Phyllanthus Niruri L. Exerts Protective Effects Against the Calcium Oxalate-Induced Renal Injury via Ellgic Acid
Background: Urolithiasis or kidney stones is a common and frequently occurring renal disease; calcium oxalate (CaOx) crystals are responsible for 80% of urolithiasis cases. Phyllanthus niruri L. (PN) has been used to treat urolithiasis. This study aimed to determine the potential protective effects...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.891788/full |
| _version_ | 1797808902892421120 |
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| author | Mao-Ting Li Lu-Lu Liu Qi Zhou Lin-Xi Huang Yu-Xuan Shi Jie-Bin Hou Hong-Tao Lu Bing Yu Wei Chen Zhi-Yong Guo |
| author_facet | Mao-Ting Li Lu-Lu Liu Qi Zhou Lin-Xi Huang Yu-Xuan Shi Jie-Bin Hou Hong-Tao Lu Bing Yu Wei Chen Zhi-Yong Guo |
| author_sort | Mao-Ting Li |
| collection | DOAJ |
| description | Background: Urolithiasis or kidney stones is a common and frequently occurring renal disease; calcium oxalate (CaOx) crystals are responsible for 80% of urolithiasis cases. Phyllanthus niruri L. (PN) has been used to treat urolithiasis. This study aimed to determine the potential protective effects and molecular mechanism of PN on calcium oxalate-induced renal injury.Methods: Microarray data sets were generated from the calcium oxalate-induced renal injury model of HK-2 cells and potential disease-related targets were identified. Network pharmacology was employed to identify drug-related targets of PN and construct the active ingredient-target network. Finally, the putative therapeutic targets and active ingredients of PN were verified in vitro and in vivo.Results: A total of 20 active ingredients in PN, 2,428 drug-related targets, and 127 disease-related targets were identified. According to network pharmacology analysis, HMGCS1, SQLE, and SCD were identified as predicted therapeutic target and ellagic acid (EA) was identified as the active ingredient by molecular docking analysis. The increased expression of SQLE, SCD, and HMGCS1 due to calcium oxalate-induced renal injury in HK-2 cells was found to be significantly inhibited by EA. Immunohistochemical in mice also showed that the levels of SQLE, SCD, and HMGCS1 were remarkably restored after EA treatment.Conclusion: EA is the active ingredient in PN responsible for its protective effects against CaOx-induced renal injury. SQLE, SCD, and HMGCS1 are putative therapeutic targets of EA. |
| first_indexed | 2024-03-13T06:44:36Z |
| format | Article |
| id | doaj.art-bf154fec4db14b4ebc8db0ce4f5060f9 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-13T06:44:36Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-bf154fec4db14b4ebc8db0ce4f5060f92023-06-08T10:40:14ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-06-011310.3389/fphar.2022.891788891788Phyllanthus Niruri L. Exerts Protective Effects Against the Calcium Oxalate-Induced Renal Injury via Ellgic AcidMao-Ting Li0Lu-Lu Liu1Qi Zhou2Lin-Xi Huang3Yu-Xuan Shi4Jie-Bin Hou5Hong-Tao Lu6Bing Yu7Wei Chen8Zhi-Yong Guo9Changhai Hospital, Naval Medical University, Shanghai, ChinaChanghai Hospital, Naval Medical University, Shanghai, ChinaChanghai Hospital, Naval Medical University, Shanghai, ChinaChanghai Hospital, Naval Medical University, Shanghai, ChinaChanghai Hospital, Naval Medical University, Shanghai, ChinaDepartment of Nephrology, the Second Medical Centre, Chinese PLA General Hospital, Beijing, ChinaDepartment of Naval Medicine, Naval Medical University, Shanghai, ChinaDepartment of Cell Biology, Center for Stem Cell and Medicine, Navy Medical University, Shanghai, ChinaChanghai Hospital, Naval Medical University, Shanghai, ChinaChanghai Hospital, Naval Medical University, Shanghai, ChinaBackground: Urolithiasis or kidney stones is a common and frequently occurring renal disease; calcium oxalate (CaOx) crystals are responsible for 80% of urolithiasis cases. Phyllanthus niruri L. (PN) has been used to treat urolithiasis. This study aimed to determine the potential protective effects and molecular mechanism of PN on calcium oxalate-induced renal injury.Methods: Microarray data sets were generated from the calcium oxalate-induced renal injury model of HK-2 cells and potential disease-related targets were identified. Network pharmacology was employed to identify drug-related targets of PN and construct the active ingredient-target network. Finally, the putative therapeutic targets and active ingredients of PN were verified in vitro and in vivo.Results: A total of 20 active ingredients in PN, 2,428 drug-related targets, and 127 disease-related targets were identified. According to network pharmacology analysis, HMGCS1, SQLE, and SCD were identified as predicted therapeutic target and ellagic acid (EA) was identified as the active ingredient by molecular docking analysis. The increased expression of SQLE, SCD, and HMGCS1 due to calcium oxalate-induced renal injury in HK-2 cells was found to be significantly inhibited by EA. Immunohistochemical in mice also showed that the levels of SQLE, SCD, and HMGCS1 were remarkably restored after EA treatment.Conclusion: EA is the active ingredient in PN responsible for its protective effects against CaOx-induced renal injury. SQLE, SCD, and HMGCS1 are putative therapeutic targets of EA.https://www.frontiersin.org/articles/10.3389/fphar.2022.891788/fullPhyllanthus niruri L.calcium oxalate-induced renal injurynetwork pharmacologyellagic acidlipid nephrotoxicity |
| spellingShingle | Mao-Ting Li Lu-Lu Liu Qi Zhou Lin-Xi Huang Yu-Xuan Shi Jie-Bin Hou Hong-Tao Lu Bing Yu Wei Chen Zhi-Yong Guo Phyllanthus Niruri L. Exerts Protective Effects Against the Calcium Oxalate-Induced Renal Injury via Ellgic Acid Frontiers in Pharmacology Phyllanthus niruri L. calcium oxalate-induced renal injury network pharmacology ellagic acid lipid nephrotoxicity |
| title | Phyllanthus Niruri L. Exerts Protective Effects Against the Calcium Oxalate-Induced Renal Injury via Ellgic Acid |
| title_full | Phyllanthus Niruri L. Exerts Protective Effects Against the Calcium Oxalate-Induced Renal Injury via Ellgic Acid |
| title_fullStr | Phyllanthus Niruri L. Exerts Protective Effects Against the Calcium Oxalate-Induced Renal Injury via Ellgic Acid |
| title_full_unstemmed | Phyllanthus Niruri L. Exerts Protective Effects Against the Calcium Oxalate-Induced Renal Injury via Ellgic Acid |
| title_short | Phyllanthus Niruri L. Exerts Protective Effects Against the Calcium Oxalate-Induced Renal Injury via Ellgic Acid |
| title_sort | phyllanthus niruri l exerts protective effects against the calcium oxalate induced renal injury via ellgic acid |
| topic | Phyllanthus niruri L. calcium oxalate-induced renal injury network pharmacology ellagic acid lipid nephrotoxicity |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.891788/full |
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