PMID- 28314480 OWN - NLM STAT- MEDLINE DCOM- 20170522 LR - 20181202 IS - 1618-095X (Electronic) IS - 0944-7113 (Linking) VI - 27 DP - 2017 Apr 15 TI - Airways antiallergic effect and pharmacokinetics of alkaloids from Alstonia scholaris. PG - 63-72 LID - S0944-7113(17)30034-X [pii] LID - 10.1016/j.phymed.2017.02.002 [doi] AB - BACKGROUND: Alstonia scholaris (L.) R. Br. (Apocynaceae), an important herbal medicine, has been widely used to treat respiratory tract diseases, such as cough, asthma, phlegm, and chronic obstructive pulmonary disease. PURPOSE: To evaluate pharmacological effect of alkaloids from A. scholaris on ovalbumin induced airways allergic inflammatory model, and explore whether the dosing frequency is related to pharmacokinetics. STUDY DESIGN: After oral administration of total alkaloids, the pharmacokinetic study of it was investigated. In addition, anti-allergic studies were carried out on ovalbumin-sensitized airways allergic inflammatory model of mice. METHODS: The pharmacokinetics of total alkaloids (TA) was investigated in SD rat plasma by a fully-validated LC-MS/MS method. Then, an ovalbumin (OVA)-sensitized airways allergic inflammatory model was established, in which mice were intra-gastrically administrated by 3 times a day (8.3 and 16.7mg/kg) based on the pharmacokinetic behavior of TA) and single (25, 50mg/kg) treatment regimen. Dexamethasone was used as a positive control for corticosteroid drugs. Cellular infiltration was assessed in the broncho-alveolar lavage fluid (BALF). Expressions of interleukin-4 (IL-4) and interleukin-10 (IL-10) in the BALF were determined, levels of immunoglobulin E (IgE) and eotaxin in serum were measured, and superoxide dismutase (SOD) activities as well as malondialdehyde (MDA) content in the serum and BALF were examined. Finally, histopathological examination in the lung was assessed by H. E. staining. RESULTS: The time course of plasma concentration of 4 bioactive indole alkaloids fitted an open two-compartment model after oral administration of total alkaloids at doses of 10, 25, and 50mg/kg. The area under the curve and the maximum concentration values of four major alkaloids increased dose-dependently, and half-life suggested a short-lasting pharmacological effect. Then, an ovalbumin-provoked airways allergic inflammatory model indicated that the pharmacological effect of administration of total alkaloids 3 times a day was a little better than that of single dose daily. The percentage of eosinophils in BALF was reduced obviously and the pathological damage of lung was also attenuated. There was also a significant reduction in IL-4 and promotion in IL-10 in the BALF. Serum IgE and eotaxin expression also significantly decreased in treated animals. Furthermore, the activity of SOD elevated remarkably and lipid peroxidation product (MDA) decreased in the administrated mice. CONCLUSION: The pharmacological effects administrated for 3 times a day had precedence over single dose daily, which was related to the prolonged retention time and the maintained plasma concentration. Moreover, scholaricine and vallesamine might be responsible for the treatment of allergic asthma, mainly in total alkaloids. CI - Copyright (c) 2017 Elsevier GmbH. All rights reserved. FAU - Zhao, Yun-Li AU - Zhao YL AD - State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. FAU - Cao, Jing AU - Cao J AD - State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China. FAU - Shang, Jian-Hua AU - Shang JH AD - State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. FAU - Liu, Ya-Ping AU - Liu YP AD - State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. FAU - Khan, Afsar AU - Khan A AD - State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China; Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad, 22060, Pakistan. FAU - Wang, Heng-Shan AU - Wang HS AD - Guangxi Normal University, Guangxi Province, Guilin, 541004, China. FAU - Qian, Yi AU - Qian Y AD - State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China. FAU - Liu, Lu AU - Liu L AD - State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. FAU - Ye, Min AU - Ye M AD - State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China. Electronic address: yemin@bjmu.edu.cn. FAU - Luo, Xiao-Dong AU - Luo XD AD - State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. Electronic address: xdluo@mail.kib.ac.cn. LA - eng PT - Journal Article DEP - 20170217 PL - Germany TA - Phytomedicine JT - Phytomedicine : international journal of phytotherapy and phytopharmacology JID - 9438794 RN - 0 (Alkaloids) RN - 0 (Anti-Allergic Agents) RN - 0 (Drugs, Chinese Herbal) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Alkaloids/*pharmacokinetics MH - Alstonia/*chemistry MH - Animals MH - Anti-Allergic Agents/*pharmacology MH - Drugs, Chinese Herbal/pharmacokinetics MH - Eosinophils/*drug effects MH - Hypersensitivity/*drug therapy/*etiology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Ovalbumin/*adverse effects MH - Phytotherapy MH - Rats MH - Rats, Sprague-Dawley OTO - NOTNLM OT - 19-Epischolaricine OT - Asthma OT - Pharmacokinetic OT - Picrinine OT - Scholaricine OT - Vallesamine EDAT- 2017/03/21 06:00 MHDA- 2017/05/23 06:00 CRDT- 2017/03/19 06:00 PHST- 2016/09/29 00:00 [received] PHST- 2017/01/24 00:00 [revised] PHST- 2017/02/12 00:00 [accepted] PHST- 2017/03/19 06:00 [entrez] PHST- 2017/03/21 06:00 [pubmed] PHST- 2017/05/23 06:00 [medline] AID - S0944-7113(17)30034-X [pii] AID - 10.1016/j.phymed.2017.02.002 [doi] PST - ppublish SO - Phytomedicine. 2017 Apr 15;27:63-72. doi: 10.1016/j.phymed.2017.02.002. Epub 2017 Feb 17.