Melatonin Receptors Agonistic Activities of Phenols from Gastrodia elata

Abstract

Gastrodia elata is a famous traditional Chinese herb with medicinal and edible application. In this study, three new polybenzyls, gastropolybenzylols G-I ( 1–3 ) were isolated from the EtOAc extract of G. elata. Their structures were identified by extensive spectroscopic analyses involving HRESIMS, UV, IR, 1D and 2D NMR. Compound 1 showed agonistic effects on MT 1 and MT 2 receptors with agonistic rates of 55.91±4.84% and 165.13±5.65% at the concentration of 0.5 mM, respectively, and an EC 50 value of 76.24 μ M on MT 2 receptor. Graphic Abstract Electronic supplementary material The online version of this article (10.1007/s13659-019-0213-2) contains supplementary material, which is available to authorized users.

Insight into Medicinal Chemistry Behind Traditional Chinese Medicines: p-Hydroxybenzyl Alcohol-Derived Dimers and Trimers from Gastrodia elata

“…The previous study on the isolated guinea-pig ileum smooth muscle showed that 17 and the alcohol form of 11 had inhibitory effects on neurotransmitter release induced by stimulation of nicotine, serotonin, and vanilloid receptors, while 18 and 21 affected acetylcholine-induced contraction more directly [ 90 ]. Compounds 13 , 14 , 17 , 18 , and 21 were activators of melatonin receptors [ 7 ]. In addition, 15 , 17 , and the methyl ether analogue of 11 exhibited significant inhibitory effects on collagen, epinephrine, arachidonic acid, U46619 induced platelet aggregation [ 93 ], 17 had vasodilatory effect [ 94 ], and 18 was found to be a heat shock factor 1 (HSF1) inhibitor [ 95 ].…”

“…To satisfy medicinal utilization and to protect the wildly endangered species and ecological environment, starting in the late 1950′s, tremendous efforts were made and succeeded in agricultural cultivation of this plant by Chinese scientists [3,4]. Meanwhile, considerable chemical and pharmacological studies of the raw material and the processed "tian ma" led to isolation and identification of around 100 constituents with diverse chemical structures and biological activities from extracts of this herbal medicine [2,[5][6][7][8]. Most the constituents feature characteristic structures deriving from or modified by p-hydroxybenzyl alcohol [2,[5][6][7][8].…”

“…Meanwhile, considerable chemical and pharmacological studies of the raw material and the processed "tian ma" led to isolation and identification of around 100 constituents with diverse chemical structures and biological activities from extracts of this herbal medicine [2,[5][6][7][8]. Most the constituents feature characteristic structures deriving from or modified by p-hydroxybenzyl alcohol [2,[5][6][7][8]. Notably, vanillyl alcohol and vanillin exhibited antiepileptic and anticonvulsant activities similar to that of the water extract of G. elata rhizomes, which promoted the clinic application of vanillin as an antiepileptic drug in China [9][10][11][12][13] 3 .…”

“…The occurrence of antiepileptic vanillin in "tian ma" was questioned until 2006 [48,49]. Meanwhile, new constituents from "tian ma" and their bioactivities were frequently discovered [2,[5][6][7][8].…”

“…Thus, there are important secrets of medicinal chemistry hiding behind processing and/or decocting protocols in TCM though these are yet to be confirmed in many cases including "tian ma" [50][51][52][53][54][55][56][57][58]. Because the previous phytochemical studies of "tian ma" were performed mostly by extracting the drug material with ethanol or methanol [2,[5][6][7][8], the extracting protocol completely differed from that of conventional application by decocting with water. Therefore, an aqueous extract of "tian ma" (the steamed and dried G. elata rhizomes [50][51][52][53][54][55][56][57][58]) was investigated as part of our project to investigate chemical diversity and biological activities of several commonly used TCM [59][60][61][62][63][64][65][66][67][68][69][70].…”