Key Takeaways & Executive Findings
- •• Ginsenosides (Rg3, Rh4, Rc) inhibit osteoclast differentiation via the karyopherin α2-NF-κB axis, reducing bone resorption in osteoporosis. • Ginseng polysaccharides exert anti-inflammatory effects through the MAPK/NF-κB pathway, with processing methods influencing their immunomodulatory activity. • Ginseng peptides improve mitochondrial function via the NAD+/SIRT1/PGC-1α axis, counteracting sarcopenia. • Ginseng's multi-component, multi-target approach offers a promising strategy for treating musculoskeletal degenerative diseases, though bioavailability and clinical validation remain challenges.
Abstract
BACKGROUND: Current therapies for musculoskeletal degenerative diseases merely alleviate symptoms with significant adverse effects. As a traditional Chinese medicine, active ingredients of ginseng exhibit protective effects on bone and muscle through multi-target regulation of signaling pathways, and breakthroughs have been made in mechanism research in recent years. OBJECTIVE: To provide a systematical review of the latest molecular mechanisms of active ingredients of ginseng (ginsenosides, polysaccharides, and peptides) in preventing and treating musculoskeletal degenerative diseases via key signaling pathways, providing a basis for targeted drug development. METHODS: A systematic search was performed in multiple databases, including PubMed, Web of Science, Embase, CNKI, Wanfang, and VIP, with the search period from inception to April 2025. Chinese search terms included "musculoskeletal diseases, osteoporosis, osteoarthritis, intervertebral disc herniation, sarcopenia, ginsenosides, ginseng polysaccharides, ginseng peptides, signaling pathways"; English search terms included "musculoskeletal degenerative diseases, osteoporosis, osteoarthritis, intervertebral disc degeneration, sarcopenia, ginsenosides, ginseng polysaccharides, ginseng peptides, signaling pathways". Finally, 75 eligible articles were included. RESULTS AND CONCLUSION: (1) Ginsenosides (e.g., Rg3, Rh4, Rc): target the karyopherin α2-nuclear factor-κB axis to inhibit osteoclast differentiation and reduce bone resorption; activate the sirtuin 1 pathway to enhance mitochondrial biogenesis and delay sarcopenia; regulate Yes-associated protein 1/transcriptional coactivator and p38 mitogen-activated protein kinase to alleviate intervertebral disc degeneration. (2) Polysaccharides: processing techniques affect immunomodulatory activity, inhibiting inflammation via the mitogen-activated protein kinase/nuclear factor-κB pathway. (3) Peptides: activate the NAD+/sirtuin 1/peroxisome proliferator-activated receptor γ coactivator 1α axis to improve mitochondrial function. These findings suggest that ginseng exerts synergistic regulation of bone metabolism balance, inhibition of cartilage degradation, and delay of muscle aging through a "multi-component, multi-target" mechanism, but challenges remain regarding low bioavailability and lack of large-scale clinical trials for translation.
1. Introduction
Musculoskeletal degenerative diseases, as a class of chronic diseases seriously threatening global public health, encompass typical conditions such as osteoarthritis, intervertebral disc degeneration, sarcopenia, and osteoporosis [1-2]. Among them, intervertebral disc degeneration and osteoporosis are the main causes of disability in the elderly [3-4], not only leading to chronic pain and dysfunction, but also imposing a heavy burden on the global healthcare system [5].
Current clinical interventions for musculoskeletal degenerative diseases still focus on symptom control: osteoporosis primarily uses bisphosphonates to inhibit bone resorption [6], but long-term use may cause serious complications such as osteonecrosis of the jaw and atypical femoral fractures, and patients often find it difficult to adhere to long-term medication [7]; intervertebral disc degeneration is treated by surgical fusion to relieve nerve compression, but this accelerates degeneration of adjacent segments [8-9]. These therapies cannot halt disease progression.
Ginseng (Panax ginseng C.A. Mey.), as a traditional tonic Chinese medicine, is recorded in the Chinese Pharmacopoeia to have the effect of "calming the five viscera and settling the spirit." Modern research has confirmed that ginseng contains active ingredients such as saponins, polysaccharides, and peptides, with multiple pharmacological activities including immunomodulation, antioxidant, and metabolic improvement [10]. Recent breakthrough studies have found that ginseng active ingredients can intervene in the core pathological processes of musculoskeletal degenerative diseases through synergistic regulation of multiple pathways: including bone metabolic imbalance in osteoporosis, extracellular matrix degradation in bone and joint and intervertebral disc tissues, and decline in skeletal muscle mass and function [11-12]. This "multi-component, multi-target" characteristic overcomes the limitations of traditional therapies targeting a single pathology, providing new ideas for the prevention and treatment of musculoskeletal degenerative diseases. This article systematically reviews the multi-target regulatory mechanisms and related signaling pathways of ginseng active ingredients in musculoskeletal degenerative diseases.
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Xia Tiange, Zhou Yi, Li Shaoshuo, Wang Jianwei, Shao Yang (2026). Signaling pathways related to active ingredients of ginseng in the treatment of musculoskeletal degenerative diseases. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21423
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Frequently Asked Questions
What are the main active ingredients of ginseng and their roles in treating musculoskeletal degenerative diseases?
The main active ingredients include ginsenosides (e.g., Rg3, Rh4, Rc), polysaccharides, and peptides. Ginsenosides inhibit osteoclast differentiation and reduce bone resorption, activate sirtuin 1 to enhance mitochondrial biogenesis, and regulate YAP1 and p38 MAPK to alleviate intervertebral disc degeneration. Polysaccharides exert anti-inflammatory effects via the MAPK/NF-κB pathway. Peptides improve mitochondrial function via the NAD+/SIRT1/PGC-1α axis.
How do ginsenosides affect osteoporosis?
Ginsenosides such as Rg3, Rh4, and Rc target the karyopherin α2-nuclear factor-κB axis to inhibit osteoclast differentiation, thereby reducing bone resorption and helping to prevent or treat osteoporosis.
What signaling pathways are involved in the effects of ginseng on osteoarthritis?
Ginseng active ingredients modulate several pathways relevant to osteoarthritis, including the Wnt/β-catenin pathway, MAPK pathway, NF-κB pathway, and PI3K/Akt pathway, which collectively regulate inflammation, cartilage degradation, and cellular homeostasis.
Can ginseng help with sarcopenia?
Yes, ginseng peptides and ginsenosides can activate the SIRT1 pathway and enhance mitochondrial biogenesis, which helps improve muscle function and delay muscle aging, thus benefiting sarcopenia.
What are the challenges for clinical translation of ginseng-based therapies?
Challenges include low bioavailability of active compounds and the lack of large-scale clinical trials to confirm efficacy and safety. Further research is needed to develop targeted delivery systems and validate therapeutic benefits in human populations.
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