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Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases (CVDs), the world's primary cause of death. Ginkgo biloba, a well-known traditional Chinese medicine with notable cardiovascular actions, has been used as a cardio- and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries. Preclinical studies have shown that ginkgolide B, a bioactive component in Ginkgo biloba, can ameliorate atherosclerosis in cultured vascular cells and disease models. Of clinical relevance, several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases, such as ischemia stroke. Here, we present a comprehensive review of the pharmacological activities, pharmacokinetic characteristics, and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy. We highlight new molecular targets of ginkgolide B, including nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidase), lectin-like oxidized LDL receptor-1 (LOX-1), sirtuin 1 (SIRT1), platelet-activating factor (PAF), proprotein convertase subtilisin/kexin type 9 (PCSK9) and others. Finally, we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.

KLF2 is a therapeutic target for COVID-19 induced endothelial dysfunction

Coronavirus disease 2019 (COVID-19) is regarded as an endothelial disease (endothelialitis) with its mechanism being incompletely understood. Emerging evidence has demonstrated that the endothelium represents the Achilles' heel in COVID-19 patients and that endothelial dysfunction precipitates COVID-19 and accompanying multi-organ injuries. Thus, pharmacotherapies targeting endothelial dysfunction have potential to ameliorate COVID-19 and its cardiovascular complications. Primary human umbilical vein endothelial cells (HUVECs) and human pulmonary microvascular endothelial cells (HPMECs) were treated with serum from control subjects or COVID-19 patients. Downstream monocyte adhesion and associated gene/protein expression was evaluated in endothelial cells exposed to COVID-19 patient serum in the presence of KLF2 activator (Atorvastatin) or KLF2 overexpression by an adenoviral vector. Here, we demonstrate that the expression of KLF2 was significantly reduced and monocyte adhesion was increased in endothelial cells treated with COVID-19 patient serum due to elevated levels of pro-adhesive molecules, ICAM1 and VCAM1. IL-1{beta} and TNF-, two cytokines observed in cytokine release syndrome in COVID-19 patients, decreased KLF2 gene expression. Next-generation RNA-sequencing data showed that atorvastatin treatment leads to a cardiovascular protective transcriptome associated with improved endothelial function (vasodilation, anti-inflammation, antioxidant status, anti-thrombosis/-coagulation, anti-fibrosis and reduced angiogenesis). Treatment of HPMECs with atorvastatin or KLF2 adenovirus ameliorate COVID-19 serum-induced increase in endothelial inflammation and monocyte adhesion by increasing KLF2 expression. Altogether, the present study demonstrates that genetic and pharmacological activation of KLF2 represses COVID-19 associated endothelial dysfunction, heralding a potentially new direction to treat endothelialitis accompanying COVID-19.

Natural products, PGC-1 , and Duchenne muscular dystrophy

Peroxisome proliferator-activated receptor (PPAR) is a transcriptional coactivator that binds to a diverse range of transcription factors. PPAR coactivator 1 (PGC-1) coactivators possess an extensive range of biological effects in different tissues, and play a key part in the regulation of the oxidative metabolism, consequently modulating the production of reactive oxygen species, autophagy, and mitochondrial biogenesis. Owing to these findings, a large body of studies, aiming to establish the role of PGC-1 in the neuromuscular system, has shown that PGC-1 could be a promising target for therapies targeting neuromuscular diseases. Among these, some evidence has shown that various signaling pathways linked to PGC-1 are deregulated in muscular dystrophy, leading to a reduced capacity for mitochondrial oxidative phosphorylation and increased reactive oxygen species (ROS) production. In the light of these results, any intervention aimed at activating PGC-1 could contribute towards ameliorating the progression of muscular dystrophies. PGC-1 is influenced by different patho-physiological/pharmacological stimuli. Natural products have been reported to display modulatory effects on PPAR activation with fewer side effects in comparison to synthetic drugs. Taken together, this review summarizes the current knowledge on Duchenne muscular dystrophy, focusing on the potential effects of natural compounds, acting as regulators of PGC-1.

C-reactive protein and atherosclerotic inflammation / 中国病理生理杂志

Inflammation plays a pivotal role in atherogenesis. In addition to being a potent predictive and prognostic marker for major cardiovascular events, recent evidence indicates that C-reactive protein (CRP) might directly promote atherogenesis by exerting direct effects on vascular cells. Thus, CRP will become important novel pharmaceutical targets for the treatment of atherosclerosis. This review presents an overview of the current knowledge about the pathological role of CRP in atherosclerosis initiation and progression.