In vitro and in silico studies of 7′′,8′′-buddlenol D anti-inflammatory lignans from Carallia brachiata as p38 MAP kinase inhibitors
Abstract Excessive macrophage activation induces the release of high levels of inflammatory mediators which not only amplify chronic inflammation and degenerative diseases but also exacerbate fever and retard wound healing. To identify anti-inflammatory molecules, we examined Carallia brachiata—a me...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-30475-5 |
| _version_ | 1797864654551121920 |
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| author | Nonthaneth Nalinratana Utid Suriya Chanyanuch Laprasert Nakuntwalai Wisidsri Preeyaporn Poldorn Thanyada Rungrotmongkol Wacharee Limpanasitthikul Ho-Cheng Wu Hsun-Shuo Chang Chaisak Chansriniyom |
| author_facet | Nonthaneth Nalinratana Utid Suriya Chanyanuch Laprasert Nakuntwalai Wisidsri Preeyaporn Poldorn Thanyada Rungrotmongkol Wacharee Limpanasitthikul Ho-Cheng Wu Hsun-Shuo Chang Chaisak Chansriniyom |
| author_sort | Nonthaneth Nalinratana |
| collection | DOAJ |
| description | Abstract Excessive macrophage activation induces the release of high levels of inflammatory mediators which not only amplify chronic inflammation and degenerative diseases but also exacerbate fever and retard wound healing. To identify anti-inflammatory molecules, we examined Carallia brachiata—a medicinal terrestrial plant from Rhizophoraceae. Furofuran lignans [(−)-(7′′R,8′′S)-buddlenol D (1) and (−)-(7′′S,8′′S)-buddlenol D (2)] isolated from the stem and bark inhibited nitric oxide (half maximal inhibitory concentration (IC50): 9.25 ± 2.69 and 8.43 ± 1.20 micromolar for 1 and 2, respectively) and prostaglandin E2 (IC50: 6.15 ± 0.39 and 5.70 ± 0.97 micromolar for 1 and 2, respectively) productions in lipopolysaccharide-induced RAW264.7 cells. From western blotting, 1 and 2 suppressed LPS-induced inducible nitric oxide synthase and cyclooxygenase-2 expression in a dose-dependent manner (0.3–30 micromolar). Moreover, analysis of the mitogen-activated protein kinase (MAPK) signaling pathway showed decreased p38 phosphorylation levels in 1- and 2-treated cells, while phosphorylated ERK1/2 and JNK levels were unaffected. This discovery agreed with in silico studies which suggested 1 and 2 bound to the ATP-binding site in p38-alpha MAPK based on predicted binding affinity and intermolecular interaction docking. In summary, 7′′,8′′-buddlenol D epimers demonstrated anti-inflammatory activities via p38 MAPK inhibition and may be used as viable anti-inflammatory therapies. |
| first_indexed | 2024-04-09T22:56:30Z |
| format | Article |
| id | doaj.art-ba735781d3224e15a6f06eab04bd0595 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T22:56:30Z |
| publishDate | 2023-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ba735781d3224e15a6f06eab04bd05952023-03-22T11:16:04ZengNature PortfolioScientific Reports2045-23222023-03-0113111310.1038/s41598-023-30475-5In vitro and in silico studies of 7′′,8′′-buddlenol D anti-inflammatory lignans from Carallia brachiata as p38 MAP kinase inhibitorsNonthaneth Nalinratana0Utid Suriya1Chanyanuch Laprasert2Nakuntwalai Wisidsri3Preeyaporn Poldorn4Thanyada Rungrotmongkol5Wacharee Limpanasitthikul6Ho-Cheng Wu7Hsun-Shuo Chang8Chaisak Chansriniyom9Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn UniversityProgram in Biotechnology, Faculty of Science, Chulalongkorn UniversityDepartment of Pharmacology, Faculty of Medicine, Chulalongkorn UniversityFaculty of Integrative Medicine, Rajamangala University of Technology ThanyaburiBiocatalyst and Environmental Biotechnology Research Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn UniversityBiocatalyst and Environmental Biotechnology Research Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn UniversityDepartment of Pharmacology, Faculty of Medicine, Chulalongkorn UniversityGraduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical UniversitySchool of Pharmacy, College of Pharmacy, Kaohsiung Medical UniversityDepartment of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn UniversityAbstract Excessive macrophage activation induces the release of high levels of inflammatory mediators which not only amplify chronic inflammation and degenerative diseases but also exacerbate fever and retard wound healing. To identify anti-inflammatory molecules, we examined Carallia brachiata—a medicinal terrestrial plant from Rhizophoraceae. Furofuran lignans [(−)-(7′′R,8′′S)-buddlenol D (1) and (−)-(7′′S,8′′S)-buddlenol D (2)] isolated from the stem and bark inhibited nitric oxide (half maximal inhibitory concentration (IC50): 9.25 ± 2.69 and 8.43 ± 1.20 micromolar for 1 and 2, respectively) and prostaglandin E2 (IC50: 6.15 ± 0.39 and 5.70 ± 0.97 micromolar for 1 and 2, respectively) productions in lipopolysaccharide-induced RAW264.7 cells. From western blotting, 1 and 2 suppressed LPS-induced inducible nitric oxide synthase and cyclooxygenase-2 expression in a dose-dependent manner (0.3–30 micromolar). Moreover, analysis of the mitogen-activated protein kinase (MAPK) signaling pathway showed decreased p38 phosphorylation levels in 1- and 2-treated cells, while phosphorylated ERK1/2 and JNK levels were unaffected. This discovery agreed with in silico studies which suggested 1 and 2 bound to the ATP-binding site in p38-alpha MAPK based on predicted binding affinity and intermolecular interaction docking. In summary, 7′′,8′′-buddlenol D epimers demonstrated anti-inflammatory activities via p38 MAPK inhibition and may be used as viable anti-inflammatory therapies.https://doi.org/10.1038/s41598-023-30475-5 |
| spellingShingle | Nonthaneth Nalinratana Utid Suriya Chanyanuch Laprasert Nakuntwalai Wisidsri Preeyaporn Poldorn Thanyada Rungrotmongkol Wacharee Limpanasitthikul Ho-Cheng Wu Hsun-Shuo Chang Chaisak Chansriniyom In vitro and in silico studies of 7′′,8′′-buddlenol D anti-inflammatory lignans from Carallia brachiata as p38 MAP kinase inhibitors Scientific Reports |
| title | In vitro and in silico studies of 7′′,8′′-buddlenol D anti-inflammatory lignans from Carallia brachiata as p38 MAP kinase inhibitors |
| title_full | In vitro and in silico studies of 7′′,8′′-buddlenol D anti-inflammatory lignans from Carallia brachiata as p38 MAP kinase inhibitors |
| title_fullStr | In vitro and in silico studies of 7′′,8′′-buddlenol D anti-inflammatory lignans from Carallia brachiata as p38 MAP kinase inhibitors |
| title_full_unstemmed | In vitro and in silico studies of 7′′,8′′-buddlenol D anti-inflammatory lignans from Carallia brachiata as p38 MAP kinase inhibitors |
| title_short | In vitro and in silico studies of 7′′,8′′-buddlenol D anti-inflammatory lignans from Carallia brachiata as p38 MAP kinase inhibitors |
| title_sort | in vitro and in silico studies of 7 8 buddlenol d anti inflammatory lignans from carallia brachiata as p38 map kinase inhibitors |
| url | https://doi.org/10.1038/s41598-023-30475-5 |
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