PMID- 31747910 OWN - NLM STAT- MEDLINE DCOM- 20200121 LR - 20200121 IS - 1472-6882 (Electronic) IS - 1472-6882 (Linking) VI - 19 IP - 1 DP - 2019 Nov 20 TI - Inhibitory effects of ChondroT and its constituent herbs on RANKL-induced osteoclastogenesis. PG - 319 LID - 10.1186/s12906-019-2737-8 [doi] LID - 319 AB - BACKGROUND: ChondroT is a complex herbal medicine consisting of water extracts of Ostericum koreanum (Maxim.) Kitag., Lonicera japonica Thunb., Angelica gigas Nakai, Clematis manshurica Rupr., and Phellodendron amurense Rupr. (6:4:4:4:3). Previous studies have reported that ChondroT possesses chondroprotective and anti-inflammatory, anti-osteoarthritic, and anti-hyperuricemic activities. The study is aim to demonstrate the effects of ChondroT and its five constituent herbs on receptor activator of NF-kappaB ligand (RANKL)-induced osteoclastogenesis and the underlying mechanisms. METHODS: Osteoclastogenesis was identified in bone marrow-derived macrophages (BMDMs) by tartrate-resistant acid phosphatase (TRAP) staining assay, actin ring formation assay and the bone resorption assay. For the molecular mechanisms, activation of RANKL-induced NF-kappaB and MAPK signaling pathways and the expression levels of osteoclast-specific proteins were investigated by Western blotting. Cell viability was assessed by MTT assay. Actin ring formation and NF-kappaB translocation were evaluated by immunostaining. RESULTS: ChondroT and each of its constituent herbs significantly suppressed osteoclast differentiation dose dependently, and decreased actin ring formation as well as bone-resorbing capacity. Mechanistically, ChondroT and its constituent herbs downregulated the expressional levels of osteoclast-specific proteins such as NFATc1, c-Fos, Cathepsin K, and matrix metalloproteinase 9 (MMP9) by suppressing NF-kappaB translocation to nucleus and MAPKs phosphorylation at different levels. Compared to its five constituent herbs, ChondroT exhibited the best inhibitory efficiency against osteoclastogenesis. CONCLUSIONS: Taken together, ChondroT has anti-osteoclastogenesis properties by inhibiting NF-kappaB and MAPKs pathways. It could be considered as a potential therapeutic candidate for the treatment of osteoclast-related bone diseases. FAU - Guo, Rui Hong AU - Guo RH AD - College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, 500-757, Republic of Korea. FAU - Kim, Seon-Jong AU - Kim SJ AD - College of Korean Medicine, Dongshin University, 185 Geonjae-ro, Naju-si, Jeollanam-do, 58245, Republic of Korea. FAU - Choi, Chan-Hun AU - Choi CH AD - College of Korean Medicine, Dongshin University, 185 Geonjae-ro, Naju-si, Jeollanam-do, 58245, Republic of Korea. FAU - Na, Chang-Su AU - Na CS AD - College of Korean Medicine, Dongshin University, 185 Geonjae-ro, Naju-si, Jeollanam-do, 58245, Republic of Korea. FAU - Kang, Bok Yun AU - Kang BY AD - College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, 500-757, Republic of Korea. FAU - Kim, Young Ran AU - Kim YR AD - College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, 500-757, Republic of Korea. kimyr@chonnam.ac.kr. LA - eng GR - HI17C0911/Korea Health Industry Development Institute/Republic of Korea PT - Journal Article DEP - 20191120 PL - England TA - BMC Complement Altern Med JT - BMC complementary and alternative medicine JID - 101088661 RN - 0 (Plant Preparations) RN - 0 (RANK Ligand) SB - IM MH - Animals MH - Cell Line MH - Cell Survival/drug effects MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Osteoclasts/*drug effects MH - Osteogenesis/*drug effects MH - Plant Preparations/*pharmacology MH - RANK Ligand/*pharmacology PMC - PMC6864957 OTO - NOTNLM OT - Bone resorption OT - ChondroT OT - MAPKs OT - NF-kappaB OT - Osteoclast COIS- The authors declare that they have no competing interests. EDAT- 2019/11/22 06:00 MHDA- 2020/01/22 06:00 PMCR- 2019/11/20 CRDT- 2019/11/22 06:00 PHST- 2019/06/07 00:00 [received] PHST- 2019/10/31 00:00 [accepted] PHST- 2019/11/22 06:00 [entrez] PHST- 2019/11/22 06:00 [pubmed] PHST- 2020/01/22 06:00 [medline] PHST- 2019/11/20 00:00 [pmc-release] AID - 10.1186/s12906-019-2737-8 [pii] AID - 2737 [pii] AID - 10.1186/s12906-019-2737-8 [doi] PST - epublish SO - BMC Complement Altern Med. 2019 Nov 20;19(1):319. doi: 10.1186/s12906-019-2737-8.