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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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Related in: MedlinePlus

SH-SY5Y cell apoptosis in response to xingshentongqiao decoction (XSTQ) treatment. (a) Apoptosis was measured using an annexin V-fluorescein isothiocyanate apoptosis detection kit for SH-SY5Y cells incubated with XSTQ (0, 10, 100 or 1000 μg/mL) for 24 h. (b) The results from panel A were quantified for three independent experiments. The data are expressed as mean ± standard deviation (**P < 0.01 vs. untreated control).
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Figure 2: SH-SY5Y cell apoptosis in response to xingshentongqiao decoction (XSTQ) treatment. (a) Apoptosis was measured using an annexin V-fluorescein isothiocyanate apoptosis detection kit for SH-SY5Y cells incubated with XSTQ (0, 10, 100 or 1000 μg/mL) for 24 h. (b) The results from panel A were quantified for three independent experiments. The data are expressed as mean ± standard deviation (**P < 0.01 vs. untreated control).

Mentions: To determine whether XSTQ also affects cell apoptosis, we performed Annexin V-FITC staining assays after 24 h treatment of SH-SY5Y cells with a range of doses of XSTQ (0, 10, 100 and 1000 μg/mL). The apoptotic rates were 3.65% ± 0.12%, 3.05% ± 0.18%, 3.23% ± 0.22% and 4.72% ± 0.16%, respectively. Statistical analysis suggests that the apoptotic rate of cells treated with 1000 μg/ml XSTQ was higher than that of the control group [Figure 2]. These findings suggest that XSTQ promotes apoptosis.


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)

SH-SY5Y cell apoptosis in response to xingshentongqiao decoction (XSTQ) treatment. (a) Apoptosis was measured using an annexin V-fluorescein isothiocyanate apoptosis detection kit for SH-SY5Y cells incubated with XSTQ (0, 10, 100 or 1000 μg/mL) for 24 h. (b) The results from panel A were quantified for three independent experiments. The data are expressed as mean ± standard deviation (**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 2: SH-SY5Y cell apoptosis in response to xingshentongqiao decoction (XSTQ) treatment. (a) Apoptosis was measured using an annexin V-fluorescein isothiocyanate apoptosis detection kit for SH-SY5Y cells incubated with XSTQ (0, 10, 100 or 1000 μg/mL) for 24 h. (b) The results from panel A were quantified for three independent experiments. The data are expressed as mean ± standard deviation (**P < 0.01 vs. untreated control).
Mentions: To determine whether XSTQ also affects cell apoptosis, we performed Annexin V-FITC staining assays after 24 h treatment of SH-SY5Y cells with a range of doses of XSTQ (0, 10, 100 and 1000 μg/mL). The apoptotic rates were 3.65% ± 0.12%, 3.05% ± 0.18%, 3.23% ± 0.22% and 4.72% ± 0.16%, respectively. Statistical analysis suggests that the apoptotic rate of cells treated with 1000 μg/ml XSTQ was higher than that of the control group [Figure 2]. These findings suggest that XSTQ promotes apoptosis.

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