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Evidence from In Vitro Studies

Several in vitro studies (i.e. cellular studies that do not involve animals or humans) have shed light on the potential molecular targets of ASU ExpanscienceTM. Most studies have measured the in vitro effects of ASU ExpanscienceTM on cartilage, bone, synovial cell cultures which have been exposed to substances known to cause inflammation such as interleukins.

The addition of pro-inflammatory molecules to cartilage cell cultures has enabled scientists to generate a working model of osteoarthritis and understand the pathophysiology of osteoarthritis. In osteoarthritic joints, cartilage and synovial cells secrete IL-1ß which is thought to be one of the most damaging factors in osteoarthritis. IL-1ß is an important mediator of the inflammatory response and plays a role in various pathways involved in cartilage destruction 1 (see figure). In vitro studies have identified a potential role of ASU ExpanscienceTM in cartilage repair and destruction.

 

IL-1ß plays a role in various pathways involved in cartilage matrix destruction 4

IL-1ß plays a role in various pathways involved in cartilage matrix destruction


Data from in vitro studies show:

ASU ExpanscienceTM regulate molecules involved in cartilage degradation: 

Results suggest that ASU ExpanscienceTM are potent inhibitors of molecules involved in inflammation (IL-6, IL-8), cartilage matrix destruction (MMP-3, collagenase), bone breakdown (PGE2), which indicate that they may protect against cartilage degradation 2, 7. It was also found that ASU ExpanscienceTM can increase the production of molecules involved in tissue regeneration (TGF-ß1, TGF-ß2, PAI-1), and hence may be involved in cartilage homeostasis and repair 3. Additional in vitro data show that ASU ExpanscienceTM inhibit pro-inflammatory mediators 4. (see figure).

ASU Expanscience TM inhibits pro-inflammatory mediators in vitro (Adapted from Henrotin et al., 2003 5)

ASU Expanscience TM inhibits pro-inflammatory mediators in vitro (Adapted from Henrotin et al., 2003)

Interestingly, an additional study provided further evidence as to how ASU modulate signaling pathways in osteoarthritis, and suggests a "unique range of activities" that includes ERK1/2 and NF-κB inhibition, molecules that regulate the expression of certain key genes such as inflammatory mediators 6.

 

ASU ExpanscienceTM restore aggrecan production 4

ASU have demonstrated an ability to restore aggrecan production impaired by inflammation, and stimulate levels of TIMP-1 (an inhibitor of the MMP3 mentioned above). Thus, in vitro data suggest that ASU ExpanscienceTM might potentially mitigate cartilage destruction and repair processes.

 

ASU Expanscience™ modulate osteoblast phenotype 5 ,6 

In osteoarthritis, subchondral bone cells also called osteoblasts could contribute to abnormal bone and cartilage remodeling by releasing various molecules. Data have shown that ASU ExpanscienceTM restore normal levels of cartilage matrix molecules (e.g. aggrecan and collagen II) by counteracting the inhibitory effects of osteoblasts on matrix component production 5. Thus, ASU ExpanscienceTM might prevent cartilage degradation by acting directly on osteoblasts.

 

1. Dinarello CA. The IL 1 family and inflammatory diseases. Clin Exp Rheumatol. 2002 SepOct;20(5 Suppl 27):S1 13.
2. Boumediene K, Felisaz N, Bogdanowicz P, Galera P, Guillou GB, Pujol JP. Avocado/soya unsaponifiables enhance the expression of transforming growth factor beta1 and beta2 in cultured articular chondrocytes. Arthritis Rheum 1999;42:148 56.
3. Khayyal MT, el Ghazaly MA. The possible "chondroprotective" effect of the unsaponifiable constituents of avocado and soya in vivo. Drugs Exp Clin Res 1998; 24: 41 50.
4. Henrotin YE, Sanchez C, Deberg MA, Piccardi N, Guillou GB, Msika P et al. Avocado/soybean unsaponifiables increase aggrecan synthesis and reduce catabolic and proinflammatory mediator production by human osteoarthritic chondrocytes. J Rheumatol 2003;30:1825 34.
5. Henrotin YE, Deberg MA, Crielaard JM, Piccardi N, Msika P, Sanchez C. Avocado/soybean unsaponifiables prevent the inhibitory effect of osteoarthritic subchondral osteoblasts on aggrecan and type II collagen synthesis by chondrocytes. J Rheumatol 2006;33:1668 78.
6. Gabay O, Gosset M, Levy A, Salvat C, Sanchez C, Pigenet A et al. Stress induced signaling pathways in hyalin chondrocytes: inhibition by Avocado Soybean Unsaponifiables (ASU). Osteoarthritis Cartilage 2008;373 84.
7. Henrotin YE, Labasse AH, Jaspar JM, De Groote DD, Zheng SX, Guillou GB et al. Effects of three avocado/soybean unsaponifiable mixtures on metalloproteinases, cytokines and prostaglandin E2 by human articular chondrocytes. Clin Rheumatol 1998; 17 : 31-39.