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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

Xingshentongqiao decoction (XSTQ) enhances orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R) expression in SH-SY5Y cells. Induction of OX1R (a) and OX2R (b) was determined by quantitative real-time polymerase chain reaction at a range of times of exposure to 1000 μg/ml XSTQ. The data are expressed as mean ± standard deviation of OX1R or OX2R messenger ribonucleic acid (mRNA) expression relative to β-actin mRNA expression for three independent experiments and are standardized to 1.0 in the control sample (**P < 0.01, *P < 0.05 vs. untreated control).
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Figure 3: Xingshentongqiao decoction (XSTQ) enhances orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R) expression in SH-SY5Y cells. Induction of OX1R (a) and OX2R (b) was determined by quantitative real-time polymerase chain reaction at a range of times of exposure to 1000 μg/ml XSTQ. The data are expressed as mean ± standard deviation of OX1R or OX2R messenger ribonucleic acid (mRNA) expression relative to β-actin mRNA expression for three independent experiments and are standardized to 1.0 in the control sample (**P < 0.01, *P < 0.05 vs. untreated control).

Mentions: Deficiency of the HCRT system has been confirmed as an underlying cause of most cases of narcolepsy.[2] To test whether XSTQ counteracts narcolepsy by modulating components within the HCRT signaling cascade, we assessed levels of expression of the HCRT receptors OX1R and OX2R. mRNA was collected from SH-SY5Y cells treated with XSTQ (1000 μg/ml) for 0, 24, 48, and 72 hours, and transcript levels were quantified by qRT-PCR. XSTQ induced an obvious increase in OX1R and OX2R mRNA expression, reaching a maximum at 24–48 hours [Figure 3]. These results suggest that XSTQ may counteract narcolepsy by enhancing the expression of HCRT signaling receptors.


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) enhances orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R) expression in SH-SY5Y cells. Induction of OX1R (a) and OX2R (b) was determined by quantitative real-time polymerase chain reaction at a range of times of exposure to 1000 μg/ml XSTQ. The data are expressed as mean ± standard deviation of OX1R or OX2R messenger ribonucleic acid (mRNA) expression relative to β-actin mRNA expression for three independent experiments and are standardized to 1.0 in the control sample (**P < 0.01, *P < 0.05 vs. untreated control).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Xingshentongqiao decoction (XSTQ) enhances orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R) expression in SH-SY5Y cells. Induction of OX1R (a) and OX2R (b) was determined by quantitative real-time polymerase chain reaction at a range of times of exposure to 1000 μg/ml XSTQ. The data are expressed as mean ± standard deviation of OX1R or OX2R messenger ribonucleic acid (mRNA) expression relative to β-actin mRNA expression for three independent experiments and are standardized to 1.0 in the control sample (**P < 0.01, *P < 0.05 vs. untreated control).
Mentions: Deficiency of the HCRT system has been confirmed as an underlying cause of most cases of narcolepsy.[2] To test whether XSTQ counteracts narcolepsy by modulating components within the HCRT signaling cascade, we assessed levels of expression of the HCRT receptors OX1R and OX2R. mRNA was collected from SH-SY5Y cells treated with XSTQ (1000 μg/ml) for 0, 24, 48, and 72 hours, and transcript levels were quantified by qRT-PCR. XSTQ induced an obvious increase in OX1R and OX2R mRNA expression, reaching a maximum at 24–48 hours [Figure 3]. These results suggest that XSTQ may counteract narcolepsy by enhancing the expression of HCRT signaling receptors.

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