Bioactive Compounds in Osteoarthritis: Molecular Mechanisms and Therapeutic Roles
Abstract
1. Introduction
2. Physiopathology of Osteoarthritis
2.1. Cellular Mechanisms in Osteoarthritis
2.2. Molecular Mechanisms in Osteoarthritis
3. Natural Bioactive Compounds Against OA
3.1. Curcuma longa/Curcumin
3.1.1. In Vitro
3.1.2. In Vivo
3.1.3. Clinical Trial
3.2. Boswellia serrata/Boswellic Acid
3.2.1. In Vitro
3.2.2. In Vivo
3.2.3. Clinical Trial
3.3. Zingiber officinale
3.3.1. In Vitro
3.3.2. In Vivo
3.3.3. Clinical Trial
3.4. Avocado/Soybean Unsaponifiables (ASU)
3.4.1. In Vitro
3.4.2. In Vivo
3.4.3. Clinical Study
3.5. Tea Extracts
3.5.1. In Vitro
3.5.2. In Vivo
3.5.3. Clinical Studies
3.6. Harpagophytum procumbens
3.6.1. In Vitro
3.6.2. In Vivo
3.6.3. Clinical Trials
3.7. Resveratrol
3.7.1. In Vitro
Plant Name | Cell Type | Effect | References |
---|---|---|---|
Curcuma longa | Chondrocytes | ↘ MMP-1, MMP-3 and MMP-13; ↘ TNF-α, IL-1β, and IL-6 (inhibition of NF-kB pathway). ↗ type II collagen and aggrecan. | [55] |
Synoviocytes | ↘ pro-inflamatory cytokines, ↘ PGE2, ↘ ROS | [59] | |
Bone cells | ↘ osteoclastogeneis (RANKL pathway), ↗ BMP, ↗ SMAD | [64] | |
Boswellia serrata | Chondrocytes | ↘ of MMP-3 and MMP-13, ↗ type II collagen, ↘ TIMP-1 and TIMP-3 | [77] |
Synoviocytes | ↘ inflamatory cytokine (inhibition of NF-kB pathway), modulation of COX2, ↘ 5-LOX pathway. | [78] | |
Bone cells | ↘ osteoclastogeneis (RANKL pathway), ↘ VEGF | [79] | |
Zingiber officinale | Chondrocytes | Down regulation of TNF-α, IL-6, and IL-8, inhibits NO production and reduction of PGE2 and ROS | [101] |
Synoviocytes | Inhibits IL-1β, TNF-α, and COX-2 | [106] | |
SW1353 | ↘ of p38 and JNK and ↘ of MMP-13 | [99] | |
RAW264.7 cells | Inhibition of osteoclast differentiation | [109] | |
Avocado/Soybean Unsaponifiables | Chondrocytes | Inhibition of IL-1β, IL-6, IL-8, PGE2, COX-2, MMP-13 and iNOS | [119] |
Synoviocytes | inhibition of pro-inflamatory cytokine | [118] | |
Bone cells | inhibition MMP-13 activity and nitric oxide synthase (iNOS) | [118] | |
Tea extracts (Epigallocatechin-3-gallate (EGCG)) | Chondrocytes | supress production of IL-1β and TNF-α, inhibition of iNOS, ↘ of MMP-13 | [133,134,135] |
Synoviocytes | ↘ synovial inflamation | [137] | |
Harpagoside (from Harpagophytum procumbens) | Chondrocytes | ↘ IL-6 and MMP-13 expression (inhibition of NF-κB pathway) | [150,151] |
Synoviocytes | ↘ TNF-α and IL-1β production (anti-inflammatory effect) | [152] | |
Bone cells | ↘ RANKL (reduces bone resorption), Regulates osteophyte formation (via TGF-β and BMP-2 pathways) | [153] | |
Resveratrol | Chondrocytes | ↘ PGE2, MMP-1, MMP-3, MMP-13; ↘ COX-2/NF-κB pathway; ↘ iNOS and ROS | [162] |
Synoviocytes | ↘ ROS and pro-inflammatory mediators (inhibits NF-κB pathway) | [163,164] | |
Bone cells | ↑ SIRT1 expression, ↑ Erk1/2 phosphorylation and ↘ RANKL | [166] |
3.7.2. In Vivo
Plant Name | Model | Effect | References |
---|---|---|---|
Curcuma longa | Rats (MIA) | ↘ Pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) | [66] |
↘ Inflammatory cell infiltration | [67] | ||
↘ Bone resorption and osteophyte formation | [68] | ||
Boswellia serrata | Rats (MIA) | ↘ MMPs, COX-2, 5-LOX and ↘ iNOS | [77] |
↘ Inflammatory mediators (IL-1, IL-6, TNF-α) | [83] | ||
Reduces cortical bone erosion | [82] | ||
Zingiber officinale | Rats (CIA) | ↘ MMPs, IL-1β, TNF-α, and PGE2 | [110] |
↘ Synovial hyperplasia and inflammatory cell infiltration | [98] | ||
Protective effects on subchondral bone | [111] | ||
Avocado/Soybean Unsaponifiables | Rats (MIA) | ↘ Catabolic factors | |
↑ Anabolic activity (promotes cartilage regeneration) | [118] | ||
Canine (ACL) | Reduces synovial inflammation | [121] | |
Merinos sheep (meniscectomy model OA) | Enhances articular regeneration | [122] | |
Epigallocatechin-3-gallate (EGCG) | Rats (DMM) | ↘ ECM degradation, cartilage inflammation, and cell senescence | [144] |
Canine (OA model) | Reduced pain, improuvement of joint fuction | [140] | |
Mice (DMM) | Reduces inflammation in joint synovium, Prevents chondrocyte apoptosis (via Nrf2 pathway) | [141] | |
Pig (OA model) | Inhibits osteoclastogenesis, promotes osteoblast differentiation | [142] | |
Harpagoside (from Harpagophytum procumbens) | Rats (OA model) | Prevents cartilage degradation, reduces IL-6 and MMP-13 | [154] |
Resveratrol | Rats (OA model) | ↘ Pro-inflammatory mediators and reactive oxygen species (inhibits NF-κB pathway), ↑ Collagen II expression. | [168] |
↑ SIRT1 expression, ↑ Erk1/2 phosphorylation, ↘ RANKL | [170] | ||
Inhibits osteoclast differentiation, promotes osteoblast differentiation | [165] |
Plant Name | Sample/Cohort | Supplementation | Effect | References |
---|---|---|---|---|
Curcuma longa | n = 101 (randomized, placebo-controlled) | 500 mg of standardized curcumin extract twice daily | Significant reduction in knee pain, improved physical function, 37% reduced analgesic use compared to 13% in placebo group | [69] |
Meta-analysis | Bioavailable turmeric extract | As effective as paracetamol for pain relief, more effective in reducing CRP and TNF-α | [71,72,73] | |
Meta-analysis, 11 RCTs, 1258 participants | Low (<1000 mg)- and high (≥1000 mg)-dose curcumin | Better pain relief than NSAIDs, similar effects across doses, curcumin recommended as adjunctive treatment for knee OA | [74] | |
Boswellia serrata | Meta-analysis, 7 trials, n = 545 | 100–250 mg of BSE for 4 weeks | Effective in reducing pain, improving joint function, and reducing inflammation in OA patients | [76] |
Meta-analysis, 9 RCTs n = 712 | Aflapin® (BSE suplementation, 20% AKBA) | Effective in managing OA symptoms | [92] | |
n = 43 (randomized and double-blind) | 333 mg of SLBSP (100 mg of BSE) WokVel™ vs. 333 mg of standardized BSE, three time daily for two months | significant symptomatic relief for knee osteoarthritis, improving pain and function scores as measured by the WOMAC and VAS scales | [96] | |
Zingiber officinale | n = 43 (randomized, double-blind, placebo-controlled) | 30 mL of G-Rup® syrup (containing 150 mg/mL of ginger extract), administered twice daily for twelve week. | Significant improvements in pain scores and physical function compared to placebo | [114] |
Meta-analysis, 3 RCTs, n = 330 | Ginger supplementation | Reduces pain and enhances quality of life without significant adverse effects | [113] | |
n = 120 (double-blind, placebo-controlled clinical trial) | 500 mg ginger extract twice daily (3 months) | Significant reduction in pain intensity, improved mobility, and reduced TNF-α and IL-1β serum levels | [115] | |
Avocado/Soybean Unsaponifiables | Meta-analysis, 4 RCTs, n = 664 | 300 mg ASU, Average trial duration was 6 months (range: 3 to 12 months) | Significant improvement in VAS and Lequesne index in knee OA, not hip OA. Safe treatment with no difference in adverse events compared to placebo | [126] |
Meta-analysis, 5 RCTs, n = 1095 | 300–600 mg/day of ASU, 3 months to 3 years | Beneficial effect in symptomatic knee OA but not hip OA, no significant difference in adverse events vs. placebo | [127] | |
Tea extracts (Epigallocatechin-3-gallate (EGCG)) | n = 50 (Randomized, open-label, active-controlled clinical trial) | Green tea extract 1500 mg + diclofenac 100mg/day for 4 weeks | Significant reductions in pain, improved physical function, though limited impact on joint stiffness over short periods | [147] |
Harpagoside (from Harpagophytum procumbens) | n = 122 (double-blind, randomized, multicenter) | 2.6 g of HP extract (Harpadol®) daily for 4 months | Significant improvement in pain and functional disability, as effective as diacerein, fewer gastrointestinal side effects compared to NSAIDs | [155] |
n = 75 (Open-label) | 2.4 g of HP extract (Doloteffin™) daily for 12 weeks | Significant improvements in pain, stiffness, and physical function, favorable safety profile | [156] | |
n = 38 (randomized-controlled trial) | Two tablets of HP procumbens (2 × 480 mg) Teltonal® daily for 1 month | Significant improvement in pain and function, as effective as meloxicam, high patient satisfaction with minimal side effects | [157] | |
Resveratrol | n = 142 (randomized placebo-controlled trial) | 40 mg twice daily for 1 week, then 20 mg twice daily for 6 month. | No significant difference in knee pain reduction between RSV and placebo groups at 3 and 6 months | [172] |
3.7.3. Clinical
3.8. Others Bioactive Compounds
4. Discussion
4.1. Standardization of Plant Extracts and Potential Contaminations
4.2. Cytotoxicity and Safety of Bioactive Compounds
4.3. Bioavailability and Pharmacokinetics
4.4. Limitations in Design of Preclinical and Clinical Studies
5. Conclusions
6. Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Maouche, A.; Boumediene, K.; Baugé, C. Bioactive Compounds in Osteoarthritis: Molecular Mechanisms and Therapeutic Roles. Int. J. Mol. Sci. 2024, 25, 11656. https://doi.org/10.3390/ijms252111656
Maouche A, Boumediene K, Baugé C. Bioactive Compounds in Osteoarthritis: Molecular Mechanisms and Therapeutic Roles. International Journal of Molecular Sciences. 2024; 25(21):11656. https://doi.org/10.3390/ijms252111656
Chicago/Turabian StyleMaouche, Ahmed, Karim Boumediene, and Catherine Baugé. 2024. "Bioactive Compounds in Osteoarthritis: Molecular Mechanisms and Therapeutic Roles" International Journal of Molecular Sciences 25, no. 21: 11656. https://doi.org/10.3390/ijms252111656
APA StyleMaouche, A., Boumediene, K., & Baugé, C. (2024). Bioactive Compounds in Osteoarthritis: Molecular Mechanisms and Therapeutic Roles. International Journal of Molecular Sciences, 25(21), 11656. https://doi.org/10.3390/ijms252111656