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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

Effects of Xingshentongqiao decoction (XSTQ) on proliferation of SH-SY5Y cells. (a) SH-SY5Y cell proliferation was determined by cell counting kit-8 assay after 0, 24, 48, 72, or 96 hours incubation without XSTQ (control) or with XSTQ at a concentration of 100, 200, 400, 600, 800, or 1000 μg/ml. Results are standardized to 1.0 at 0 hour. (b) The average proliferation of XSTQ-treated-SH-SY5Y cells is shown after 72 hours. Results are standardized to an average of 1.0 in the control. (c) Average proliferation of XSTQ-treated-SH-SY5Y cells is shown after 96 h. Results are standardized to an average of 1.0 in the control. Data represent the mean ± standard deviation of three independent experiments (**P < 0.01, *P < 0.05, vs. untreated control).
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Figure 1: Effects of Xingshentongqiao decoction (XSTQ) on proliferation of SH-SY5Y cells. (a) SH-SY5Y cell proliferation was determined by cell counting kit-8 assay after 0, 24, 48, 72, or 96 hours incubation without XSTQ (control) or with XSTQ at a concentration of 100, 200, 400, 600, 800, or 1000 μg/ml. Results are standardized to 1.0 at 0 hour. (b) The average proliferation of XSTQ-treated-SH-SY5Y cells is shown after 72 hours. Results are standardized to an average of 1.0 in the control. (c) Average proliferation of XSTQ-treated-SH-SY5Y cells is shown after 96 h. Results are standardized to an average of 1.0 in the control. Data represent the mean ± standard deviation of three independent experiments (**P < 0.01, *P < 0.05, vs. untreated control).

Mentions: To determine whether XSTQ affects cell proliferation, we treated SH-SY5Y cells with a range of doses and times of XSTQ. SH-SY5Y proliferation was inhibited in a dose-dependent manner after 72 hours and 96 hours treatment with XSTQ at concentrations of 400–1000 μg/ml [Table 1, Figure 1]. These results suggest that XSTQ inhibits proliferation.


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)

Effects of Xingshentongqiao decoction (XSTQ) on proliferation of SH-SY5Y cells. (a) SH-SY5Y cell proliferation was determined by cell counting kit-8 assay after 0, 24, 48, 72, or 96 hours incubation without XSTQ (control) or with XSTQ at a concentration of 100, 200, 400, 600, 800, or 1000 μg/ml. Results are standardized to 1.0 at 0 hour. (b) The average proliferation of XSTQ-treated-SH-SY5Y cells is shown after 72 hours. Results are standardized to an average of 1.0 in the control. (c) Average proliferation of XSTQ-treated-SH-SY5Y cells is shown after 96 h. Results are standardized to an average of 1.0 in the control. Data represent the mean ± standard deviation of three independent experiments (**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 1: Effects of Xingshentongqiao decoction (XSTQ) on proliferation of SH-SY5Y cells. (a) SH-SY5Y cell proliferation was determined by cell counting kit-8 assay after 0, 24, 48, 72, or 96 hours incubation without XSTQ (control) or with XSTQ at a concentration of 100, 200, 400, 600, 800, or 1000 μg/ml. Results are standardized to 1.0 at 0 hour. (b) The average proliferation of XSTQ-treated-SH-SY5Y cells is shown after 72 hours. Results are standardized to an average of 1.0 in the control. (c) Average proliferation of XSTQ-treated-SH-SY5Y cells is shown after 96 h. Results are standardized to an average of 1.0 in the control. Data represent the mean ± standard deviation of three independent experiments (**P < 0.01, *P < 0.05, vs. untreated control).
Mentions: To determine whether XSTQ affects cell proliferation, we treated SH-SY5Y cells with a range of doses and times of XSTQ. SH-SY5Y proliferation was inhibited in a dose-dependent manner after 72 hours and 96 hours treatment with XSTQ at concentrations of 400–1000 μg/ml [Table 1, Figure 1]. These results suggest that XSTQ inhibits proliferation.

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