Polydatin, also known as piceid, is a monocrystalline compound found in the roots and rhizomes of the herbaceous plant Japanese knotweed (Polygonum cuspidatum), which is used in traditional Chinese medicine. Polydatin is the glycoside form of resveratrol and is the most abundant form of resveratrol in nature. Albeit in small amounts, polydatin is also present in grapes, peanuts, hop cones, and cocoas, all of which are known sources of resveratrol. (Related: Resveratrol Prevents Brain and Heart Damage While Assisting Weight Loss.)
According to studies, polydatin has numerous medicinal benefits. Some of the most important ones include anti-platelet aggregation, antioxidant action, cardioprotection, anti-inflammation, and immune regulation. Polydatin can also protect myocardial cells from injury due to oxygen and glucose deprivation, alleviate liver injury caused by continuous consumption of a high-fat diet, reverse genetic alterations in the brain caused by chronic alcoholism, and protect the lungs from acute or chronic lung disease.
The antioxidant activity of polydatin is the focus of many studies. This is because polydatin is more resistant to enzymatic oxidation than resveratrol. Besides scavenging free radicals, polydatin can also prevent the oxidation of low-density lipoproteins. The oxidation of LDL produces a harmful type of cholesterol known as oxidized LDL (ox-LDL), which promotes atherosclerosis and increases the risk of heart attack or stroke. Having excessive amounts of free radicals in the blood can result in the formation of ox-LDL.
Cholesterol metabolism becomes imbalanced during the formation of macrophage-derived foam cells. These immune cells are loaded with lipids and serve as key regulators of the pathologic behavior of plaques that cause atherosclerosis. In this disease, a pro-inflammatory protein called pre-B-cell colony-enhancing factor (PBEF) influences lipid deposition and inflammation.
To assess the effects of polydatin on atherosclerosis, the researchers used 30 ApoE??? mice that were fed a high-fat diet for 12 weeks. The ApoE??? mouse model is the most widely used murine model in studies involving atherosclerosis. ApoE or apolipoprotein E is a protein involved in fat metabolism, and its deletion in ApoE??? mice ensures that the animals will display poor lipoprotein clearance.
The researchers treated ApoE??? mice on a high-fat diet with polydatin for another 12 weeks before collecting whole aortas and cryosections, which they stained with oil red O for visualization. They used an assay called ELISA to measure blood lipid, PBEF, and cytokine levels. They also determined the mRNA and protein levels of cholesterol metabolism-related genes, as well as the cell cholesterol content and viability in macrophages and RAW 264.7 cells. Finally, they used PBEF siRNA to study the effect of polydatin on cholesterol metabolism in macrophages incubated with ox-LDL. siRNA refers to a synthetic RNA duplex designed to target a specific mRNA for degradation – in this case, PBEF.
The researchers reported that polydatin lowered blood lipids and decreased atherosclerotic lesions in ApoE??? mice. Polydatin also regulated the expression of signaling molecules and the mRNA of cholesterol metabolism-related genes. On the other hand, polydatin down-regulated the expression of PBEF mRNA and protein. mRNAs are molecules that carry genetic information bound to be translated into proteins.
The researchers also found that polydatin protected RAW 264.7 cells treated with ox-LDL and inhibited cholesterol uptake by macrophages in vitro. From the results of their experiment involving the use of PBEF siRNA, they reported that polydatin can modulate cholesterol metabolism in macrophages, partly through the down-regulation of PBEF.
Based on these results, the researchers concluded that polydatin relieves atherosclerosis injury in ApoE??? mice by down-regulating PBEF expression and inhibiting PBEF-inducing cholesterol deposits in macrophages.