INGREDIENTS FOR CARTILAGE SUPPORT 
▪ FORTIGEL® for sustainable mobility & Cartilage Regeneration
- Stimulates the body's own mechanisms for maintaining healthy joints and optimum mobility
- Promotes joint health naturally with no side effects - Structural improvement may occur as
early as 3 months.
▪ FORTIGEL® promotes growth of cartilage tissue The effectiveness of FORTIGEL® has been scientifically proven in numerous studies. According to published research, orally administered FORTIGEL® is absorbed intestinally and accumulates in cartilage. The ingestion of FORTIGEL® stimulates a statistically significant increase of cartilage tissue metabolism.
▪ Support Ingredients: Andrographolide, Hyaluronic Acid, Glucosamine, Epimedium Extract
- Andrographolide: Potent Inhibitor of destructive chondrocyte inflammation. Naturally invigorates the PPAR? response, essential to support anti-arthritic phenotype on cartilage. (3,4,5) According to researchers "PPAR?-deficient articular cartilage exhibits elevated expression of the additional catabolic factors" and accelerates development of osteo arthritis inflammation and cartilage destruction. Supports maintenance of cartilage producing cells subsequent to inflammation, promoting expression of aggrecan, collagen II instead of replacement by weaker collagen type I. (10). Therefore, andrographolide is very important for maintaining the chondrocyte phenotyp for the production of cartrilage. Andrographolide is also one of the strongest activators of the powerful nrf2 antioxidant response pathway.(9) Furthermore, andrographolide supports anti-aging of muscle, by inhibiting the development of fibrosis. As a muscle ages, it increases fibrosis formation which weakens the muscle. In animal studies, andrographolide has been shown to significantly mitigate the fibrosis formation. thereby helping to maintain stronger muscles, which supports strong joints.
- Andrographolide: Potent Inhibitor of destructive chondrocyte inflammation. Naturally invigorates the PPAR? response, essential to support anti-arthritic phenotype on cartilage. (3,4,5) According to researchers "PPAR?-deficient articular cartilage exhibits elevated expression of the additional catabolic factors" and accelerates development of osteo arthritis inflammation and cartilage destruction. Supports maintenance of cartilage producing cells subsequent to inflammation, promoting expression of aggrecan, collagen II instead of replacement by weaker collagen type I. (10). Therefore, andrographolide is very important for maintaining the chondrocyte phenotyp for the production of cartrilage. Andrographolide is also one of the strongest activators of the powerful nrf2 antioxidant response pathway.(9) Furthermore, andrographolide supports anti-aging of muscle, by inhibiting the development of fibrosis. As a muscle ages, it increases fibrosis formation which weakens the muscle. In animal studies, andrographolide has been shown to significantly mitigate the fibrosis formation. thereby helping to maintain stronger muscles, which supports strong joints.
- Hyaluronic Acid: Provides additional cushioning for the joint.
- Glucosamine: Is a precursor nutrient which helps form the cartilage matrix
- Epimedium (Icariin): Promotes extracellular matrix (ECM) synthesis and expression of chondrogenesis genes of chondrocytes (in vitro). Exerts a potent chondrogenic and chondroprotective effect. (6,7,8) Icariin is also a strong inhibitor of the enzyme MMP-13, matrix metalloproteinase-13, which plays a critical role in cartilage breakdown.(7)
- Luteolin and Apigenin: Protects the cartilage extracellular matrix from enzymatic breakdown, especially in inflammatory states, including arthritis (11,12,13).
REFERENCES:
1. Schunck M, Schulze CH, Oesser S, 2009. Collagen peptide supplementation stimulates proteoglycan biosynthesis and aggrecan expression of articular chondrocytes, Osteoarthritis and Cartilage Vol. 17, Suppl.1, 261
2. McAlindon TE, Nuite M, Krishnan N, Ruthazer R, Price LL, Burstein D, Griffith J,Flechsenhar K, Change in knee osteoarthritis cartilage detected by delayed gadolinium enhanced magnetic resonance imaging following treatment with collagen hydrolysate: a pilot randomized controlled trial. Osteoarthritis andCartilage (2011), online 3 January 2011
3. Ding QH, et al. Inhibition of matrix metalloproteinases and inducible nitric oxide synthase by andrographolide in human osteoarthritic chondrocytes. Mod Rheumatol. 2013 Nov;23(6):1124-32
4. Vasheghani F, et al. Adult cartilage-specific peroxisome proliferator-activated receptor gamma knockout mice exhibit the spontaneous osteoarthritis phenotype. Am J Pathol. 2013 Apr;182(4):1099-106
5. Afif H, et al. Peroxisome proliferator-activated receptor gamma1 expression is diminished in human osteoarthritic cartilage and is downregulated by interleukin-1beta in articular chondrocytes. Arthritis Res Ther. 2007;9(2):R31
6. Zhang L, et al. Icariin promotes extracellular matrix synthesis and gene expression of chondrocytes in vitro. Phytother Res. 2012 Sep;26(9):1385-92.
7. Zeng L, et al. Chondroprotective effects and multi-target mechanisms of Icariin in IL-1 beta-induced human SW 1353 chondrosarcoma cells and a rat osteoarthritis model. Int Immunopharmacol. 2014 Jan;18(1):175-81.
8. Li D, et al. Icariin: a potential promoting compound for cartilage tissue engineering. Osteoarthritis Cartilage. 2012 Dec;20(12):1647-56
9. Wu KC, et al. Screening of natural compounds as activators of the keap1-nrf2 pathway. Planta Med. 2014 Jan;80(1):97-104.
1. Schunck M, Schulze CH, Oesser S, 2009. Collagen peptide supplementation stimulates proteoglycan biosynthesis and aggrecan expression of articular chondrocytes, Osteoarthritis and Cartilage Vol. 17, Suppl.1, 261
2. McAlindon TE, Nuite M, Krishnan N, Ruthazer R, Price LL, Burstein D, Griffith J,Flechsenhar K, Change in knee osteoarthritis cartilage detected by delayed gadolinium enhanced magnetic resonance imaging following treatment with collagen hydrolysate: a pilot randomized controlled trial. Osteoarthritis andCartilage (2011), online 3 January 2011
3. Ding QH, et al. Inhibition of matrix metalloproteinases and inducible nitric oxide synthase by andrographolide in human osteoarthritic chondrocytes. Mod Rheumatol. 2013 Nov;23(6):1124-32
4. Vasheghani F, et al. Adult cartilage-specific peroxisome proliferator-activated receptor gamma knockout mice exhibit the spontaneous osteoarthritis phenotype. Am J Pathol. 2013 Apr;182(4):1099-106
5. Afif H, et al. Peroxisome proliferator-activated receptor gamma1 expression is diminished in human osteoarthritic cartilage and is downregulated by interleukin-1beta in articular chondrocytes. Arthritis Res Ther. 2007;9(2):R31
6. Zhang L, et al. Icariin promotes extracellular matrix synthesis and gene expression of chondrocytes in vitro. Phytother Res. 2012 Sep;26(9):1385-92.
7. Zeng L, et al. Chondroprotective effects and multi-target mechanisms of Icariin in IL-1 beta-induced human SW 1353 chondrosarcoma cells and a rat osteoarthritis model. Int Immunopharmacol. 2014 Jan;18(1):175-81.
8. Li D, et al. Icariin: a potential promoting compound for cartilage tissue engineering. Osteoarthritis Cartilage. 2012 Dec;20(12):1647-56
9. Wu KC, et al. Screening of natural compounds as activators of the keap1-nrf2 pathway. Planta Med. 2014 Jan;80(1):97-104.
10. Luo, LK, et al. Andrographolide enhances proliferation and prevents dedifferentiation of rabbit articular chondrocytes: an in vitro study. Evid Based Complement Alternat Med 2015;2015:984850.
11. Moncada-Pazos A, et al. The nutraceutical flavonoid luteolin inhibits ADAMTS-4 and ADAMTS-5 aggrecanase activities. J Mol Med. 2011 Jun.
12. Durogova M, et al.Mechanism of proteoglycan aggregate degradation in cartilage stimulated with oncostatin M. Osteoarthritis Cartilage. 2008 Jan.
13. Lim H, et al. Effects of flavonoids on matrix metalloproteinase-13 expression of interleukin-1B-treated articular chondrocytes and their cellular mechanisms: Inhibition of c-Fos/AP-1 and JAK/STAT signaling pathways.
