morroniside and Osteoarthritis

Corni Fructus (CF), the red fruit of Cornus officinalis Siebold & Zucc, has been used both as food and medicinal herb in traditional Chinese medicine (TCM). Our previous studies showed that Yougui pills and Bushenhuoxue formula, both TCM prescriptions containing Corni Fructus (CF), have protective effects on osteoarthritis (OA). However, the underlying detailed components in both TCM prescriptions that play therapeutic roles have not been fully defined. Morroniside is a major iridoid glycoside and one of the quality control metrics of CF, but the effects of morroniside on OA remain largely elusive.. The study aims to assess the therapeutic effects of morroniside on cartilage degeneration using a mouse model of OA.. 8-week-old male C57BL/6J mice were randomly divided into 4 groups: Sham, destabilization of the medial meniscus (DMM)-treated with vehicle, DMM-treated with low dose morroniside and DMM-treated with high dose morroniside. Histological staining, immunostaining, and TUNEL staining were conducted to detect changes in tissue morphology, expression of key molecules in chondrocytes, and chondrocyte apoptosis, respectively. Osteophyte formation, meniscus calcification, and subchondral sclerosis were quantitated using micro-CT. The expression of chondrocyte markers was also analyzed by Western blot in primary chondrocytes derived from mice treated with morroniside.. Morroniside attenuated the progression of OA in mice, resulting in substantially reduced osteophyte formation and subchondral sclerosis and lower OARSI scores. Specifically, morroniside significantly promoted cartilage matrix synthesis by increasing collagen type II expression and suppressing chondrocyte pyroptosis. Morroniside administration led to inhibition of matrix metalloproteinase-13 (MMP13), Caspase-1 and nod-like receptor protein-3 (NLRP3) expression in DMM mice and IL-1β-stimulated chondrocytes. In addition, morroniside attenuated the progression of OA by enhancing chondrocyte proliferation and inhibiting chondrocyte apoptosis. Morroniside also attenuated the progression of OA by inhibiting nuclear factor-κB (NF-κB) signaling.. Morroniside was protective against cartilage matrix degradation and reduced DMM-induced chondrocyte pyroptosis and apoptosis by the inhibition of NF-κB signaling.

Topics: Animals; Apoptosis; Arthritis, Experimental; Cartilage, Articular; Chondrocytes; Disease Progression; Glycosides; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Osteoarthritis; Pyroptosis; Signal Transduction

Osteoarthritis (OA) is a common degenerative disease that results in joint inflammation as well as pain and stiffness. A previous study has reported that

Topics: Animals; Cartilage, Articular; Chondrocytes; Cornus; Cyclooxygenase 2; Dinoprostone; Disease Models, Animal; Gene Expression Regulation; Glycosides; Humans; Inflammation; Interleukin-1beta; Matrix Metalloproteinase 13; Matrix Metalloproteinase 3; Menisci, Tibial; Mice; Osteoarthritis; Plant Extracts; Primary Cell Culture; RAW 264.7 Cells; Signal Transduction

Despite extensive studies on the multifaceted roles of morroniside, the main active constituent of iridoid glycoside from Corni Fructus, the effect of morroniside on osteoarthritis (OA) chondrocytes remains poorly understood. Here, we investigated the influence of morroniside on cultured human OA chondrocytes and a rat experimental model of OA. The results showed that morroniside enhanced the cell viability and the levels of proliferating cell nuclear antigen expression (PCNA), type II collagen and aggrecan in human OA chondrocytes, indicating that morroniside promoted chondrocyte survival and matrix synthesis. Furthermore, different doses of morroniside activated protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) in human OA chondrocytes, and in turn, triggered AKT/S6 and ERK/P70S6K/S6 pathway, respectively. The PI3K/AKT inhibitor LY294002 or the MEK/ERK inhibitor U0126 attenuated the effect of morroniside on human OA chondrocytes, indicating that the activation of AKT and ERK contributed to the regulation of morroniside in human OA chondrocytes. In addition, the intra-articular injection of morroniside elevated the level of proteoglycans in cartilage matrix and the thickness of articular cartilage in a rat experimental model of OA, with the increase of AKT and ERK activation. As a consequence, morroniside has chondroprotective effect on OA chondrocytes, and may have the therapeutic potential for OA treatment.

Topics: Aged; Animals; Arthroplasty, Replacement, Knee; Cartilage; Cell Survival; Chondrocytes; Disease Models, Animal; Enzyme Activation; Extracellular Matrix; Extracellular Signal-Regulated MAP Kinases; Female; Glycosides; Humans; Male; Middle Aged; Models, Biological; Osteoarthritis; Phosphorylation; Protective Agents; Proto-Oncogene Proteins c-akt