Metabolites from Actinomyces strain H6552 extract inhibit transforming growth factor mediated pulmonary fibrosis
Purpose: To evaluate the effects of H6552 extract in inhibiting transforming growth factor (TGF)-mediated pulmonary fibrosis in vitro and in vivo. Methods: Maximum-nontoxic dose (MNTD) of Actinomyces H6552 extract was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphhenyltetrazolium bromide (M...
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| Format: | Article |
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Pharmacotherapy Group, Faculty of Pharmacy, University of Benin
2014
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| Online Access: | http://psasir.upm.edu.my/id/eprint/34496/ |
| _version_ | 1848847789305364480 |
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| author | Koh, Rhun Yian Lim, Chooi Ling Ho, Coy Choke Uhal, Bruce David Abdullah, Maha Vidyadaran, Sharmili Seow, Heng Fong |
| author_facet | Koh, Rhun Yian Lim, Chooi Ling Ho, Coy Choke Uhal, Bruce David Abdullah, Maha Vidyadaran, Sharmili Seow, Heng Fong |
| author_sort | Koh, Rhun Yian |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Purpose: To evaluate the effects of H6552 extract in inhibiting transforming growth factor (TGF)-mediated pulmonary fibrosis in vitro and in vivo.
Methods: Maximum-nontoxic dose (MNTD) of Actinomyces H6552 extract was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphhenyltetrazolium bromide (MTT) assay. Effect of the extract on IMR-90 lung fibroblasts proliferation was determined by calculating the population doubling time (PDT). Collagen gel contraction assay was carried out to determine cell contractility while α-smooth muscle actin (SMA) level in cells was evaluated by quantitative real-time polymerase chain reaction (PCR) and immunostaining methods. A bleomycin-induced ICR mouse model was used in the study to determine the effect of the extract in vivo. The animals received treatments in two regimes: early treatment in which treatment was given on Day 0 and delayed treatment with treatment on Days 5 and 10. The animals were sacrificed on Day 14 and the lungs removed for histopathological assessment.
Results: The MNTD of the H6552 extract was 1625 ± 459.62 μg/ml. H6552 extract significantly reduced TGF- β-mediated cell proliferation, gel contraction and α-SMA expression. PDT was increased up to 83.84 % in the treated cells. Gel contraction was inhibited by the addition of 1000 μg/ml of H6552 extract. Immunostaining results revealed negligible α-SMA antibody staining after H6552 extract treatment at 500 μg/ml. The extract also inhibited lung injury (54 % reduction in Ashcroft score) when early treatment was provided. Delayed treatment with the extract did not show any significant changes in the animals.
Conclusion: H6552 extract inhibited TGF-β-induced pulmonary fibrosis and elucidation of its bioactive metabolites may yield a potential agent to treat the disease. |
| first_indexed | 2025-11-15T09:24:11Z |
| format | Article |
| id | upm-34496 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-15T09:24:11Z |
| publishDate | 2014 |
| publisher | Pharmacotherapy Group, Faculty of Pharmacy, University of Benin |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-344962015-12-15T07:03:54Z http://psasir.upm.edu.my/id/eprint/34496/ Metabolites from Actinomyces strain H6552 extract inhibit transforming growth factor mediated pulmonary fibrosis Koh, Rhun Yian Lim, Chooi Ling Ho, Coy Choke Uhal, Bruce David Abdullah, Maha Vidyadaran, Sharmili Seow, Heng Fong Purpose: To evaluate the effects of H6552 extract in inhibiting transforming growth factor (TGF)-mediated pulmonary fibrosis in vitro and in vivo. Methods: Maximum-nontoxic dose (MNTD) of Actinomyces H6552 extract was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphhenyltetrazolium bromide (MTT) assay. Effect of the extract on IMR-90 lung fibroblasts proliferation was determined by calculating the population doubling time (PDT). Collagen gel contraction assay was carried out to determine cell contractility while α-smooth muscle actin (SMA) level in cells was evaluated by quantitative real-time polymerase chain reaction (PCR) and immunostaining methods. A bleomycin-induced ICR mouse model was used in the study to determine the effect of the extract in vivo. The animals received treatments in two regimes: early treatment in which treatment was given on Day 0 and delayed treatment with treatment on Days 5 and 10. The animals were sacrificed on Day 14 and the lungs removed for histopathological assessment. Results: The MNTD of the H6552 extract was 1625 ± 459.62 μg/ml. H6552 extract significantly reduced TGF- β-mediated cell proliferation, gel contraction and α-SMA expression. PDT was increased up to 83.84 % in the treated cells. Gel contraction was inhibited by the addition of 1000 μg/ml of H6552 extract. Immunostaining results revealed negligible α-SMA antibody staining after H6552 extract treatment at 500 μg/ml. The extract also inhibited lung injury (54 % reduction in Ashcroft score) when early treatment was provided. Delayed treatment with the extract did not show any significant changes in the animals. Conclusion: H6552 extract inhibited TGF-β-induced pulmonary fibrosis and elucidation of its bioactive metabolites may yield a potential agent to treat the disease. Pharmacotherapy Group, Faculty of Pharmacy, University of Benin 2014-11 Article PeerReviewed Koh, Rhun Yian and Lim, Chooi Ling and Ho, Coy Choke and Uhal, Bruce David and Abdullah, Maha and Vidyadaran, Sharmili and Seow, Heng Fong (2014) Metabolites from Actinomyces strain H6552 extract inhibit transforming growth factor mediated pulmonary fibrosis. Tropical Journal of Pharmaceutical Research, 13 (11). pp. 1815-1823. ISSN 1596-5996; ESSN: 1596-9827 http://www.tjpr.org/vol13_no11/2014_13_11_7.php 10.4314/tjpr.v13i11.7 |
| spellingShingle | Koh, Rhun Yian Lim, Chooi Ling Ho, Coy Choke Uhal, Bruce David Abdullah, Maha Vidyadaran, Sharmili Seow, Heng Fong Metabolites from Actinomyces strain H6552 extract inhibit transforming growth factor mediated pulmonary fibrosis |
| title | Metabolites from Actinomyces strain H6552 extract inhibit transforming growth factor mediated pulmonary fibrosis |
| title_full | Metabolites from Actinomyces strain H6552 extract inhibit transforming growth factor mediated pulmonary fibrosis |
| title_fullStr | Metabolites from Actinomyces strain H6552 extract inhibit transforming growth factor mediated pulmonary fibrosis |
| title_full_unstemmed | Metabolites from Actinomyces strain H6552 extract inhibit transforming growth factor mediated pulmonary fibrosis |
| title_short | Metabolites from Actinomyces strain H6552 extract inhibit transforming growth factor mediated pulmonary fibrosis |
| title_sort | metabolites from actinomyces strain h6552 extract inhibit transforming growth factor mediated pulmonary fibrosis |
| url | http://psasir.upm.edu.my/id/eprint/34496/ http://psasir.upm.edu.my/id/eprint/34496/ http://psasir.upm.edu.my/id/eprint/34496/ |