Salviae Miltiorrhizae Radix et Rhizoma Extract Regulates Blood Pressure in Rat Model of Metabolic Hypertension Induced by High-sugan and High-fat Diet via TRPC3/6/NOX2/4 Sigraling Pathway
10.13422/j.cnki.syfjx.20260201
- VernacularTitle:基于TRPC3/6/NOX2/4信号通路探究丹参提取物改善高脂高糖致代谢型高血压大鼠血压的作用机制
- Author:
Chang CHEN
1
;
Hongyu WU
1
;
Ling LI
1
;
Yuebo JIANG
1
;
Sheng ZHANG
2
;
Yunna CHEN
2
;
Weidong CHEN
1
;
Daiyin PENG
1
;
Lei WANG
1
Author Information
1. School of Pharmacy， Anhui University of Chinese Medicine， Hefei 230012， China
2. School of Traditional Chinese Medicine， Anhui University of Chinese Medicine， Hefei 230012， China
- Publication Type:Journal Article
- Keywords:
metabolic hypertension induced by a high-sugar and high-fat diet;
Salviae Miltiorrhizae Radix et Rhizoma extract;
transient receptor potential cation channel （TRPC）3/6/NADPH oxidase （NOX）2/4 signaling pathway;
oxidative stress;
inflammation
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(19):217-228
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the mechanisms of Salviae Miltiorrhizae Radix et Rhizoma in treating metabolic hypertension induced by a high-sugar and high-fat diet in rats based on network pharmacology， proteomics， and animal experiments. MethodsThirty male SD rats were randomized into the control， model， positive drug （tetrandrine， Tet， 50 mg·kg-1·d-1）， low-dose Salviae Miltiorrhizae Radix et Rhizoma （DS-L， 45×104 mg·kg-1·d-1）， and high-dose Salviae Miltiorrhizae Radix et Rhizoma （DS-H， 90×104 mg·kg-1·d-1） groups. Except for the control group， each group was fed a high-fat and high-sugar diet for 8 weeks for the modeling of metabolic hypertension. Following successful modeling， drug interventions were conducted through gavage for 4 weeks. Blood pressure and lipid indicators were monitored， and cardiac function was assessed via echocardiography. Samples from the thoracic aorta and cardiac tissue were collected for histopathological examination. Network pharmacology analysis identified key active components， potential targets， and mechanisms of Salviae Miltiorrhizae Radix et Rhizoma in treating hypertension. Proteomics technology was employed to analyze the differential proteins and major pathway targets to synergistically elucidate the antihypertensive mechanism of Salviae Miltiorrhizae Radix et Rhizoma. Ca2+ concentrations in the thoracic aorta and cardiac tissue were measured. The protein levels of transient receptor potential cation channel （TRPC）3， TRPC6， NADPH oxidase （NOX）2， and NOX4 were quantified via Western blotting. The levels of oxidative stress markers and inflammatory factors， including superoxide dismutase （SOD）， malondialdehyde （MDA）， tumor necrosis factor-α （TNF-α）， and interleukin-1β （IL-1β）， were determined by enzyme-linked immunosorbent assay （ELISA）. Molecular docking analysis was performed for the main components of Salviae Miltiorrhizae Radix et Rhizoma with TRPC3， TRPC6， NOX2， and NOX4. ResultsThe experimental results indicated that compared with the control group， the model group exhibited abnormally elevated blood pressure and increased lipid levels （P<0.01）. Compared with the model group， the DS-L group exhibited reduced systolic blood pressure （SBP）， diastolic blood pressure （DBP）， and mean arterial pressure （MAP） （P<0.05）， decreased serum levels of triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.05）， and increased level of high-density lipoprotein cholesterol （HDL-C） （P<0.01）. The DS-H and Tet groups showed more significant effects （P<0.01）. Moreover， the interventions attenuated vascular wall thickening， myocardial cell injury， and collagen and lipid deposition. Network pharmacology and proteomics prediction results indicated that the core targets of Salviae Miltiorrhizae Radix et Rhizoma in treating hypertension were TRPC3， TRPC6， NOX2， and NOX4， and the core pathways included calcium signaling， cyclic guanosine monophosphate （cGMP）/cGMP-dependent protein kinase （PKG） signaling， and atherosclerosis-related pathways. The molecular mechanism experiment results indicated that compared with the control group， the model group exhibited significantly elevated tissue Ca2+ concentrations， exacerbated oxidative stress and inflammatory responses， and upregulated protein levels of TRPC3， TRPC6， NOX2， and NOX4 in the thoracic aorta and myocardial tissue （P<0.01）. Compared with the model group， DS-L reduced the free Ca2+ concentration， lowered the levels of IL-1β， TNF-α， SOD， and MDA （P<0.05）， and downregulated the protein levels of TRPC3， TRPC6， NOX2， and NOX4 in the thoracic aorta and myocardial tissue （P<0.05）. DS-H and Tet exhibited more significant effects （P<0.01）. Meanwhile， the main components of Salviae Miltiorrhizae Radix et Rhizoma had strong binding affinity with the core targets of hypertension. ConclusionSalviae Miltiorrhizae Radix et Rhizoma may ameliorate oxidative stress and mitigate inflammatory responses by regulating the TRPC3/6/NOX2/4 signaling pathway， thereby alleviating abnormal blood pressure abnormality and myocardial injury in hypertensive rats.
