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DXXK exerts anti-inflammatory effects by inhibiting the lipopolysaccharide-induced NF-κB/COX-2 signalling pathway and the expression of inflammatory mediators.
J Ethnopharmacol 2016; 178:199-208JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Diao Xin Xue Kang (DXXK) is the active pharmaceutical ingredient of the traditional Chinese medicinal product DXXK capsules, which have been approved for the treatment of cardiovascular disease and have been widely used clinically in China for many years with distinct curative effects. In March 2012, DXXK capsules were approved in the Netherlands, making them the first traditional herbal medicinal product (THMP) made outside of Europe.

AIM

To assess the anti-inflammatory effects of DXXK and the underlying mechanisms at the cellular and molecular levels.

MATERIALS AND METHODS

In this study, lipopolysaccharide (LPS) was used to induce inflammation in RAW 264.7 cells. The sulphorhodamine B (SRB) assay was used to study the effect of DXXK on the proliferation of RAW 264.7 cells. Gene expression levels of cyclooxygenase 1 (COX-1), COX-2, tumour necrosis factor-alpha (TNF-α), IL-1β and IL-6 were assessed by reverse transcription polymerase chain reaction (RT-PCR), while COX-2 protein levels were evaluated using western blotting. The levels of PGE2 in the culture media were detected by enzyme-linked immunosorbent assay (ELISA), while TNF-α, IL-1β and IL-6 levels were detected using a Milliplex Map Mouse Cytokine Panel system. The activation and nuclear translocation of nuclear transcription factor κB (NF-κB) were studied using western blotting. In vivo studies in mice were carried out using the carrageenan-air pouch models of inflammation. In exudates, leucocytes were counted, total protein was determined using the Bradford assay, nitric oxide(NO) levels were assessed using the Griess reagent, and PGE2 and TNF-α levels were quantified by ELISA.

RESULTS

The SRB assay showed that at the doses used in this study (10, 20 and 40 μg/mL), DXXK did not affect the proliferation of RAW 264.7 cells. DXXK (10, 20 and 40 μg/mL) inhibited LPS-induced PGE2 production by down-regulating the expression of COX-2, without influencing COX-1 expression. We also demonstrated that DXXK reduced the expression of pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6, at both the gene and protein levels. Furthermore, DXXK inhibited LPS-induced NF-κB activation and nuclear translocation by suppressing the phosphorylation of IκB. Consistent with the in vitro results, the in vivo studies demonstrated that DXXK reduced leucocyte counts as well as total protein, NO, PGE2 and TNF-α levels in the exudates of mice with carrageenan-air pouch inflammation.

CONCLUSIONS

The current study revealed that DXXK has a significant anti-inflammatory effect that may be attributed to its inhibitory effect on the NF-κB/COX-2 pathway and associated inflammatory mediators, including PGE2, NO, TNF-α, IL-1β and IL-6. The current study provides additional evidence of the effects of DXXK in inflammation. Based on the combination of our results and previously reported data, we propose that DXXK has multiple pharmacological effects that could be harnessed to treat systemic diseases.

Authors+Show Affiliations

Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China.Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China.Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China.Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China.Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China.Sino-Dutch Centre for Preventative and Personalized Medicine, P.O. Box 360, 3700 AJ Zeist, The Netherlands.Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China. Electronic address: zouwenjun@vip.163.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26571085

Citation

Yu, Ya, et al. "DXXK Exerts Anti-inflammatory Effects By Inhibiting the Lipopolysaccharide-induced NF-κB/COX-2 Signalling Pathway and the Expression of Inflammatory Mediators." Journal of Ethnopharmacology, vol. 178, 2016, pp. 199-208.
Yu Y, Li X, Qu L, et al. DXXK exerts anti-inflammatory effects by inhibiting the lipopolysaccharide-induced NF-κB/COX-2 signalling pathway and the expression of inflammatory mediators. J Ethnopharmacol. 2016;178:199-208.
Yu, Y., Li, X., Qu, L., Chen, Y., Dai, Y., Wang, M., & Zou, W. (2016). DXXK exerts anti-inflammatory effects by inhibiting the lipopolysaccharide-induced NF-κB/COX-2 signalling pathway and the expression of inflammatory mediators. Journal of Ethnopharmacology, 178, pp. 199-208. doi:10.1016/j.jep.2015.11.016.
Yu Y, et al. DXXK Exerts Anti-inflammatory Effects By Inhibiting the Lipopolysaccharide-induced NF-κB/COX-2 Signalling Pathway and the Expression of Inflammatory Mediators. J Ethnopharmacol. 2016 Feb 3;178:199-208. PubMed PMID: 26571085.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - DXXK exerts anti-inflammatory effects by inhibiting the lipopolysaccharide-induced NF-κB/COX-2 signalling pathway and the expression of inflammatory mediators. AU - Yu,Ya, AU - Li,Xiang, AU - Qu,Liping, AU - Chen,Yang, AU - Dai,Yanping, AU - Wang,Mei, AU - Zou,Wenjun, Y1 - 2015/11/10/ PY - 2015/05/07/received PY - 2015/08/05/revised PY - 2015/11/06/accepted PY - 2015/11/17/entrez PY - 2015/11/17/pubmed PY - 2016/10/16/medline KW - Anti-inflammatory effect KW - COX KW - Diao Xin Xue Kang KW - Inflammatory mediators KW - NF-κB SP - 199 EP - 208 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 178 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Diao Xin Xue Kang (DXXK) is the active pharmaceutical ingredient of the traditional Chinese medicinal product DXXK capsules, which have been approved for the treatment of cardiovascular disease and have been widely used clinically in China for many years with distinct curative effects. In March 2012, DXXK capsules were approved in the Netherlands, making them the first traditional herbal medicinal product (THMP) made outside of Europe. AIM: To assess the anti-inflammatory effects of DXXK and the underlying mechanisms at the cellular and molecular levels. MATERIALS AND METHODS: In this study, lipopolysaccharide (LPS) was used to induce inflammation in RAW 264.7 cells. The sulphorhodamine B (SRB) assay was used to study the effect of DXXK on the proliferation of RAW 264.7 cells. Gene expression levels of cyclooxygenase 1 (COX-1), COX-2, tumour necrosis factor-alpha (TNF-α), IL-1β and IL-6 were assessed by reverse transcription polymerase chain reaction (RT-PCR), while COX-2 protein levels were evaluated using western blotting. The levels of PGE2 in the culture media were detected by enzyme-linked immunosorbent assay (ELISA), while TNF-α, IL-1β and IL-6 levels were detected using a Milliplex Map Mouse Cytokine Panel system. The activation and nuclear translocation of nuclear transcription factor κB (NF-κB) were studied using western blotting. In vivo studies in mice were carried out using the carrageenan-air pouch models of inflammation. In exudates, leucocytes were counted, total protein was determined using the Bradford assay, nitric oxide(NO) levels were assessed using the Griess reagent, and PGE2 and TNF-α levels were quantified by ELISA. RESULTS: The SRB assay showed that at the doses used in this study (10, 20 and 40 μg/mL), DXXK did not affect the proliferation of RAW 264.7 cells. DXXK (10, 20 and 40 μg/mL) inhibited LPS-induced PGE2 production by down-regulating the expression of COX-2, without influencing COX-1 expression. We also demonstrated that DXXK reduced the expression of pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6, at both the gene and protein levels. Furthermore, DXXK inhibited LPS-induced NF-κB activation and nuclear translocation by suppressing the phosphorylation of IκB. Consistent with the in vitro results, the in vivo studies demonstrated that DXXK reduced leucocyte counts as well as total protein, NO, PGE2 and TNF-α levels in the exudates of mice with carrageenan-air pouch inflammation. CONCLUSIONS: The current study revealed that DXXK has a significant anti-inflammatory effect that may be attributed to its inhibitory effect on the NF-κB/COX-2 pathway and associated inflammatory mediators, including PGE2, NO, TNF-α, IL-1β and IL-6. The current study provides additional evidence of the effects of DXXK in inflammation. Based on the combination of our results and previously reported data, we propose that DXXK has multiple pharmacological effects that could be harnessed to treat systemic diseases. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/26571085/DXXK_exerts_anti_inflammatory_effects_by_inhibiting_the_lipopolysaccharide_induced_NF_κB/COX_2_signalling_pathway_and_the_expression_of_inflammatory_mediators_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(15)30218-X DB - PRIME DP - Unbound Medicine ER -