Ginkgo Flavonol Glycosides or Ginkgolides Tend to Differentially Protect Myocardial or Cerebral Ischemia–Reperfusion Injury via Regulation of TWEAK-Fn14 Signaling in Heart and Brain

Xiao, Guangxu; Lyu, Ming; Wang, Yule; He, Shuang; Li, Xinyan; Ni, Jingyu; Li, Lan; Fan, Guanwei; Han, Jihong; Gao, Xiumei; Wang, Xiaoying; Zhu, Yan

doi:10.3389/fphar.2019.00735

Cited by 48 publications

(22 citation statements)

References 89 publications

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“…A standardized Ginkgo biloba extract 761 (EGb 761) has been used as strong antioxidative and neuroprotective agent to treat neurodegenerative diseases [21]. Furthermore, several researches have indicated that EGb 761 protects against renal, myocardial, and cerebral ischemiareperfusion injury [22][23][24][25], and improves hepatic DNA damage and liver microcirculation after warm ischemia [26,27]. Ginkgo biloba Dropping Pill (GBDP) is a unique Ginkgo biloba leaf extract preparation produced in China for treating angina pectoris and cerebral infarction caused by blood stasis.…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Ginkgo Biloba Dropping Pills Against Liver Ischemia/reperfusion Injury in Mice

Wang

Zhang

Wang³

et al. 2020

Preprint

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Background: Liver ischemia-reperfusion (I/R) injury is an inevitable pathological phenomenon in various clinical conditions, such as liver transplantation, resection surgery, or shock, which is the major cause of morbidity and mortality after operation. Ginkgo Biloba Dropping Pill (GBDP) is a unique Chinese Ginkgo Biloba leaf extract preparation that exhibits a variety of beneficial biological activities. The aim of this study is to investigate the protective effects of GBDP on the liver I/R injury both in vitro and in vivo. Methods: Hypoxia/reoxygenation (H/R) experiments were performed in AML-12 cells and primary hepatocytes, which were pretreated with GBDP (60 or 120 μg/mL) followed by incubation in a hypoxia chamber. Cell viability and cell apoptosis were detected by MTT assay and annexin V staining respectively. C57BL/6 mice were used to establish liver I/R injury model, and were pretreated with GBDP (100 or 200 mg/kg/day, i.g.) for two weeks. Liver damage was detected by plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST). Liver necrosis and neutrophil infiltration were determined by H&E and myeloperoxidase immunohistochemistry staining. Finally, TUNEL staining and western blot analysis of apoptosis-related proteins were used to investigate the anti-apoptotic effect of GBDP. Results: In the in vitro study, GBDP pretreatment improved the cell viability of AML-12 cells in H/R injury model. Similarly, the same result was found in the primary hepatocytes isolated from C57BL/6 mice. Moreover, GBDP decreased the number of apoptotic cells induced by H/R. In the in vivo study, oral administration of GBDP ameliorated liver injury evidenced by a significant decline in the levels of ALT and AST. Furthermore, the result of H&E staining showed that GBDP reduced the size of necrosis area. In addition, the decreased infiltration of neutrophils indicated that GBDP may play an anti-inflammatory effect. More importantly, GBDP reduced TUNEL-positive cells and the expression of Bax and caspase-3 in liver indicating GBDP has anti-apoptotic effects.Conclusion: Our findings elucidated that GBDP has potential effects for protecting against liver I/R injury characterized by its anti-apoptotic, anti-necrotic, and anti-inflammatory properties, which would promisingly make a contribution to the exploration of therapeutic strategies in the liver I/R injury.

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Section: Introductionmentioning

confidence: 99%

Protective Effects of Ginkgo Biloba Dropping Pills Against Liver Ischemia/reperfusion Injury in Mice

Wang

Zhang

Wang³

et al. 2020

Preprint

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“…Ginkgolide B stimulated the proliferation and differentiation of neural stem cells in the in vivo models of NSCs in the rat brain following cerebral ischemia, thereby increasing the proportion of neurons to improve neurological outcomes [102]. Ginkgolide B is a potential neuro-protectant and in a study, the cellular and molecular mechanisms were dissected out by following the BDNF, EGF, and Suppressor of cytokine signaling 2 (SOCS2) [185]. Another phytochemical, curcumin, extensively studied shows beneficial effect in case of stroke too.…”

Section: Vascular Cognitive Impairmentmentioning

confidence: 99%

Neuroprotection: Targeting Multiple Pathways by Naturally Occurring Phytochemicals

et al. 2020

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With the increase in the expectancy of the life span of humans, neurodegenerative diseases (NDs) have imposed a considerable burden on the family, society, and nation. In defiance of the breakthroughs in the knowledge of the pathogenesis and underlying mechanisms of various NDs, very little success has been achieved in developing effective therapies. This review draws a bead on the availability of the nutraceuticals to date for various NDs (Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, Huntington’s disease, vascular cognitive impairment, Prion disease, Spinocerebellar ataxia, Spinal muscular atrophy, Frontotemporal dementia, and Pick’s disease) focusing on their various mechanisms of action in various in vivo and in vitro models of NDs. This review is distinctive in its compilation to critically review preclinical and clinical studies of the maximum phytochemicals in amelioration and prevention of almost all kinds of neurodegenerative diseases and address their possible mechanism of action. PubMed, Embase, and Cochrane Library searches were used for preclinical studies, while ClinicalTrials.gov and PubMed were searched for clinical updates. The results from preclinical studies demonstrate the efficacious effects of the phytochemicals in various NDs while clinical reports showing mixed results with promise for phytochemical use as an adjunct to the conventional treatment in various NDs. These studies together suggest that phytochemicals can significantly act upon different mechanisms of disease such as oxidative stress, inflammation, apoptotic pathways, and gene regulation. However, further clinical studies are needed that should include the appropriate biomarkers of NDs and the effect of phytochemicals on them as well as targeting the appropriate population.

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“…GK, a derivate of GB, given at a higher dose also attenuated cerebral infarction and repressed brain edema formation in MCAO rats (Ma et al 2012). In a cerebral ischemia-reperfusion injury (CIRI) model, pretreatment with Ginkgolides at 2.5 ml/kg reduced cerebral infarction area and cerebral edema, partly through TWEAK–Fn14 cytokine receptor axis (Xiao et al 2019). The effect of bilobalide on brain edemas has been demonstrated in animal experiments.…”

Section: Mechanisms Of Ginkgolides and Bilobalide In Neuron Protectiomentioning

confidence: 99%

The neuroprotective mechanisms of ginkgolides and bilobalide in cerebral ischemic injury: a literature review

Feng

Sun

Chen

et al. 2019

Mol Med

101

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The incidence and mortality of strokes have increased over the past three decades in China. Ischemic strokes can cause a sequence of detrimental events in patients, including increased permeability and dysfunction of the blood-brain barrier, brain edema, metabolic disturbance, endoplasmic reticulum stress, autophagy, oxidative stress, inflammation, neuron death and apoptosis, and cognitive impairment. Thrombolysis using recombinant tissue plasminogen activator (rtPA) and mechanical embolectomy with a retrievable stent are two recognized strategies to achieve reperfusion after a stroke. Nevertheless, rtPA has a narrow therapeutic timeframe, and mechanical embolectomy has limited rates of good neurological outcomes. EGb761 is a standardized and extensively studied extract of Ginkgo biloba leaves. The ginkgolides and bilobalide that constitute a critical part of EGb761 have demonstrated protective properties towards cerebral injury. Ginkgolides include Ginkgolide A (GA), Ginkgolide B (GB), Ginkgolide C (GC), Ginkgolide J (GJ), Ginkgolide K (GK), Ginkgolide L (GL), and Ginkgolide M (GM). This review seeks to elucidate the neuroprotective effects and mechanisms of ginkgolides, especially GA and GB, and bilobalide in cerebral injury following ischemic strokes.

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Ginkgo Flavonol Glycosides or Ginkgolides Tend to Differentially Protect Myocardial or Cerebral Ischemia–Reperfusion Injury via Regulation of TWEAK-Fn14 Signaling in Heart and Brain

Cited by 48 publications

References 89 publications

Protective Effects of Ginkgo Biloba Dropping Pills Against Liver Ischemia/reperfusion Injury in Mice

Protective Effects of Ginkgo Biloba Dropping Pills Against Liver Ischemia/reperfusion Injury in Mice

Neuroprotection: Targeting Multiple Pathways by Naturally Occurring Phytochemicals

The neuroprotective mechanisms of ginkgolides and bilobalide in cerebral ischemic injury: a literature review

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