G. biloba

An interaction between G. biloba administered as 80 mg leaf extract twice a day and low-dose trazodone (20 mg twice daily) was suspected in a patient with Alzheimer s disease, who took the two products together. It is postulated that a pharmacodynamic (increased gamma-aminobutyric acid-ergic activity) and pharmacokinetic mechanisms [increased metabolism of trazodone to w-chlorophenylpiperazine (w -CPP), which acts on the benzodiazepine-binding sites and releases gamma-aminobutyric acid] contribute to the observed effect (32). Table 2 provides a list of reported pharmacodynamic and pharmacokinetic interactions involving ginkgo. 

G. biloba L. is a member of the Ginkgoaceae family, a gymnosperm that has survived unchanged from the Triassic period. In traditional Chinese medicine, the seeds (nuts) of G. biloba were used as an antitussive, expectorant, and antiasthmatic, and in bladder infection (20). In China, the leaves of G. biloba were also used for the treatment of asthma and cardiovascular disorders (21). Today, standardized concentrated extracts prepared from the leaves of G. biloba are used for the treatment of peripheral circulatory insufficiency, cerebrovascular disorders, geriatric complaints, and for Alzheimer dementia. For a more extensive treatment, readers are referred to the many authoritative reviews available, e.g.. Refs. (22-27). 

Increasing doses of a commercial special extract of G. biloba (LI 1370) were administered to two healthy volunteers (50, 100, and 300 mg) (38). The amounts of kaempferol and quercetin were significantly higher compared to... 

Traditional Chinese physicians used ginkgo leaves to treat asthma and chilblains. Today, G. biloba is used to improve both blood flow to the brain and peripheral circulation (see Chapter 36). 

Recently, a key player in the ginkgolide biosynthesis has been isolated and characterized A cDNA that encodes G. biloba levopimaradiene synthase, a diterpene synthase involved in ginkgolide biosynthesis, was isolated and characterized. Similarly, a new geranylgeranyl diphosphate synthase gene from G. biloba, was characterized. ... 

In 2003, Krane et al. used a functional assay, microphysiometry, to evaluate the effects of ginkgolides on the human PAF receptor. GB and lO-O-benzyl-GB showed 81% and 93% (100-pM concentration) inhibition, respectively, of the PAF receptor response, the latter being equivalent to the effect of WEB2086. G. biloba extract mixtures were also tested, which indicated potential synergistic effects among the components in the extract. 

Extracts from the leaves of G. biloba are marketed in some countries for the treatment of cerebral dysfunction and of intermittent claudication. In a review it was concluded that seven out of eight controlled trials of good quality showed positive effects of G. biloba compared with placebo on the following symptoms memory difficulties, dizziness, tinnitus, headache, and emotional instability with anxiety (3). For intermittent claudication, the evidence for efficacy was judged unconvincing. 

No serious adverse effects have been noted in any trial. However, G. biloba has been associated with gastrointestinal complaints, headache, and allergic skin reactions (SED-13, 538). Bleeding has been associated with chronic G. biloba ingestion because of its adverse effects on platelet aggregabihty, since the ginkgolide constituents of G. biloba inhibit platelet-activating factor. 

A 78-year-old man and an 84-year-old woman with previously well-controlled epilepsy presented with recurrent seizures (4). There were no obvious reasons for these events, and the investigator suspected self-medication with G. biloba extracts. Both patients had started taking G. biloba within 2 weeks of the start of the seizures. The herbal remedy was withdrawn and both patients remained seizure-free several months later. No other change of medication was made. 

The author postulated that 4-0-methylpyridoxine, a constituent of G. biloba and a known neurotoxin, had caused the seizures. 

A 78-year-old man developed progressive right-sided muscular weakness after a fall (6). A CT scan showed a subdural hematoma. He had taken 150 mg of G. biloba extract. 

A 56-year-old man had a stroke without apparent risk factors (7). A CT scan confirmed a right parietal hematoma. He had not taken any medications, except for a G. biloba extract (3 x 40 mg/day) which he had started 18 months before. 

Hyphema led to temporarily impaired vision in a man who had taken G. biloba for 2 weeks no other cause was found the lesion regressed after withdrawal and did not recur (9). 

A spontaneous cerebellar bleed occurred in a man who had taken G. biloba (10). 

In each case the authors believed that self-medication with G. biloba had caused the bleeding through its effect on platelets. In some cases another factor that implicated the extract was the absence of recurrence after withdrawal, although this is a weak argument. 

Spontaneous bilateral subdural hematomas and increased bleeding time have been associated with chronic ingestion of G. biloba (120 mg/day for 2 years) (11). 

A 40-year-old Afro-American woman developed an exfoliative rash and blistering and swelling of the tongue (12). A diagnosis of Stevens-Johnson syndrome was made. She had not taken any medications other than two doses of a formulation that contained G. biloba. Her condition responded to treatment with prednisolone, clotrimazole, and famotidine. G. biloba was withdrawn and no further events occurred. However, 5 months later she still had tenderness in the soles of the feet, peeling of the nails, and discoloration of the skin. 

Subarachnoid hemorrhage associated with G. biloba (13) stimulated a vigorous discussion on the differences between the usual extract sold over the counter and a ginkgolide mixture, and their respective (absence of) effects on platelet-aggregating factor and bleeding time (14,15). The dispute points to confusion that can arise when formulations of similar origin but with variable composition are available. 

Acute poisoning with G. biloba seeds is occasionally seen in East Asian countries. 

A 36-year-old woman, without any past or family history of epilepsy, developed frequent vomiting and generalized convulsions about 4 hours after taking about 70-80 ginkgo nuts, seeds of G. biloba, in an attempt to improve her health (16). 

Because of its antiplatelet activity G. biloba can interact with anticoagulants. 

A 78-year-old woman who had taken warfarin for 5 years, took G. biloba for 2 months, when she developed signs of a stroke, diagnosed as intracerebral hemorrhage (13). 

Ginkgolide A, B, C, and bilobalide in G. biloba leaves were determined simultaneously by RP-HPLC-ELSD. Methanolic extracts (10%) of the leaves were cleaned up by solid phase extraction via polyamide cartridge and silica gel cartridge, successively. RP-HPLC was carried out on a Cl 8 column with Me0H-H20 as mobile phase, eluted in gradient mode, and detected by ELSD. The poor linear response of ELSD could be compensated by multilevel calibration and logarithmic calculation. Meth-anol-water-orthophosphoric acid mobile phase was used in conjunction with refractive index (RI) detection. 

Terpenes in G. biloba L. extracts were analyzed on a column packed with Cg Nucleosil 300, and PrOH-THF-H2O was used as the mobile phase with detection at 220 nm. 

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