Ginkgolide A Ameliorates LPS-Induced Inflammatory Responses In Vitro and In Vivo

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.

Protective effects ofGinkgo bilobaL. against natural toxins, chemical toxicities, and radiation: A comprehensive review

“…Li et al () assayed ginkgolide A, as an active ingredient of GBLE. This compound attenuated the expression of proinflammatory mediators, such as COX‐2 and NO as well as proinflammatory cytokines, including TNF‐α, IL‐6, and IL‐1 in mouse peritoneal macrophages, mouse macrophage RAW264.7 cells, and differentiated human monocytes, which all cell types were intoxicated by LPS in vitro.…”

“…These effects were partially attributed to the down regulation of NF‐κB, P38 MAPK, and activation of AMPK signalling pathways. Moreover, ginkgolide A was able to inhibit the release of TNF‐α and IL‐6 induced by LPS in mice (Li et al, ). As it is reported above, the results obtained from the in vitro study on inflammatory cells support the outcomes of the in vivo research projects.…”

“…Therefore, it can be concluded that the one of possible protection mechanisms of GBLE is the NF-κB pathway suppression via the revival of tissue antioxidant capacity (Huang et al, 2013). Li et al (2017) assayed ginkgolide A, as an active ingredient of GBLE. This compound attenuated the expression of proinflammatory mediators, such as COX-2 and NO as well as proinflammatory cytokines, including TNF-α, IL-6, and IL-1 in mouse peritoneal macrophages, mouse macrophage RAW264.7 cells, and differentiated human monocytes, which all cell types were intoxicated by LPS in vitro.…”

Anti‐inflammatory effects of chemical components from Ginkgo biloba L. male flowers on lipopolysaccharide‐stimulated RAW264.7 macrophages

“…Regarding the anti‐inflammatory activity of Ginkgo , previous studies have shown that the standard G. biloba leaf extract (EGb761) can modulate inflammatory mediators and cytokines to suppress inflammation in vitro and in vivo, and the main active components of EGb761, total ginkgo flavonoid O ‐glycosides, can also inhibit lipopolysaccharide (LPS)‐induced nitric oxide (NO) release in RAW264.7 macrophages (Zhang et al, ). Among the active compounds, Ginkgolide A was reported to ameliorate inflammatory responses induced by LPS in vitro and in vivo (Li et al, ). Ginkgolide B also possesses anti‐inflammatory effects (Chen et al, ).…”

“…Stimulated by LPS, RAW264.7 macrophages can secrete various inflammatory mediators, such as NO, iNOS, PGE 2 , and COX‐2, and inflammatory cytokines, such as TNF‐α and IL‐6. The elevation of inflammatory mediator and cytokine levels is closely associated with the development of inflammatory diseases (Li et al, ). Therefore, screening the agents that can suppress inflammatory mediators and cytokines is essential for developing new anti‐inflammatory drugs (Yoon, Kim, Lee, Kim, & Oh, ).…”