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Xingshentongqiao decoction mediates proliferation, apoptosis, orexin-A receptor and orexin-B receptor messenger ribonucleic acid expression and represses mitogen-activated protein kinase signaling.

Dong Y, Li M, Wang S, Dong Y, Zhao H, Dai Z - Chin. Med. J. (2015)

Bottom Line: XSTQ reduced the proliferation and induced apoptosis of SH-SY5Y cells.This effect was accompanied by the upregulation of OX1R and OX2R expression and the reduced phosphorylation of extracellular signal-regulated kinase (Erk) 1/2, p38 MAPK and c-Jun N-terminal kinase (JNK).These effects are associated with the repression of the Erk1/2, p38 MAPK, and JNK signaling pathways.

View Article: PubMed Central - PubMed

Affiliation: Department of Traditional Chinese Medicine, Peking University People's Hospital, Beijing 100044, China.

ABSTRACT

Background: Hypocretin (HCRT) signaling plays an important role in the pathogenesis of narcolepsy and can be significantly influenced by Chinese herbal therapy. Our previous study showed that xingshentongqiao decoction (XSTQ) is clinically effective for the treatment of narcolepsy. To determine whether XSTQ improves narcolepsy by modulating HCRT signaling, we investigated its effects on SH-SY5Y cell proliferation, apoptosis, and HCRT receptor 1/2 (orexin receptor 1 [OX1R] and orexin receptor 2 [OX2R]) expression. The signaling pathways involved in these processes were also assessed.

Methods: The effects of XSTQ on proliferation and apoptosis in SH-SY5Y cells were assessed using cell counting kit-8 and annexin V-fluorescein isothiocyanate assays. OX1R and OX2R expression was assessed by quantitative real-time polymerase chain reaction analysis. Western blotting for mitogen-activated protein kinase (MAPK) pathway activation was performed to further assess the signaling mechanism of XSTQ.

Results: XSTQ reduced the proliferation and induced apoptosis of SH-SY5Y cells. This effect was accompanied by the upregulation of OX1R and OX2R expression and the reduced phosphorylation of extracellular signal-regulated kinase (Erk) 1/2, p38 MAPK and c-Jun N-terminal kinase (JNK).

Conclusions: XSTQ inhibits proliferation and induces apoptosis in SH-SY5Y cells. XSTQ also promotes OX1R and OX2R expression. These effects are associated with the repression of the Erk1/2, p38 MAPK, and JNK signaling pathways. These results define a molecular mechanism for XSTQ in regulating HCRT and MAPK activation, which may explain its ability to treat narcolepsy.

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Xingshentongqiao decoction (XSTQ) mediates dose-dependent downregulation of the phosphorylation of extracellular signal-regulated kinase (Erk1/2), p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). (a) SH-SY5Y cells were incubated with XSTQ (0, 10, 100 or 1000 μg/ml) for 2 hours, and levels of phosphorylated Erk1/2, p38 MAPK and JNK were determined relative to total Erk1/2, p38 MAPK and JNK levels by western blotting analysis. (b-d) Levels of phosphorylated proteins were normalized to levels of total protein by densitometry. Data represent the mean ± standard deviation of three independent experiments and are standardized to 1.0 in the control (untreated) cells (**P < 0.01 vs. untreated control).
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Figure 4: Xingshentongqiao decoction (XSTQ) mediates dose-dependent downregulation of the phosphorylation of extracellular signal-regulated kinase (Erk1/2), p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). (a) SH-SY5Y cells were incubated with XSTQ (0, 10, 100 or 1000 μg/ml) for 2 hours, and levels of phosphorylated Erk1/2, p38 MAPK and JNK were determined relative to total Erk1/2, p38 MAPK and JNK levels by western blotting analysis. (b-d) Levels of phosphorylated proteins were normalized to levels of total protein by densitometry. Data represent the mean ± standard deviation of three independent experiments and are standardized to 1.0 in the control (untreated) cells (**P < 0.01 vs. untreated control).

Mentions: To identify HCRT-related signaling pathways that may be affected by XSTQ, we examined the effects on Erk1/2, p38 MAPK and JNK activation. Increasing concentrations of XSTQ were added to SH-SY5Y cells, and levels of phosphorylated and total protein were assessed by western blotting. XSTQ significantly downregulated the phosphorylation of Erk1/2, p38 MAPK and JNK at 1000 μg/ml concentration. Furthermore, XSTQ downregulated the phosphorylation of Erk1/2 and JNK at 100 μg/ml and Erk1/2 at 10 μg/ml [Figure 4].


Xingshentongqiao decoction mediates proliferation, apoptosis, orexin-A receptor and orexin-B receptor messenger ribonucleic acid expression and represses mitogen-activated protein kinase signaling.

Dong Y, Li M, Wang S, Dong Y, Zhao H, Dai Z - Chin. Med. J. (2015)

Xingshentongqiao decoction (XSTQ) mediates dose-dependent downregulation of the phosphorylation of extracellular signal-regulated kinase (Erk1/2), p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). (a) SH-SY5Y cells were incubated with XSTQ (0, 10, 100 or 1000 μg/ml) for 2 hours, and levels of phosphorylated Erk1/2, p38 MAPK and JNK were determined relative to total Erk1/2, p38 MAPK and JNK levels by western blotting analysis. (b-d) Levels of phosphorylated proteins were normalized to levels of total protein by densitometry. Data represent the mean ± standard deviation of three independent experiments and are standardized to 1.0 in the control (untreated) cells (**P < 0.01 vs. untreated control).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837828&req=5

Figure 4: Xingshentongqiao decoction (XSTQ) mediates dose-dependent downregulation of the phosphorylation of extracellular signal-regulated kinase (Erk1/2), p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). (a) SH-SY5Y cells were incubated with XSTQ (0, 10, 100 or 1000 μg/ml) for 2 hours, and levels of phosphorylated Erk1/2, p38 MAPK and JNK were determined relative to total Erk1/2, p38 MAPK and JNK levels by western blotting analysis. (b-d) Levels of phosphorylated proteins were normalized to levels of total protein by densitometry. Data represent the mean ± standard deviation of three independent experiments and are standardized to 1.0 in the control (untreated) cells (**P < 0.01 vs. untreated control).
Mentions: To identify HCRT-related signaling pathways that may be affected by XSTQ, we examined the effects on Erk1/2, p38 MAPK and JNK activation. Increasing concentrations of XSTQ were added to SH-SY5Y cells, and levels of phosphorylated and total protein were assessed by western blotting. XSTQ significantly downregulated the phosphorylation of Erk1/2, p38 MAPK and JNK at 1000 μg/ml concentration. Furthermore, XSTQ downregulated the phosphorylation of Erk1/2 and JNK at 100 μg/ml and Erk1/2 at 10 μg/ml [Figure 4].

Bottom Line: XSTQ reduced the proliferation and induced apoptosis of SH-SY5Y cells.This effect was accompanied by the upregulation of OX1R and OX2R expression and the reduced phosphorylation of extracellular signal-regulated kinase (Erk) 1/2, p38 MAPK and c-Jun N-terminal kinase (JNK).These effects are associated with the repression of the Erk1/2, p38 MAPK, and JNK signaling pathways.

View Article: PubMed Central - PubMed

Affiliation: Department of Traditional Chinese Medicine, Peking University People's Hospital, Beijing 100044, China.

ABSTRACT

Background: Hypocretin (HCRT) signaling plays an important role in the pathogenesis of narcolepsy and can be significantly influenced by Chinese herbal therapy. Our previous study showed that xingshentongqiao decoction (XSTQ) is clinically effective for the treatment of narcolepsy. To determine whether XSTQ improves narcolepsy by modulating HCRT signaling, we investigated its effects on SH-SY5Y cell proliferation, apoptosis, and HCRT receptor 1/2 (orexin receptor 1 [OX1R] and orexin receptor 2 [OX2R]) expression. The signaling pathways involved in these processes were also assessed.

Methods: The effects of XSTQ on proliferation and apoptosis in SH-SY5Y cells were assessed using cell counting kit-8 and annexin V-fluorescein isothiocyanate assays. OX1R and OX2R expression was assessed by quantitative real-time polymerase chain reaction analysis. Western blotting for mitogen-activated protein kinase (MAPK) pathway activation was performed to further assess the signaling mechanism of XSTQ.

Results: XSTQ reduced the proliferation and induced apoptosis of SH-SY5Y cells. This effect was accompanied by the upregulation of OX1R and OX2R expression and the reduced phosphorylation of extracellular signal-regulated kinase (Erk) 1/2, p38 MAPK and c-Jun N-terminal kinase (JNK).

Conclusions: XSTQ inhibits proliferation and induces apoptosis in SH-SY5Y cells. XSTQ also promotes OX1R and OX2R expression. These effects are associated with the repression of the Erk1/2, p38 MAPK, and JNK signaling pathways. These results define a molecular mechanism for XSTQ in regulating HCRT and MAPK activation, which may explain its ability to treat narcolepsy.

Show MeSH
Related in: MedlinePlus