Hua-Ying Fan1, Xue-Kai Wang2, Xin Li2, Kai Ji2, Shi-Hao Du2, Yu Liu3, Lin-Lin Kong2, Jing-Chen Xu2, Gang-Qiang Yang4, Da-Quan Chen5, Dong Qi6. 1. School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, PR China. Electronic address: katiefhydong@sina.com. 2. School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, PR China. 3. Fushan District People's Hospital of Yantai City, 265500, Yantai, Shandong, PR China. 4. School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, PR China. Electronic address: oceanygq@163.com. 5. School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, PR China. Electronic address: cdq1981@126.com. 6. Department of Nephrology, Yu-Huang-Ding Hospital/Qingdao University, 264000, Yantai, Shandong, PR China. Electronic address: qidong8028@sina.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Curcumin, a phenolic compound extracted from the rhizome of turmeric (Curcuma longa L.), has been reported to have broad biological functions including potent antioxidant and renoprotective effects. It has been reported that Curcumin has a certain protective effect on the kidney. However, its mechanism of action needs further study. AIM OF THE STUDY: The present research aims at investigating the therapeutic effects and its underlying mechanism of curcumin on NS. MATERIALS AND METHODS: The conditionally immortalized mouse podocyte cell line was utilized to evaluate the podocyte-protective effect of curcumin and its effects on NF-κB pathway and Nrf2/ARE pathway in podocyte in vitro. Furthermore, the DOX-induced NS rats were utilized to investigate the therapeutic effects and its underlying mechanism of curcumin against NS in vivo. RESULTS: The consequences of this study revealed that curcumin activated Nrf2, inhibited NF-κB pathway and up-regulated podocin in DOX-induced podocyte. Further research results showed that curcumin can considerably alleviate proteinuria and improve hypoalbuminemia in NS rats, and lower blood lipid levels to alleviate hyperlipidemia in NS rats, indicating that curcumin has significant therapeutic effects on rat NS. Further observation by electron microscopy and detection showed that curcumin can improve renal function and podocyte injury, which may be related to the repairment of mRNA expression and podocin protein. Interestingly, the results of the blood rheology test showed that curcumin can effectively reduce whole blood viscosity (WBV) and plasma viscosity (PV), and reduce hematocrit (Hct). In addition, the oxidative stress state of kidney in NS rats was considerably reversed by curcumin, which may be achieved by activating Nrf2 and increasing the expression of antioxidant enzymes HO-1, NQO-1. We also found that NF-κB pathway is activated in the kidney of NS rats, and curcumin can inhibit the activation of NF-κB by down-regulating the expression of NF-κB p65, reducing the level of p-IκBα and up-regulating the expression of IκBα. CONCLUSION: These findings suggest that curcumin, as a multifunctional agent, exerts a protective effect on DOX-induced nephrotic syndrome in rats, which provides a pharmacological basis for the further development of curcumin and also provides a basis for the advantages of multi-targeted drugs in the processing of NS.
ETHNOPHARMACOLOGICAL RELEVANCE: Curcumin, a phenolic compound extracted from the rhizome of turmeric (Curcuma longa L.), has been reported to have broad biological functions including potent antioxidant and renoprotective effects. It has been reported that Curcumin has a certain protective effect on the kidney. However, its mechanism of action needs further study. AIM OF THE STUDY: The present research aims at investigating the therapeutic effects and its underlying mechanism of curcumin on NS. MATERIALS AND METHODS: The conditionally immortalized mouse podocyte cell line was utilized to evaluate the podocyte-protective effect of curcumin and its effects on NF-κB pathway and Nrf2/ARE pathway in podocyte in vitro. Furthermore, the DOX-induced NS rats were utilized to investigate the therapeutic effects and its underlying mechanism of curcumin against NS in vivo. RESULTS: The consequences of this study revealed that curcumin activated Nrf2, inhibited NF-κB pathway and up-regulated podocin in DOX-induced podocyte. Further research results showed that curcumin can considerably alleviate proteinuria and improve hypoalbuminemia in NS rats, and lower blood lipid levels to alleviate hyperlipidemia in NSrats, indicating that curcumin has significant therapeutic effects on rat NS. Further observation by electron microscopy and detection showed that curcumin can improve renal function and podocyte injury, which may be related to the repairment of mRNA expression and podocin protein. Interestingly, the results of the blood rheology test showed that curcumin can effectively reduce whole blood viscosity (WBV) and plasma viscosity (PV), and reduce hematocrit (Hct). In addition, the oxidative stress state of kidney in NS rats was considerably reversed by curcumin, which may be achieved by activating Nrf2 and increasing the expression of antioxidant enzymes HO-1, NQO-1. We also found that NF-κB pathway is activated in the kidney of NS rats, and curcumin can inhibit the activation of NF-κB by down-regulating the expression of NF-κB p65, reducing the level of p-IκBα and up-regulating the expression of IκBα. CONCLUSION: These findings suggest that curcumin, as a multifunctional agent, exerts a protective effect on DOX-induced nephrotic syndrome in rats, which provides a pharmacological basis for the further development of curcumin and also provides a basis for the advantages of multi-targeted drugs in the processing of NS.
Authors: Cristina Vázquez-Carballo; Melania Guerrero-Hue; Cristina García-Caballero; Sandra Rayego-Mateos; Lucas Opazo-Ríos; José Luis Morgado-Pascual; Carmen Herencia-Bellido; Mercedes Vallejo-Mudarra; Isabel Cortegano; María Luisa Gaspar; Belén de Andrés; Jesús Egido; Juan Antonio Moreno Journal: Int J Mol Sci Date: 2021-01-15 Impact factor: 5.923