Planta Med
DOI: 10.1055/s-0043-111896
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 Tu1, *, Naveen Sharma1, *, Eun-Joo Shin1, Hai-Quyen Tran1, Yu Jeung Lee2, Seung-Yeol Nah3, Hoang-Yen Phi Tran4, Ji Hoon Jeong5, Jung Hwan Jeong6, Sung Kwon Ko7, Jae Kyung Byun8, Hyoung-Chun Kim1
  • 1Neuropsychopharmacology and Toxicology Program, BK21 PLUS Project, College of Pharmacy, Kangwon National University, Chunchon, Republic of Korea
  • 2Clinical Pharmacy, College of Pharmacy, Kangwon National University, Chunchon, Republic of Korea
  • 3Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, Republic of Korea
  • 4Physical Chemistry Department, University of Medicine and Pharmacy, Ho Chi Minh City, Viet Nam
  • 5Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea
  • 6Headquarters of Forestry Support, Korea Forestry Promotion Institute, Seoul, Republic of Korea
  • 7Department of Oriental Medical Food & Nutrition, Semyung University, Jecheon, Republic of Korea
  • 8Korean society of forest environment research, Namyangju, Republic of Korea
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