Osteoarthritis (OA) is the most common form of arthritis. It affects millions of people worldwide. OA can damage any joint in your body, the disorder most commonly affects joints in your hands, knees, hips and spine. It occurs when the protective cartilage on the ends of your bones disappears over time. Currently the underlying process cannot be reversed. Staying active, maintaining a healthy weight and other treatments may slow progression of the disease and help improve pain and joint function.
The erosion and destruction of articular cartilage are the specific characteristics of OA, accompanied by the loss of chondrocyte number & function and degradation of extracellular matrix. Research into the mechanism and therapies for OA has shifted from structural to the molecular changes in particular inflammation and oxidative stress and it has been demonstrated that inflammation-associated changes in the OA cartilage take place. Inflammatory mediators including chemokines, adipokines, and pro-inflammation cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-4, and IL-6 have been found to be increased in the serum and OA cartilage. These cytokines stimulate chondrocytes to secrete synthesize cyclooxygenase 2 (COX-2), nitric oxide (NO), prostaglandin E2 (PGE2), and matrix metalloproteinase (MMPs), leading to the destruction of cartilages. In addition there is oxidative stress, impacting intracellular signaling processes, chondrocyte senescence, apoptosis and autophagy, ECM synthesis and degradation. This pro-inflammatory action caused by reactive oxygen species (ROS) works through the nuclear factor-kappa B (NF-ĸB) pathway in OA chondrocytes.
In this study a team of researchers from China investigated whether pterostilbene could protect chondrocytes from inflammation and ROS production. They decided to research this because several studies in other cell types have reported the suppressive effects of pterostilbene on inflammation, oxidative stress, and apoptosis. Pterostilbene also is shown to reduce the ROS production and the expression of inflammatory mediators including IL-1β, IL-6, TNF-α, metalloproteinase-2 (MMP-2), and MMP-9.
For the study the researchers used an OA cartilage degeneration rat model (Sprague-Dawley rats). The osteoarthritis model was established by the transection of anterior cruciate ligament and partial medial meniscectomy in rats. In order to determine dosing they first they tested the cytotoxicity of pterostilbene (in vitro) on extracted chondrocytes and concluded that 20 μM pterostilbene with 24 h treatment did not affect the chondrocyte viability. Based on that the OA model rats received pterostilbene 30 mg/kg, daily for 8 weeks in sunflower oil.
The researchers found in vivo that nuclear translocation of Nrf2 was stimulated by pterostilbene without cellular toxicity. Pterostilbene inhibited the level of COX-2, iNOS, PGE2, and NO, as well as the mitochondrial and total intracellular ROS production induced by IL-1β in chondrocytes, partially reversed by the Nrf2 silencing. After the rats were euthanized analyses showed that compared with the OA cartilage, the pterostilbene-treated OA cartilage showed more smooth, more deposit of proteoglycan in ECM and less formation of fibrillations.
Finally lets calculate the Human Equivalent Dose (HED) of pterostibene dose the rats received. Using FDA specified guidelines the calculation shows the HED is roughly 5mg/kg. Or approximately a 350mg daily pterstilbene dose for a person weighing 70kg. Typical supplements on the market have serving sizes of 100mg. Pterostilbene in this human study is found to be safe at 250mg/kg for longer term use. Chromadex indicates an upper safety limit for a daily dose of 1890mg.
In conclusion, this work demonstrates the protective role of pterostilbene on OA in vivo and suggests that pterostilbene has potential as a drug to alleviate the cartilage degeneration. Moreover the effects were achieved with pterostilbene consumed orally at realistic dosing levels for humans.