Pharmacological Management of Alzheimer’s Disease
Sahab Uddin, Rashid Mamunur in Advances in Neuropharmacology, 2020
Ginkgo biloba belongs to family Ginkgoaceae, a member of the gymnosperms. The rest plants of the Ginkgoaceae family are now extinct and found as fossils. Ginkgo biloba is a small tree that originated in China but now planted worldwide as an ornamental plant. It is also cultivated in Korea, France, and the United States. The major chemical constituents present in Ginkgo biloba as the mixture of flavonoids and terpenoids. The dried leaves of Ginkgo biloba contain ginkgolides (A, B, C, J, and M), bilobalide and 0.1–0.25% terpene, and lactones. 30–40% of the mixture is bilobalide whereas ginkgolide A is present in maximum amount and accounts about 30% of the mixture. The nature of ginkgolides is diterpenoid while bilobalide is sesquiterpenoid (Paul, 2002).
Dementia and Cognitive Impairment
Ethan Russo in Handbook of Psychotropic Herbs, 2015
An important finding reported in 1992 (Kleijnen and Knipschild, 1992a) pertained to pharmacokinetics of Ginkgo biloba components. The authors reported that, after oral use of EGb 761 80 mg, ginkgo flavone glycosides had a bioavailability of greater than 60 percent and elimination half-life of 2 to 4 h. Similarly, ginkgolides A and? were greater than 98 percent bioavailable, with elimination half-life of 4 to 6 h. Finally, bilobalide was 70 percent bioavailable, with a 3 h half-life. Altogether, these findings support the advisability of frequent dosing with ginkgo preparations but may not truly reflect their cognitive or other cerebral effects.
Phytotherapeutic Agents in Epilepsy
Vikas Kumar, Addepalli Veeranjaneyulu in Herbs for Diabetes and Neurological Disease Management, 2018
Bilobalide is a sesquiterpene trilactone isolated from the leaves of Ginkgo biloba L. (Fam. Ginkgoaceae) which shows significant reduction in convulsions induced by 4-O-methylpyridoxine (MPN) or INH in mice. The study indicates that the anticonvulsant effect of bilobalide against MPN-induced convulsions partly involves modulation of hepatic drug-metabolizing enzyme activity leading to accelerated elimination of MPN.73 Further, bilobalide can elevate GABA levels, possibly through potentiation of GABA synthesis.
Ginkgo biloba leaves extract’s cosmeceutical evaluation: a preliminary assessments on human volunteers towards achieving improved skin condition and rejuvenation
Published in Drug Development and Industrial Pharmacy, 2023
Ahmed A. H. Abdellatif, Hamdoon A. Mohammed, Ali M. Al-Khalaf, Omar Khan, Mahmoud A. H. Mostafa, Rwaida A. Al Haidari, Hesham H. Taha, Riaz A. Khan
Chemically, the EGb 761® contains nearly 24% flavone glycosides, which are primarily composed of quercetin, kaempferol, luteolin, myricetin, and isorhamnetin, together with 6% terpene lactones, of which 2.8–3.4% (w/w) is ginkgolides A, B, C, and J, and 2.6–3.2% (w/w) is bilobalide. The ginkgolide B and bilobalide account for about 0.8% and 3% of the total leaf extract, respectively. In contrast, other extract constituents are proanthocyanidin, polysaccharide, biflavonoids, glucose, rhamnose, organic acids, D-glucaric and ginkgolic acids, etc. Some of the major, chemically, and pharmacologically important Ginkgo constituents’ structures are presented (Figure 1). For all the major compounds’ structures, refer to the Supplementary file S1 ((A) Flavonoid glycoside, (B) Ginkgolide, (C) Flavonoid aglycone.
The effect of intravenous ginkgolide on clinical improvement of patients with acute ischemic stroke
Published in Neurological Research, 2020
Yi Dong, Huiqin Li, Qiang Dong
Ginkgolide (Baiyu®) is consisted with two major components, includes ginkgoid and bilobalide. Early in-vitro studies found that ginkgolide injection could inhibit platelet aggregation and that the antagonism of platelet-activating factor (PAF)-induced platelet aggregation was superior to that of aspirin and clopidogrel [35,36]. Clinically, ginkgolide has been reported the potential efficacy in the treatment of atherosclerotic cerebral infarction, recanalization of occluded basilar arteries and treatment of acute ischemic stroke when given in combination with alteplase (within the thrombolysis time window) [37,38]. Bilobalide has been reported as neuroprotection, maintains the integrity of vascular endothelial cells, promotes angiogenesis and inhibits microglia [39], and numerous studies have demonstrated that bilobalide can attenuate infarct volume, cerebral edema, neuronal damage and neurologic deficits [40,41]. Clinically, a combination of bilobalide with mecobalamin might be associated with a better outcome in the treatment of diabetic peripheral neuropathy than mecobalamin alone [42].
Structure–activity relationship of a peptide permeation enhancer
Published in Tissue Barriers, 2023
L-R5 is more successful in increasing the permeability of FD-4 compared to the PEs bilobalide and latrunculin A (Figure 2A). The mechanisms of action of these two molecules are similar, as they both influence the cytoskeleton of the cell. By interacting with the adenosine A1 receptor, bilobalide causes contraction of the actin filament, which transiently opens intercellular junctions.41 Latrunculin A enters the cell and disrupts the cytoskeletal filaments, distorting the cell and allowing larger molecules to pass through cellular junctions.42 L-R5 has been designed to inhibit the activity of PKC ζ in phosphorylating TJs proteins. Opening of TJs may be also due to influence of L-R5 cytoskeleton, as the enzyme was shown to be involved in cytoskeletal organization.31,45 The opening induced by L-R5 appears to lead to a higher permeability with a faster onset, however, it should be noted that the applied concentrations of the other two molecules necessary to open TJs are much lower. An equivalent concentration of the peptide may give the same or even better results. The problem is that since latrunculin A is derived from a sponge toxin,46 an increase in concentration may lead to safety issues. By contrast, bilobalide showed no cytotoxicity at a concentration of 625 µM and may be more effective at higher concentrations if no increase in toxicity is observed.41 The fast increase in the first 15 minutes of each condition may be due to a hormetic effect,47 even if this difference is not significant. More specifically, the modification of the ambient environment will inevitably force the cell to adapt. A greater disruption of the cell membrane by FAs is also a potential reason for this increase, which would lead to a short increase in paracellular permeability. Another explanation of this short greater permeation enhancement the formation of micelles between FD-4 and FAs.
Related Knowledge Centers
- Ginkgo Biloba
- Mevalonate Pathway
- Sesquiterpene
- Terpenoid
- Lactone
- Farnesyl Pyrophosphate
- Geranylgeranyl Pyrophosphate
- Isopentenyl Pyrophosphate
- NON-Mevalonate Pathway
- Abietadiene Synthase