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

Riwon Hong,Hyang Sook Lee,Hi-Joon Park,Gwang Muk Choi,Mijung Yeom,Bombi Lee,Sanghyun Lee,Kyoung Soo Kim,Dae-Hyun Hahm,Ki Sung Kang

doi:10.3390/ijms20215488

Riwon Hong, Hyang Sook Lee + Show 8 more

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https://doi.org/10.3390/ijms20215488

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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.

Highlights

Non-mechanical wear and tear, as well as destructive inflammation in the joint cartilage, synovium and subchondral bones, is a relevant pathological condition causing the increase in morbidity and incident mortality in osteoarthritis (OA) patients
The 100% ethanolic extract exhibited serious inhibition of cell proliferation at 100 μg/mL, even though the contents of continentalic and kaurenoic acids were highest in 50%, not the 100%, ethanolic extraction (Table S1)
It can be assumed that the toxicity of Manchurian spikenard roots may not be attributed to continentalic or kaurenoic acid, and unidentified toxic compounds in the extract are probably more miscible in ethanol than in those two tested compounds

Summary

Introduction

Non-mechanical wear and tear, as well as destructive inflammation in the joint cartilage, synovium and subchondral bones, is a relevant pathological condition causing the increase in morbidity and incident mortality in osteoarthritis (OA) patients. Strategies to reduce such side effects should be considered when developing new medicines to treat OA in addition to the aim of improving the medicinal effectiveness of pain alleviation. In this respect, natural herbs and their active compounds targeting pain, inflammation or destructive joint erosion are an appropriate screening resource for isolating candidate medicines

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