Network analysis, in vivo, and in vitro experiments identified the mechanisms by which Piper longum L. [Piperaceae] alleviates cartilage destruction, joint inflammation, and arthritic pain
Osteoarthritis (OA) is characterized by irreversible joint destruction, pain, and dysfunction. Piper longum L. [Piperaceae] (PL) is an East Asian herbal medicine with reported anti-inflammatory, analgesic, antioxidant, anti-stress, and anti-osteoporotic effects. This study aimed to evaluate the effi...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-01-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1282943/full |
| _version_ | 1797347873077067776 |
|---|---|
| author | Hee Geun Jo Hee Geun Jo Chae Yun Baek Donghwan Kim Sangjin Kim Yewon Han Chanlim Park Ho Sueb Song Donghun Lee |
| author_facet | Hee Geun Jo Hee Geun Jo Chae Yun Baek Donghwan Kim Sangjin Kim Yewon Han Chanlim Park Ho Sueb Song Donghun Lee |
| author_sort | Hee Geun Jo |
| collection | DOAJ |
| description | Osteoarthritis (OA) is characterized by irreversible joint destruction, pain, and dysfunction. Piper longum L. [Piperaceae] (PL) is an East Asian herbal medicine with reported anti-inflammatory, analgesic, antioxidant, anti-stress, and anti-osteoporotic effects. This study aimed to evaluate the efficacy of PL in inhibiting pain and progressive joint destruction in OA based on its anti-inflammatory activity, and to explore its potential mechanisms using in vivo and in vitro models of OA. We predicted the potential hub targets and signaling pathways of PL through network analysis and molecular docking. Network analysis results showed that the possible hub targets of PL against OA were F2R, F3, MMP1, MMP2, MMP9, and PTGS2. The molecular docking results predicted strong binding affinities for the core compounds in PL: piperlongumine, piperlonguminine, and piperine. In vitro experiments showed that PL inhibited the expression of LPS-induced pro-inflammatory factors, such as F2R, F3, IL-1β, IL-6, IL-17A, MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, NOS2, PTGS2, PGE2, and TNF-β. These mechanisms and effects were dose-dependent in vivo models. Furthermore, PL inhibited cartilage degradation in an OA-induced rat model. Thus, this study demonstrated that multiple components of PL may inhibit the multilayered pathology of OA by acting on multiple targets and pathways. These findings highlight the potential of PL as a disease-modifying OA drug candidate, which warrants further investigation. |
| first_indexed | 2024-03-08T11:54:09Z |
| format | Article |
| id | doaj.art-2c2f141ca4c24b40901b016ceb2344c1 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-08T11:54:09Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-2c2f141ca4c24b40901b016ceb2344c12024-01-24T04:49:20ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-01-011410.3389/fphar.2023.12829431282943Network analysis, in vivo, and in vitro experiments identified the mechanisms by which Piper longum L. [Piperaceae] alleviates cartilage destruction, joint inflammation, and arthritic painHee Geun Jo0Hee Geun Jo1Chae Yun Baek2Donghwan Kim3Sangjin Kim4Yewon Han5Chanlim Park6Ho Sueb Song7Donghun Lee8Department of Herbal Pharmacology, College of Korean Medicine, Gachon University, Seongnam-si, Republic of KoreaNaturalis Inc., Seongnam-si, Gyeonggi-do, Republic of KoreaDepartment of Herbal Pharmacology, College of Korean Medicine, Gachon University, Seongnam-si, Republic of KoreaDepartment of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul, Republic of KoreaNational Institute for Korean Medicine Development, Gyeongsan-si, Gyeongsangbuk-do, Republic of KoreaNational Institute for Korean Medicine Development, Gyeongsan-si, Gyeongsangbuk-do, Republic of KoreaSmart Software Lab Inc., Jeonju-si, Jeollabuk-do, Republic of KoreaDepartment of Acupuncture and Moxibustion Medicine, College of Korean Medicine, Gachon University, Seongnam-si, Republic of KoreaDepartment of Herbal Pharmacology, College of Korean Medicine, Gachon University, Seongnam-si, Republic of KoreaOsteoarthritis (OA) is characterized by irreversible joint destruction, pain, and dysfunction. Piper longum L. [Piperaceae] (PL) is an East Asian herbal medicine with reported anti-inflammatory, analgesic, antioxidant, anti-stress, and anti-osteoporotic effects. This study aimed to evaluate the efficacy of PL in inhibiting pain and progressive joint destruction in OA based on its anti-inflammatory activity, and to explore its potential mechanisms using in vivo and in vitro models of OA. We predicted the potential hub targets and signaling pathways of PL through network analysis and molecular docking. Network analysis results showed that the possible hub targets of PL against OA were F2R, F3, MMP1, MMP2, MMP9, and PTGS2. The molecular docking results predicted strong binding affinities for the core compounds in PL: piperlongumine, piperlonguminine, and piperine. In vitro experiments showed that PL inhibited the expression of LPS-induced pro-inflammatory factors, such as F2R, F3, IL-1β, IL-6, IL-17A, MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, NOS2, PTGS2, PGE2, and TNF-β. These mechanisms and effects were dose-dependent in vivo models. Furthermore, PL inhibited cartilage degradation in an OA-induced rat model. Thus, this study demonstrated that multiple components of PL may inhibit the multilayered pathology of OA by acting on multiple targets and pathways. These findings highlight the potential of PL as a disease-modifying OA drug candidate, which warrants further investigation.https://www.frontiersin.org/articles/10.3389/fphar.2023.1282943/fullPiper longum L. [Piperaceae]network analysisexperimental verificationosteoarthritisEast Asian herbal medicine |
| spellingShingle | Hee Geun Jo Hee Geun Jo Chae Yun Baek Donghwan Kim Sangjin Kim Yewon Han Chanlim Park Ho Sueb Song Donghun Lee Network analysis, in vivo, and in vitro experiments identified the mechanisms by which Piper longum L. [Piperaceae] alleviates cartilage destruction, joint inflammation, and arthritic pain Frontiers in Pharmacology Piper longum L. [Piperaceae] network analysis experimental verification osteoarthritis East Asian herbal medicine |
| title | Network analysis, in vivo, and in vitro experiments identified the mechanisms by which Piper longum L. [Piperaceae] alleviates cartilage destruction, joint inflammation, and arthritic pain |
| title_full | Network analysis, in vivo, and in vitro experiments identified the mechanisms by which Piper longum L. [Piperaceae] alleviates cartilage destruction, joint inflammation, and arthritic pain |
| title_fullStr | Network analysis, in vivo, and in vitro experiments identified the mechanisms by which Piper longum L. [Piperaceae] alleviates cartilage destruction, joint inflammation, and arthritic pain |
| title_full_unstemmed | Network analysis, in vivo, and in vitro experiments identified the mechanisms by which Piper longum L. [Piperaceae] alleviates cartilage destruction, joint inflammation, and arthritic pain |
| title_short | Network analysis, in vivo, and in vitro experiments identified the mechanisms by which Piper longum L. [Piperaceae] alleviates cartilage destruction, joint inflammation, and arthritic pain |
| title_sort | network analysis in vivo and in vitro experiments identified the mechanisms by which piper longum l piperaceae alleviates cartilage destruction joint inflammation and arthritic pain |
| topic | Piper longum L. [Piperaceae] network analysis experimental verification osteoarthritis East Asian herbal medicine |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1282943/full |
| work_keys_str_mv | AT heegeunjo networkanalysisinvivoandinvitroexperimentsidentifiedthemechanismsbywhichpiperlongumlpiperaceaealleviatescartilagedestructionjointinflammationandarthriticpain AT heegeunjo networkanalysisinvivoandinvitroexperimentsidentifiedthemechanismsbywhichpiperlongumlpiperaceaealleviatescartilagedestructionjointinflammationandarthriticpain AT chaeyunbaek networkanalysisinvivoandinvitroexperimentsidentifiedthemechanismsbywhichpiperlongumlpiperaceaealleviatescartilagedestructionjointinflammationandarthriticpain AT donghwankim networkanalysisinvivoandinvitroexperimentsidentifiedthemechanismsbywhichpiperlongumlpiperaceaealleviatescartilagedestructionjointinflammationandarthriticpain AT sangjinkim networkanalysisinvivoandinvitroexperimentsidentifiedthemechanismsbywhichpiperlongumlpiperaceaealleviatescartilagedestructionjointinflammationandarthriticpain AT yewonhan networkanalysisinvivoandinvitroexperimentsidentifiedthemechanismsbywhichpiperlongumlpiperaceaealleviatescartilagedestructionjointinflammationandarthriticpain AT chanlimpark networkanalysisinvivoandinvitroexperimentsidentifiedthemechanismsbywhichpiperlongumlpiperaceaealleviatescartilagedestructionjointinflammationandarthriticpain AT hosuebsong networkanalysisinvivoandinvitroexperimentsidentifiedthemechanismsbywhichpiperlongumlpiperaceaealleviatescartilagedestructionjointinflammationandarthriticpain AT donghunlee networkanalysisinvivoandinvitroexperimentsidentifiedthemechanismsbywhichpiperlongumlpiperaceaealleviatescartilagedestructionjointinflammationandarthriticpain |