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Biomolecular evidence of anti-inflammatory effects by Clematis mandshurica Ruprecht root extract in rodent cells.
J Ethnopharmacol. 2014 Sep 11; 155(2):1141-55.JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Clematis mandshurica Ruprecht root is widely used in Asia as an analgesic and anti-inflammatory agent. This research investigated the anti-inflammatory effects of Clematis mandshurica Ruprecht root extract (CRE) using RAW 264.7 macrophage cells and carrageenan- (CA-) induced rat paw edema.

MATERIALS AND METHODS

Production of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, nitric oxide (NO) and prostaglandin E2 (PGE2) in the culture supernatant, mRNA expression of TNF-α, IL-1β, IL-6, iNOS and COX-2, protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) in the extract were assayed. In addition, the effect of CRE on acute inflammation in vivo was observed using CA-induced rat hind paw edema assay. The changes on the histopathology and histomorphometry of hind paw skins-dorsum and ventrum pedis were observed using CA-treated rats.

RESULTS

Treatment with CRE (0.25, 0.5, and 1 mg/mL) resulted in inhibited levels of protein expression of lipopolysaccharide- (LPS-) induced iNOS, COX-2, NF-κB, and MAPKs (ERK, JNK, and p38) as well as production of TNF-α, IL-1β, IL-6, NO, and PGE2 induced by LPS. Consistent with these results, CRE reduced the LPS-induced expressions of these cytokines, iNOS and COX-2 at the mRNA levels in a dose-dependent manner. In particular, results of the CA-induced rat hind paw edema assay showed an anti-edema effect of CRE. In addition, treatment with CRE resulted in dose-dependent inhibition of CA-induced increases of skin thickness, mast cell degranulation, and infiltrated inflammatory, TNF-α, IL-1β, iNOS, and COX-2-positive cells in both dorsum and ventrum pedis skin, respectively.

CONCLUSIONS

These results demonstrate that CRE exhibits anti-inflammatory activities via decreasing production of pro-inflammatory mediators through suppression of the pathways of NF-κB and MAPKs in LPS-induced macrophage cells. In addition, results of the CA-induced rat hind paw edema assay show an anti-edema effect of CRE. Our findings also support the traditional use of CRE in the inflammatory symptoms of rheumatic arthritis and acute icteric hepatitis. Thus, CRE may have therapeutic potential for a variety of inflammation-mediated diseases and may be developed into potent anti-inflammatory drugs.

Authors+Show Affiliations

Institute of Marine BioTechnology, Pusan National University, Busan 609-735, Republic of Korea.College of Oriental Medicine, Daegu Haany University, Gyeongsan 712-715, Republic of Korea.School of Medicine, Pusan National University, Yangsan 626-870, Republic of Korea.College of Oriental Medicine, Daegu Haany University, Gyeongsan 712-715, Republic of Korea.Department of Pharmaceutical Engineering, Daegu Haany University, Gyeongsan 712-715, Republic of Korea.College of Oriental Medicine, Daegu Haany University, Gyeongsan 712-715, Republic of Korea.College of Oriental Medicine, Daegu Haany University, Gyeongsan 712-715, Republic of Korea.Institute of Marine BioTechnology, Pusan National University, Busan 609-735, Republic of Korea.Institute of Marine BioTechnology, Pusan National University, Busan 609-735, Republic of Korea.Institute of Marine BioTechnology, Pusan National University, Busan 609-735, Republic of Korea.Biomedical Research Center, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan 680-749, Republic of Korea.College of Oriental Medicine, Daegu Haany University, Gyeongsan 712-715, Republic of Korea. Electronic address: sckim@dhu.ac.kr.Institute of Marine BioTechnology, Pusan National University, Busan 609-735, Republic of Korea; Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea. Electronic address: wgan@pusan.ac.kr.

Pub Type(s)

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

Language

eng

PubMed ID

24975194

Citation

Lee, Chul Won, et al. "Biomolecular Evidence of Anti-inflammatory Effects By Clematis Mandshurica Ruprecht Root Extract in Rodent Cells." Journal of Ethnopharmacology, vol. 155, no. 2, 2014, pp. 1141-55.
Lee CW, Park SM, Kim YS, et al. Biomolecular evidence of anti-inflammatory effects by Clematis mandshurica Ruprecht root extract in rodent cells. J Ethnopharmacol. 2014;155(2):1141-55.
Lee, C. W., Park, S. M., Kim, Y. S., Jegal, K. H., Lee, J. R., Cho, I. J., Ku, S. K., Lee, J. Y., Ahn, Y. T., Son, Y., Ju, S. A., Kim, S. C., & An, W. G. (2014). Biomolecular evidence of anti-inflammatory effects by Clematis mandshurica Ruprecht root extract in rodent cells. Journal of Ethnopharmacology, 155(2), 1141-55. https://doi.org/10.1016/j.jep.2014.06.048
Lee CW, et al. Biomolecular Evidence of Anti-inflammatory Effects By Clematis Mandshurica Ruprecht Root Extract in Rodent Cells. J Ethnopharmacol. 2014 Sep 11;155(2):1141-55. PubMed PMID: 24975194.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Biomolecular evidence of anti-inflammatory effects by Clematis mandshurica Ruprecht root extract in rodent cells. AU - Lee,Chul Won, AU - Park,Sang Mi, AU - Kim,Youn Sook, AU - Jegal,Kyung Hwan, AU - Lee,Jong Rok, AU - Cho,Il Je, AU - Ku,Sae Kwang, AU - Lee,Ji Yeon, AU - Ahn,Yong-Tae, AU - Son,Yonghae, AU - Ju,Seong A, AU - Kim,Sang Chan, AU - An,Won G, Y1 - 2014/06/27/ PY - 2014/02/14/received PY - 2014/06/17/revised PY - 2014/06/18/accepted PY - 2014/7/1/entrez PY - 2014/7/1/pubmed PY - 2015/10/23/medline KW - Anti-inflammation KW - Clematis mandshurica Ruprecht KW - Histological examination KW - Mitogen-activated protein kinases KW - Nuclear factor-kappa B KW - Rat paw edema SP - 1141 EP - 55 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 155 IS - 2 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Clematis mandshurica Ruprecht root is widely used in Asia as an analgesic and anti-inflammatory agent. This research investigated the anti-inflammatory effects of Clematis mandshurica Ruprecht root extract (CRE) using RAW 264.7 macrophage cells and carrageenan- (CA-) induced rat paw edema. MATERIALS AND METHODS: Production of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, nitric oxide (NO) and prostaglandin E2 (PGE2) in the culture supernatant, mRNA expression of TNF-α, IL-1β, IL-6, iNOS and COX-2, protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) in the extract were assayed. In addition, the effect of CRE on acute inflammation in vivo was observed using CA-induced rat hind paw edema assay. The changes on the histopathology and histomorphometry of hind paw skins-dorsum and ventrum pedis were observed using CA-treated rats. RESULTS: Treatment with CRE (0.25, 0.5, and 1 mg/mL) resulted in inhibited levels of protein expression of lipopolysaccharide- (LPS-) induced iNOS, COX-2, NF-κB, and MAPKs (ERK, JNK, and p38) as well as production of TNF-α, IL-1β, IL-6, NO, and PGE2 induced by LPS. Consistent with these results, CRE reduced the LPS-induced expressions of these cytokines, iNOS and COX-2 at the mRNA levels in a dose-dependent manner. In particular, results of the CA-induced rat hind paw edema assay showed an anti-edema effect of CRE. In addition, treatment with CRE resulted in dose-dependent inhibition of CA-induced increases of skin thickness, mast cell degranulation, and infiltrated inflammatory, TNF-α, IL-1β, iNOS, and COX-2-positive cells in both dorsum and ventrum pedis skin, respectively. CONCLUSIONS: These results demonstrate that CRE exhibits anti-inflammatory activities via decreasing production of pro-inflammatory mediators through suppression of the pathways of NF-κB and MAPKs in LPS-induced macrophage cells. In addition, results of the CA-induced rat hind paw edema assay show an anti-edema effect of CRE. Our findings also support the traditional use of CRE in the inflammatory symptoms of rheumatic arthritis and acute icteric hepatitis. Thus, CRE may have therapeutic potential for a variety of inflammation-mediated diseases and may be developed into potent anti-inflammatory drugs. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/24975194/Biomolecular_evidence_of_anti_inflammatory_effects_by_Clematis_mandshurica_Ruprecht_root_extract_in_rodent_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(14)00496-6 DB - PRIME DP - Unbound Medicine ER -