Shang-Yu Yang,1,† Chi-Jung Fang,2,† Yu-Wen Chen,3 Wan-Ping Chen,3 Li-Ya Lee,3 Chin-Chu Chen,4,5,6 Yen-You Lin,7 Shan-Chi Liu,8 Chun-Hao Tsai,9,10 Wei-Chien Huang,11,12 Yang-Chang Wu,13,14 and Chih-Hsin Tang7,11,15,16,*
Keywords: osteoarthritis, Hericium erinaceus, mycelium, anterior cruciate ligament transection, interleukin 1 beta, tumor necrosis factor-alpha
Abstract
Osteoarthritis (OA) is an age-related disorder that affects the joints and causes functional disability. Hericium erinaceus is a large edible mushroom with several known medicinal functions. However, the therapeutic effects of H. erinaceus in OA are unknown. In this study, data from Sprague-Dawley rats with knee OA induced by anterior cruciate ligament transection (ACLT) indicated that H. erinaceus mycelium improves ACLT-induced weight-bearing asymmetry and minimizes pain. ACLT-induced increases in articular cartilage degradation and bone erosion were significantly reduced by treatment with H. erinaceus mycelium. In addition, H. erinaceus mycelium reduced the synthesis of proinflammatory cytokines interleukin-1β and tumor necrosis factor-α in OA cartilage and synovium. H. erinaceus mycelium shows promise as a functional food in the treatment of OA.
Introduction
Osteoarthritis (OA) is an age-related disorder that affects the joints and causes functional disability [1]. During OA development, low-grade inflammatory reactions progressively degrade the joints [2]. Typical OA symptoms include joint swelling and deformities that are associated with constant pain and consequent interference with normal daily life activities [2]. Around 80% of OA patients face movement disorders, 20% cannot perform basic activities and 10% require daily care [3]. The ever-growing numbers of elderly people worldwide are confounding the already large healthcare and economic burdens imposed by patients with OA [2,4].
Two major proinflammatory cytokines, interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), facilitate the development of OA by increasing catabolic enzyme formation that degrades the cartilage extracellular matrix [5,6]. Levels of IL-1β and TNF-α expression are higher in human OA serum and synovial fluid than in samples from healthy individuals [7,8], and they are targeted by therapies such as the anti-IL-1β antibody canakinumab and the TNF-α-blocking agent adalimumab [7]. Inhibiting proinflammatory cytokine expression successfully inhibits OA progression [5,9].
Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are commonly applied to inhibit ongoing inflammation and reduce the pain associated with OA [10,11]. However, the undesirable side effects of these synthetic agents make the discovery of anti-OA ingredients from natural products an attractive proposition. Hericium erinaceus is a large edible mushroom that is popularly consumed in Asian countries and is accepted as a dietary supplement or functional food [12,13]. H. erinaceus is rich in bioactive compounds including glycoproteins, polysaccharides and ketones [14]. In addition, the mushroom fruiting bodies, mycelium and bioactive pure compounds of H. erinaceus exhibit several medicinal functions including antitumor, anti-inflammatory, nephroprotective, neuroprotective effects, antimicrobial, antioxidant, immunomodulatory and antihyperglycemic properties [12,15,16,17,18,19,20]. A standardized extract containing H. erinaceus (Bull.) Persoon, Kalopanax pictus Castor-Aralia and Astragalus membranaceus Schischkin has shown in vitro and in vivo chondroprotective effects in OA models [21]. However, the therapeutic effects of H. erinaceus in human OA remain unknown. Here, we found that H. erinaceus mycelium prevents disease progression in an anterior cruciate ligament transection (ACLT) model of OA, suggesting that H. erinaceus mycelium has therapeutic utility for OA.