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3,4-Dihydroxytoluene, a metabolite of rutin, inhibits inflammatory responses in lipopolysaccharide-activated macrophages by reducing the activation of NF-κB signaling.

Abstract

BACKGROUND

Saussurea involucrata (Kar. et Kir.) (S. involucrate), is a rare traditional Chinese medicinal herb. Rutin and hispidulin as well as their metabolites are flavonoids of the flavonol type that abound in S. involucrata, which has been reported to inhibit nonoxidative advanced glycation end products which was involved in physiological inflammation. This study aims to investigate the role of 3,4-dihydroxytoluene (DHT), a metabolite of rutin, in inflammatory inhibition and its involved mechanism.

METHODS

This study utilized lipopolysaccharide (LPS) stimulated murine macrophage cell line RAW 264.7 as inflammatory model. The inhibitory effects of DHT were evaluated by the expression level of several inflammation markers such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW264.7 after LPS treatment. In addition, underlying mechanisms, the activation of mitogen-activated protein kinases (MAPKs) and NF-κB, were also investigated.

RESULTS

Our results showed that DHT significantly suppressed the LPS-induced production of nitric oxide (NO), iNOS, and COX-2 in a dose-dependent manner without cytotoxicity. DHT also reduced the generation of proinflammatory cytokines majorly in tumor necrosis factor (TNF)-α and minor in interleukin (IL)-1β and IL-6. In addition, LPS-stimulated I-κBα phosphorylation and degradation followed by translocation of the nuclear factor κB (NF-kB)-p65 from the cytoplasm to the nucleus were attenuated after DHT treatment.

CONCLUSIONS

Combined, the results suggest that DHT might exert anti-inflammatory effects in vitro in LPS stimulated RAW 264.7 macrophages and is potential in adjuvant treatment in inflammation disease.

Authors+Show Affiliations

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableDepartment of Biotechnology and Animal Science, National Ilan University, Shen-Lung Road, Ilan 260, Taiwan. a221865880@yahoo.com.tw.

Pub Type(s)

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

Language

eng

PubMed ID

24417898

Citation

Su, Kang-Yi, et al. "3,4-Dihydroxytoluene, a Metabolite of Rutin, Inhibits Inflammatory Responses in Lipopolysaccharide-activated Macrophages By Reducing the Activation of NF-κB Signaling." BMC Complementary and Alternative Medicine, vol. 14, 2014, p. 21.
Su KY, Yu CY, Chen YP, et al. 3,4-Dihydroxytoluene, a metabolite of rutin, inhibits inflammatory responses in lipopolysaccharide-activated macrophages by reducing the activation of NF-κB signaling. BMC Complement Altern Med. 2014;14:21.
Su, K. Y., Yu, C. Y., Chen, Y. P., Hua, K. F., & Chen, Y. L. (2014). 3,4-Dihydroxytoluene, a metabolite of rutin, inhibits inflammatory responses in lipopolysaccharide-activated macrophages by reducing the activation of NF-κB signaling. BMC Complementary and Alternative Medicine, 14, p. 21. doi:10.1186/1472-6882-14-21.
Su KY, et al. 3,4-Dihydroxytoluene, a Metabolite of Rutin, Inhibits Inflammatory Responses in Lipopolysaccharide-activated Macrophages By Reducing the Activation of NF-κB Signaling. BMC Complement Altern Med. 2014 Jan 13;14:21. PubMed PMID: 24417898.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 3,4-Dihydroxytoluene, a metabolite of rutin, inhibits inflammatory responses in lipopolysaccharide-activated macrophages by reducing the activation of NF-κB signaling. AU - Su,Kang-Yi, AU - Yu,Chao Yuan, AU - Chen,Ya-Ping, AU - Hua,Kuo-Feng, AU - Chen,Yi-Lin Sophia, Y1 - 2014/01/13/ PY - 2013/06/22/received PY - 2014/01/10/accepted PY - 2014/1/15/entrez PY - 2014/1/15/pubmed PY - 2015/5/23/medline SP - 21 EP - 21 JF - BMC complementary and alternative medicine JO - BMC Complement Altern Med VL - 14 N2 - BACKGROUND: Saussurea involucrata (Kar. et Kir.) (S. involucrate), is a rare traditional Chinese medicinal herb. Rutin and hispidulin as well as their metabolites are flavonoids of the flavonol type that abound in S. involucrata, which has been reported to inhibit nonoxidative advanced glycation end products which was involved in physiological inflammation. This study aims to investigate the role of 3,4-dihydroxytoluene (DHT), a metabolite of rutin, in inflammatory inhibition and its involved mechanism. METHODS: This study utilized lipopolysaccharide (LPS) stimulated murine macrophage cell line RAW 264.7 as inflammatory model. The inhibitory effects of DHT were evaluated by the expression level of several inflammation markers such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW264.7 after LPS treatment. In addition, underlying mechanisms, the activation of mitogen-activated protein kinases (MAPKs) and NF-κB, were also investigated. RESULTS: Our results showed that DHT significantly suppressed the LPS-induced production of nitric oxide (NO), iNOS, and COX-2 in a dose-dependent manner without cytotoxicity. DHT also reduced the generation of proinflammatory cytokines majorly in tumor necrosis factor (TNF)-α and minor in interleukin (IL)-1β and IL-6. In addition, LPS-stimulated I-κBα phosphorylation and degradation followed by translocation of the nuclear factor κB (NF-kB)-p65 from the cytoplasm to the nucleus were attenuated after DHT treatment. CONCLUSIONS: Combined, the results suggest that DHT might exert anti-inflammatory effects in vitro in LPS stimulated RAW 264.7 macrophages and is potential in adjuvant treatment in inflammation disease. SN - 1472-6882 UR - https://www.unboundmedicine.com/medline/citation/24417898/34_Dihydroxytoluene_a_metabolite_of_rutin_inhibits_inflammatory_responses_in_lipopolysaccharide_activated_macrophages_by_reducing_the_activation_of_NF_κB_signaling_ L2 - https://bmccomplementalternmed.biomedcentral.com/articles/10.1186/1472-6882-14-21 DB - PRIME DP - Unbound Medicine ER -