## 1 Introduction
The common medication for osteoarthritis is topical or oral non-steroidal anti-inflammatory drugs (NSAIDs), intra-articular steroid injections, and duloxetine [18]. The toxicity of NSAIDs includes decreasing renal blood flow, gastrointestinal ulceration, and bleeding. To prevent the gastrointestinal ulceration caused by NSAIDs, misoprostol, proton pump inhibitors, and histamine-2-receptor antagonists were helpful [19]. The side effects of intra-articular steroid injections included the destruction of cartilage, infectious arthritis, and the systemic effects of steroids [20]. The major adverse events of duloxetine for osteoarthritis were nausea, constipation, and fatigue [21]. As for rheumatoid arthritis, a chronic systemic autoimmune disease, the inflammation of the joint is induced by a reaction of autoantibody to self-citrullinated protein [22]. Joint inflammation and joint deformity impairments in rheumatoid arthritis then contribute to functional limitations in daily life [23]. As for rheumatoid arthritis, first-line treatments aim to control pain and reduce inflammation, so analgesics such as NSAIDs and corticosteroids are often used. Second-line treatment is disease-modifying antirheumatic drugs (DMARDs), promoting joint destruction and deformity remission. DMARDS include methotrexate, hydroxychloroquine, and sulfasalazine [24]. The adverse events of systemic corticosteroid therapy for rheumatoid arthritis included hyperglycemia, immunosuppression, gastrointestinal events, and osteoporosis [25]. Of all the DMARDs, hydroxychloroquine was the safest drug. Hydroxychloroquine did not increase the risk of hepatotoxicity, severe infection, and renal dysfunction. The major side effects of hydroxychloroquine included diarrhea and rash. Methotrexate, sulfasalazine, and leflunomide have similar side effects, including bone marrow suppression, allergy, gastrointestinal events, and severe infections [26]. Multiple animal models and in vitro trials possibly explained the mechanisms of efficacy from the willow bark extract. For instance, willow bark extract inhibits proinflammatory cytokines, such as tumor necrosis factor \(\alpha\) (TNF\(\alpha\)), cyclooxygenase-2 (COX-2), and the nuclear translocation of the transcription factor in proinflammatory activated monocytes, resulting in its anti-inflammatory effect [27]. Moreover, willow bark extract has the therapeutic effect of preventing oxidative stress [28] and induces apoptosis in human colon and lung cancer cells [29]. Several studies have been conducted to analyze which component in the willow bark is responsible for its therapeutic effect. There were at least 13 different main compounds, including saligenin, salicylic acid, salicin, isosalicin, piccin, salidroside, triandrin, salicosilicin, salicortin, isosalipurposide, naringenin-7-O-glucoside, and tremulacin, in willow bark identified and analyzed with the high-performance liquid chromatography technique and mass spectrometry [30]. As the precursor of aspirin, however, salicin cannot fully explain the clinical effect of willow bark [31]. Both flavonoids and polyphenols in the willow bark were proven to be attributed to anti-inflammatory effects [32]. Willow bark extract is now widely used for conditions associated with inflammation or fever, and it can be applied to various types of pain, such as joint or knee pain, acute back pain, osteoarthritis, headache, menstrual cramps, tendonitis, and generalized pain [33]. For arthritis per se, the efficacy of willow bark from various studies is diverse. Three studies with RCT showed that both willow bark extract alone [34] and compound drugs [35; 36] had an analgesic effect versus placebo. In contrast, three studies with RCT showed that willow bark extract yielded no significant benefit [37; 38]. According to [PERSON] et al., although salicin derivatives in the willow bark were metabolized in vivo to salicylic acid, serum salicate concentration was too low to reach clinical effects [37].