A strategy for selective screening of dual-target bioactive compounds against hypertrophic scar through inhibiting angiotensin II type 1 receptor while stimulating type 2 receptor from Chinese herbs
Abstract Background Cutaneous hypertrophic scar is a fibro-proliferative hard-curing disease. Recent studies have proved that antagonists of angiotensin II type 1 receptor (AT1R) and agonists of type 2 receptor (AT2R) were able to relieve hypertrophic scar. Therefore, establishing new methods to pur...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Chinese Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13020-025-01065-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832571293607657472 |
|---|---|
| author | Lejing Qu Meizhi Jiao Zilong Zhang Yuanyuan Ou Xue Zhao Yajun Zhang Xinfeng Zhao |
| author_facet | Lejing Qu Meizhi Jiao Zilong Zhang Yuanyuan Ou Xue Zhao Yajun Zhang Xinfeng Zhao |
| author_sort | Lejing Qu |
| collection | DOAJ |
| description | Abstract Background Cutaneous hypertrophic scar is a fibro-proliferative hard-curing disease. Recent studies have proved that antagonists of angiotensin II type 1 receptor (AT1R) and agonists of type 2 receptor (AT2R) were able to relieve hypertrophic scar. Therefore, establishing new methods to pursue dual-target lead compounds from Chinese herbs is in much demand for treating scar. Methods To this end, we immobilized AT1R or AT2R onto the surface of silica gel from cell lysates through a specific covalent bond by bioorthogonal chemistry. The columns containing immobilized AT1R or AT2R were jointly utilized to pursue potential bioactive compounds simultaneously binding to AT1R and AT2R from the extract of Rhei Radix et Rhizoma. Their functions on AT1R and AT2R expressions were investigated by in vitro and in vivo experiments. Results Aloe-emodin and emodin were identified as the potential bioactive compounds binding to both of the two receptors, thereby improving the appearance and pathomorphology of hypertrophic scar. They blocked the AT1R pathway to down-regulate the expression of transforming growth factor-β1 (TGF-β1) and stimulate matrix metalloproteinase-1 (MMP-1) expression. As such, the expression of collagen I/III reduced. Conversely, the bindings of the two compounds to AT2R reduced the production of nuclear factor-кB1 (NF-кB1), whereby the generation of interleukin-6 (IL-6) was blocked. Conclusion We reasoned that aloe-emodin and emodin had the potential to become dual-target candidates against hypertrophic scar through the regulation of AT1R and AT2R signaling pathways. It showed considerable potential to become a universal strategy for pursuing multi-target bioactive compounds from Chinese herbs by the utilization of diverse immobilized receptors in a desired order. |
| format | Article |
| id | doaj-art-37fc80498d98444fb08baa64adf9dd5b |
| institution | Kabale University |
| issn | 1749-8546 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Chinese Medicine |
| spelling | doaj-art-37fc80498d98444fb08baa64adf9dd5b2025-02-02T12:42:35ZengBMCChinese Medicine1749-85462025-01-0120111510.1186/s13020-025-01065-6A strategy for selective screening of dual-target bioactive compounds against hypertrophic scar through inhibiting angiotensin II type 1 receptor while stimulating type 2 receptor from Chinese herbsLejing Qu0Meizhi Jiao1Zilong Zhang2Yuanyuan Ou3Xue Zhao4Yajun Zhang5Xinfeng Zhao6Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest UniversityKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest UniversityKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest UniversityKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest UniversityKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest UniversityKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest UniversityKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest UniversityAbstract Background Cutaneous hypertrophic scar is a fibro-proliferative hard-curing disease. Recent studies have proved that antagonists of angiotensin II type 1 receptor (AT1R) and agonists of type 2 receptor (AT2R) were able to relieve hypertrophic scar. Therefore, establishing new methods to pursue dual-target lead compounds from Chinese herbs is in much demand for treating scar. Methods To this end, we immobilized AT1R or AT2R onto the surface of silica gel from cell lysates through a specific covalent bond by bioorthogonal chemistry. The columns containing immobilized AT1R or AT2R were jointly utilized to pursue potential bioactive compounds simultaneously binding to AT1R and AT2R from the extract of Rhei Radix et Rhizoma. Their functions on AT1R and AT2R expressions were investigated by in vitro and in vivo experiments. Results Aloe-emodin and emodin were identified as the potential bioactive compounds binding to both of the two receptors, thereby improving the appearance and pathomorphology of hypertrophic scar. They blocked the AT1R pathway to down-regulate the expression of transforming growth factor-β1 (TGF-β1) and stimulate matrix metalloproteinase-1 (MMP-1) expression. As such, the expression of collagen I/III reduced. Conversely, the bindings of the two compounds to AT2R reduced the production of nuclear factor-кB1 (NF-кB1), whereby the generation of interleukin-6 (IL-6) was blocked. Conclusion We reasoned that aloe-emodin and emodin had the potential to become dual-target candidates against hypertrophic scar through the regulation of AT1R and AT2R signaling pathways. It showed considerable potential to become a universal strategy for pursuing multi-target bioactive compounds from Chinese herbs by the utilization of diverse immobilized receptors in a desired order.https://doi.org/10.1186/s13020-025-01065-6Rhei Radix et RhizomaDrug discoveryMulti-target drugsHypertrophic scarAngiotensin receptorImmobilized receptor |
| spellingShingle | Lejing Qu Meizhi Jiao Zilong Zhang Yuanyuan Ou Xue Zhao Yajun Zhang Xinfeng Zhao A strategy for selective screening of dual-target bioactive compounds against hypertrophic scar through inhibiting angiotensin II type 1 receptor while stimulating type 2 receptor from Chinese herbs Chinese Medicine Rhei Radix et Rhizoma Drug discovery Multi-target drugs Hypertrophic scar Angiotensin receptor Immobilized receptor |
| title | A strategy for selective screening of dual-target bioactive compounds against hypertrophic scar through inhibiting angiotensin II type 1 receptor while stimulating type 2 receptor from Chinese herbs |
| title_full | A strategy for selective screening of dual-target bioactive compounds against hypertrophic scar through inhibiting angiotensin II type 1 receptor while stimulating type 2 receptor from Chinese herbs |
| title_fullStr | A strategy for selective screening of dual-target bioactive compounds against hypertrophic scar through inhibiting angiotensin II type 1 receptor while stimulating type 2 receptor from Chinese herbs |
| title_full_unstemmed | A strategy for selective screening of dual-target bioactive compounds against hypertrophic scar through inhibiting angiotensin II type 1 receptor while stimulating type 2 receptor from Chinese herbs |
| title_short | A strategy for selective screening of dual-target bioactive compounds against hypertrophic scar through inhibiting angiotensin II type 1 receptor while stimulating type 2 receptor from Chinese herbs |
| title_sort | strategy for selective screening of dual target bioactive compounds against hypertrophic scar through inhibiting angiotensin ii type 1 receptor while stimulating type 2 receptor from chinese herbs |
| topic | Rhei Radix et Rhizoma Drug discovery Multi-target drugs Hypertrophic scar Angiotensin receptor Immobilized receptor |
| url | https://doi.org/10.1186/s13020-025-01065-6 |
| work_keys_str_mv | AT lejingqu astrategyforselectivescreeningofdualtargetbioactivecompoundsagainsthypertrophicscarthroughinhibitingangiotensiniitype1receptorwhilestimulatingtype2receptorfromchineseherbs AT meizhijiao astrategyforselectivescreeningofdualtargetbioactivecompoundsagainsthypertrophicscarthroughinhibitingangiotensiniitype1receptorwhilestimulatingtype2receptorfromchineseherbs AT zilongzhang astrategyforselectivescreeningofdualtargetbioactivecompoundsagainsthypertrophicscarthroughinhibitingangiotensiniitype1receptorwhilestimulatingtype2receptorfromchineseherbs AT yuanyuanou astrategyforselectivescreeningofdualtargetbioactivecompoundsagainsthypertrophicscarthroughinhibitingangiotensiniitype1receptorwhilestimulatingtype2receptorfromchineseherbs AT xuezhao astrategyforselectivescreeningofdualtargetbioactivecompoundsagainsthypertrophicscarthroughinhibitingangiotensiniitype1receptorwhilestimulatingtype2receptorfromchineseherbs AT yajunzhang astrategyforselectivescreeningofdualtargetbioactivecompoundsagainsthypertrophicscarthroughinhibitingangiotensiniitype1receptorwhilestimulatingtype2receptorfromchineseherbs AT xinfengzhao astrategyforselectivescreeningofdualtargetbioactivecompoundsagainsthypertrophicscarthroughinhibitingangiotensiniitype1receptorwhilestimulatingtype2receptorfromchineseherbs AT lejingqu strategyforselectivescreeningofdualtargetbioactivecompoundsagainsthypertrophicscarthroughinhibitingangiotensiniitype1receptorwhilestimulatingtype2receptorfromchineseherbs AT meizhijiao strategyforselectivescreeningofdualtargetbioactivecompoundsagainsthypertrophicscarthroughinhibitingangiotensiniitype1receptorwhilestimulatingtype2receptorfromchineseherbs AT zilongzhang strategyforselectivescreeningofdualtargetbioactivecompoundsagainsthypertrophicscarthroughinhibitingangiotensiniitype1receptorwhilestimulatingtype2receptorfromchineseherbs AT yuanyuanou strategyforselectivescreeningofdualtargetbioactivecompoundsagainsthypertrophicscarthroughinhibitingangiotensiniitype1receptorwhilestimulatingtype2receptorfromchineseherbs AT xuezhao strategyforselectivescreeningofdualtargetbioactivecompoundsagainsthypertrophicscarthroughinhibitingangiotensiniitype1receptorwhilestimulatingtype2receptorfromchineseherbs AT yajunzhang strategyforselectivescreeningofdualtargetbioactivecompoundsagainsthypertrophicscarthroughinhibitingangiotensiniitype1receptorwhilestimulatingtype2receptorfromchineseherbs AT xinfengzhao strategyforselectivescreeningofdualtargetbioactivecompoundsagainsthypertrophicscarthroughinhibitingangiotensiniitype1receptorwhilestimulatingtype2receptorfromchineseherbs |