Ginkgo diterpene lactones inhibit cerebral ischemia/reperfusion induced inflammatory response in astrocytes via TLR4/NF-κB pathway in rats
Xiang LiLiangliang HuangGe LiuWenxiang FanBinbin LiRui LiuZiyu WangQiru FanWei XiaoYunman LiWeirong Fang
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Abstract Sepsis, characterized by a systemic bacterial infection, is a life-threatening condition that can lead to multi-organ failure and death from septic shock. We have observed that CD14- and TLR4-deficient mice are resistant to death by sepsis from several different clinical isolates of E. coli injected intra-peritoneally. This resistance has been attributed to the 10-fold lower levels of the proinflammatory cytokines TNF and IL-6 induced in these mice. Surprisingly, however, neither TLR4- nor CD14-deficient mice were resistant to two closely related organisms that differed only in that they expressed a K1 polysaccharide capsule, even though these mice continued to express low levels of the proinflammatory cytokines. These and other observations suggest that the ability to limit bacterial dissemination may be equally or even more important than reducing the levels of these proinflammatory cytokines in preventing death from sepsis. We present evidence here, that the pathogenic role for the CD14/TLR4 pathway in severe infection, whereby it mediates the induction of proinflammatory cytokines, may be secondary to a more important insidious role whereby differential activation of local and systemic pathways of chemokine induction via CD14/TLR4-dependent and independent mechanisms generate chemokine gradients that prevent PMN transmigration from the blood to infected tissue and facilitates the dissemination of bacteria from a localized site of infection.
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Ginkgo biloba is the oldest living tree species in the world. Despite less than encouraging clinical results, extracts from its leaves are among the most used herbal preparations in the prevention and treatment of cardiovascular diseases. Most data on the efficacy of Ginkgo biloba on cardiovascular disease is from clinical studies, with few results from healthy subjects. This paper aims to provide a comprehensive review of the mechanisms underlying the known beneficial cardiovascular activities of Ginkgo biloba. It displays myocardial suppressant and vasorelaxant activities ex vivo, potentiating endothelial-dependent and -independent pathways. It improves perfusion in different vascular beds, namely ocular, cochlear, cutaneous, cerebral, and coronary. Although scarce, evidence suggests that Ginkgo biloba displays a heterogeneous effect on tissue perfusion which is dependent on the individual elimination pathways. It displays an acceptable safety profile, with most reported adverse reactions constituting rare occurrences. Collectively, Ginkgo biloba positively impacts cardiovascular physiology, improving hemodynamics and organ perfusion. In the future, better controlled clinical studies should be performed in order to identify the target populations who may benefit the most from pharmacotherapeutic interventions involving Ginkgo biloba.
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Transplanted Ginkgo biloba seedlings were treated with different contents of indoleacetic acid (IAA) solution in 2001. The results indicated that 500 μg/g and 250 μg/g of IAA treatments could significantly increase the height of Ginkgo biloba seedlings, and relatively enhance the diameter and leaf number of Ginkgo biloba seedlings when compared with other IAA treatments and CK. Considering treatment effect and cost, 500 μg/g and 250 μg/g of IAA treatments were the best.
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Objective This study was to investigate the effect of Danhong injection on proinflammatory cytokine release from lipopolysaccharide( LPS)-induced THP-1 macrophages. Methods Human THP-1 macrophages were induced using phorbol-12-myristate acetate( PMA,160 nmol /L) for 24 h,then cells were divided into four groups: control group,LPS group,Danhong group and LPS + Danhong group. Secretion of proinflammatory cytokines,including tumor necrosis factor-α( TNF-α),interleukin-6( IL-6) and interleukin-1β( IL-1β) was performed by enzyme-linked immunosorbent assay( ELISA). The protein expression of nuclear factor-κB( NF-κB) p65 and Toll-like receptor 4( TLR4) were examined by Western blot. Results Danhong injection inhibited the release of TNF-α,IL-6 and IL-1β induced by LPS,repressed the translocation of NF-κB to the nucleus and TLR4 expression. Conclusions Danhong injection inhibited the release of inflammatory cytokine that induced by LPS,and the mechanisms may be related to the TLR4 and NF-κB expressions.
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Ginkgo biloba is a valuable herb that has been used as traditional medicine for thousands of years. Extract of Ginkgo biloba leaves possesses several clinical beneficial effects such as antiinflammatory property. In this study, we investigated the effect of purified polysaccharides from Ginkgo biloba leaf (P-PGBL) on inflammatory reaction induced by lipopolysaccharides (LPS) in RAW264.7 mouse macrophage cells and the potential underlying mechanisms. The results showed that P-PGBL treatment significantly inhibited the LPS-induced protein and mRNA expression of Toll-like receptor 4 (TLR4) in a dose-dependent manner. P-PGBL treatment downregulated the nuclear factor-κB (NF-κB)p65 protein expression in LPS-stimulated RAW264.7 macrophage cells. Meanwhile, the levels of pro-inflammatory cytokines, such as IL-1β and IL-6 were suppressed by P-PGBL. In conclusion, P-PGBL exerts an anti-inflammatory effect by inhibiting TLR4/NF-κB signaling pathway, thereby lowering production of inflammatory cytokines.
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It has been well documented that the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway mediates early inflammatory responses during myocardial ischemia and reperfusion (MI/R). Mycophenolate mofetil (MMF), an immunosuppressive agent, has been shown to confer protective effects against ischemia/reperfusion injury, possibly through its immunosuppressive and anti-inflammatory actions. The aim of the present study was to investigate whether MMF could modulate the TLR4/NF-κB signaling, inhibit cell apoptosis and subsequently attenuate MI/R injury. MMF (20 mg/kg) or vehicle was administered to SD rats by gavage. The rats were then subjected to MI/R injury. The results showed that after MI/R, the expressions of myocardial TLR4 and NF-κB were significantly increased, and apoptosis of cardiomyocytes was induced, as evidenced by the decreased mitochondrial membrane potential (MMP), decreased Bcl-2 protein level, and increased Bax expression. Administration of MMF attenuated MI/R injury. Further studies demonstrated that MMF inhibited the induction of TLR4, NF-κB and Bax expression, and restored the expression of bcl-2. Moreover, increased myeloperoxidase activity and serum level of tumor necrotic factor α induced by MI/R injury were also inhibited by MMF treatment. In conclusion, our results demonstrated that MMF attenuates MI/R injury through inhibition of the TLR4/NF-κB signaling pathway, which led to reduced inflammatory reaction and subsequently myocardial cell apoptosis.
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Ginkgo biloba is the oldest tree on the planet. Its healing characteristics have been well known for more than 3000 years. The aim of this investigation to establish the influence of Ginkgo biloba extract (Egb 761 Tanakan) on bioelectric activity of brain in humans. 30 subjects aged from 52 to 56 years were included in study. The bioelectric activity (EEG) was registrated before and after three month therapy with Ginkgo biloba extract. The obtained results showed that summary bioelectric activity speeds up. Frequency of alpha rhytms increases significantly, number of desinchrayitation decreases, decreases number of non specific activity.
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The authors retrospectively analyzed the effect of Ginkgo biloba in the treatment of clinical disease,and its summary. Ginkgo biloba to treat cardiovascular and cerebrovascular disease,dementia,increasing blood flow,and to good effect. Rational use of analytical chemistry,plant chemistry and pharmacology of Ginkgo biloba deep-step study,by the active ingredients in Ginkgo biloba extract and separation efficiency,the development of new products Ginkgo biloba,providing a broader market for the fields.
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With deeper understanding and study of Ginkgo biloba L, natural Ginkgo biloba L can't satisfy the needs of the people. The people follow with interest cultivation techniques of Ginkgo biloba L. To further develop the resource of Ginkgo biloba L and raise quality and output of Ginkgo biloba L, the cultivation techniques of Ginkgo biloba L for top guality and high output are presented in this paper. Advanced and modern techniques about grafting and artificial pollination of Ginkgo biloba L are introduced and Ginkgo biloba L cultivation techniques and good experience are sammarized ,Some questions which remain to be answered have been put forward concerning the development of Ginkgo biloba L resource at present.
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Ginkgo biloba extract (EGb 761) is a standardized extract of Ginkgo biloba leaves and has anti- atherosclerosis properties. Many patients with atherosclerosis disorders take Ginkgo biloba extracts to supplement current therapy. In addition, normal healthy individuals also take Ginkgo biloba extracts...
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