Intervertebral disc degeneration (IDD) is a chronic skeletal muscle degenerative disease, which is considered the main cause of low back pain. It seriously affects the quality of life of patients and consequently brings a heavy economic burden to their families and the society. Although IDD is considered a natural process in degenerative lesions, it is mainly caused by aging, trauma, genetic susceptibility and other factors. It is closely related to changes in the tissue structure and function, including the progressive destruction of extracellular matrix, cell aging, cell death of the intervertebral disc (IVD), inflammation, and impairment of tissue biomechanical function. Currently, the treatment of IDD is aimed at alleviating symptoms rather than at targeting pathological changes in the IVD. Furthermore, the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway is closely related to various pathological processes in IDD, and the activation of the MAPK/ERK pathway promotes the degradation of the IVD extracellular matrix, cell aging, apoptosis, and inflammatory responses. It also induces autophagy and oxidative stress that accelerate the IVD process. In our current review, we summarize the latest developments in the negative regulation of IDD after activation of the MAPK/ERK signaling pathway and emphasize on its influence on IDD. Targeting this pathway may become an attractive treatment strategy for IDD in the near future.

Objective: This paper briefly reviews the structure and function of NLRP3 inflammasomes, signaling pathway, relationship with synovitis in KOA, and intervention of traditional Chinese medicine (TCM) in NLRP3 inflammasomes as a means to improve its therapeutic potential and clinical application.Method: Literatures about NLRP3 inflammasomes and synovitis in KOA were reviewed to analyze and discuss.Result: NLRP3 inflammasome can activate NF-κB mediated signal transduction, which in turn causes the expression of proinflammatory cytokines, initiates the innate immune response, and triggers synovitis in KOA. The TCM monomer/active ingredient, decoction, external ointment, and acupuncture regulating NLRP3 inflammasomes are helpful to alleviate synovitis in KOA.Conclusion: The NLRP3 inflammasome plays a significant role in the pathogenesis of synovitis in KOA, TCM intervention targeting the NLRP3 inflammasome can be a novel approach and therapeutic direction for the treatment of synovitis in KOA.

Research on postmenopausal osteoporosis (PMOP), a common bone metabolic disease, has traditionally focused on bone loss and imbalance in bone remodeling. However, with the development of bone immunology, the complex interactions between immune cells and bone cells in the bone marrow microenvironment have gradually been revealed, and “immune reprogramming” is considered a key factor driving the persistent bone loss in PMOP. Current evidence indicates that the postmenopausal bone marrow microenvironment undergoes significant structural and functional changes. These changes are characterized by a myeloid bias in hematopoietic stem/progenitor cells, aging of bone marrow mesenchymal stem cells (BMSCs) with a tendency toward differentiation into the adipocyte lineage, an imbalance of key immune cell subpopulations such as M1 and M2 macrophages and Th17 and regulatory T cells (Treg), as well as remodeling of cytokine and chemokine axis networks. Signaling pathways such as RANK/RANKL/OPG, Wnt/β-catenin, CXCL12–CXCR4, and S1P — along with systemic factors like estrogen deficiency, inflammatory aging, and the gut-bone-immune axis-collectively shape the characteristic bone immune microenvironment of PMOP. Based on this, this article systematically reviews the changes in cell lineage and molecular mechanisms underlying PMOP bone marrow immune reprogramming. It focuses on the key signaling networks in the bone immune microenvironment and their relationship with the mechanisms of existing anti-osteoporosis drugs. Furthermore, it proposes an immunotherapy approach represented by a three-tiered framework: traditional bone-targeted drugs, immune-guided therapy, and comprehensive intervention of the bone marrow microenvironment. Finally, in conjunction with emerging technologies such as multi-omics, single-cell, and spatial omics, this article discusses future directions for constructing a PMOP bone immune map and achieving precise stratification and individualized intervention, aiming to provide a theoretical basis and methodological reference for mechanistic research and bone immune-targeted therapy of PMOP.

Objectives: As a medicinal and edible resource, Eucommia ulmoides leaf (EUL) shows considerable promise in facilitating healthy aging. However, its precise biological mechanisms remain unclear. This study aimed to investigate the anti-aging efficacy and underlying pathways of Eucommia ulmoides leaf extract (EULE) using the Caenorhabditis elegans ( C. elegans ) model. Methods: Phytochemical profiling of the extract was performed. C. elegans were supplemented with the extract, and the effects on lifespan, healthspan indicators (muscle deterioration, intestinal barrier function, mitochondrial homeostasis), and gene expression were evaluated via transcriptomic analysis. Results: Phytochemical analysis revealed that the extract is abundant in bioactive compounds such as flavonoids, iridoids, and lignans. Supplementation with the extract significantly prolonged the lifespan of C. elegans by up to 14.69% and improved healthspan by alleviating age-related muscle deterioration, preserving intestinal barrier function, and regulating mitochondrial homeostasis. Transcriptomic analysis identified the mitogen activated protein kinase (MAPK) signaling pathway as the primary mediator of these anti-aging benefits. Conclusions: These results provide robust evidence supporting the use of EUL as a natural dietary supplement to prolong healthspan, establishing a scientific rationale for its application in promoting healthy aging.

In recent years, with the continuous development of social productivity and improvements in living standards, the issue of population aging has intensified. As the elderly are susceptible to cardiovascular diseases, osteoporosis, Alzheimer’s disease, and other conditions, the economic and resource burdens associated with treating, caring for, and supporting this demographic rise with their growing numbers, imposing significant pressure on societal development. In light of these challenges, research on natural products possessing anti-aging properties for treating aging-related chronic diseases has gained prominence. Flavonoids, a class of natural bioactive compounds abundantly found in plants, exhibit diverse pharmacological effects, including antioxidant, anti-inflammatory, and anti-osteoporosis activities. Therefore, studying the anti-aging effects of flavonoids is of significant value. This paper reviews recent research on the anti-aging effects of flavonoids by searching databases including CNKI, PubMed, Web of Science, and Google Scholar. The findings are summarized based on research subjects (C. elegans, animal models, and cells), effects, and mechanisms, to provide references for future in-depth research on the anti-aging effects of flavonoids.

Background: Knee osteoarthritis (KOA) is a common chronic disorder of knee and the leading cause of pain in the elderly with an overall prevalence of 50% in people over 60 years of age. This disease is an important factor affecting the quality of life of middle-aged and elderly people, and its main symptom is knee joint pain. Due to the pain, the knee joint activity function is limited, bringing great pain to patients, affecting their quality of life, effective prevention, and treatment of KOA is a modern medical problem. Methods: The 60 patients who met the inclusion criteria were randomly divided into the treatment group and the control group. In this study, single center, randomized control and equivalent clinical trial were used for treatment. The treatment group received Yuanhu Zhitong dropping pills within 4 weeks, and the control group received diclofenac sodium sustained-release capsule treatment within 4 weeks. The main measures were visual analogue scale (VAS), WOMAC osteoarthritis index score and gastrointestinal symptoms rating scale (GSRS).Secondary measures included biochemical markers and adverse reactions during treatment. Result: The results of this trial will be published on the website of China Clinical Trial Registration Center (http://www.chictr.org.cn/searchprojen.aspx) and in peer-reviewed journals or academic conferences. Conclusions: This study is to assess the efficacy and safety of Yuanhu Zhitong dropping pills for knee osteoarthritis (KOA). Registration: PROSPERO (registration number ChiCTR1900024712).