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Int J Mol Sci. 2019 Nov 4;20(21). pii: E5488. doi: 10.3390/ijms20215488.

Continentalic Acid Rather Than Kaurenoic Acid Is Responsible for the Anti-Arthritic Activity of Manchurian Spikenard In Vitro and In Vivo.

Author information

1
Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul 02447, Korea. smsmjhjh@naver.com.
2
Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Seoul 02447, Korea. labrea46@naver.com.
3
Department of Biomedical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Korea. alsdud335@naver.com.
4
Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul 02447, Korea. myeom@khu.ac.kr.
5
Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul 02447, Korea. bombi@khu.ac.kr.
6
Department of Plant Science and Technology, Chung-Ang University, Anseong 17546, Korea. slee@cau.ac.kr.
7
College of Korean Medicine, Gachon University, Seongnam 13120, Korea. kkang@gachon.ac.kr.
8
Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul 02447, Korea. erc633@khu.ac.kr.
9
Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul 02447, Korea. acufind@khu.ac.kr.
10
Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul 02447, Korea. dhhahm@khu.ac.kr.
11
Department of Physiology, College of Medicine, Kyung Hee University, Seoul 02447, Korea. dhhahm@khu.ac.kr.
12
BioNanocomposite Research Center, Kyung Hee University, Seoul 02447, Korea. dhhahm@khu.ac.kr.

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)-1β-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-1β-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-1β-induced translocation of NF-κB/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.

KEYWORDS:

Manchurian spikenard; chondrocyte; continentalic acid; monoiodoacetate; osteoarthritis

PMID:
31690022
DOI:
10.3390/ijms20215488
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