L-Theanine Reduced the Development of Knee Osteoarthritis in Rats via Its Anti-Inflammation and Anti-Matrix Degradation Actions: In Vivo and In Vitro Study

Abstract

<jats:p>The etiology of osteoarthritis (OA) is multifactorial, with no effective disease-modifying-drugs. L-theanine has been reported to inhibit inflammatory responses in some diseases and this study aimed to investigate the effect of L-theanine on Interleukin-1(IL-1)β-stimulated chondrocytes, and in an injury-induced OA rat model. Primary chondrocytes were stimulated by IL-1β (10 ng/mL) for 24 h and then co-cultured with L-theanine for 24 h. The effects of L-theanine on IL-1β-stimulated expression of pro-inflammatory cytokines and hydrolytic enzyme were analyzed using Western blotting, quantitative polymerase chain reaction (q-PCR) and enzyme-linked immunosorbent assay (ELISA) kits. An immunofluorescence assay was used to detect nuclear factor kappa B (NF-κB) phosphorylation. OA was induced by anterior cruciate ligament transection (ACLT) surgery in rats and celecoxib was used as a positive control. OA severity was measured using the Osteoarthritis Research Society International (OARSI) grading system to describe histological changes. The results showed that L-theanine decreased the expression of pro-inflammatory mediators, including cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE-2), inducible nitric oxide synthase (iNOS), and nitric oxide (NO), both in vivo and in vitro. L-theanine treatment inhibited IL-1β-induced upregulation of matrix metalloproteinases (MMP)-3 and MMP-13, as well as inhibited NF-κB p65 activation. In vivo animal model showed that L-theanine administration (200 mg/kg) significantly alleviated OA lesions and decreased OARSI score. Our data indicated that L-theanine decreased inflammatory cytokines and protected extracellular matrix degradation through inhibition of the NF-κB pathway, and L-theanine may be considered a promising therapeutic strategy in OA prevention.</jats:p>

Puerarin inhibits the development of osteoarthritis through antiinflammatory and antimatrix‐degrading pathways in osteoarthritis‐induced rat model

“…In the pathogenesis of OA, MMP‐3, MMP‐13, and ADAMTS‐5 are closely related to inflammation (Bai et al, 2020; Verma & Dalal, 2011) and are the main proteases that degrade the ECM and can cause articular cartilage damage (Malemud, 2019). When OA occurs, COX‐2 and PGE‐2 in cartilage increase significantly and promote cartilage damage by activating inflammatory pathways (Xue, Xue, Hu, Shi, & Yang, 2020).…”

“…Two weeks after induction, 50 and 100 mg/kg of puerarin were given to the OAP‐1 group and the OAP‐2 group, respectively, by oral gavage every day for 8 weeks. The control group was given an appropriate amount of sterile saline by oral gavage, and the OAC group was given 2.86 mg/kg celecoxib (Pfizer Pharmaceutical, New York, USA; Bai et al, 2020; Panahifar et al, 2014) for eight consecutive weeks. The puerarin dosage was based on previous research (Peng et al, 2019; C. Wang et al, 2016; L. Wang et al, 2018).…”

Role of Physical Exercise and Nutraceuticals in Modulating Molecular Pathways of Osteoarthritis

“…Other nutraceuticals that could have a role in modulating the OA pathways seem to be the green tea catechins (GTCs), which could protect against cartilage loss and reduce the progression of OA through the modulation of NF-κB inhibitor expression and targeting the PI3K/AKT pathway. Another main component of the green tea is the epigallo-catechin-3 gallate that might inhibit NF-κB nuclear translocation by blocking IkB degradation in human chondrocytes stimulated with IL-1β [ 122 , 123 , 124 ].…”

The Protective Effect of Dietary Administration of Puerarin on Canine Osteoarthritis Model With Anterior Cruciate Ligament Transected

“…We use the typical COX-2 inhibitor celecoxib as a positive control. Celecoxib has relatively small side effects and is widely used in the treatment of OA [32,33]. In recent years, more and more researches on herbal extracts and dietary supplements have opened up new horizons for the treatment of OA [34][35][36].…”