Continentalic Acid Rather Than Kaurenoic Acid Is Responsible for the Anti-Arthritic Activity of Manchurian Spikenard In Vitro and In Vivo
- Authors
- Hong, Riwon; Kim, Kyoung Soo; Choi, Gwang Muk; Yeom, Mijung; Lee, Bombi; Lee, Sanghyun; Kang, Ki Sung; Lee, Hyang Sook; Park, Hi-Joon; Hahm, Dae-Hyun
- Issue Date
- Nov-2019
- Publisher
- MDPI
- Keywords
- continentalic acid; Manchurian spikenard; osteoarthritis; chondrocyte; monoiodoacetate
- Citation
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.20, no.21
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- Volume
- 20
- Number
- 21
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/17998
- DOI
- 10.3390/ijms20215488
- ISSN
- 1661-6596
- Abstract
- The aim of this study was to identify the active compound responsible for the pharmacological activities of Manchurian spikenard (Aralia continentalis Kitag.). Interleukin (IL)-1 beta -stimulated human chondrocytes and monoiodoacetate (MIA)-induced osteoarthritic rats were treated with the 50% ethanolic extract of spikenard or its major components, such as continentalic acid (ent-pimara-8(14),15-diene-19-oic acid) and kaurenoic acid (ent-kaura-16-en-19-oic acid). The spikenard extract significantly inhibited IL-1 beta -stimulated production of IL-6, IL-8, metalloproteinase (MMP)-1, MMP-13, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) and prostaglandin(PG)E2 in a dose-dependent manner but not MMP-3 production. The extract also inhibited the IL-1 beta -induced translocation of NF-kappa B/p65 into the nucleus and dose-dependent phosphorylation levels of extracellular signal-regulated kinase (ERK), Jun amino-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase. Continentalic acid exhibited significant anti-arthritic activity corresponding exactly to that of the extract containing an equivalent amount of continentalic acid. On the other hand, kaurenoic acid exhibited a compatible activity at about a 10-times higher molar concentration than that of continentalic acid. In vitro anti-arthritic activities of the spikenard extract and continentalic acid were also confirmed in MIA-induced osteoarthritic rats. The 50% ethanolic extract of Manchurian spikenard exhibited promising anti-arthritic activities in the in vitro and in vivo osteoarthritis models, and continentalic acid, not kaurenoic acid, was most probably responsible for those activities.
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