Abstract
Ginkgolide A (GA) is a natural compound isolated from Ginkgo biloba and has been used to treat cardiovascular diseases and diabetic vascular complications. However, only a few studies have been conducted on the anti-inflammatory effects of GA. In particular, no related reports have been published in a common inflammation model of lipopolysaccharide (LPS)-stimulated macrophages, and the anti-inflammatory mechanisms of GA have not been fully elucidated. In the present study, we extensively investigated the anti-inflammatory potential of GA in vitro and in vivo. We showed that GA could suppress the expression of pro-inflammatory mediators (cyclooxygenase-2 (COX-2) and nitric oxide (NO) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β) in LPS-treated mouse peritoneal macrophages, mouse macrophage RAW264.7 cells, and differentiated human monocytes (dTHP-1) in vitro. These effects were partially carried out via downregulating Nuclear factor kappa-B (NF-κB), Mitogen-activated protein kinases (MAPKs) (p38 mitogen-activated protein kinase and extracellular signal-regulated kinase (ERK), but not c-Jun N-terminal kinase (JNK), and activating the AMP-activated protein kinase (AMPK) signaling pathway also seems to be important. Consistently, GA was also shown to inhibit the LPS-stimulated release of TNF-α and IL-6 in mice. Taken together, these findings suggest that GA can serve as an effective inflammatory inhibitor in vitro and in vivo.
Highlights
Inflammation is a complex pathological process which results from tissue injury or infection [1]
nitric oxide (NO) is another important inflammatory mediator, which is involved in regulating many physiological processes, including neurotransmission, vascular relaxation, platelet aggregation, and the immune response [4]
The exposure of macrophages to LPS in this study resulted in a significant secretion of NO after 24 h of incubation, while ginkgolide A (GA) was found to downregulate NO production in LPS-stimulated mouse peritoneal macrophages and RAW264.7 cells
Summary
Inflammation is a complex pathological process which results from tissue injury or infection [1]. It is an important defensive immune response with health benefits [2]. Macrophages, as primary immune cells, play a key role in homeostasis and defense, in the initial stage of the inflammatory process [4] and the modulation of host defense mechanisms via the production of pro-inflammatory mediators, such as nitric oxide (NO) and cytokines [1]. Lipopolysaccharide (LPS), the primary component of the outer membrane of Gram-negative bacteria, stimulates the activity of immune cells and triggers an inflammatory response against bacterial invasion [4,5]. The elevation of inflammatory cytokine levels is closely linked to the development of inflammation-associated diseases such as atherosclerosis [2]
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