Journal of Traditional Chinese Medicine ›› 2025, Vol. 45 ›› Issue (6): 1254-1262.DOI: 10.19852/j.cnki.jtcm.2025.06.006
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Hypoglycemic mechanism of modified Gegen Qinlian decoction (加味葛根芩连汤) based on regulating the expression and DNA methylation of cholesterol transporters in the adipose tissue of type 2 diabetes mellitus rats
PENG Shuhong1, YANG Lingkun1, LIU Xinyi1, ZHANG Mengyu1, LIN Seqi1, ZHANG Changhua2, XU Guoliang1, ZHU Weifeng3(
), YAO Pengcheng4()
- 1 Research Center for Differentiation and Development of TCM Basic Theory, Jiangxi University of Chinese Medicine, Nanchang 330004, China
2 School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, China
3 State Key Laboratory of Modern Preparation of TCM, Ministry of Education, Nanchang 330004, China
4 Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, China
-
Received:2024-11-11Accepted:2025-03-27Online:2025-12-15Published:2025-11-24 -
Contact:YAO Pengcheng, Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, China, yaopengcheng2001@163.com, Telephone: +86-791-87118109; +86-791-87119060
Prof. ZHU Weifeng, State Key Laboratory of Modern Preparation of TCM, Ministry of Education, Nanchang 330004, China, zwf0322@126.com -
Supported by:Investigation on the Mechanism of Gegen Qinlian Decoction in Lowering Blood Glucose Based on Improving Cholesterol Homeostasis of Lipid Rafts in Adipocytes(82060741);Cause of “Dampness Stagnating in Pi” in Type 2 Diabetes Mellitus by Overeating High Fat and Sugar Diet Based on Glycerol Transport Which Is Affected by Methylation/Hormones Signal(82160830);Investigation on the Mechanism of Gegen Qinlian Decoction in Lowering Blood Glucose Based on Improving Phosphatidylcholine Biosynthesis in Adipose Tissue(82360799);Relationship between Adipose Tissue and Spleen Image Based on Multivariate Analysis of Modern Literature (No. 2020B0328). Ganpo Juncai-Training Program for Academic and Technical Leaders in Major Disciplines of the Province (Leading Talents-Academic Category)(20232BCJ22022);Jiangxi University of Chinese Medicine, First-level Discipline of Integrative Medicine (Jiangxi Province Double First-class Discipline)(zxyylxk20220103);Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program(CXTD22007)
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PENG Shuhong, YANG Lingkun, LIU Xinyi, ZHANG Mengyu, LIN Seqi, ZHANG Changhua, XU Guoliang, ZHU Weifeng, YAO Pengcheng. Hypoglycemic mechanism of modified Gegen Qinlian decoction (加味葛根芩连汤) based on regulating the expression and DNA methylation of cholesterol transporters in the adipose tissue of type 2 diabetes mellitus rats[J]. Journal of Traditional Chinese Medicine, 2025, 45(6): 1254-1262.
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Figure 1 Blood glucose and glucose tolerance test in serum of each group A: FBG; B: GSP; C: glucose tolerance test; D: AUC. CON: normal rats treated with control diet and normal saline; T2DM: diabetic rats treated with high-fat diet and normal saline. MET: diabetic rats treated with high-fat diet and 200 mg·kg?1·d?1 of metformin hydrochloric acid for 14 weeks; MGQDL: diabetic rats treated with high-fat diet and 5 g·kg?1·d?1 of MGQD for 14 weeks; MGQDH: diabetic rats treated with high-fat diet and 10 g·kg?1·d?1 of MGQD for 14 weeks. CON: control; T2DM: type 2 diabetes mellitus; MET: metformin; MGQDL: low-dose Modified Gegen Qinlian decoction; MGQDH: high-dose Modified Gegen Qinlian decoction; FBG: fasting blood glucose; GSP: glycosylated serum protein; AUC: area under curve. The data were expressed as mean ± standard deviation. The Shapiro-Wilk test was used to determine if a distribution was normal or not. Statistical differences between treatments were analyzed using a one-way analysis of variance or Mann-Whitney U test (n = 7-10 for FBG and GSP, n = 6 for glucose tolerance test). aP < 0.01 vs the CON group; bP < 0.05, cP < 0.01 vs the T2DM group.
Figure 1 Blood glucose and glucose tolerance test in serum of each group A: FBG; B: GSP; C: glucose tolerance test; D: AUC. CON: normal rats treated with control diet and normal saline; T2DM: diabetic rats treated with high-fat diet and normal saline. MET: diabetic rats treated with high-fat diet and 200 mg·kg?1·d?1 of metformin hydrochloric acid for 14 weeks; MGQDL: diabetic rats treated with high-fat diet and 5 g·kg?1·d?1 of MGQD for 14 weeks; MGQDH: diabetic rats treated with high-fat diet and 10 g·kg?1·d?1 of MGQD for 14 weeks. CON: control; T2DM: type 2 diabetes mellitus; MET: metformin; MGQDL: low-dose Modified Gegen Qinlian decoction; MGQDH: high-dose Modified Gegen Qinlian decoction; FBG: fasting blood glucose; GSP: glycosylated serum protein; AUC: area under curve. The data were expressed as mean ± standard deviation. The Shapiro-Wilk test was used to determine if a distribution was normal or not. Statistical differences between treatments were analyzed using a one-way analysis of variance or Mann-Whitney U test (n = 7-10 for FBG and GSP, n = 6 for glucose tolerance test). aP < 0.01 vs the CON group; bP < 0.05, cP < 0.01 vs the T2DM group.
Figure 2 Protein and mRNA levels of LDLR and SR-B1 in eWAT of each group A: relative protein expression of LDLR; B: relative protein expression of SR-B1; C: protein images of LDLR; D: protein images of SR-B1; E: relative mRNA levels of Ldlr and Srb1 were detected by qPCR.CON: normal rats treated with control diet and normal saline; T2DM: diabetic rats treated with high-fat diet and normal saline. MET: diabetic rats treated with high-fat diet and 200 mg·kg?1·d?1 of metformin hydrochloric acid for 14 weeks; MGQDL: diabetic rats treated with high-fat diet and 5 g·kg?1·d?1 of MGQD for 14 weeks; MGQDH: diabetic rats treated with high-fat diet and 10 g·kg?1·d?1 of MGQD for 14 weeks. CON: control; T2DM: type 2 diabetes mellitus; MET: metformin; MGQDL: low-dose modified Gegen Qinlian decoction; MGQDH: high-dose modified Gegen Qinlian decoction; eWAT: epididymal adipose tissue; LDLR: low-density lipoprotein receptor; SR-B1: scavenger receptor class B type 1; Ldlr: the gene encoding LDLR; Srb1: the gene encoding SR-B1; qPCR: quantitative real-time polymerase chain reaction. The data measured in this research were expressed as mean ± standard deviation. Statistical differences between treatments were analyzed using a one-way analysis of variance (n = 3 for protein levels and n = 5-10 for mRNA levels). aP < 0.01, cP < 0.05 vs the CON group; bP < 0.05, dP < 0.01, and eP = 0.059 vs the T2DM group.
Figure 2 Protein and mRNA levels of LDLR and SR-B1 in eWAT of each group A: relative protein expression of LDLR; B: relative protein expression of SR-B1; C: protein images of LDLR; D: protein images of SR-B1; E: relative mRNA levels of Ldlr and Srb1 were detected by qPCR.CON: normal rats treated with control diet and normal saline; T2DM: diabetic rats treated with high-fat diet and normal saline. MET: diabetic rats treated with high-fat diet and 200 mg·kg?1·d?1 of metformin hydrochloric acid for 14 weeks; MGQDL: diabetic rats treated with high-fat diet and 5 g·kg?1·d?1 of MGQD for 14 weeks; MGQDH: diabetic rats treated with high-fat diet and 10 g·kg?1·d?1 of MGQD for 14 weeks. CON: control; T2DM: type 2 diabetes mellitus; MET: metformin; MGQDL: low-dose modified Gegen Qinlian decoction; MGQDH: high-dose modified Gegen Qinlian decoction; eWAT: epididymal adipose tissue; LDLR: low-density lipoprotein receptor; SR-B1: scavenger receptor class B type 1; Ldlr: the gene encoding LDLR; Srb1: the gene encoding SR-B1; qPCR: quantitative real-time polymerase chain reaction. The data measured in this research were expressed as mean ± standard deviation. Statistical differences between treatments were analyzed using a one-way analysis of variance (n = 3 for protein levels and n = 5-10 for mRNA levels). aP < 0.01, cP < 0.05 vs the CON group; bP < 0.05, dP < 0.01, and eP = 0.059 vs the T2DM group.
Table 1 Effect of MGQD on methylation level of Ldlr and Srb1 in eWAT of T2DM rats (%,$\bar{x}$ ± s)
| Group | n | Ldlr | Srb1 | |||
|---|---|---|---|---|---|---|
| CpG | Non-CpG | CpG | Non-CpG | |||
| CON | 6 | 0.56±0.62 | 0.46±0.35 | 0.11±0.27 | 0.33±0.13 | |
| T2DM | 6 | 0.25±0.62 | 0.11±0.12 | 0.30±0.46 | 0.00±0.00b | |
| MET | 6 | 0.32±0.54 | 0.56±0.47a | 0.16±0.39 | 0.21±0.18a | |
| MGQDL | 6 | 0.19±0.46 | 0.32±0.40 | 0.16±0.39 | 0.25±0.23a | |
| MGQDH | 6 | 0.00±0.00 | 0.56±0.39a | 0.00±0.00 | 0.22±0.22a | |
Table 1 Effect of MGQD on methylation level of Ldlr and Srb1 in eWAT of T2DM rats (%,$\bar{x}$ ± s)
| Group | n | Ldlr | Srb1 | |||
|---|---|---|---|---|---|---|
| CpG | Non-CpG | CpG | Non-CpG | |||
| CON | 6 | 0.56±0.62 | 0.46±0.35 | 0.11±0.27 | 0.33±0.13 | |
| T2DM | 6 | 0.25±0.62 | 0.11±0.12 | 0.30±0.46 | 0.00±0.00b | |
| MET | 6 | 0.32±0.54 | 0.56±0.47a | 0.16±0.39 | 0.21±0.18a | |
| MGQDL | 6 | 0.19±0.46 | 0.32±0.40 | 0.16±0.39 | 0.25±0.23a | |
| MGQDH | 6 | 0.00±0.00 | 0.56±0.39a | 0.00±0.00 | 0.22±0.22a | |
Table 2 Correlation between the methylation level of Srb1 and FBG, cholesterol, and mRNA level in eWAT
| Srb1 | FBG | Cholesterol in eWAT | Srb1 mRNA | |||||
|---|---|---|---|---|---|---|---|---|
| P value | P value | P value | P value | P value | P value | |||
| CpG | 0.128 | 0.500 | －0.168 | 0.374 | －0.014 | 0.948 | ||
| Non-CpG | －0.470 | 0.009 | 0.322 | 0.083 | －0.410 | 0.042 | ||
Table 2 Correlation between the methylation level of Srb1 and FBG, cholesterol, and mRNA level in eWAT
| Srb1 | FBG | Cholesterol in eWAT | Srb1 mRNA | |||||
|---|---|---|---|---|---|---|---|---|
| P value | P value | P value | P value | P value | P value | |||
| CpG | 0.128 | 0.500 | －0.168 | 0.374 | －0.014 | 0.948 | ||
| Non-CpG | －0.470 | 0.009 | 0.322 | 0.083 | －0.410 | 0.042 | ||
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