Echinacoside Isolated from Cistanche tubulosa Putatively Stimulates Growth Hormone Secretion via Activation of the Ghrelin Receptor

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 4; p. 720
• Main Authors: Wu, Chieh-Ju, Chien, Mei-Yin, Lin, Nan-Hei, Lin, Yi-Chiao, Chen, Wen-Ying, Chen, Chao-Hsiang, Tzen, Jason T C
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.02.2019; MDPI
• Subjects: Activation; Aging; Animals; Binding; Carpal tunnel syndrome; Chemical energy; Chromatography, High Pressure Liquid; Chromatography, Liquid; Cistanche - chemistry; Cistanche - metabolism; cistanche tubulosa; Deserts; echinacoside; Geriatrics; Ghrelin; Glycosides - chemistry; Glycosides - isolation & purification; Glycosides - pharmacology; Growth Hormone - biosynthesis; growth hormone secretion; Growth hormones; Gynecomastia; Herbal medicine; Hormones; Insulin; Inverse agonists; Ligands; Male; Mass Spectrometry; Models, Molecular; Molecular Conformation; Molecular Structure; Older people; Organic chemistry; Overuse injuries; Pain; phenylethanoid glycosides; Physiology; Pituitary; Plant Extracts - chemistry; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Prostate cancer; Rats; Receptors, Ghrelin - agonists; Secretion; Substance P; China; phenylethanoid glycosides; ghrelin; cistanche tubulosa; echinacoside; growth hormone secretion
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24040720

species, the ginseng of the desert, has been recorded to possess many biological activities in traditional Chinese pharmacopoeia and has been used as an anti-aging medicine. Three phenylethanoid glycosides-echinacoside, tubuloside A, and acteoside-were detected in the water extract of (Schenk) R. Wight and the major constituent, echinacoside, was further purified. Echinacoside of a concentration higher than 10 M displayed significant activity to stimulate growth hormone secretion of rat pituitary cells. Similar to growth hormone-releasing hormone-6, a synthetic analog of ghrelin, the stimulation of growth hormone secretion by echinacoside was inhibited by [D-Arg¹, D-Phe⁵, D-Trp , Leu ]-substance P, an inverse agonist of the ghrelin receptor. Molecular modeling showed that all the three phenylethanoid glycosides adequately interacted with the binding pocket of the ghrelin receptor, and echinacoside displayed a slightly better interaction with the receptor than tubuloside A and acteoside. The results suggest that phenylethanoid glycosides, particularly echinacoside, are active constituents putatively responsible for the anti-aging effects of and may be considered to develop as non-peptidyl analogues of ghrelin.