scholarly journals Anticancer Activity of Tubulosine through Suppression of Interleukin-6-Induced Janus Kinase 2/Signal Transducer and Activation of Transcription 3 Signaling

2019 ◽  
Vol 22 (3) ◽  
pp. 362 ◽  
Author(s):  
Byung-Hak Kim ◽  
Eun Hee Yi ◽  
Yu-Chen Li ◽  
In-Chul Park ◽  
Jung Youl Park ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Interleukin 6 ◽  
Janus Kinase ◽  
Signal Transducer ◽  
Janus Kinase 2 ◽  
Activation Of Transcription ◽  
Transcription 3

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

Planta Medica ◽  
2017 ◽  
Vol 83 (17) ◽  
pp. 1342-1350 ◽  
Author(s):  
Thu-Hien Thi Tu ◽  
Naveen Sharma ◽  
Eun-Joo Shin ◽  
Hai-Quyen Tran ◽  
Yu Jeung Lee ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Interleukin 6 ◽  
Janus Kinase ◽  
Signal Transducer ◽  
Janus Kinase 2 ◽  
Kinase Signaling ◽  
Wild Type ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Transcription 3

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.

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