Osthole inhibits proliferation and induces apoptosis in BV-2 microglia cells in kainic acid-induced epilepsy via modulating PI3K/AKt/mTOR signalling way

Context: Osthole is a natural coumarin compound most frequently extracted from plants of the Apiaceae family such as Cnidium monnieri (L.) Cusson, Angelica pubescens Maxin.f., and Peucedanum ostruthium (L.). Osthole is considered to have potential therapeutic applications for the treatment of diseas...

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Autores principales:	Meng Du, Zheng Sun, Yao Lu, Yu-Zhu Li, Hong-Rui Xu, Chang-Qian Zeng
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2019
Materias:	herbal medicine proliferative inhibition apoptosis promotion Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/5d8495eb9fc34fff997eeebfd2ec2570
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spelling	oai:doaj.org-article:5d8495eb9fc34fff997eeebfd2ec25702021-11-17T14:21:56ZOsthole inhibits proliferation and induces apoptosis in BV-2 microglia cells in kainic acid-induced epilepsy via modulating PI3K/AKt/mTOR signalling way1388-02091744-511610.1080/13880209.2019.1588905https://doaj.org/article/5d8495eb9fc34fff997eeebfd2ec25702019-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2019.1588905https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context: Osthole is a natural coumarin compound most frequently extracted from plants of the Apiaceae family such as Cnidium monnieri (L.) Cusson, Angelica pubescens Maxin.f., and Peucedanum ostruthium (L.). Osthole is considered to have potential therapeutic applications for the treatment of diseases including epilepsy. However, the mechanism of osthole induced-apoptosis in BV-2 microglia cells is not yet clear. Objective: To investigate the molecular mechanisms underlying the effect of osthole on PI3K/AKt/mTOR expression in kainic acid (KA)-activated BV-2 microglia cells. Materials and methods: Optimal culture concentration and time of osthole were investigated by MTT assay. The concentration of osthole was tested from 10 to 400 μM and the culture time was tested from 2 to 72 h. Ultrastructure difference among control, KA and osthole group was analyzed under transmission electron microscope. The mRNA expression of PI3K/AKt/mTOR was investigated using reverse transcription (RT)-PCR and the protein expression was investigated using western blotting and immunofluorescence assay. Apoptosis rate of BV-2 cells between each group was measured by flow cytometry. Results: IC50 for cell viability of BV-2 cells by osthole was 157.7 µM. Treated with osthole (140 µM) for 24 h significantly increased the inhibition rate. Pretreatment with osthole inhibited the KA-induced PI3K/AKt/mTOR mRNA and protein expression. The results of flow cytometry analysis showed that the apoptotic rate of osthole group was obviously higher than KA group. Conclusions: Date showed that osthole may be useful in the treatment of epilepsy and other neurodegenerative diseases that are characterized by over expression of PI3K/Akt/mTOR.Meng DuZheng SunYao LuYu-Zhu LiHong-Rui XuChang-Qian ZengTaylor & Francis Grouparticleherbal medicineproliferative inhibitionapoptosis promotionTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 57, Iss 1, Pp 238-244 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	herbal medicine proliferative inhibition apoptosis promotion Therapeutics. Pharmacology RM1-950
spellingShingle	herbal medicine proliferative inhibition apoptosis promotion Therapeutics. Pharmacology RM1-950 Meng Du Zheng Sun Yao Lu Yu-Zhu Li Hong-Rui Xu Chang-Qian Zeng Osthole inhibits proliferation and induces apoptosis in BV-2 microglia cells in kainic acid-induced epilepsy via modulating PI3K/AKt/mTOR signalling way
description	Context: Osthole is a natural coumarin compound most frequently extracted from plants of the Apiaceae family such as Cnidium monnieri (L.) Cusson, Angelica pubescens Maxin.f., and Peucedanum ostruthium (L.). Osthole is considered to have potential therapeutic applications for the treatment of diseases including epilepsy. However, the mechanism of osthole induced-apoptosis in BV-2 microglia cells is not yet clear. Objective: To investigate the molecular mechanisms underlying the effect of osthole on PI3K/AKt/mTOR expression in kainic acid (KA)-activated BV-2 microglia cells. Materials and methods: Optimal culture concentration and time of osthole were investigated by MTT assay. The concentration of osthole was tested from 10 to 400 μM and the culture time was tested from 2 to 72 h. Ultrastructure difference among control, KA and osthole group was analyzed under transmission electron microscope. The mRNA expression of PI3K/AKt/mTOR was investigated using reverse transcription (RT)-PCR and the protein expression was investigated using western blotting and immunofluorescence assay. Apoptosis rate of BV-2 cells between each group was measured by flow cytometry. Results: IC50 for cell viability of BV-2 cells by osthole was 157.7 µM. Treated with osthole (140 µM) for 24 h significantly increased the inhibition rate. Pretreatment with osthole inhibited the KA-induced PI3K/AKt/mTOR mRNA and protein expression. The results of flow cytometry analysis showed that the apoptotic rate of osthole group was obviously higher than KA group. Conclusions: Date showed that osthole may be useful in the treatment of epilepsy and other neurodegenerative diseases that are characterized by over expression of PI3K/Akt/mTOR.
format	article
author	Meng Du Zheng Sun Yao Lu Yu-Zhu Li Hong-Rui Xu Chang-Qian Zeng
author_facet	Meng Du Zheng Sun Yao Lu Yu-Zhu Li Hong-Rui Xu Chang-Qian Zeng
author_sort	Meng Du
title	Osthole inhibits proliferation and induces apoptosis in BV-2 microglia cells in kainic acid-induced epilepsy via modulating PI3K/AKt/mTOR signalling way
title_short	Osthole inhibits proliferation and induces apoptosis in BV-2 microglia cells in kainic acid-induced epilepsy via modulating PI3K/AKt/mTOR signalling way
title_full	Osthole inhibits proliferation and induces apoptosis in BV-2 microglia cells in kainic acid-induced epilepsy via modulating PI3K/AKt/mTOR signalling way
title_fullStr	Osthole inhibits proliferation and induces apoptosis in BV-2 microglia cells in kainic acid-induced epilepsy via modulating PI3K/AKt/mTOR signalling way
title_full_unstemmed	Osthole inhibits proliferation and induces apoptosis in BV-2 microglia cells in kainic acid-induced epilepsy via modulating PI3K/AKt/mTOR signalling way
title_sort	osthole inhibits proliferation and induces apoptosis in bv-2 microglia cells in kainic acid-induced epilepsy via modulating pi3k/akt/mtor signalling way
publisher	Taylor & Francis Group
publishDate	2019
url	https://doaj.org/article/5d8495eb9fc34fff997eeebfd2ec2570
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Osthole inhibits proliferation and induces apoptosis in BV-2 microglia cells in kainic acid-induced epilepsy via modulating PI3K/AKt/mTOR signalling way

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