In Vitro Study of Licorice on IL-1β-Induced Chondrocytes and In Silico Approach for Osteoarthritis

Osteoarthritis (OA) is a common degenerative joint disorder that affects joint function, mobility, and pain. The release of proinflammatory cytokines stimulates matrix metalloproteinases (MMPs) and aggrecanase production which further induces articular cartilage degradation. Hypertrophy-like changes...

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Main Authors: Akhtar Ali, YoungJoon Park, Jeonghoon Lee, Hyo-Jin An, Jong-Sik Jin, Jong-Hyun Lee, Jaeki Chang, Dong-Keun Kim, Bonhyuk Goo, Yeon Cheol Park, Kang-Hyun Leem, Shin Seong, Wonnam Kim
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/14/12/1337
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author Akhtar Ali
YoungJoon Park
Jeonghoon Lee
Hyo-Jin An
Jong-Sik Jin
Jong-Hyun Lee
Jaeki Chang
Dong-Keun Kim
Bonhyuk Goo
Yeon Cheol Park
Kang-Hyun Leem
Shin Seong
Wonnam Kim
author_facet Akhtar Ali
YoungJoon Park
Jeonghoon Lee
Hyo-Jin An
Jong-Sik Jin
Jong-Hyun Lee
Jaeki Chang
Dong-Keun Kim
Bonhyuk Goo
Yeon Cheol Park
Kang-Hyun Leem
Shin Seong
Wonnam Kim
author_sort Akhtar Ali
collection DOAJ
description Osteoarthritis (OA) is a common degenerative joint disorder that affects joint function, mobility, and pain. The release of proinflammatory cytokines stimulates matrix metalloproteinases (MMPs) and aggrecanase production which further induces articular cartilage degradation. Hypertrophy-like changes in chondrocytes are considered to be an important feature of OA pathogenesis. A <i>Glycyrrhiza</i> new variety, Wongam (WG), was developed by the Korea Rural Development Administration to enhance the cultivation and quality of Glycyrrhizae Radix et Rhizoma (licorice). This study examined the regulatory effect of WG against hypertrophy-like changes such as RUNX2, Collagen X, VEGFA, MMP-13 induction, and Collagen II reduction induced by IL-1β in SW1353 human chondrocytes. Additionally, in silico methods were performed to identify active compounds in licorice to target chondrocyte hypertrophy-related proteins. WG showed inhibitory effects against IL-1β-induced chondrocyte hypertrophy by regulating both HDAC4 activation via the PTH1R/PKA/PP2A pathway and the SOX9/β-catenin signaling pathway. In silico analysis demonstrated that 21 active compounds from licorice have binding potential with 11 targets related to chondrocyte hypertrophy. Further molecular docking analysis and in vivo studies elicited four compounds. Based on HPLC, isoliquiritigenin and its precursors were identified and quantified. Taken together, WG is a potential therapeutic agent for chondrocyte hypertrophy-like changes in OA.
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spelling doaj.art-c46d59e1246f42b1a96ed032b346be9c2023-11-23T10:04:17ZengMDPI AGPharmaceuticals1424-82472021-12-011412133710.3390/ph14121337In Vitro Study of Licorice on IL-1β-Induced Chondrocytes and In Silico Approach for OsteoarthritisAkhtar Ali0YoungJoon Park1Jeonghoon Lee2Hyo-Jin An3Jong-Sik Jin4Jong-Hyun Lee5Jaeki Chang6Dong-Keun Kim7Bonhyuk Goo8Yeon Cheol Park9Kang-Hyun Leem10Shin Seong11Wonnam Kim12Cnh Center for Cancer Research, Cnh Corporation, Gangnam-gu, Seoul 06154, KoreaCnh Center for Cancer Research, Cnh Corporation, Gangnam-gu, Seoul 06154, KoreaHerbal Crop Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 27709, Chungcheongbuk-do, KoreaDepartment of Pharmacology, College of Korean Medicine, Sangji University, Wonju 26339, Gangwon-do, KoreaDepartment of Oriental Medicine Resources, Jeonbuk National University, Iksan 54596, Jeollabuk-do, KoreaDepartment of Natural Medicine, College of Pharmacy, Dongduk Women’s University, Seongbuk-gu, Seoul 02748, KoreaCrop Production & Physiology Division, National Institute of Crop Science, Rural Development Administration, Wanju 55365, Jeollabuk-do, KoreaDepartment of Oriental Medicine Resources, Jeonbuk National University, Iksan 54596, Jeollabuk-do, KoreaDepartment of Acupuncture & Moxibustion, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul 05278, KoreaDepartment of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Kyung Hee University, Dongdaemun-gu, Seoul 02447, KoreaDivision of Pharmacology, College of Korean Medicine, Semyung University, Jecheon 27136, Chungcheongbuk-do, KoreaSoram Korean Medicine Hospital, Gangnam-gu, Seoul 06154, KoreaCnh Center for Cancer Research, Cnh Corporation, Gangnam-gu, Seoul 06154, KoreaOsteoarthritis (OA) is a common degenerative joint disorder that affects joint function, mobility, and pain. The release of proinflammatory cytokines stimulates matrix metalloproteinases (MMPs) and aggrecanase production which further induces articular cartilage degradation. Hypertrophy-like changes in chondrocytes are considered to be an important feature of OA pathogenesis. A <i>Glycyrrhiza</i> new variety, Wongam (WG), was developed by the Korea Rural Development Administration to enhance the cultivation and quality of Glycyrrhizae Radix et Rhizoma (licorice). This study examined the regulatory effect of WG against hypertrophy-like changes such as RUNX2, Collagen X, VEGFA, MMP-13 induction, and Collagen II reduction induced by IL-1β in SW1353 human chondrocytes. Additionally, in silico methods were performed to identify active compounds in licorice to target chondrocyte hypertrophy-related proteins. WG showed inhibitory effects against IL-1β-induced chondrocyte hypertrophy by regulating both HDAC4 activation via the PTH1R/PKA/PP2A pathway and the SOX9/β-catenin signaling pathway. In silico analysis demonstrated that 21 active compounds from licorice have binding potential with 11 targets related to chondrocyte hypertrophy. Further molecular docking analysis and in vivo studies elicited four compounds. Based on HPLC, isoliquiritigenin and its precursors were identified and quantified. Taken together, WG is a potential therapeutic agent for chondrocyte hypertrophy-like changes in OA.https://www.mdpi.com/1424-8247/14/12/1337osteoarthritischondrocyte hypertrophylicoriceWongam
spellingShingle Akhtar Ali
YoungJoon Park
Jeonghoon Lee
Hyo-Jin An
Jong-Sik Jin
Jong-Hyun Lee
Jaeki Chang
Dong-Keun Kim
Bonhyuk Goo
Yeon Cheol Park
Kang-Hyun Leem
Shin Seong
Wonnam Kim
In Vitro Study of Licorice on IL-1β-Induced Chondrocytes and In Silico Approach for Osteoarthritis
Pharmaceuticals
osteoarthritis
chondrocyte hypertrophy
licorice
Wongam
title In Vitro Study of Licorice on IL-1β-Induced Chondrocytes and In Silico Approach for Osteoarthritis
title_full In Vitro Study of Licorice on IL-1β-Induced Chondrocytes and In Silico Approach for Osteoarthritis
title_fullStr In Vitro Study of Licorice on IL-1β-Induced Chondrocytes and In Silico Approach for Osteoarthritis
title_full_unstemmed In Vitro Study of Licorice on IL-1β-Induced Chondrocytes and In Silico Approach for Osteoarthritis
title_short In Vitro Study of Licorice on IL-1β-Induced Chondrocytes and In Silico Approach for Osteoarthritis
title_sort in vitro study of licorice on il 1β induced chondrocytes and in silico approach for osteoarthritis
topic osteoarthritis
chondrocyte hypertrophy
licorice
Wongam
url https://www.mdpi.com/1424-8247/14/12/1337
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