Neuritogenic steroid glycosides from crown-of-thorns starfish: Possible involvement of p38 mitogen-activated protein kinase and attenuation of cognitive impairment in senescence-accelerated mice (SAMP8) by peripheral administration

• Published in: Bioorganic & medicinal chemistry Vol. 78; p. 117144
• Main Authors: Sasayama, Yumi, Mamiya, Takayoshi, Qi, Jianhua, Shibata, Takahiro, Uchida, Koji, Nabeshima, Toshitaka, Ojika, Makoto
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.01.2023; Elsevier
• Subjects: Acanthaster planci; Acanthasteroside; Animals; Biochemistry & Molecular Biology; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Cognitive Dysfunction - metabolism; Life Sciences & Biomedicine; MAP kinase; Mice; Mitogen-Activated Protein Kinase 14 - metabolism; Nerve Growth Factor - metabolism; Nerve Growth Factor - pharmacology; Neurite outgrowth; Neurites - metabolism; p38 Mitogen-Activated Protein Kinases - metabolism; PC12 Cells; Pharmacology & Pharmacy; Physical Sciences; Rats; Science & Technology; Senescence-accelerated mouse; Starfish - metabolism; Steroid glycoside; Steroids; Acanthasteroside; Senescence-accelerated mouse; MAP kinase; Acanthaster planci; Neurite outgrowth; Steroid glycoside; CELLS; KEY REGULATOR; SAPOGENOL; OLIGOGLYCOSIDES; SAPONINS; ASTEROIDEA; DIFFERENTIATION; ACANTHASTER-PLANCI L
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2022.117144

[Display omitted] Novel steroid glycosides, acanthasterosides A1, B1, and B3, have been isolated from the crown-of-thorns starfish Acanthaster planci. Acanthasterosides B1 and B3 having two separated xyloses induced neurite outgrowth as like as nerve growth factor (NGF) in the rat pheochromocytoma cell line PC12, whereas acanthasteroside A1, having one xylose, did not induce neurite outgrowth. The acanthasteroside B3 induced neuritogenesis via the significant activation of p38 mitogen-activated protein kinase after the activation of the small G-protein Cdc42 rather than via Ras–MEK–ERK pathway that is predominantly activated by NGF. Following subcutaneous administration, acanthasteroside B3 attenuated cognitive impairment of senescence-accelerated mice (SAMP8) in two different cognitive tests. Liquid chromatography–mass spectrometry-assisted quantitative analysis demonstrated that acanthasteroside B3 could be transported into the brain via the circulatory system in mice. Thus, acanthasteroside B3 (and possibly B1) are a novel class of potential drug candidates for neurodegenerative diseases.