Yougui Pills Attenuate Cartilage Degeneration via Activation of TGF-β/Smad Signaling in Chondrocyte of Osteoarthritic Mouse Model

Abstract

Yougui pills (YGPs) have been used for centuries in the treatment of Chinese patients with Kidney-Yang Deficiency Syndrome. Despite the fact that the efficiency of YGPs on treating osteoarthritis has been verified in clinic, the underlying mechanisms are not totally understood. The present study observes the therapeutic role of YGPs and mechanisms underlying its chondroprotective action in osteoarthritic cartilage. To evaluate the chondroprotective effects of YGPs, we examined the impact of orally administered YGPs in a model of destabilization of the medial meniscus (DMM). Male C57BL/6J mice were provided a daily treatment of YGPs and a DMM surgery was performed on the right knee. At 12 weeks post-surgery, the joints were harvested for tissue analyses, including histomorphometry, OARSI scoring, micro-CT and immunohistochemistry for COL-2, MMP-13 and pSMAD-2. We also performed the relative experiments mentioned above in mice with Tgfbr2 conditional knockout (TGF-βRIICol2ER mice) in articular cartilage. To evaluate the safety of YGPs, hematology was determined in each group. Amelioration of cartilage degradation was observed in the YGPs group, with increases in cartilage area and thickness, proteoglycan matrix, and decreases in OARSI score at 12 weeks post surgery. In addition, reduced BV/TV and Tb. Th, and elevated Tb. Sp were observed in DMM-induced mice followed by YGPs treatment. Moreover, the preservation of cartilage correlated with reduced MMP-13, and elevated COL-2 and pSMAD-2 protein expressional levels were also revealed in DMM-induced mice treated with YGPs. Similarly, TGF-βRIICol2ER mice exhibited significant OA-like phenotype. However, no significant difference in cartilage structure was observed in TGF-βRIICol2ER mice after YGPs treatment. Interestingly, no obvious adverse effects were observed in mice from each group based on the hematologic analyses. These findings suggested that YGPs could inhibit cartilage degradation through enhancing TGF-β/Smad signaling activation, and be considered a good option for the treatment of osteoarthritis.

Integrated Systems Pharmacology, Urinary Metabonomics, and Quantitative Real-Time PCR Analysis to Uncover Targets and Metabolic Pathways of the You-Gui Pill in Treating Kidney-Yang Deficiency Syndrome

“…In contrast, the You-gui pill (YGP) is a classic traditional Chinese medicine (TCM) formula for the treatment of KYDS and has been widely used to warm and recuperate KYDS clinically for hundreds of years in China [6]. It was originally described by “Jing-Yue Complete Works” in the year 1624 and consisted of ten herbs, including Radix Rehmanniae Praeparata (SDH, Shu-Di-Huang), Radix Aconiti Lateralis Prreparata (FZ, Fu-Zi), Cinnamomi cortex (RG, Rou-Gui ), Rhizoma Dioscoreae (SY, Shan-Yao), Fructus Corni (SZY, Shan-Zhu-Yu), Semen Cuscutae (TSZ, Tu-Si-Zi), Fructus Lycii (GQ, Gou-Qi), Cervi cornus colla (LJJ, Lu-Jiao-jiao), Eucommiae cortex (DZ, Du-Zhong), and Radix Angeliccae Sinensis (DG, Dang-Gui) [6,7,8]. The ratio of ten herbs in YGP was: SDH (8); SY (4); SZY (3); GQ (4); LJJ (4); TSZ (4); DZ (4); RG (2); FZ (2); DG (3).…”

Bushenhuoxue Formula Facilitates Articular Cartilage Repair and Attenuates Matrix Degradation by Activation of TGF‐β Signaling Pathway

“…Ample evidence suggests TCM as being effective in articular cartilage protection. For example, Zhang et al described protective activity for cartilage via reducing the expression of Mmp13 and elevating Col2 with the TCM Yougui pills which were administered to mouse model induced by destabilization of the medial meniscus [ 29 ]. Wang et al reported Bi-Qi capsule alleviated cartilage destruction by downregulating the expression of tumor necrosis factor- α (TNF- α ) and Interleukin-18 (IL-18) [ 30 ].…”

From Pathogenesis to Therapy in Knee Osteoarthritis: Bench-to-Bedside

“…Furthermore, the changes in subchondral bone are related to several signaling pathways such as the Wnt/β-Catenin, TGF-β/Smad, RANK/RANKL/OPG (Receptor activator of nuclear factor kappa-Β, RANK ligand, and osteoprotegerin), and MAPK (mitogen-activated protein kinase) signaling pathways [ 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ]. Moreover, identification of the molecular pathways involved in OA-related bone remodeling has led to certain therapeutic agents targeting the mechanisms considered as possible DMOADs [ 85 , 86 , 87 , 88 , 89 , 90 ].…”