, TNF-\(\alpha\), COX-2, iNOS) and to have antioxidant effects (by down-regulation of SOD, MDA, CAT activities, inhibition of caspase pathway) in studies performed on cells culture and animal models [13]. _Achyranthes bidentate_ extract, a traditional Chinese medicinal plant with saponin components, presented protective effects against inflammation induced by IL-1\(\beta\) in human chondrocytes due to the reduction of proinflammatory factors expression (such as IL-6, TNF-\(\alpha\), COX-2, iNOS, PGE2, NO) and the inhibition of NF-kB activity [18]. Plants from _Arecaceae_ family present potential as anti-OA agents due to their metabolites (galactomanan, fatty acids, flavonoids, phenolic acids, polyphenols and steroids) which show anti-inflammatory and chondrocytes effects [12]. In an in vivo study on rats, [PERSON] et al. showed the anti-arthritic potential of walnut oil, which decreased anti-arthritic biomarkers and improved morphological appearance [19]. The effect of walnut extract included in the daily diet demonstrated beneficial effects on rheumatoid arthritis in rats, such as decreased cellular infiltration, bone erosion and paw inflammation (histological examination); and a negative regulation of the RANKL-OPG pathway (gene expression analysis) [20]. In another study, the same authors showed the antioxidant role of walnuts, without hepatic or renal side effects [21]. Another study validated the anti-inflammatory effects of walnut leaves extract in rheumatoid arthritis, both in acute and chronic inflammation. The extract possessed anti-inflammatory and immunomodulatory properties, by decreasing pro-inflammatory markers (TNF-\(\alpha\), IL-1\(\beta\), IL-6, NF-\(\kappa\)B, COX-2 and PGE2), but also by up-regulating anti-inflammatory ones (IL-4) [22]. EA may help modulate osteoclast activity, reducing bone reabsorption, while promoting osteoblast activity to support bone formation, potentially helping to prevent bone loss [23]. Ellagic acid, a natural polyphenol found in many plants products, with anti-inflammatory and antioxidant proprieties was also used in the in vitro and in vivo experiments illustrating anti-inflammatory effects by inducing OA protectiveness [18]. The in vitro study on human chondrocytes shown that IL-6 and TNF-\(\alpha\) levels were significantly decreased in the group treated with EA in a dose-dependent way [18]. According to our previous study, where we performed the phytochemical composition analyses of walnut extract [24], we found the presence of ellagic acid, which motivatedus to carry out this comparative study between the effects of ellagic acid and walnut extract. The therapeutic effects of _Iuglans regia_ L. can be attributed to its bioactive constituents, including ellagic acid, quercetin and catechins.