Ginseng Gintonin Attenuates Lead-Induced Rat Cerebellar Impairments during Gestation and Lactation

Gintonin, a novel ginseng-derived lysophosphatidic acid receptor ligand, improves brain functions and protects neurons from oxidative stress. However, little is known about the effects of gintonin against Pb-induced brain maldevelopment. We investigated the protective effects of gintonin on the deve...

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Main Authors: Sung Min Nam, Sun-Hye Choi, Hee-Jung Cho, Jin Seok Seo, Minsuk Choi, Sang-Soep Nahm, Byung-Joon Chang, Seung-Yeol Nah
Format: Article
Language:English
Published: MDPI AG 2020-03-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/10/3/385
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author Sung Min Nam
Sun-Hye Choi
Hee-Jung Cho
Jin Seok Seo
Minsuk Choi
Sang-Soep Nahm
Byung-Joon Chang
Seung-Yeol Nah
author_facet Sung Min Nam
Sun-Hye Choi
Hee-Jung Cho
Jin Seok Seo
Minsuk Choi
Sang-Soep Nahm
Byung-Joon Chang
Seung-Yeol Nah
author_sort Sung Min Nam
collection DOAJ
description Gintonin, a novel ginseng-derived lysophosphatidic acid receptor ligand, improves brain functions and protects neurons from oxidative stress. However, little is known about the effects of gintonin against Pb-induced brain maldevelopment. We investigated the protective effects of gintonin on the developing cerebellum after prenatal and postnatal Pb exposure. Pregnant female rats were randomly divided into three groups: control, Pb (0.3% Pb acetate in drinking water), and Pb plus gintonin (100 mg/kg, p.o.). Blood Pb was increased in dams and pups; gintonin treatment significantly decreased blood Pb. On postnatal day 21, the number of degenerating Purkinje cells was remarkably increased while the number of calbindin-, GAD67-, NMDAR1-, LPAR1-immunoreactive intact Purkinje cells, and GABA transporter 1-immunoreactive pinceau structures were significantly reduced in Pb-exposed offspring. Following Pb exposure, gintonin ameliorated cerebellar degenerative effects, restored increased pro-apoptotic Bax, and decreased anti-apoptotic Bcl2. Gintonin treatment attenuated Pb-induced accumulation of oxidative stress (Nrf2 and Mn-SOD) and inflammation (IL-1β and TNFα,), restoring the decreased cerebellar BDNF and Sirt1. Gintonin ameliorated Pb-induced impairment of myelin basic protein-immunoreactive myelinated fibers of Purkinje cells. Gintonin attenuated Pb-induced locomotor dysfunctions. The present study revealed the ameliorating effects of gintonin against Pb, suggesting the potential use of gintonin as a preventive agent in Pb poisoning during pregnancy and lactation.
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spelling doaj.art-061ad1756b4243e084bd37a40c9fd32e2022-12-22T02:48:28ZengMDPI AGBiomolecules2218-273X2020-03-0110338510.3390/biom10030385biom10030385Ginseng Gintonin Attenuates Lead-Induced Rat Cerebellar Impairments during Gestation and LactationSung Min Nam0Sun-Hye Choi1Hee-Jung Cho2Jin Seok Seo3Minsuk Choi4Sang-Soep Nahm5Byung-Joon Chang6Seung-Yeol Nah7Department of Anatomy, College of Veterinary Medicine, Konkuk University, Seoul 05029, KoreaGinsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, KoreaGinsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, KoreaDepartment of Anatomy, College of Veterinary Medicine, Konkuk University, Seoul 05029, KoreaDepartment of Anatomy, College of Veterinary Medicine, Konkuk University, Seoul 05029, KoreaDepartment of Anatomy, College of Veterinary Medicine, Konkuk University, Seoul 05029, KoreaDepartment of Anatomy, College of Veterinary Medicine, Konkuk University, Seoul 05029, KoreaGinsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, KoreaGintonin, a novel ginseng-derived lysophosphatidic acid receptor ligand, improves brain functions and protects neurons from oxidative stress. However, little is known about the effects of gintonin against Pb-induced brain maldevelopment. We investigated the protective effects of gintonin on the developing cerebellum after prenatal and postnatal Pb exposure. Pregnant female rats were randomly divided into three groups: control, Pb (0.3% Pb acetate in drinking water), and Pb plus gintonin (100 mg/kg, p.o.). Blood Pb was increased in dams and pups; gintonin treatment significantly decreased blood Pb. On postnatal day 21, the number of degenerating Purkinje cells was remarkably increased while the number of calbindin-, GAD67-, NMDAR1-, LPAR1-immunoreactive intact Purkinje cells, and GABA transporter 1-immunoreactive pinceau structures were significantly reduced in Pb-exposed offspring. Following Pb exposure, gintonin ameliorated cerebellar degenerative effects, restored increased pro-apoptotic Bax, and decreased anti-apoptotic Bcl2. Gintonin treatment attenuated Pb-induced accumulation of oxidative stress (Nrf2 and Mn-SOD) and inflammation (IL-1β and TNFα,), restoring the decreased cerebellar BDNF and Sirt1. Gintonin ameliorated Pb-induced impairment of myelin basic protein-immunoreactive myelinated fibers of Purkinje cells. Gintonin attenuated Pb-induced locomotor dysfunctions. The present study revealed the ameliorating effects of gintonin against Pb, suggesting the potential use of gintonin as a preventive agent in Pb poisoning during pregnancy and lactation.https://www.mdpi.com/2218-273X/10/3/385ginsenggintoninpregnancy and lactationcerebellar lead (pb) poisoningneuroprotection
spellingShingle Sung Min Nam
Sun-Hye Choi
Hee-Jung Cho
Jin Seok Seo
Minsuk Choi
Sang-Soep Nahm
Byung-Joon Chang
Seung-Yeol Nah
Ginseng Gintonin Attenuates Lead-Induced Rat Cerebellar Impairments during Gestation and Lactation
Biomolecules
ginseng
gintonin
pregnancy and lactation
cerebellar lead (pb) poisoning
neuroprotection
title Ginseng Gintonin Attenuates Lead-Induced Rat Cerebellar Impairments during Gestation and Lactation
title_full Ginseng Gintonin Attenuates Lead-Induced Rat Cerebellar Impairments during Gestation and Lactation
title_fullStr Ginseng Gintonin Attenuates Lead-Induced Rat Cerebellar Impairments during Gestation and Lactation
title_full_unstemmed Ginseng Gintonin Attenuates Lead-Induced Rat Cerebellar Impairments during Gestation and Lactation
title_short Ginseng Gintonin Attenuates Lead-Induced Rat Cerebellar Impairments during Gestation and Lactation
title_sort ginseng gintonin attenuates lead induced rat cerebellar impairments during gestation and lactation
topic ginseng
gintonin
pregnancy and lactation
cerebellar lead (pb) poisoning
neuroprotection
url https://www.mdpi.com/2218-273X/10/3/385
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