Planta Med 2017; 83(17): 1342-1350
DOI: 10.1055/s-0043-111896
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Treatment with Mountain-Cultivated Ginseng Alleviates Trimethyltin-Induced Cognitive Impairments in Mice via IL-6-Dependent JAK2/STAT3/ERK Signaling

Thu-Hien Thi Tu*
1  Neuropsychopharmacology and Toxicology Program, BK21 PLUS Project, College of Pharmacy, Kangwon National University, Chunchon, Republic of Korea
,
Naveen Sharma*
1  Neuropsychopharmacology and Toxicology Program, BK21 PLUS Project, College of Pharmacy, Kangwon National University, Chunchon, Republic of Korea
,
Eun-Joo Shin
1  Neuropsychopharmacology and Toxicology Program, BK21 PLUS Project, College of Pharmacy, Kangwon National University, Chunchon, Republic of Korea
,
Hai-Quyen Tran
1  Neuropsychopharmacology and Toxicology Program, BK21 PLUS Project, College of Pharmacy, Kangwon National University, Chunchon, Republic of Korea
,
Yu Jeung Lee
2  Clinical Pharmacy, College of Pharmacy, Kangwon National University, Chunchon, Republic of Korea
,
Seung-Yeol Nah
3  Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, Republic of Korea
,
Hoang-Yen Phi Tran
4  Physical Chemistry Department, University of Medicine and Pharmacy, Ho Chi Minh City, Viet Nam
,
Ji Hoon Jeong
5  Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea
,
Jung Hwan Jeong
6  Headquarters of Forestry Support, Korea Forestry Promotion Institute, Seoul, Republic of Korea
,
Sung Kwon Ko
7  Department of Oriental Medical Food & Nutrition, Semyung University, Jecheon, Republic of Korea
,
Jae Kyung Byun
8  Korean society of forest environment research, Namyangju, Republic of Korea
,
Hyoung-Chun Kim
1  Neuropsychopharmacology and Toxicology Program, BK21 PLUS Project, College of Pharmacy, Kangwon National University, Chunchon, Republic of Korea
› Author Affiliations
Further Information

Publication History

received 21 December 2016
revised 02 May 2017

accepted 13 May 2017

Publication Date:
30 May 2017 (eFirst)

Abstract

Panax ginseng is the most widely used herbal medicine for improving cognitive functions. The pharmacological activity and underlying mechanisms of mountain-cultivated ginseng, however, have yet to be clearly elucidated, in particular, against trimethyltin-induced cognitive dysfunction. We previously reported that interleukin-6 plays a protective role against trimethyltin-induced cognitive dysfunction. Because of this, we have implemented a study system that uses interleukin-6 null (−/−) and wild-type mice. Interestingly, mountain-cultivated ginseng significantly upregulated interleukin-6 expression. With this study, we sought to determine whether the interleukin-6-dependent modulation of the Janus kinase 2/signal transducer activator of transcription 3 and extracellular signal-regulated kinase signaling network is also associated with the pharmacological activity of mountain-cultivated ginseng against trimethyltin-induced cognitive dysfunction. Trimethyltin treatment (2.4 mg/kg, intraperitoneal) causes the downregulation of Janus kinase 2/signal transducer activator of transcription 3, extracellular signal-regulated kinase signaling, and impairment of the cholinergic system. We found that mountain-cultivated ginseng treatment (50 mg/kg, intraperitoneal) significantly attenuated cognitive impairment normally induced by trimethyltin by upregulating p-Janus kinase 2/signal transducer activator of transcription 3, p-extracellular signal-regulated kinase signaling, and the cholinergic system. Trimethyltin-induced cognitive impairments were more pronounced in interleukin-6 (−/−) mice than wild-type mice, and they were markedly reduced by treatment with either mountain-cultivated ginseng or recombinant interleukin-6 protein (6 ng, intracerebroventricular). Additionally, treatment with either AG490 (20 mg/kg, intraperitoneal), a Janus kinase 2/signal transducer activator of transcription 3 inhibitor, or U0126 (2 µg/head, intracerebroventricular), an extracellular signal-regulated kinase inhibitor, reversed the effects of mountain-cultivated ginseng treatment. The effects of mountain-cultivated ginseng treatment were comparable to those of recombinant interleukin-6 protein in interleukin-6 (−/−) mice. Our results, therefore, suggest that mountain-cultivated ginseng acts through interleukin-6-dependent activation of Janus kinase 2/signal transducer activator of transcription 3/extracellular signal-regulated kinase signaling in order to reverse cognitive impairment caused by trimethyltin treatment.

* Thu-Hien Thi Tu and Naveen Sharma contributed equally to this work.


Supporting Information