Hypouricemic Effects of Extracts From Agrocybe aegerita on Hyperuricemia Mice and Virtual Prediction of Bioactives by Molecular Docking
Agrocybe aegerita has long been utilized for promoting diuresis in traditional Chinese medicine (TCM) with a close correlation to hypouricemia. Ethanol (AAE) and water (AAW) extracts of the compound led to a remarkable decrease in serum uric acid levels (SUA) in hyperuricemia mice, approaching that...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-05-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2018.00498/full |
| _version_ | 1818257125106778112 |
|---|---|
| author | Tianqiao Yong Tianqiao Yong Shaodan Chen Shaodan Chen Yizhen Xie Yizhen Xie Ou Shuai Ou Shuai Xiangmin Li Xiangmin Li Diling Chen Diling Chen Jiyan Su Jiyan Su Chunwei Jiao Chunwei Jiao Yalei Liang Yalei Liang |
| author_facet | Tianqiao Yong Tianqiao Yong Shaodan Chen Shaodan Chen Yizhen Xie Yizhen Xie Ou Shuai Ou Shuai Xiangmin Li Xiangmin Li Diling Chen Diling Chen Jiyan Su Jiyan Su Chunwei Jiao Chunwei Jiao Yalei Liang Yalei Liang |
| author_sort | Tianqiao Yong |
| collection | DOAJ |
| description | Agrocybe aegerita has long been utilized for promoting diuresis in traditional Chinese medicine (TCM) with a close correlation to hypouricemia. Ethanol (AAE) and water (AAW) extracts of the compound led to a remarkable decrease in serum uric acid levels (SUA) in hyperuricemia mice, approaching that of the normal control. Both AAE and AAW exhibited suppression effects on hepatic xanthine oxidase (XOD) activities and elevation effects on renal OAT1 (organic anion transporter 1). However, only little negative impact was observed on the inner organ functions. The molecular docking was used to screen our in-home compound database for A. aegerita, and four compounds including 2-formyl-3,5-dihydroxybenzyl acetate, 2,4-dihydroxy-6-methylbenzaldehyde, 2-(6-hydroxy-1H-indol-3-yl)acetamide, and 6-hydroxy-1H-indole-3-carbaldehyde (HHC) were identified as potential active compounds. Their inhibitory mechanism on XOD might be attributed to their localization in the tunnel for the entrance of substrates to XOD active site, preventing the entrance of the substrates. To confirm the activity of the screened compounds experimentally, HHC was selected due to its high ranking and availability. The assaying result suggested the significant inhibitory activity of HHC on XOD. Also, these compounds were predicted to carry good ADME (absorption, distribution, metabolism, and excretion) properties, thereby necessitating further investigation. The current results provided an insight into the hypouricemic effects of macrofungi and their bioactives, which might provide the significant theoretical foundation for identifying and designing novel hypouricemia compounds. |
| first_indexed | 2024-12-12T17:38:40Z |
| format | Article |
| id | doaj.art-511cbe8e47d04d21ab3942477e6ace32 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-12T17:38:40Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-511cbe8e47d04d21ab3942477e6ace322022-12-22T00:17:08ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-05-01910.3389/fphar.2018.00498272873Hypouricemic Effects of Extracts From Agrocybe aegerita on Hyperuricemia Mice and Virtual Prediction of Bioactives by Molecular DockingTianqiao Yong0Tianqiao Yong1Shaodan Chen2Shaodan Chen3Yizhen Xie4Yizhen Xie5Ou Shuai6Ou Shuai7Xiangmin Li8Xiangmin Li9Diling Chen10Diling Chen11Jiyan Su12Jiyan Su13Chunwei Jiao14Chunwei Jiao15Yalei Liang16Yalei Liang17State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application and Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou, ChinaGuangdong Yuewei Edible Fungi Technology Co., Guangzhou, ChinaState Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application and Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou, ChinaGuangdong Yuewei Edible Fungi Technology Co., Guangzhou, ChinaState Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application and Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou, ChinaGuangdong Yuewei Edible Fungi Technology Co., Guangzhou, ChinaState Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application and Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou, ChinaGuangdong Yuewei Edible Fungi Technology Co., Guangzhou, ChinaState Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application and Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou, ChinaGuangdong Yuewei Edible Fungi Technology Co., Guangzhou, ChinaState Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application and Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou, ChinaGuangdong Yuewei Edible Fungi Technology Co., Guangzhou, ChinaState Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application and Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou, ChinaGuangdong Yuewei Edible Fungi Technology Co., Guangzhou, ChinaState Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application and Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou, ChinaGuangdong Yuewei Edible Fungi Technology Co., Guangzhou, ChinaState Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application and Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou, ChinaGuangdong Yuewei Edible Fungi Technology Co., Guangzhou, ChinaAgrocybe aegerita has long been utilized for promoting diuresis in traditional Chinese medicine (TCM) with a close correlation to hypouricemia. Ethanol (AAE) and water (AAW) extracts of the compound led to a remarkable decrease in serum uric acid levels (SUA) in hyperuricemia mice, approaching that of the normal control. Both AAE and AAW exhibited suppression effects on hepatic xanthine oxidase (XOD) activities and elevation effects on renal OAT1 (organic anion transporter 1). However, only little negative impact was observed on the inner organ functions. The molecular docking was used to screen our in-home compound database for A. aegerita, and four compounds including 2-formyl-3,5-dihydroxybenzyl acetate, 2,4-dihydroxy-6-methylbenzaldehyde, 2-(6-hydroxy-1H-indol-3-yl)acetamide, and 6-hydroxy-1H-indole-3-carbaldehyde (HHC) were identified as potential active compounds. Their inhibitory mechanism on XOD might be attributed to their localization in the tunnel for the entrance of substrates to XOD active site, preventing the entrance of the substrates. To confirm the activity of the screened compounds experimentally, HHC was selected due to its high ranking and availability. The assaying result suggested the significant inhibitory activity of HHC on XOD. Also, these compounds were predicted to carry good ADME (absorption, distribution, metabolism, and excretion) properties, thereby necessitating further investigation. The current results provided an insight into the hypouricemic effects of macrofungi and their bioactives, which might provide the significant theoretical foundation for identifying and designing novel hypouricemia compounds.http://journal.frontiersin.org/article/10.3389/fphar.2018.00498/fullAgrocybe aegeritahyperuricemiaxanthine oxidasebioactivesvirtual screening |
| spellingShingle | Tianqiao Yong Tianqiao Yong Shaodan Chen Shaodan Chen Yizhen Xie Yizhen Xie Ou Shuai Ou Shuai Xiangmin Li Xiangmin Li Diling Chen Diling Chen Jiyan Su Jiyan Su Chunwei Jiao Chunwei Jiao Yalei Liang Yalei Liang Hypouricemic Effects of Extracts From Agrocybe aegerita on Hyperuricemia Mice and Virtual Prediction of Bioactives by Molecular Docking Frontiers in Pharmacology Agrocybe aegerita hyperuricemia xanthine oxidase bioactives virtual screening |
| title | Hypouricemic Effects of Extracts From Agrocybe aegerita on Hyperuricemia Mice and Virtual Prediction of Bioactives by Molecular Docking |
| title_full | Hypouricemic Effects of Extracts From Agrocybe aegerita on Hyperuricemia Mice and Virtual Prediction of Bioactives by Molecular Docking |
| title_fullStr | Hypouricemic Effects of Extracts From Agrocybe aegerita on Hyperuricemia Mice and Virtual Prediction of Bioactives by Molecular Docking |
| title_full_unstemmed | Hypouricemic Effects of Extracts From Agrocybe aegerita on Hyperuricemia Mice and Virtual Prediction of Bioactives by Molecular Docking |
| title_short | Hypouricemic Effects of Extracts From Agrocybe aegerita on Hyperuricemia Mice and Virtual Prediction of Bioactives by Molecular Docking |
| title_sort | hypouricemic effects of extracts from agrocybe aegerita on hyperuricemia mice and virtual prediction of bioactives by molecular docking |
| topic | Agrocybe aegerita hyperuricemia xanthine oxidase bioactives virtual screening |
| url | http://journal.frontiersin.org/article/10.3389/fphar.2018.00498/full |
| work_keys_str_mv | AT tianqiaoyong hypouricemiceffectsofextractsfromagrocybeaegeritaonhyperuricemiamiceandvirtualpredictionofbioactivesbymoleculardocking AT tianqiaoyong hypouricemiceffectsofextractsfromagrocybeaegeritaonhyperuricemiamiceandvirtualpredictionofbioactivesbymoleculardocking AT shaodanchen hypouricemiceffectsofextractsfromagrocybeaegeritaonhyperuricemiamiceandvirtualpredictionofbioactivesbymoleculardocking AT shaodanchen hypouricemiceffectsofextractsfromagrocybeaegeritaonhyperuricemiamiceandvirtualpredictionofbioactivesbymoleculardocking AT yizhenxie hypouricemiceffectsofextractsfromagrocybeaegeritaonhyperuricemiamiceandvirtualpredictionofbioactivesbymoleculardocking AT yizhenxie hypouricemiceffectsofextractsfromagrocybeaegeritaonhyperuricemiamiceandvirtualpredictionofbioactivesbymoleculardocking AT oushuai hypouricemiceffectsofextractsfromagrocybeaegeritaonhyperuricemiamiceandvirtualpredictionofbioactivesbymoleculardocking AT oushuai hypouricemiceffectsofextractsfromagrocybeaegeritaonhyperuricemiamiceandvirtualpredictionofbioactivesbymoleculardocking AT xiangminli hypouricemiceffectsofextractsfromagrocybeaegeritaonhyperuricemiamiceandvirtualpredictionofbioactivesbymoleculardocking AT xiangminli hypouricemiceffectsofextractsfromagrocybeaegeritaonhyperuricemiamiceandvirtualpredictionofbioactivesbymoleculardocking AT dilingchen hypouricemiceffectsofextractsfromagrocybeaegeritaonhyperuricemiamiceandvirtualpredictionofbioactivesbymoleculardocking AT dilingchen hypouricemiceffectsofextractsfromagrocybeaegeritaonhyperuricemiamiceandvirtualpredictionofbioactivesbymoleculardocking AT jiyansu hypouricemiceffectsofextractsfromagrocybeaegeritaonhyperuricemiamiceandvirtualpredictionofbioactivesbymoleculardocking AT jiyansu hypouricemiceffectsofextractsfromagrocybeaegeritaonhyperuricemiamiceandvirtualpredictionofbioactivesbymoleculardocking AT chunweijiao hypouricemiceffectsofextractsfromagrocybeaegeritaonhyperuricemiamiceandvirtualpredictionofbioactivesbymoleculardocking AT chunweijiao hypouricemiceffectsofextractsfromagrocybeaegeritaonhyperuricemiamiceandvirtualpredictionofbioactivesbymoleculardocking AT yaleiliang hypouricemiceffectsofextractsfromagrocybeaegeritaonhyperuricemiamiceandvirtualpredictionofbioactivesbymoleculardocking AT yaleiliang hypouricemiceffectsofextractsfromagrocybeaegeritaonhyperuricemiamiceandvirtualpredictionofbioactivesbymoleculardocking |