Treatment with Mountain-Cultivated Ginseng Alleviates Trimethyltin-Induced Cognitive Impairments in Mice via IL-6-Dependent JAK2/STAT3/ERK Signaling
- Authors
- Thu-Hien Thi Tu; Sharma, Naveen; Shin, Eun-Joo; Hai-Quyen Tran; Lee, Yu Jeung; Nah, Seung-Yeol; Hoang-Yen Phi Tran; Jeong, Ji Hoon; Jeong, Jung Hwan; Ko, Sung Kwon; Byun, Jae Kyung; Kim, Hyoung-Chun
- Issue Date
- Nov-2017
- Publisher
- GEORG THIEME VERLAG KG
- Keywords
- cognitive dysfunction; IL-6 knockout mice; JAK2/STAT3/ERK signaling; cholinergic system; Panax ginseng; Araliaceae; trimethyltin
- Citation
- PLANTA MEDICA, v.83, no.17, pp 1342 - 1350
- Pages
- 9
- Journal Title
- PLANTA MEDICA
- Volume
- 83
- Number
- 17
- Start Page
- 1342
- End Page
- 1350
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/3712
- DOI
- 10.1055/s-0043-111896
- ISSN
- 0032-0943
1439-0221
- 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 mu g/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.
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