Andrographis paniculata (AP) has been widely used in China for centuries to treat various diseases, and especially to treat inflammation. Diterpenoid lactones are the main anti-inflammatory components of AP. However, systematic chemical composition and biological activities, as well as key pharmacophores, of these diterpenoid lactones from AP have not yet been clearly understood. In this study, 17 diterpenoid lactones, including 2 new compounds, were identified by spectroscopic methods, and most of them attenuated the generation of TNF-α and IL-6 in LPS-induced RAW 274.7 cells examined by ELISA. Pharmacophores of diterpenoid lactones responsible for the anti-inflammatory activities were revealed based on the quantitative structure-activity relationship (QSAR) models. Moreover, new compounds (AP-1 and AP-4) exerted anti-inflammatory activity in LPS microinjection-induced zebrafish, which might be correlated with the inhibition of the translocation of NF-κB p65 from cytoplasm to nucleus. Our study provides guidelines for future structure modification and rational drug design of diterpenoid lactones with anti-inflammatory properties in medical chemistry.

Inactivity is a significant risk factor for cardiovascular disease. Exercise may greatly enhance the metabolism and function of the cardiovascular system, lower several risk factors, and prevent the development and treatment of cardiovascular disease while delivering easy, physical, and emotional enjoyment. Exercise regulates the cardiovascular system by reducing oxidative stress and chronic inflammation, regulating cardiovascular insulin sensitivity and the body’s metabolism, promoting stem cell mobilization, strengthening autophagy and myocardial mitochondrial function, and enhancing cardiovascular damage resistance, among other effects. Appropriate exercise intervention has become an essential adjuvant therapy in clinical practice for treating and rehabilitating various cardiovascular diseases. However, the prescription of exercise for preventing and treating cardiovascular diseases, particularly the precise selection of individual exercise techniques and their volume, remains controversial. Using multiomics to explain further the molecular process underlying the positive effects of exercise on cardiovascular health will not only improve our understanding of the effects of exercise on health but also establish a scientific basis and supply new ideas for preventing and treating cardiovascular diseases by activating the endogenous protective mechanisms of the body and suggesting more specific exercise prescriptions for cardiovascular rehabilitation.

The Journal of Clinical Medicine retracts the article entitled “Cardiovascular Disease and Exercise: From Molecular Mechanisms to Clinical Applications”