The pharmacokinetics study of ginkgolide A, B and the effect of food on bioavailability after oral administration of ginkgolide extracts in beagle dogs

Aa, Lixiang; Fei, Fei; Tan, Zhaoyi; Aa, Jiye; Wang, Guangji; Liu, Changxiao

doi:10.1002/bmc.4212

Cited by 9 publications

(4 citation statements)

References 25 publications

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“…In this context, there are several aspects of this observation that need to be addressed. First, a study of the pharmacokinetics and bioavailability of GA and ginkgolide B using beagle dogs has revealed that the free form of these prototype ginkgolides and their absolute bioavailabilities are high . This suggests that administration of ginkgolides is able to promotes the in vivo exposure to and in vivo bioavailability of GA. Second, there is evidence to support the idea that GA might find it difficult to pass through the blood–brain barrier. , Thus, this becomes one possible reason why GA is not able to boost the memory behavior of J20 mice.…”

Section: Discussionmentioning

confidence: 99%

Ginkgolide A Prevents the Amyloid-β-Induced Depolarization of Cortical Neurons

Kuo

Song

Yao

et al. 2018

J. Agric. Food Chem.

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Utilizing the N-methyl-D-aspartate (NMDA) receptor antagonist as a strategy, memantine is the only agent available for clinically treating mild to severe Alzheimer's disease (AD). Our aim was to develop novel similar herb-based drugs. Using a screening platform, ginkgolide A (GA), a pure compound extracted from Ginkgo biloba, was found to attenuate amyloid β (Aβ)-induced abnormal depolarization in mouse primary cortical neurons. Using receptor agonists, it was determined that GA inhibits both NMDA receptors and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Furthermore, the Aβ-induced increase in c-Jun N-terminal kinase phosphorylation in neurons was prevented by GA. Body weight, glutamate oxaloacetate transaminase, glutamic−pyruvic transaminase, liver histology, and kidney histology were similar when the wildtype/AD animal model mice with and without GA treatment were compared. This pure compound improves the memory of wild-type mice. Our findings indicate that GA has great potential clinically for the treatment of AD because it might target NMDA receptors just like memantine.

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Section: Discussionmentioning

confidence: 99%

Ginkgolide A Prevents the Amyloid-β-Induced Depolarization of Cortical Neurons

Kuo

Song

Yao

et al. 2018

J. Agric. Food Chem.

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“…A study in Beagle dogs receiving, by oral administration, ginkgolide extracts (6.0 mg/kg) containing 28% (w/w) ginkgolide A and 63% (w/w) ginkgolide B showed that the bioavailability of the ginkgolides A and B increased significantly when the extracts were given together with food (Aa et al., 2018 ). The absorption rate for ginkgolide A and ginkgolide B increased from 34.8% and 5.2% in fasted dogs to 78.6% and 17.0% in dogs receiving the compounds together with a meal.…”

Section: Assessmentmentioning

confidence: 99%

Safety and efficacy of a feed additive consisting of a dry extract obtained from the leaves of Ginkgo biloba L. (ginkgo extract) for horses, dogs, cats, rabbits and guinea pigs (FEFANA asbl)

Bampidis,

Azimonti,

Bastos

et al. 2024

EFS2

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Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of a feed additive obtained from the dried leaves of Ginkgo biloba L. (ginkgo extract) when used as a sensory additive in feed for horses, dogs, cats, rabbits and guinea pigs. Ginkgo extract contains ≥ 24% total flavonoids, ≥ 6% total terpene lactones and ≤ 1 mg/kg ginkgolic acids. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that ginkgo extract is safe for the target species at the following concentrations in complete feed: 2.8 mg/kg for horses and cats, 1.1 mg/ kg for rabbits and guinea pigs, and 3.3 mg/kg for dogs. No safety concern would arise for the consumers from the use of ginkgo extract up to the highest level in feed which is considered safe for food-producing species (horses and rabbits). The additive should be considered as irritant to skin and eyes, and as a dermal and respiratory sensitiser. The use of the additive at the proposed level in feed for the target species is not considered to be a risk to the environment. While the available data indicate that Ginkgo preparations have a distinctive flavour profile, there is no evidence that the ginkgo extract would impart flavour to a food or feed matrix. Therefore, the FEEDAP Panel cannot conclude on the efficacy of the additive.

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“…Ginkgo biloba leaf contains many components, but most of the bioactivity is attributed to the terpene lactones and flavonols. Many constituents are largely unabsorbed in parent forms, such as the terpene lactones [ 128 , 129 , 130 ], flavonols, and glycosides, some of which must be broken down into readily absorbable compounds. This is where the gut microbiota may play a significant role, providing enzymes such as glycosidase and metabolism to break down the glycosides and release the absorbable forms and aglycones [ 131 , 132 , 133 ].…”

Section: Bioavailability Bioactivity Of Gle Components and Antibiotic...mentioning

confidence: 99%

Natural Product Co-Metabolism and the Microbiota–Gut–Brain Axis in Age-Related Diseases

Obrenovich

Singh²,

et al. 2022

Life

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Complementary alternative medicine approaches are growing treatments of diseases to standard medicine practice. Many of these concepts are being adopted into standard practice and orthomolecular medicine. Age-related diseases, in particular neurodegenerative disorders, are particularly difficult to treat and a cure is likely a distant expectation for many of them. Shifting attention from pharmaceuticals to phytoceuticals and “bugs as drugs” represents a paradigm shift and novel approaches to intervention and management of age-related diseases and downstream effects of aging. Although they have their own unique pathologies, a growing body of evidence suggests Alzheimer’s disease (AD) and vascular dementia (VaD) share common pathology and features. Moreover, normal metabolic processes contribute to detrimental aging and age-related diseases such as AD. Recognizing the role that the cerebral and cardiovascular pathways play in AD and age-related diseases represents a common denominator in their pathobiology. Understanding how prosaic foods and medications are co-metabolized with the gut microbiota (GMB) would advance personalized medicine and represents a paradigm shift in our view of human physiology and biochemistry. Extending that advance to include a new physiology for the advanced age-related diseases would provide new treatment targets for mild cognitive impairment, dementia, and neurodegeneration and may speed up medical advancements for these particularly devastating and debilitating diseases. Here, we explore selected foods and their derivatives and suggest new dementia treatment approaches for age-related diseases that focus on reexamining the role of the GMB.

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The pharmacokinetics study of ginkgolide A, B and the effect of food on bioavailability after oral administration of ginkgolide extracts in beagle dogs

Cited by 9 publications

References 25 publications

Ginkgolide A Prevents the Amyloid-β-Induced Depolarization of Cortical Neurons

Ginkgolide A Prevents the Amyloid-β-Induced Depolarization of Cortical Neurons

Safety and efficacy of a feed additive consisting of a dry extract obtained from the leaves of Ginkgo biloba L. (ginkgo extract) for horses, dogs, cats, rabbits and guinea pigs (FEFANA asbl)

Natural Product Co-Metabolism and the Microbiota–Gut–Brain Axis in Age-Related Diseases

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