Antidiabetic Effect of Rehmanniae Radix Based on Regulation of TRPV1 and SCD1

Purpose: This study aimed to disclose the antidiabetic mechanisms of Rehmanniae Radix (RR).Methods: The antidiabetic effect of RR was studied in Streptozocin (STZ)–induced diabetes mellitus (DM) rats and HepG2 cells with insulin resistance (IR). Antidiabetic targets and signaling pathways of RR were...

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Main Authors: Ye Liu, Ruizheng Zhu, Bei Liu, Wuqing Wang, Ping Yang, Zhonglian Cao, Xiaolei Yang, Wandi Du, Qing Yang, Jingru Liang, Jiarong Hu, Guo Ma
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-05-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.875014/full
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author Ye Liu
Ruizheng Zhu
Bei Liu
Bei Liu
Wuqing Wang
Ping Yang
Zhonglian Cao
Xiaolei Yang
Wandi Du
Qing Yang
Jingru Liang
Jiarong Hu
Guo Ma
author_facet Ye Liu
Ruizheng Zhu
Bei Liu
Bei Liu
Wuqing Wang
Ping Yang
Zhonglian Cao
Xiaolei Yang
Wandi Du
Qing Yang
Jingru Liang
Jiarong Hu
Guo Ma
author_sort Ye Liu
collection DOAJ
description Purpose: This study aimed to disclose the antidiabetic mechanisms of Rehmanniae Radix (RR).Methods: The antidiabetic effect of RR was studied in Streptozocin (STZ)–induced diabetes mellitus (DM) rats and HepG2 cells with insulin resistance (IR). Antidiabetic targets and signaling pathways of RR were confirmed by the network pharmacology and transcriptome analysis as well as HK2 cells induced by high glucose (HG).Results: After the DM rats were administrated RR extract (RRE) for 4 weeks, their body weight was 10.70 ± 2.00% higher than those in the model group, and the fasting blood glucose (FBG), AUC of the oral glucose tolerance test, and insulin sensitivity test values were 73.23 ± 3.33%, 12.31 ± 2.29%, and 13.61 ± 5.60% lower in the RRE group, respectively. When compared with the model group, an increase of 45.76 ± 3.03% in the glucose uptake of HepG2 cells with IR was seen in the RRE group. The drug (RR)–components–disease (DM)–targets network with 18 components and 58 targets was established. 331 differentially expressed genes (DEGs) were identified. TRPV1 and SCD1 were important DEGs by the intersectional analysis of network pharmacology and renal transcriptome. The TRPV1 overexpression significantly inhibited apoptosis and oxidative stress of the HK2 cells induced by HG, while SCD1 overexpression induced apoptosis and oxidative stress of the HK2 cells induced by low and high glucose. When compared to the HG group, the mRNA and protein expressions of TRPV1 in the presence of RRE (100 μg/ml) increased by 3.94 ± 0.08 and 2.83 ± 0.40 folds, respectively.Conclusion: In summary, RR displayed an inspiring antidiabetic effect by reducing FBG and IR, upregulating the mRNA and protein expressions of TRPV1, and downregulating mRNA expression of SCD1. Induction of TRPV1 and inhibition of SCD1 by RR was possibly one of its antidiabetic mechanisms.
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spelling doaj.art-40a91f3a41fd486594abbf3dfde520e82022-12-22T00:27:57ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-05-011310.3389/fphar.2022.875014875014Antidiabetic Effect of Rehmanniae Radix Based on Regulation of TRPV1 and SCD1Ye Liu0Ruizheng Zhu1Bei Liu2Bei Liu3Wuqing Wang4Ping Yang5Zhonglian Cao6Xiaolei Yang7Wandi Du8Qing Yang9Jingru Liang10Jiarong Hu11Guo Ma12School of Pharmacy, Fudan University, Shanghai, ChinaDepartment of Dermatology, Minhang Hospital, Fudan University, Shanghai, ChinaSchool of Pharmacy, Fudan University, Shanghai, ChinaRuijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Dermatology, Minhang Hospital, Fudan University, Shanghai, ChinaSchool of Pharmacy, Fudan University, Shanghai, ChinaSchool of Pharmacy, Fudan University, Shanghai, ChinaSchool of Pharmacy, Fudan University, Shanghai, ChinaSchool of Pharmacy, Fudan University, Shanghai, ChinaSchool of Pharmacy, Fudan University, Shanghai, ChinaSchool of Pharmacy, Fudan University, Shanghai, ChinaSchool of Pharmacy, Fudan University, Shanghai, ChinaSchool of Pharmacy, Fudan University, Shanghai, ChinaPurpose: This study aimed to disclose the antidiabetic mechanisms of Rehmanniae Radix (RR).Methods: The antidiabetic effect of RR was studied in Streptozocin (STZ)–induced diabetes mellitus (DM) rats and HepG2 cells with insulin resistance (IR). Antidiabetic targets and signaling pathways of RR were confirmed by the network pharmacology and transcriptome analysis as well as HK2 cells induced by high glucose (HG).Results: After the DM rats were administrated RR extract (RRE) for 4 weeks, their body weight was 10.70 ± 2.00% higher than those in the model group, and the fasting blood glucose (FBG), AUC of the oral glucose tolerance test, and insulin sensitivity test values were 73.23 ± 3.33%, 12.31 ± 2.29%, and 13.61 ± 5.60% lower in the RRE group, respectively. When compared with the model group, an increase of 45.76 ± 3.03% in the glucose uptake of HepG2 cells with IR was seen in the RRE group. The drug (RR)–components–disease (DM)–targets network with 18 components and 58 targets was established. 331 differentially expressed genes (DEGs) were identified. TRPV1 and SCD1 were important DEGs by the intersectional analysis of network pharmacology and renal transcriptome. The TRPV1 overexpression significantly inhibited apoptosis and oxidative stress of the HK2 cells induced by HG, while SCD1 overexpression induced apoptosis and oxidative stress of the HK2 cells induced by low and high glucose. When compared to the HG group, the mRNA and protein expressions of TRPV1 in the presence of RRE (100 μg/ml) increased by 3.94 ± 0.08 and 2.83 ± 0.40 folds, respectively.Conclusion: In summary, RR displayed an inspiring antidiabetic effect by reducing FBG and IR, upregulating the mRNA and protein expressions of TRPV1, and downregulating mRNA expression of SCD1. Induction of TRPV1 and inhibition of SCD1 by RR was possibly one of its antidiabetic mechanisms.https://www.frontiersin.org/articles/10.3389/fphar.2022.875014/fullRehmanniae Radixdiabetes mellitustransient receptor potential vanilloid 1stearoyl-CoA desaturase 1network pharmacologytranscriptome
spellingShingle Ye Liu
Ruizheng Zhu
Bei Liu
Bei Liu
Wuqing Wang
Ping Yang
Zhonglian Cao
Xiaolei Yang
Wandi Du
Qing Yang
Jingru Liang
Jiarong Hu
Guo Ma
Antidiabetic Effect of Rehmanniae Radix Based on Regulation of TRPV1 and SCD1
Frontiers in Pharmacology
Rehmanniae Radix
diabetes mellitus
transient receptor potential vanilloid 1
stearoyl-CoA desaturase 1
network pharmacology
transcriptome
title Antidiabetic Effect of Rehmanniae Radix Based on Regulation of TRPV1 and SCD1
title_full Antidiabetic Effect of Rehmanniae Radix Based on Regulation of TRPV1 and SCD1
title_fullStr Antidiabetic Effect of Rehmanniae Radix Based on Regulation of TRPV1 and SCD1
title_full_unstemmed Antidiabetic Effect of Rehmanniae Radix Based on Regulation of TRPV1 and SCD1
title_short Antidiabetic Effect of Rehmanniae Radix Based on Regulation of TRPV1 and SCD1
title_sort antidiabetic effect of rehmanniae radix based on regulation of trpv1 and scd1
topic Rehmanniae Radix
diabetes mellitus
transient receptor potential vanilloid 1
stearoyl-CoA desaturase 1
network pharmacology
transcriptome
url https://www.frontiersin.org/articles/10.3389/fphar.2022.875014/full
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