Abstract

The objective of this randomized, open-label, single-dose, two-phase crossover study was to determine the effect of ascorbic acid on pharmacokinetics of ganoderic acid A, an important biologically active triterpenoid compound with anticancer activities, following oral administration of water extract of fruiting bodies of Ling Zhi in 12 healthy male subjects. Each subject was randomized to receive either one of the two regimens: (1) a single dose of 3,000 mg of the Ling Zhi preparation or (2) a single dose of 3,000 mg of the Ling Zhi preparation in combination with 2,500 mg of ascorbic acid. After a washout period of at least two weeks, subjects were switched to receive the alternate regimen. Blood samples were collected in each phase immediately before dosing and at specific time points for 8 hours after dosing. Plasma ganoderic acid A concentrations were quantified using liquid chromatography-mass spectrometry (LC-MS). The pharmacokinetic parameters analyzed were maximal plasma concentration (C max), time to reach peak concentration (T max), area under the plasma concentration-time curve (AUC), and half-life (t 1/2). An oral coadministration of ascorbic acid with Ling Zhi preparation did not significantly alter the pharmacokinetic parameters of ganoderic acid A in healthy male subjects.

Highlights

  • Ganoderma lucidum (Leyss. ex Fr.) Karst., called Ling Zhi in China and Reishi in Japan, is an oriental mushroom that has been used for thousands of years in East Asia to improve health and longevity [1]

  • The inhibition of cancer cell proliferation of ganoderic acid A is believed to be mediated via the downregulation of Cdk4 expression, while its antimetastatic effects appear to be mediated through the inhibition of AP-1/ NF-κB-dependent secretion of urokinase plasminogen activator [8]

  • The mean values (±standard deviation) of age, weight, height, and body mass index (BMI) of the 12 subjects enrolled in this study were 24.33 ± 2.35 years, 64.88 ± 6.47 kg, 1.69 ± 0.06 m, and 22.79 ± 1.43 kg/m2, respectively

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Summary

Introduction

Ganoderma lucidum (Leyss. ex Fr.) Karst., called Ling Zhi in China and Reishi in Japan, is an oriental mushroom that has been used for thousands of years in East Asia to improve health and longevity [1]. One recent study has found that oral administration of Ling Zhi preparation for 12 weeks seems more capable of stabilizing tumor size compared with a placebo in patients with recurrent gynecologic cancers [6]. Many bioactive components such as polysaccharides and triterpenoids are thought to be associated with the anticancer activities of Ling Zhi [7]. The inhibition of cancer cell proliferation of ganoderic acid A is believed to be mediated via the downregulation of Cdk expression, while its antimetastatic effects appear to be mediated through the inhibition of AP-1/ NF-κB-dependent secretion of urokinase plasminogen activator (uPA) [8]. Its inhibitory effect on farnesyl protein transferase (FPT), an enzyme that catalyzes

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