Chemical Identification of Isoflavonoids from a Termite-Associated Streptomyces sp. RB1 and Their Neuroprotective Effects in Murine Hippocampal HT22 Cell Line

• Published in: International journal of molecular sciences 2018-09, Vol.19 (9), p.2640
• Main Authors: Lee, Seoung Rak, Song, Ji Hoon, Song, Jae-Hyoung, Ko, Hyun-Jeong, Baek, Ji Yun, Trinh, Tuy An, Beemelmanns, Christine, Yamabe, Noriko, Kim, Ki Hyun
• Format: Article
• Language: English
• Subjects: Absolute configuration; Animals; Apoptosis; Apoptosis - drug effects; Bacteria; Cell death; Cell Line; Cell Survival; Chemical reactions; Chromatography, Liquid; Damage prevention; Fungi; Glutamic Acid - adverse effects; Hippocampus; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - metabolism; Humans; Hydrocarbons; Insects; Isoflavones - chemistry; Isoflavones - isolation & purification; Isoflavones - pharmacology; Isoflavonoids; Isoptera - microbiology; Lead compounds; Mass Spectrometry; Metabolites; Mice; Molecular Structure; Natural products; Natural resources; Neuroprotection; Neuroprotective Agents - chemistry; Neuroprotective Agents - isolation & purification; Neuroprotective Agents - pharmacology; NMR; Nuclear magnetic resonance; Organic chemistry; Oxidative stress; Oxidative Stress - drug effects; Pharmacology; Pharmacy; Reactive oxygen species; Reactive Oxygen Species - metabolism; Retinoblastoma; Rhamnose; Secondary metabolites; Spectrum analysis; Streptomyces; Streptomyces - chemistry; Two dimensional analysis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19092640

Insect-associated bacteria have been recognized as a very promising natural resource for discovering bioactive secondary metabolites with diverse pharmacological effects. One new isoflavonoid glycoside, termisoflavone D ( ), together with seven known isoflavonoids ( ⁻ ), were identified from MeOH extracts of the fungus-growing termite-associated sp. RB1. The chemical structure of the new compound was elucidated using comprehensive spectroscopic methods including 1D and 2D NMR, along with LC/MS analysis. The existence of two rhamnose moieties in was determined with comparative NMR analysis, and the absolute configuration was elucidated using chemical reactions. The neuroprotective activities of compounds ⁻ were thoroughly investigated using the murine hippocampal HT22 cell line. Compound prevented glutamate-induced HT22 cell death by blocking intracellular reactive oxygen species (ROS) accumulation. The present study provides the first experimental evidence for the potential use of isoflavonoids from termite-associated bacteria as lead compounds that can prevent neuronal damage induced by glutamate.