Clinical Study Effect of Oral Coadministration of Ascorbic Acid with Ling Zhi Preparation on Pharmacokinetics of Ganoderic Acid A in Healthy Male Subjects: A Randomized Crossover Study Patcharanee Tawasri, 1 Chadarat Ampasavate, 2 Somsak Tharatha, 3 Natthakarn Chiranthanut, 1 and Supanimit Teekachunhatean 1,4 1 Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Tailand 2 Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Tailand 3 Central Laboratory (Tailand) Co., Ltd,. Ministry of Agriculture and Cooperatives, Mae Rim, Chiang Mai 50180, Tailand 4 Center of Tai Traditional and Complementary Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Tailand Correspondence should be addressed to Supanimit Teekachunhatean; supanimit.t@cmu.ac.th Received 10 May 2016; Revised 26 July 2016; Accepted 25 August 2016 Academic Editor: Stephen H. Safe Copyright © 2016 Patcharanee Tawasri et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Te objective of this randomized, open-label, single-dose, two-phase crossover study was to determine the efect 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. Afer 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 specifc time points for 8 hours afer dosing. Plasma ganoderic acid A concentrations were quantifed using liquid chromatography-mass spectrometry (LC-MS). Te pharmacokinetic parameters analyzed were maximal plasma concentration ( max ), time to reach peak concentration ( max ), area under the plasma concentration-time curve (), and half-life ( 1/2 ). An oral coadministration of ascorbic acid with Ling Zhi preparation did not signifcantly alter the pharmacokinetic parameters of ganoderic acid A in healthy male subjects. 1. Introduction Ganoderma lucidum (Leyss. ex Fr.) Karst., also 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]. Ling Zhi has also been used to pre- vent and treat various human diseases including bronchitis, allergies, hepatitis, hypertension, and immunological disor- ders as well as cancer [1–4]. Oral administration of Ling Zhi extract for 12 weeks has been demonstrated to signifcantly enhance the immune response in patients with advanced- stage cancers [5]. Additionally, 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 tri- terpenoids are thought to be associated with the anticancer activities of Ling Zhi [7]. Ganoderic acid A, a highly oxy- genated C30 lanostane-type triterpenoid, exhibits signifcant anticancer activities through inhibition of cancer cell prolifer- ation and metastasis [7, 8]. Te inhibition of cancer cell proli- feration of ganoderic acid A is believed to be mediated via the downregulation of Cdk4 expression, while its antimetastatic efects appear to be mediated through the inhibition of AP-1/ NF-B-dependent secretion of urokinase plasminogen acti- vator (uPA) [8]. Ganoderic acid A has also been shown to suppress the JAK/STAT3 signaling pathway leading to an enhancement of chemosensitivity to cisplatin in human hep- atocellular carcinoma HepG2 cells [9]. Its inhibitory efect on farnesyl protein transferase (FPT), an enzyme that catalyzes Hindawi Publishing Corporation BioMed Research International Volume 2016, Article ID 2819862, 7 pages http://dx.doi.org/10.1155/2016/2819862