title: Mori folium inhibits interleukin-1β-induced expression of matrix metalloproteinases and inflammatory mediators by suppressing the activation of NF-κB and p38 MAPK in SW1353 human chondrocytes.
abstract: The pro-inflammatory cytokine interleukin-1β (IL-1β) is known to play a crucial role in the pathogenesis of osteoarthritis (OA) by stimulating several mediators that contribute to cartilage degradation. Mori folium, the leaves of Morus alba L., has long been used in traditional medicine to treat diabetes, protect the liver, and lower blood pressure; however, the role of Mori folium in OA is not yet fully understood. Therefore, in the present study, we investigated whether Mori folium water extract (MF) inhibited the catabolic effects of IL-1β in vitro, and also whether it inhibited the matrix metalloproteinases (MMPs), inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2) through the attenuation of nuclear factor-κB (NF-κB) and mitogen activated protein kinase (MAPK) pathways in SW1353 human chondrocytes. MMP proteins in culture medium were determined using a cytokine‑specific enzyme-linked immunosorbent assay (ELISA). The production of NO and prostaglandin E2 (PGE2) were evaluated using Griess reagent and ELISA. Subsequently, the mRNA and protein levels of MMPs, iNOS, COX-2, NF-κB and MAPKs were examined by RT-qPCR and/or western blot analysis. The results indicate that MF significantly reduced the IL-1β‑induced release of MMP-1 and -13 in SW1353 cells, which was associated with the inhibition of MMP-1 and -13 mRNA and protein expression in a concentration‑dependent manner at concentrations with no cytotoxicity. MF also attenuated the IL-1β-induced production of NO and PGE2, and reduced iNOS and COX-2 expression. Furthermore, we noted that MF markedly suppressed the IL-1β‑induced nuclear translocation of NF-κB, which correlated with the inhibitory effects of MF on inhibitor-κB (IκB) degradation, and the phosphorylation of p38 MAPK was selectively restored by MF upon IL-1β stimulation. These results indicate that MF inhibited the production and expression of MMP-1 and -13 and inflammatory mediators, at least in part, through suppressing the activation of either NF-κB or p38 MAPK in IL-1β-treated SW1353 chondrocytes. Therefore, the novel findings of the present study suggest that MF is a potential therapeutic choice for chondroprotection against the collagen matrix breakdown in the cartilage of diseased tissues, such as those found in patients with arthritic disorders.
authors.affiliation: Anti-Aging Research Center, Dongeui University, Busan 614-714, Republic of Korea.
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Jeong
authors.affiliation: Anti-Aging Research Center, Dongeui University, Busan 614-714, Republic of Korea.
authors.forename: Hye Hyeon
authors.initials: HH
authors.lastname: Lee
authors.affiliation: Research Institute, Bio-Port Korea Inc., MarineBio-industry Development Center, Busan 619-912, Republic of Korea.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Research Institute, Bio-Port Korea Inc., MarineBio-industry Development Center, Busan 619-912, Republic of Korea.
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Kim
authors.affiliation: Research Institute, Bio-Port Korea Inc., MarineBio-industry Development Center, Busan 619-912, Republic of Korea.
authors.forename: Sung Goo
authors.initials: SG
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.
authors.forename: Su Hyun
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.affiliation: Department of Molecular Biology, College of Natural Sciences and Human Ecology, Dongeui University, Busan 614-714, Republic of Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Park
authors.affiliation: Herbal Medicine Resources Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea.
authors.forename: Ho Kyoung
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Horticultural Bioscience, College of Natural Resource and Life Sciences, Pusan National University, Miryang 627-706, Republic of Korea.
authors.forename: Young Whan
authors.initials: YW
authors.lastname: Choi
authors.affiliation: Anti-Aging Research Center, Dongeui University, Busan 614-714, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D002356:Cartilage / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D031625:Morus / Q000737:chemistry; D016328:NF-kappa B / Q000096:biosynthesis; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010003:Osteoarthritis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis*
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; D010936:Plant Extracts; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048051:p38 Mitogen-Activated Protein Kinases; D020782:Matrix Metalloproteinases; D015232:Dinoprostone