PDF(Pubmed)
Abstract：
UNASSIGNED: Knee osteoarthritis (KOA) is a persistent degenerative condition characterized by the deterioration of cartilage. The Chinese herbal formula Radix Rehmanniae Praeparata- Angelica Sinensis-Radix Achyranthis Bidentatae (RAR) has often been used in effective prescriptions for KOA as the main functional drug, but its underlying mechanism remains unclear. Therefore, network pharmacology and verification experiments were employed to investigate the impact and mode of action of RAR in the treatment of KOA.
UNASSIGNED: The destabilization of the medial meniscus model (DMM) was utilized to assess the anti-KOA effect of RAR by using gait analysis, micro-computed tomography (Micro-CT), and histology. Primary chondrocytes were extracted from the rib cartilage of a newborn mouse. The protective effects of RAR on OA cells were evaluated using a CCK-8 assay. The antioxidative effect of RAR was determined by measuring reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione (GSH) production. Furthermore, network pharmacology and molecular docking were utilized to propose possible RAR targets for KOA, which were further verified through experiments.
UNASSIGNED: In vivo, RAR significantly ameliorated DMM-induced KOA characteristics, such as subchondral bone sclerosis, cartilage deterioration, gait abnormalities, and the degree of knee swelling. In vitro, RAR stimulated chondrocyte proliferation and the expression of Col2a1, Comp, and Acan. Moreover, RAR treatment significantly reduced ROS accumulation in an OA cell model induced by IL-1β and increased the activity of antioxidant enzymes (SOD and GSH). Network pharmacology analysis combined with molecular docking showed that Mapk1 might be a key therapeutic target. Subsequent research showed that RAR could downregulate Mapk1 mRNA levels in IL-1β-induced chondrocytes and DMM-induced rats.
UNASSIGNED: RAR inhibited extracellular matrix (ECM) degradation and oxidative stress response via the MAPK signaling pathway in KOA, and Mapk1 may be a core target.
UNASSIGNED: The destabilization of the medial meniscus model (DMM) was utilized to assess the anti-KOA effect of RAR by using gait analysis, micro-computed tomography (Micro-CT), and histology. Primary chondrocytes were extracted from the rib cartilage of a newborn mouse. The protective effects of RAR on OA cells were evaluated using a CCK-8 assay. The antioxidative effect of RAR was determined by measuring reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione (GSH) production. Furthermore, network pharmacology and molecular docking were utilized to propose possible RAR targets for KOA, which were further verified through experiments.
UNASSIGNED: In vivo, RAR significantly ameliorated DMM-induced KOA characteristics, such as subchondral bone sclerosis, cartilage deterioration, gait abnormalities, and the degree of knee swelling. In vitro, RAR stimulated chondrocyte proliferation and the expression of Col2a1, Comp, and Acan. Moreover, RAR treatment significantly reduced ROS accumulation in an OA cell model induced by IL-1β and increased the activity of antioxidant enzymes (SOD and GSH). Network pharmacology analysis combined with molecular docking showed that Mapk1 might be a key therapeutic target. Subsequent research showed that RAR could downregulate Mapk1 mRNA levels in IL-1β-induced chondrocytes and DMM-induced rats.
UNASSIGNED: RAR inhibited extracellular matrix (ECM) degradation and oxidative stress response via the MAPK signaling pathway in KOA, and Mapk1 may be a core target.
摘要：
■膝骨关节炎（KOA）是一种持续的退行性疾病，其特征是软骨退化。中草药配方生地黄-当归-黄芩（RAR）作为主要功能药物经常被用于KOA的有效处方中，但其潜在机制仍不清楚。因此,采用网络药理学和验证实验研究RAR在KOA治疗中的作用和作用方式。
■内侧半月板模型（DMM）的失稳用于通过步态分析评估RAR的抗KOA作用，微型计算机断层扫描（Micro-CT），和组织学。从新生小鼠的肋软骨中提取原代软骨细胞。使用CCK-8测定评价RAR对OA细胞的保护作用。通过测量活性氧（ROS）来确定RAR的抗氧化作用。超氧化物歧化酶（SOD），和谷胱甘肽（GSH）生产。此外，利用网络药理学和分子对接提出了KOA可能的RAR靶标，通过实验进一步验证。
■体内，RAR显著改善DMM诱导的KOA特性，比如软骨下骨硬化，软骨恶化，步态异常,以及膝盖肿胀的程度.体外，RAR刺激软骨细胞增殖和Col2a1，Comp的表达，还有Acan.此外，RAR处理显著降低IL-1β诱导的OA细胞模型中的ROS积累,并增加抗氧化酶(SOD和GSH)的活性。结合分子对接的网络药理学分析显示，Mapk1可能是一个关键的治疗靶点。随后的研究表明，RAR可以下调IL-1β诱导的软骨细胞和DMM诱导的大鼠的Mapk1mRNA水平。
■RAR通过MAPK信号通路抑制KOA细胞外基质（ECM）降解和氧化应激反应，和Mapk1可能是一个核心目标。
■内侧半月板模型（DMM）的失稳用于通过步态分析评估RAR的抗KOA作用，微型计算机断层扫描（Micro-CT），和组织学。从新生小鼠的肋软骨中提取原代软骨细胞。使用CCK-8测定评价RAR对OA细胞的保护作用。通过测量活性氧（ROS）来确定RAR的抗氧化作用。超氧化物歧化酶（SOD），和谷胱甘肽（GSH）生产。此外，利用网络药理学和分子对接提出了KOA可能的RAR靶标，通过实验进一步验证。
■体内，RAR显著改善DMM诱导的KOA特性，比如软骨下骨硬化，软骨恶化，步态异常,以及膝盖肿胀的程度.体外，RAR刺激软骨细胞增殖和Col2a1，Comp的表达，还有Acan.此外，RAR处理显著降低IL-1β诱导的OA细胞模型中的ROS积累,并增加抗氧化酶(SOD和GSH)的活性。结合分子对接的网络药理学分析显示，Mapk1可能是一个关键的治疗靶点。随后的研究表明，RAR可以下调IL-1β诱导的软骨细胞和DMM诱导的大鼠的Mapk1mRNA水平。
■RAR通过MAPK信号通路抑制KOA细胞外基质（ECM）降解和氧化应激反应，和Mapk1可能是一个核心目标。
