Oral Administration of the Japanese Traditional Medicine Keishibukuryogan-ka-yokuinin Decreases Reactive Oxygen Metabolites in Rat Plasma: Identification of Chemical Constituents Contributing to Antioxidant Activity

Abstract

Insufficient detoxification and/or overproduction of reactive oxygen species (ROS) induce cellular and tissue damage, and generated reactive oxygen metabolites become exacerbating factors of dermatitis. Keishibukuryogan-ka-yokuinin (KBGY) is a traditional Japanese medicine prescribed to treat dermatitis such as acne vulgaris. Our aim was to verify the antioxidant properties of KBGY, and identify its active constituents by blood pharmacokinetic techniques. Chemical constituents were quantified in extracts of KBGY, crude components, and the plasma of rats treated with a single oral administration of KBGY. Twenty-three KBGY compounds were detected in plasma, including gallic acid, prunasin, paeoniflorin, and azelaic acid, which have been reported to be effective for inflammation. KBGY decreased level of the diacron-reactive oxygen metabolites (d-ROMs) in plasma. ROS-scavenging and lipid hydroperoxide (LPO) generation assays revealed that gallic acid, 3-O-methylgallic acid, (+)-catechin, and lariciresinol possess strong antioxidant activities. Gallic acid was active at a similar concentration to the maximum plasma concentration, therefore, our findings indicate that gallic acid is an important active constituent contributing to the antioxidant effects of KBGY. KBGY and its active constituents may improve redox imbalances induced by oxidative stress as an optional treatment for skin diseases.

Inhibition of Human Kallikrein 5 Protease by Triterpenoids from Natural Sources

“…We conducted a plasma pharmacokinetic study of triterpenoids wherein JHT was orally administrated to rats at 2 g/kg. As a result of time course measurement up to 24 h after a single oral administration of JHT, ursolic acid (and/or oleanolic acid), tumulosic acid, and pachymic acid were detected in the plasma as shown in Figure 5 ; pharmacokinetics of those triterpenoids were previously reported by us and others [ 31 , 32 , 33 ].…”

“…The higher absorbance of tumulosic acid than of other triterpenoids is a notable finding; the C max of tumulosic acid was 116.1 ng/mL (0.238 μM). High concentration of tumulosic acid in blood was reported after the oral administration of crude drugs containing Poria sclerotium [ 33 , 34 , 35 ]. Further pharmacokinetic studies of bioactive triterpenoids are required to examine plasma absorption and distribution in skin tissue; the results will help us understand their potential use as internal agents.…”

Depigmentory Effects of Keishibukuryogankayokuinin in Human Epidermal Melanocytes

“…mayuen Stapf [24]. Although its active ingredient and pharmacological effect remain unclear, it has been used to treat warts and skin-related issues [25] [26]. Melanocytes respond to various factors such as the surrounding environment (e.g., UV), or neighboring cells in the skin [27] [28].…”

In Vivo Pharmacokinetic Analysis Utilizing Non-Targeted and Targeted Mass Spectrometry and In Vitro Assay against Transient Receptor Potential Channels of Maobushisaishinto and Its Constituent Asiasari Radix

“…One animal (n = 1) at a time was sacrificed 1 h post-drug administration under anesthesia with isoflurane by collecting whole blood from the abdominal inferior vena cava using an EDTA-2K treated syringe. According to previous pharmacokinetic studies of herbal medicines [ 33 , 58 ], many of the components were quickly absorbed into the bloodstream, thereby providing the rationale for a sampling time at 1 h. Blood was centrifuged at 1200× g at 4 °C for 30 min to obtain plasma; then, the sample was stored at −80 °C until LC-HRMS analysis.…”