Long-Term Feeding of Ginkgo biloba Extract Impairs Peripheral Circulation and Hepatic Function in Aged Spontaneously Hypertensive Rats

Abstract

Dietary supplements are often taken for a healthy lifestyle, and their number and type have greatly increased. Ginkgo biloba extract (GBE), which is the leaf extract of Ginkgo biloba, is one of the most used herbal dietary supplements in the world. GBE products are marketed as a dietary supplement in Japan. In some European countries, GBE, designated as EGb 761, is clinically used for cerebral insufficiency, such as intermittent claudication, dementia and equilibrium disorders. [1][2][3][4] According to a recent prospective community-based cohort study 5) and a randomized, placebo-controlled, doubleblind clinical trial, 6) treatment with Ginkgo biloba extract increases the probability of survival in the elderly population and efficacy in patients aged 50 years or above with Alzheimer's disease or vascular dementia.We have previously demonstrated that GBE has an inhibitory effect on rising blood pressure and the improvement of vasodilation in young spontaneously hypertensive rats (SHR) 7) ; however, little is known about the cardiovascular therapeutic action of GBE in older SHR. Furthermore, we have demonstrated that long-term GBE intake induces marked hepatic hypertrophy and the induction of hepatic metabolic enzymes in young rats, leading to an increased risk of interaction with various medicines. 8,9) A recent report indicated that care should be taken with the combination of GBE and anti-diabetic drugs in terms of the potential interactions, especially in elderly patients.10) Thus, to investigate the safety and utility of GBE in cardiovascular and hepatic functions in the elderly, in the present study we examined the effects of long-term GBE feeding on the cardiovascular system and hepatic metabolic enzyme expression in 50-week-old male SHR. MATERIALS AND METHODS Animals and DietsMale spontaneously hypertensive rats (SHR/Izm; SHR) were purchased from Japan SLC (Hamamatsu, Japan). Experiments were performed in accordance with the Guiding Principles for Care and Use of Laboratory Animals approved by The Japanese Pharmacological Society. A standardized powder form of GBE was kindly supplied by Tama Biochemical Co., Ltd. (Tokyo, Japan). GBE contained 24.2% flavonoids (12.4% quercetin) and 9.4% terpenes, and its composition was similar to that of EGb 761 used in European countries. At 50 weeks of age, the rats were divided into two groups by determination of body weight, blood pressure and heart rate, and then administrated a commercial rodent diet (CE-2; Clea Japan Inc., Tokyo Japan) (control group, nϭ5) or a GBE-containing diet (0.5% GBE addition to CE-2) (GBE group, nϭ6) for 4 weeks, respectively. We have already demonstrated that 4-week treatment with GBE has beneficial effects on cardiovascular function in young SHR 7) ; therefore, in the present study, the same conditions of dose and period used in young rats were used to investigate the effects of GBE in aged SHR. In general, the dosage of GBE is not limited by age when used as a supplement.Once a week during the experiment, in unanaesthetized rats, blood p...

Evaluation of Food–drug Interaction of Guava Leaf Tea

“…For example, St. John's wort is the most well‐known herb that acts as an inducer of CYP3A. Ginkgo biloba, which has been used to alleviate symptoms associated with numerous cognitive disorders, is also known to induce CYP2B and CYP3A (Tada et al ., ). Induction of CYP2D in the rat liver by St. John's wort (Dostalek et al ., ) and in human hepatocytes by Valerian or Ginkgo biloba (Hellum et al ., ) has been reported.…”

Effect of Ginkgo biloba on Blood Pressure and Incidence of Hypertension in Elderly Men and Women

“…5–10 weeks old). However, one study found that 4 weeks of gingko biloba was unable to attenuate the rise in BP or PP in 50 week-old hypertensive rats 16. The authors suggested that in elderly hypertensives, long-term ginkgo biloba supplementation may not be useful in improving cardiovascular function.…”

Changes in hepatic protein expression in spontaneously hypertensive rats suggest early stages of non-alcoholic fatty liver disease

“…The liver is commonly used as an indicator of systemic oxidative stress and lipid metabolism in SHR in response to novel anti-hypertensive therapies [16][17][18][19][20], yet only a few studies have compared WKY and SHR livers in the absence of any treatment. These studies have shown that various lipogenic enzymes, such as fatty acid synthase [21] and the free fatty acid transporter CD/36 [22] are upregulated in the SHR liver and that SHRs have dyslipidemia and increased hepatic lipid accumulation compared to WKY rats [23].…”