Healthy Cartilage Support

Osteoarthritis is characterized by progressive and permanent cartilage degradation. Cartilage erosion can cause inflammation and pain, decreased mobility and reduced athletic performance (see Figure 10).

This degradation is caused by Interleukin-1β (IL-1β) cytokines, which trigger the over-production of cartilage-degrading enzymes called matrix metalloproteinases (MMPs) in the synovial cells and the chondrocytes. This leads to a progressive loss of the cartilage matrix, which is composed of biochemicals aggrecan, hyaluronan (HA) and collagen.

Controlled Study

In RA, aggressive fibroblast-like synoviocytes (FLSs) are found in the
synovial tissues. These FLSs invade and destroy joints and cartilage by actively releasing pro-inflammatory cytokines. They also produce massive amounts of cartilage-degrading enzymes, especially matrix MMPs, which contribute to the invasive growth of FLSs and subsequent joint destruction.

Researchers at the La Jolla Institute for Allergy and Immunology, in collaboration with colleagues from the University of California, San Diego (UCSD), identified FLSs as the target of a potential new RA drug that focuses on cells responsible for the cartilage damage in affected joints. Current RA treatments focus on intercepting the immune system’s misdirected attack on the lining of affected joints to alleviate the debilitating symptoms, reduce inflammation and slow the progression of the disease. “Unfortunately, for around 40% of patients, immune-targeted therapies are not sufficient to bring them into full remission,” says the study’s lead author, Nunzio Bottini, M.D., Ph.D., associate professor at La Jolla Institute and associate professor of medicine at UCSD. “Even if your inflammation is completely under control with the help of current therapies—and they are excellent—the damage to the skeletal structure is not necessarily arrested in the long term because synoviocytes continue to cause damage,” he explains.

FLSs secrete proteases that digest cartilage, and they also promote osteoclasts differentiation, which in turn attack the bone and generate erosions. Blocking the action of these synovial fibroblasts will directly protect joints from cartilage destruction (8).

FLS release pro-inflammatory cytokines & produce (MMPs) which promotes osteoclast joint & cartilage destruction

Human Clinical Study 1

International Scholarly Research Notices
Volume 2014, Article ID 464136, 8 pages

http://dx.doi.org/10.1155/2014/464136

Research Article
Andrographolide Exerts Chondroprotective Activity in Equine Cartilage Explant and Suppresses Induced MMP-2 Expression in Equine Chondrocyte Culture Siriwan Tangyuenyong,1 Nawarat Viriyakhasem,2 Siriporn Peansukmanee,1 Prachya Kongtawelert,2 and Siriwan Ongchai2

Recent research has shown that Andrographolide inhibits MMPs in IL-1β-treated human chondrocytes while increasing the natural inhibitors of these enzymes via the NF-kB pathway. A study published in International Scholarly Research Notices found that Andrographolide suppressed MMPs that were induced by IL-1β in equine cartilage (7). Andrographolide further slows cartilage degradation by dramatically reducing the loss of collagen, uronic acid, HA and sulfated glycosaminoglycans (s-GAGs) caused by IL-1β, a key inducer of cartilage degeneration. The research not only demonstrated the potent cartilage-protecting activities of Andrographolide, but also showed the ability of Andrographolide to increase the production of cartilage biomolecules including collagen, aggrecan and HA (see Figure 11).

Human Clinical Study 2

Cell Biol Toxicol (2012) 28:47–56

DOI 10.1007/s10565-011-9204-8

Andrographolide induces cell cycle arrest and apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes

Jie Yan & Yang Chen & Chao He & Zhen-zhen Yang & Cheng Lü & Xin-shan Chen

In a study published in Cell Biology Toxicology, synovial tissues were
collected from 15 RA patients who had undergone a total knee replacement therapy; the cells were treated with Andrographolide for 48 hours (9). The study found that Andrographolide induced cell death in these human RA-FLSs (rheumatoid arthritis fi broblast-like synoviocytes) via cytochrome-C release and caspase-3 activation, which play key roles in cell death. The author suggests that Andrographolide could be a potential option in supporting against joint destruction in both osteoarthritis and RA.

Human Clinical Study 3

A condition called synovial hypoxia frequently occurs in patients with RA, contributing to tendon rupture and perpetual joint destruction. Fifty percent of RA patients also experience inflammation of the synovial tissue surrounding the tendons, which is associated with multiple ruptures and a poor prognosis for longterm joint function. RA patients often have high levels hypoxia-inducible factor-1 alpha (HIF-1α), a chemical linked to inflammation in the synovial tissues.

Andrographolide inhibits the migration, invasion and matrix metalloproteinase expression of rheumatoid arthritis fibroblast-like synoviocytes via inhibition of HIF-1α signaling

Guo-feng Li, Yu-hua Qin ⁎, Peng-qiang Du

ParActin^® decreases MMPs induced by hypoxia

Human Clinical Study 4

In a study published in Life Sciences, synovial tissue was obtained from 50 RA patients during a knee joint arthroscopy (10). The researchers found that Andrographolide signifi cantly decreased the cartilage-degrading enzymes MMPs, induced by hypoxia. Andrographolide inhibited the migration, prevented the invasion of RA-FLS and increase of MMPs in RA-FLSs via the inhibition of HIF-1α signaling. Hypoxia causes RA-FLS migration and invasion. Andrographolide inhibited hypoxia-induced migration and RA-FLS invasion, thus suggesting the potential for Andrographolide in benefi ting those with joint degeneration.