Ginseng for Bone Disease: What Its Phytochemicals Can Really Do

A recent review in the journal Nutrients compiled results from 2014-2024 and showed that ginseng phytochemicals - primarily ginsenosides and polysaccharides - act on several key signaling pathways in bone tissue and tumor cells at once. This opens up windows of opportunity for three tasks: inhibiting the progression of osteosarcoma, strengthening bone in osteoporosis, and reducing inflammation in osteoarthritis. But clinical evidence is still limited, and bioavailability and standardization of extracts remain bottlenecks.

Background of the study

Musculoskeletal diseases - osteosarcoma, osteoporosis and osteoarthritis - are diverse in nature (cancer, impaired bone remodeling, cartilage degeneration), but all have a high burden of disability and limited treatment options (toxic/resistant chemotherapy for osteosarcoma, incomplete fracture prevention for osteoporosis, symptom control without course modification for osteoarthritis). Against this backdrop, there is growing interest in natural compounds that simultaneously hit multiple targets of inflammation, osteogenesis and matrix degradation. This is where ginseng and its multi-target phytochemicals fit in.

What are "ginseng phytochemicals"

The key source is Panax ginseng CA Meyer (white and red ginseng). The main active components are steroidal saponins ginsenosides (more than 100 types; Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, Rg3 are common), as well as polysaccharides, phenolic compounds, etc. Technological processing (steaming → "red" ginseng) changes the composition and potentially increases the bioavailability of individual fractions. Together, these groups provide antioxidant, anti-inflammatory and other effects of interest to bone tissue and cartilage.

What volume of data did the author collect?

This is a review paper in Nutrients (accepted May 31 and published June 1, 2025) in a special issue on anticancer phytochemicals. The author summarizes studies from 2014-2024 by in vitro and in vivo models, and discusses mechanisms, limitations, and directions for clinical validation.

Brief status quo for each nosology (introductory part of the review)

• Osteosarcoma. The most common primary bone tumor in adolescents/young adults; standard is chemotherapy + surgery; survival in the localized form has increased, but remains poor in metastases/relapses. Against this background, phytochemicals (including ginseng) are actively studied as an additive to the standard for inducing apoptosis, suppressing migration, etc.
• Osteoporosis. A "silent" disease with loss of BMD and microstructure; therapy is aimed at slowing resorption and/or stimulating bone formation (often bisphosphonates). Agents are sought that simultaneously enhance osteoblasts and inhibit osteoclasts - exactly what ginsenosides/extracts demonstrate in preclinical studies.
• Osteoarthritis. Degenerative joint disease (mainly in the elderly), where the focus of therapy is symptom control; natural anti-inflammatory compounds are considered as potential modifiers of the inflammatory and degradation cascades.

Why Ginseng Looks Promising (Review Logic)

• Multi-target. Ginsenosides and polysaccharides regulate the NF-κB, Wnt/β-catenin, Nrf2, PI3K/Akt/mTOR pathways - i.e. nodes common to inflammation, osteogenesis/osteoclastogenesis and tumor cell survival.
• Diversity of chemical families. In addition to ginsenosides, the author considers polysaccharides, phenolic compounds and alkaloids - this expands the range of mechanisms (immunomodulation, antioxidant and chondroprotective effects).
• Convenience of combinations. In theory, they can be “mixed” with standard regimens (chemotherapy, NSAIDs), counting on synergy and dose reduction. The review records such a trend in modern literature.

What the author designates in advance as field limitations

• Variability of extract composition and standardization of batches. Without chemical certification, it is difficult to compare doses and effects.
• Bioavailability. Hydrophilicity/metabolism in the gastrointestinal tract and short T½ - an argument for smart delivery systems (nanocarriers, hydrogels) and saturation modes.
• Lack of high-quality RCTs. Multicenter trials with well-defined markers of efficacy and safety are needed.

What was studied

This is a review paper (Nutrients, 2025) that systematizes in vitro and in vivo experimental data on key groups of ginseng compounds: ginsenosides (Rb1, Rg1, Rg3, Rg5, Rh2, CK/compound K, etc.), polysaccharides, phenolic components, and alkaloids. The author also discusses mechanisms of action, limitations of approaches, and directions for further research.

Main characters

Ginsenosides are steroidal saponins, of which >100 have been described; the most studied are Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, Rg3. Polysaccharides and phenolic compounds complete the picture, affecting immune and antioxidant links. Together, they “hit” the NF-κB, PI3K/Akt/mTOR, Wnt/β-catenin, Nrf2 pathways and the RANKL/OPG cascade, which affect inflammation, bone remodeling, tumor cell survival, and cartilage degradation.

Osteosarcoma: Where Ginseng Can Help

The data set for osteosarcoma is particularly rich. Individual ginsenosides:

• Rg3/Rg5/Rh2/CK - inhibit the proliferation and migration of osteosarcoma cells (MG63, U2OS, 143B), trigger apoptosis and autophagy, interfere with PI3K/Akt/mTOR, MAPK, NF-κB, EMT and the Wnt/β-catenin axis.
• Synergy with chemotherapy: Rg3 enhanced the effect of doxorubicin; CK increased the sensitivity of cells to cisplatin; with (20S)-protopanaxatriol, the viability of MG63 and the volume of xenografts were reduced.
• Polysaccharides induced apoptosis/autophagy and reduced phosphorylation of p38 MAPK and Akt; γ-irradiation in combination with polysaccharides more strongly suppressed colony formation.

What does this give? The potential is in combination regimens that simultaneously hit the survival of tumor cells, their migration/invasion and resistance to drugs. On the horizon is nanodelivery and photodynamic therapy paired with ginsenosides. But all this is still predominantly at the preclinical level.

Osteoporosis: The Balance Between Osteoblasts and Osteoclasts

Another set of data shows that ginseng may "tip" the bone remodeling pendulum toward bone formation:

• CK (compound K) activates β-catenin/Runx2, stimulates osteogenesis and H-type vessel formation in fracture zones; suppresses NF-κB-dependent osteoclast differentiation and increases BMD in castrated mice.
• Red ginseng extracts counteract glucocorticoid-induced osteoporosis: increase alkaline phosphatase activity, inhibit TRAP and osteoclastogenesis; micro-CT shows a slowdown in the decline of BMD.

Conclusion: Mechanistically, this looks convincing - more osteoblasts, fewer osteoclasts, plus improved microarchitecture. Clinical validation, alas, is still lacking.

Osteoarthritis: Reducing Inflammation and Protecting Cartilage

Here, Rb1 and a number of other ginsenosides come to the fore:

• Rb1 suppresses iNOS and NF-κB (decreases IκBα phosphorylation and p65 translocation), reduces IL-1β/IL-6 and MMP-13 expression; in models (ACLT, MIA) it reduces cartilage degradation and joint space thickness, improves histological scores.
• Non-trivial delivery approaches have also been noted - hydrogel plates with Rb1, which locally protect cartilage in a rabbit model.

Practical meaning: reducing the inflammatory cascade and enzymes that destroy the cartilage matrix is exactly what is sought in the case of slow but persistent progression of arthrosis.

Why is this not a “cure-all” pill yet?

Even with impressive preclinical effects, there are systemic barriers:

• Variable composition and standardization: what doses and quality marks should be used in the clinic? A thorough chemical characterization of the extracts is needed.
• Bioavailability: Many ginsenosides are hydrophilic, rapidly metabolized by intestinal flora, and have short T½; hence the interest in nanocarriers, prolongation, and targeted delivery.
• Safety and context: GI reactions, immunosuppression due to chemotherapy; theoretical risk of “ambiguous” effects in hormone-sensitive states due to breadth of targets (NF-κB, Wnt/β-catenin, Nrf2).
• Clinical trials: few, heterogeneous, and geographically concentrated in Asia; multicenter RCTs with appropriate comfort levels (postmenopause, elderly) are needed.

Mechanisms of action - a "quick cheat sheet"

• Anti-tumor (osteosarcoma): apoptosis/autophagy, block PI3K/Akt/mTOR and MAPK, suppression of EMT and migration, sensitization to doxorubicin/cisplatin.
• Anti-resorptive/pro-osteogenic (osteoporosis): activation of BMP-2/Runx2 and β-catenin, reduction of RANKL-induced osteoclastogenesis, increase in BMD in models.
• Anti-inflammatory/chondroprotective (osteoarthritis): inhibition of NF-κB, iNOS and proinflammatory cytokines, reduction of MMP-13, preservation of cartilage.

What's next?

The most promising are: (1) combinations of ginsenosides with chemotherapeutic agents/NSAIDs and other phytochemicals; (2) smart delivery (nanocarriers, hydrogels, photodynamics); (3) biomarker-oriented dosing schemes and patient selection; (4) standardized extracts with a reproducible profile. All this must be confirmed by rigorous RCTs, otherwise the preclinical study will remain “on the shelf”.

Source: Park SH. Recent Research on the Role of Phytochemicals from Ginseng in the Management of Osteosarcoma, Osteoporosis, and Osteoarthritis. Nutrients. 2025;17(11):1910. https://doi.org/10.3390/nu17111910