Riwon Hong1, BongJun Sur2, Mijung Yeom2, Bombi Lee2, Kyoung Soo Kim3, Joyce P Rodriguez4, Sanghyun Lee4, Ki Sung Kang5, Chang-Ki Huh6, Sang Cheon Lee7, Dae-Hyun Hahm8. 1. Department of Science in Korean Medicine, Graduate School, Kyung Hee University, 02447 Seoul, Republic of Korea; Acupuncture and Meridian Science Research Center, Kyung Hee University, 02447 Seoul, Republic of Korea. 2. Acupuncture and Meridian Science Research Center, Kyung Hee University, 02447 Seoul, Republic of Korea. 3. Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, 02447 Seoul, Republic of Korea. 4. Department of Integrative Plant Science, Chung-Ang University, 17546 Anseong, Republic of Korea. 5. College of Korean Medicine, Gachon University, 13120 Seongnam, Republic of Korea. 6. Department of Food Science and Technology, Sunchon National University, 57922 Suncheon, Republic of Korea. 7. Imsil Cheese & Food Research Institute, 55918 Imsil, Republic of Korea. 8. Acupuncture and Meridian Science Research Center, Kyung Hee University, 02447 Seoul, Republic of Korea; Department of Physiology, School of Medicine, Kyung Hee University, 02447 Seoul, Republic of Korea. Electronic address: dhhahm@khu.ac.kr.
Abstract
BACKGROUND: Blocking the formation and invasive growth of pannus and its secretion of inflammatory cytokines and MMPs is important for treating rheumatoid arthritis. HYPOTHESIS/ PURPOSE: Anti-arthritic activity of Aralia continentalis Kitag., an oriental herbal medicine, and the underlying mechanisms involved were investigated. STUDY DESIGN: Anti-inflammatory and anti-nocicpetive activities of the ethanolic extract (50% v/v) of Aralia continentalis Kitag. harvested from Imsil, Korea (ACI) were investigated in IL-1β-stimulated human fibroblast-like synoviocyte (FLS) cells and rodent models of collagen-induced polyarthritis and carrageenan-induced acute paw pain. METHODS: In IL-1β-stimulated FLS cells derived from rheumatoid arthritis patients, the anti-inflammatory activity of ACI was examined by analyzing the expression levels of inflammatory mediators such as TNF-α, IL-6, IL-8, MMP-1, MMP-3, MMP-13, PGE2, and COX-2 using ELISA and RT-PCR analysis. The anti-arthritic activity of ACI was investigated by measuring body weight, squeaking score, paw volume, and arthritis index in collagen-induced polyarthritis mice. The anti-nociceptive activity of ACI was examined in the paw-pressure test and Tail-flick latency test in rats. RESULTS: The ethanolic extract (50% v/v) of ACI reduced the levels of TNF-α, IL-6, IL-8, MMP-1, and MMP-13 secreted by IL-1β-stimulated FLS cells, whereas MMP-3, COX-2, and PGE2 were not significantly affected. ACI inhibited the migration of NF-κB into the nucleus through the inhibition of ERK- and JNK-dependent MAP kinase pathways in IL-1β-stimulated FLS cells. In collagen-induced polyarthritis mice, oral administration of ACI extract (200 mg/kg) significantly alleviated arthritic behaviors. Histological observations of arthritic mouse knees were consistent with their behaviors. The anti-arthritic and anti-inflammatory activities of 200 mg/kg ACI extract were comparable to those of 10 mg/kg prednisolone when administered to mice. However, ACI administration did not significantly affect carrageenan-induced hyperalgesia or thermal nociception in rats. CONCLUSION: These results suggest that the ethanolic extract of ACI have significant anti-inflammatory and anti-arthritic effects in a rodent arthritis model and in IL-1β-stimulated FLS cells. Thus, ACI may be a useful candidate for developing pharmaceuticals or dietary supplements for the treatment of inflammatory arthritis.
BACKGROUND: Blocking the formation and invasive growth of pannus and its secretion of inflammatory cytokines and MMPs is important for treating rheumatoid arthritis. HYPOTHESIS/ PURPOSE: Anti-arthritic activity of Aralia continentalis Kitag., an oriental herbal medicine, and the underlying mechanisms involved were investigated. STUDY DESIGN: Anti-inflammatory and anti-nocicpetive activities of the ethanolic extract (50% v/v) of Aralia continentalis Kitag. harvested from Imsil, Korea (ACI) were investigated in IL-1β-stimulated human fibroblast-like synoviocyte (FLS) cells and rodent models of collagen-induced polyarthritis and carrageenan-induced acute paw pain. METHODS: In IL-1β-stimulated FLS cells derived from rheumatoid arthritis patients, the anti-inflammatory activity of ACI was examined by analyzing the expression levels of inflammatory mediators such as TNF-α, IL-6, IL-8, MMP-1, MMP-3, MMP-13, PGE2, and COX-2 using ELISA and RT-PCR analysis. The anti-arthritic activity of ACI was investigated by measuring body weight, squeaking score, paw volume, and arthritis index in collagen-induced polyarthritis mice. The anti-nociceptive activity of ACI was examined in the paw-pressure test and Tail-flick latency test in rats. RESULTS: The ethanolic extract (50% v/v) of ACI reduced the levels of TNF-α, IL-6, IL-8, MMP-1, and MMP-13 secreted by IL-1β-stimulated FLS cells, whereas MMP-3, COX-2, and PGE2 were not significantly affected. ACI inhibited the migration of NF-κB into the nucleus through the inhibition of ERK- and JNK-dependent MAP kinase pathways in IL-1β-stimulated FLS cells. In collagen-induced polyarthritis mice, oral administration of ACI extract (200 mg/kg) significantly alleviated arthritic behaviors. Histological observations of arthritic mouse knees were consistent with their behaviors. The anti-arthritic and anti-inflammatory activities of 200 mg/kg ACI extract were comparable to those of 10 mg/kg prednisolone when administered to mice. However, ACI administration did not significantly affect carrageenan-induced hyperalgesia or thermal nociception in rats. CONCLUSION: These results suggest that the ethanolic extract of ACI have significant anti-inflammatory and anti-arthritic effects in a rodent arthritis model and in IL-1β-stimulated FLS cells. Thus, ACI may be a useful candidate for developing pharmaceuticals or dietary supplements for the treatment of inflammatory arthritis.
Authors: Ana Paula S Dornellas; Nathan W Burnham; Kendall L Luhn; Maxwell V Petruzzi; Todd E Thiele; Montserrat Navarro Journal: Neuropharmacology Date: 2021-09-20 Impact factor: 5.250