New anti-diabetic drug Morus alba L. (Sangzhi) alkaloids (SZ-A) improves diabetic nephropathy through ameliorating inflammation and fibrosis in diabetic rats
BackgroundMorus alba L. (Sangzhi) alkaloid (SZ-A) is a new antidiabetic drug approved by the China National Medical Products Administration in 2020. Diabetic nephropathy (DN) is a common diabetic complication and an important cause of morbidity and mortality in patients with diabetes. The effects of...
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2023.1164242/full |
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| author | Caina Li Caina Li Caina Li Quan Liu Quan Liu Quan Liu Wenming Ji Wenming Ji Yaxin Fu Yaxin Fu Hui Cao Hui Cao Hui Cao Yi Huan Yi Huan Yi Huan Lei Lei Lei Lei Lei Lei Xuefeng Gao Xuefeng Gao Leilei Chen Leilei Chen Cunyu Feng Cunyu Feng Lin Zhang Pingping Li Pingping Li Pingping Li Yuling Liu Yuling Liu Yuling Liu Shuainan Liu Shuainan Liu Shuainan Liu Zhufang Shen Zhufang Shen Zhufang Shen |
| author_facet | Caina Li Caina Li Caina Li Quan Liu Quan Liu Quan Liu Wenming Ji Wenming Ji Yaxin Fu Yaxin Fu Hui Cao Hui Cao Hui Cao Yi Huan Yi Huan Yi Huan Lei Lei Lei Lei Lei Lei Xuefeng Gao Xuefeng Gao Leilei Chen Leilei Chen Cunyu Feng Cunyu Feng Lin Zhang Pingping Li Pingping Li Pingping Li Yuling Liu Yuling Liu Yuling Liu Shuainan Liu Shuainan Liu Shuainan Liu Zhufang Shen Zhufang Shen Zhufang Shen |
| author_sort | Caina Li |
| collection | DOAJ |
| description | BackgroundMorus alba L. (Sangzhi) alkaloid (SZ-A) is a new antidiabetic drug approved by the China National Medical Products Administration in 2020. Diabetic nephropathy (DN) is a common diabetic complication and an important cause of morbidity and mortality in patients with diabetes. The effects of SZ-A on DN remain unknown.PurposeThis study evaluated the effects of SZ-A on DN in Zucker diabetic fatty (ZDF) rats and explored the underlying mechanisms based on nitrosative stress, inflammation, and fibrosis.MethodsDiabetic ZDF rats were orally administered 100 and 200 mg/kg of SZ-A once daily for 9 weeks. The glucose metabolism and kidney function were assayed. The pathological injury and fibrosis of the kidneys were separately evaluated using hematoxylin and eosin staining and Masson’s staining. The oxidative and nitrosative stress and inflammation were assayed by determining the levels of related indices in the blood and kidneys and quantifying the related gene and protein expression. The expression of transforming growth factor β1 (TGFβ1) gene and protein were assayed by quantitative real-time PCR and immunohistochemistry, respectively. The renal transcriptomics was analyzed using RNA sequencing.ResultsRepeated treatment with SZ-A significantly improved glucose metabolism, dose-dependently decreased the levels of blood urea nitrogen, urinary albumin, and β2-microglobulin, and evidently relieved the renal injury in diabetic ZDF rats. As for the mechanisms, SZ-A remarkably ameliorated systemic nitrosative stress through lowering the levels of blood inducible nitric oxide synthase and nitric oxide, and significantly relieved systemic and renal inflammation by reducing the levels of blood interleukin-1β and monocyte chemoattractant protein-1 (MCP-1) and decreasing the levels of renal C-reactive protein content and expression of tumor necrosis factor-α in the kidneys. SZ-A also improved renal fibrosis by lowering the expression of TGFβ1 in the kidneys. Additionally, SZ-A significantly lowered the expression of stimulator of chondrogenesis 1 in the kidneys.ConclusionRepeated treatments with SZ-A significantly ameliorates DN by regulating systemic nitrosative stress, renal inflammation, and renal fibrosis partially through inhibition of the cytokine-NO and TGF-β1 signaling in ZDF rats, providing evidence for the additional application of SZ-A in clinical use for the treatment of DN. |
| first_indexed | 2024-03-13T06:36:08Z |
| format | Article |
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| issn | 2296-858X |
| language | English |
| last_indexed | 2024-03-13T06:36:08Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-8c0f27381978470589ada8972492d0592023-06-09T05:12:47ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-06-011010.3389/fmed.2023.11642421164242New anti-diabetic drug Morus alba L. (Sangzhi) alkaloids (SZ-A) improves diabetic nephropathy through ameliorating inflammation and fibrosis in diabetic ratsCaina Li0Caina Li1Caina Li2Quan Liu3Quan Liu4Quan Liu5Wenming Ji6Wenming Ji7Yaxin Fu8Yaxin Fu9Hui Cao10Hui Cao11Hui Cao12Yi Huan13Yi Huan14Yi Huan15Lei Lei16Lei Lei17Lei Lei18Xuefeng Gao19Xuefeng Gao20Leilei Chen21Leilei Chen22Cunyu Feng23Cunyu Feng24Lin Zhang25Pingping Li26Pingping Li27Pingping Li28Yuling Liu29Yuling Liu30Yuling Liu31Shuainan Liu32Shuainan Liu33Shuainan Liu34Zhufang Shen35Zhufang Shen36Zhufang Shen37Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key Laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDiabetes Research Center of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key Laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDiabetes Research Center of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key Laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key Laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key Laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDiabetes Research Center of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key Laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDiabetes Research Center of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key Laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDiabetes Research Center of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key Laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key Laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key Laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Endocrinology, Department of Medical Records, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key Laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDiabetes Research Center of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key Laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDrug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key Laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDiabetes Research Center of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key Laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDiabetes Research Center of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBackgroundMorus alba L. (Sangzhi) alkaloid (SZ-A) is a new antidiabetic drug approved by the China National Medical Products Administration in 2020. Diabetic nephropathy (DN) is a common diabetic complication and an important cause of morbidity and mortality in patients with diabetes. The effects of SZ-A on DN remain unknown.PurposeThis study evaluated the effects of SZ-A on DN in Zucker diabetic fatty (ZDF) rats and explored the underlying mechanisms based on nitrosative stress, inflammation, and fibrosis.MethodsDiabetic ZDF rats were orally administered 100 and 200 mg/kg of SZ-A once daily for 9 weeks. The glucose metabolism and kidney function were assayed. The pathological injury and fibrosis of the kidneys were separately evaluated using hematoxylin and eosin staining and Masson’s staining. The oxidative and nitrosative stress and inflammation were assayed by determining the levels of related indices in the blood and kidneys and quantifying the related gene and protein expression. The expression of transforming growth factor β1 (TGFβ1) gene and protein were assayed by quantitative real-time PCR and immunohistochemistry, respectively. The renal transcriptomics was analyzed using RNA sequencing.ResultsRepeated treatment with SZ-A significantly improved glucose metabolism, dose-dependently decreased the levels of blood urea nitrogen, urinary albumin, and β2-microglobulin, and evidently relieved the renal injury in diabetic ZDF rats. As for the mechanisms, SZ-A remarkably ameliorated systemic nitrosative stress through lowering the levels of blood inducible nitric oxide synthase and nitric oxide, and significantly relieved systemic and renal inflammation by reducing the levels of blood interleukin-1β and monocyte chemoattractant protein-1 (MCP-1) and decreasing the levels of renal C-reactive protein content and expression of tumor necrosis factor-α in the kidneys. SZ-A also improved renal fibrosis by lowering the expression of TGFβ1 in the kidneys. Additionally, SZ-A significantly lowered the expression of stimulator of chondrogenesis 1 in the kidneys.ConclusionRepeated treatments with SZ-A significantly ameliorates DN by regulating systemic nitrosative stress, renal inflammation, and renal fibrosis partially through inhibition of the cytokine-NO and TGF-β1 signaling in ZDF rats, providing evidence for the additional application of SZ-A in clinical use for the treatment of DN.https://www.frontiersin.org/articles/10.3389/fmed.2023.1164242/fullMorus alba L. (Sangzhi) alkaloidsdiabetic nephropathyoxidative stressnitrosative stressinflammationrenal fibrosis |
| spellingShingle | Caina Li Caina Li Caina Li Quan Liu Quan Liu Quan Liu Wenming Ji Wenming Ji Yaxin Fu Yaxin Fu Hui Cao Hui Cao Hui Cao Yi Huan Yi Huan Yi Huan Lei Lei Lei Lei Lei Lei Xuefeng Gao Xuefeng Gao Leilei Chen Leilei Chen Cunyu Feng Cunyu Feng Lin Zhang Pingping Li Pingping Li Pingping Li Yuling Liu Yuling Liu Yuling Liu Shuainan Liu Shuainan Liu Shuainan Liu Zhufang Shen Zhufang Shen Zhufang Shen New anti-diabetic drug Morus alba L. (Sangzhi) alkaloids (SZ-A) improves diabetic nephropathy through ameliorating inflammation and fibrosis in diabetic rats Frontiers in Medicine Morus alba L. (Sangzhi) alkaloids diabetic nephropathy oxidative stress nitrosative stress inflammation renal fibrosis |
| title | New anti-diabetic drug Morus alba L. (Sangzhi) alkaloids (SZ-A) improves diabetic nephropathy through ameliorating inflammation and fibrosis in diabetic rats |
| title_full | New anti-diabetic drug Morus alba L. (Sangzhi) alkaloids (SZ-A) improves diabetic nephropathy through ameliorating inflammation and fibrosis in diabetic rats |
| title_fullStr | New anti-diabetic drug Morus alba L. (Sangzhi) alkaloids (SZ-A) improves diabetic nephropathy through ameliorating inflammation and fibrosis in diabetic rats |
| title_full_unstemmed | New anti-diabetic drug Morus alba L. (Sangzhi) alkaloids (SZ-A) improves diabetic nephropathy through ameliorating inflammation and fibrosis in diabetic rats |
| title_short | New anti-diabetic drug Morus alba L. (Sangzhi) alkaloids (SZ-A) improves diabetic nephropathy through ameliorating inflammation and fibrosis in diabetic rats |
| title_sort | new anti diabetic drug morus alba l sangzhi alkaloids sz a improves diabetic nephropathy through ameliorating inflammation and fibrosis in diabetic rats |
| topic | Morus alba L. (Sangzhi) alkaloids diabetic nephropathy oxidative stress nitrosative stress inflammation renal fibrosis |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2023.1164242/full |
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