ginkgetin and Disease-Models--Animal

Ginkgo biloba, a natural biflavonoid isolated from Ginkgo biloba leaves, is reported to have strong anti-inflammatory and immunosuppressive properties. The aim of this study is to investigate the potential anti-inflammatory mechanisms of ginkgo flavonoids on cerebral ischemia/reperfusion (I/R) injury. Inflammatory-associated cytokines in cerebral ischemic hemispheres were determined by immunohistochemical staining, Western blot and enzyme-like immunosorbent assay (ELISA). Our results indicated that treatment with Ginkgetin significantly restored rat brain I/R-induced neurological deficit scores. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in Ginkgetin treatment group (100 mg/kg) also significantly reduced. The expression inflammation-related protein prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and interleukin-8 (IL-8) was also decreased in Ginkgetin treatment group. However, the expression of interleukin-10 (IL-10) was remarkably increased. Thus, this study demonstrates that Ginkgetin protects neurons from I/R-induced rat injury by down-regulating pro-inflammatory cytokines and blocking the TLR4/NF-κB pathway.

Topics: Animals; Anti-Inflammatory Agents; Biflavonoids; Brain Ischemia; Cyclooxygenase 2; Dinoprostone; Disease Models, Animal; Drug Administration Schedule; Gene Expression Regulation; Ginkgo biloba; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Neuroprotective Agents; NF-kappa B; Nitric Oxide Synthase Type II; Plant Extracts; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Suilysin (SLY), a crucial virulence-related factor, has multiple cytotoxicities that are regarded as playing a key role in several diseases induced by Streptococcus suis. The aim of this study was to identify an effective inhibitor of SLY and to evaluate the potential inhibitory effect of the inhibitor against S. suis virulence.. Antibacterial activity experiments and haemolysis tests were used to identify the SLY inhibitor ginkgetin, and Western blot analysis and oligomerization inhibition tests were employed to determine the potential mechanism for its inhibition effect. The potential inhibitory effect of ginkgetin against S. suis virulence was then assessed through a cytotoxicity test and a mouse infection model. In this study, we demonstrated that the natural ingredient ginkgetin can significantly reduce the haemolytic activity of SLY to protect against S. suis-mediated cell injury in vitro by directly binding to SLY to block the oligomerization of the protein and reducing the bacterial burden in vivo.. The results suggest that ginkgetin can start being used as a potential lead drug for the treatment of S. suis infections.. The prevention and treatment of S. suis infection might be possible through the targeting of SLY by ginkgetin.

Topics: Animals; Anti-Bacterial Agents; Biflavonoids; Disease Models, Animal; Female; Hemolysin Proteins; Humans; Mice; Mice, Inbred C57BL; Streptococcal Infections; Streptococcus suis; Virulence Factors

Disruption of neuronal iron homeostasis and oxidative stress are closely related to the pathogenesis of Parkinson's disease (PD). Ginkgetin, a natural biflavonoid isolated from leaves of Ginkgo biloba L, has many known effects, including anti-inflammatory, anti-influenza virus, and anti-fungal activities, but its underlying mechanism of the neuroprotective effects in PD remains unclear. The present study utilized PD models induced by 1-methyl-4-phenylpyridinium (MPP(+)) and 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to explore the neuroprotective ability of ginkgetin in vivo and in vitro. Our results showed that ginkgetin could provide significant protection from MPP(+)-induced cell damage in vitro by decreasing the levels of intracellular reactive oxygen species and maintaining mitochondrial membrane potential. Meanwhile, ginkgetin dramatically inhibited cell apoptosis induced by MPP+ through the caspase-3 and Bcl2/Bax pathway. Moreover, ginkgetin significantly improved sensorimotor coordination in a mouse PD model induced by MPTP by dramatically inhibiting the decrease of tyrosine hydroxylase expression in the substantia nigra and superoxide dismutase activity in the striatum. Interestingly, ginkgetin could strongly chelate ferrous ion and thereby inhibit the increase of the intracellular labile iron pool through downregulating L-ferritin and upregulating transferrin receptor 1. These results indicate that the neuroprotective mechanism of ginkgetin against neurological injury induced by MPTP occurs via regulating iron homeostasis. Therefore, ginkgetin may provide neuroprotective therapy for PD and iron metabolism disorder related diseases.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 1-Methyl-4-phenylpyridinium; Animals; Antigens, CD; Apoferritins; Apoptosis; Biflavonoids; Caspase 3; Cell Line, Tumor; Cell Survival; Disease Models, Animal; Gene Expression Regulation, Enzymologic; Ginkgo biloba; Homeostasis; Humans; Iron; Iron Chelating Agents; Male; Membrane Potential, Mitochondrial; Mice; Mice, Inbred C57BL; Neurons; Neuroprotective Agents; Oxidative Stress; Parkinson Disease; Reactive Oxygen Species; Receptors, Transferrin; Superoxide Dismutase; Tyrosine 3-Monooxygenase