Pharmacological evaluation of Alstonia scholaris: anti-inflammatory and analgesic effects.
BACKGROUND
Alstonia scholaris (Apocynaceae) has been historically used in "dai" ethnopharmacy to treat chronic respiratory diseases. The leaf extract, developed as a commercially available traditional Chinese medicine, used to release tracheitis and cold symptom, has also been prescribed in hospitals and sold over the counter in drug stores.


OBJECTIVE
The investigation evaluated the anti-inflammatory and analgesic activities of the ethanolic extract, fractions and main alkaloids of Alstonia scholaris leaf to provide experimental evidence for its traditional and modern clinical use. Besides, to discover the active fraction and components for further better use in Chinese medicine is hopeful.


METHODS
The leaf of Alstonia scholaris was extracted with ethanol and then separated into different fractions. Furthermore, alkaloids were isolated by phytochemical method. The analgesic activities were investigated using acetic acid-induced writhing, hot-plate and formalin tests in mice. The anti-inflammatory activities were carried out in vivo and in vitro, including xylene-induced ear edema and carrageenan-induced air pouch formation in mice, and COX-1, -2 and 5-LOX inhibition.


RESULTS
It has been exhibited that the EtOAc and alkaloid fractions reduced acetic acid-induced writhing response in mice, significantly. The ethanolic extract, EtOAc and alkaloid fractions remarkably inhibited xylene-induced ear edema. Further investigation was focused on the alkaloids fraction and three main alkaloids isolated from the alkaloids fraction, in different animal models. Alkaloids reduced acetic acid-induced writhing response, and xylene-induced ear edema in mice. In the hot-plate test, alkaloids did not increase the latency period of mice obviously. In the formalin test, alkaloids did not inhibit the licking time in first phase, but significantly inhibited the licking time in second phase of mice. Alkaloids increased significantly SOD activity and decreased levels of NO, PGE2 and MDA significantly, in air pouch mice model. Moreover, some alkaloids isolated from the leaf of Alstonia scholaris exhibited inhibition of COX-1, COX-2 and 5-LOX in vitro anti-inflammatory assay, which supported alkaloids as the bioactive fraction.


CONCLUSIONS
The alkaloids fraction of Alstonia scholaris leaf, three main alkaloids, picrinine, vallesamine and scholaricine, may produce the anti-inflammatory and analgesic effect peripherally based on several in vivo assays. In in vitro tests, alkaloids exhibited inhibition of inflammatory mediators (COX-1, COX-2 and 5-LOX), which is accordant with results on animal models. Besides, COX-2/5-LOX dual inhibitors found in the experiment, such as 16-formyl-5alpha-methoxystrictamine, picralinal, and tubotaiwine might be valuable for further attention.
Shang
Jian-Hua
JH
Yunnan Institute of Medical Material, Kunming, PR China.
Cai
Xiang-Hai
XH
Feng
Tao
T
Zhao
Yun-Li
YL
Wang
Jing-Kun
JK
Zhang
Lu-Yong
LY
Yan
Ming
M
Luo
Xiao-Dong
XD
D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D031051:Alstonia / Q000737:chemistry*; D000700:Analgesics / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D004487:Edema / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006358:Hot Temperature; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D008517:Phytotherapy; D018515:Plant Leaves; D013482:Superoxide Dismutase / Q000378:metabolism
D000470:Alkaloids; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D018836:Inflammation Mediators; D013482:Superoxide Dismutase