Neferine exhibits therapeutic effects on anti-hypertension. However, the effect of neferine on hypertensive vascular remodeling remains unexplored. Therefore, the current study was to investigate the effect of neferine on hypertensive vascular remodeling and its underlying mechanisms. Total 30 male spontaneously hypertensive rats (SHRs) were divided randomly into five groups, including SHR, Neferine-L (2.5 mg/kg/day), Neferine-M (5 mg/kg/day), Neferine-H (10 mg/kg/day), and Valsartan (10 mg/kg/day) groups (n = 6 for each group). Wistar Kyoto (WKY) rats were set as control group (n = 6). Noninvasive blood pressure system, ultrasound, hematoxylin and eosin staining, masson trichrome staining were used to detect the blood pressure, pulse wave velocity (PWV), pathological changes and collagen content in abdominal aortas of SHRs. RNA-sequencing and immunohistochemistry(IHC) analyses were used to identify and verify the differentially expressed transcripts and activation of associated signaling pathways in SHRs. Various concentrations of neferine or valsartan treatment substantially reduced the elevation of blood pressure, PWV, and abdominal aortic thickening of SHRs. RNA-sequencing and KEGG analyses recognized 441 differentially expressed transcripts and several enriched pathways (including PI3K/AKT and TGF-β/Smad2/3 signaling pathways) after neferine treatment. Masson trichromatic staining and IHC analysis demonstrated that neferine treatment decreased the collagen content and down-regulated the protein expression of PCNA, collagen I & III, and fibronectin, as well as p-PI3K, p-AKT, TGF-β1 and p-Smad2/3 in abdominal aortic tissues of SHRs. Neferine treatment exhibits therapeutic effects on anti-hypertension and reduces vascular remodeling, as well as suppresses the abnormal activation of multiple signaling pathways, including PI3K/AKT and TGF-β1/Smad2/3 pathways.

Qingda granules (QDG) are derived from QingXuanJiangYa Decoction (QXJYD) a traditional Chinese medication that has been used to treat hypertension for more than 60 years. QXJYD has been shown to be effective in rat models of hypertension. However, the effects of QDG on hypertension remain largely unknown. In the current study, baicalin was identified as one of the main components of QDG using Ultra Performance Liquid Chromatography (UPLC) analysis. We investigated the effects of QDG on blood pressure, cardiac remodeling, and cardiac inflammation. QDG (0.8 g/kg/day) treatment attenuated the elevated blood pressure in spontaneously hypertensive rats (SHRs). Moreover, QDG treatment reduced the degree of myocardial fiber disarray, degeneration and necrosis of myocardial cells, expression of ANP and BNP, as well as collagen content of SHRs. Moreover, we further assessed the effect of QDG treatment on cardiac inflammation and found that QDG treatment reduced CD68 protein expression, decreased levels of IL-6 and TNF-α in both serum and cardiac tissues, as well as suppressed activation of NF-κB pathway in cardiac tissues of SHRs. Differential expressed metabolites (DEMs) analysis identified 41 increased and 51 decreased metabolites in the cardiac tissues of SHRs after QDG treatment. In summary, QDG treatment of SHRs attenuated the elevated blood pressure and ameliorated cardiac remodeling and inflammation, in part, through suppression of NF-κB pathway and DEMs, which provide a basis for other therapeutic uses of this TCM.

Hypertension, a highly prevalent chronic disease, is known to inflict severe damage upon blood vessels. In our previous study, isoliensinine, a kind of bibenzyl isoquinoline alkaloid which isolated from a TCM named Lotus Plumule (Nelumbo nucifera Gaertn), exhibits antihypertensive and vascular smooth muscle proliferation-inhibiting effects, but its application is limited due to poor water solubility and low bioavailability. In this study, we proposed to prepare isoliensinine loaded by PEG-PLGA polymer nanoparticles to increase its efficacy METHOD: We synthesized and thoroughly characterized PEG-PLGA nanoparticles loaded with isoliensinine using a nanoprecipitation method, denoted as, PEG-PLGA@Isoliensinine. Additionally, we conducted comprehensive investigations into the stability of PEG-PLGA@Isoliensinine, in vitro drug release profiles, and in vivo pharmacokinetics. Furthermore, we assessed the antihypertensive efficacy of this nano-system through in vitro experiments on A7R5 cells and in vivo studies using AngII-induced mice. The findings reveal that PEG-PLGA@Isoliensinine significantly improves isoliensinine absorption by A7R5 cells and enhances targeted in vivo distribution. This translates to a more effective reduction of AngII-induced hypertension and vascular smooth muscle proliferation. In this study, we successfully prepared PEG-PLGA@Isoliensinine by nano-precipitation, and we confirmed that PEG-PLGA@Isoliensinine surpasses free isoliensinine in its effectiveness for the treatment of hypertension, as demonstrated through both in vivo and in vitro experiments. This study lays the foundation for isoliensinine's clinical use in hypertension treatment and vascular lesion protection, offering new insights for enhancing the bioavailability of traditional Chinese medicine components. Importantly, no toxicity was observed, affirming the successful implementation of this innovative drug delivery system in vivo and offers a promising strategy for enhancing the effectiveness of Isoliensinine and propose an innovative avenue for developing novel formulations of traditional Chinese medicine monomers.

Gastrodin, a highly potent compound found in the traditional Chinese medicine Gastrodia elata Blume, exhibits significant antihypertensive properties. However, its role and the mechanism behind its protective effects on hypertensive cardiac conditions are not well understood. This study aims to investigate the cardiac protective effects and underlying mechanisms of gastrodin in angiotensin II (Ang II)-induced hypertensive models, both in vivo and in vitro. Treatment with gastrodin significantly decreased blood pressure and the heart weight/tibial length (HW/TL) ratio and attenuated cardiac dysfunction and pathological damage in Ang II-infused C57BL/6 mice. RNA sequencing analysis (RNA-seq) revealed 697 up-regulated and 714 down-regulated transcripts, along with 1105 signaling pathways, in Ang II-infused C57BL/6 mice following gastrodin treatment, compared to Ang II-induced hypertensive mice. Furthermore, the analyses of the top 30 Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway indicated significant enrichment in apoptosis and the peroxiredoxin 2 (PRDX2)/p53 pathway. Consistently, gastrodin treatment significantly reduced myocardial apoptosis in both the cardiac tissues of Ang II-induced hypertensive mice and Ang II-stimulated H9c2 cells. Additionally, gastrodin treatment significantly decreased the protein levels of PRDX2, p53, cleaved caspase-3, cleaved caspase-9, and Bax/Bcl-2 ratio in the cardiac tissues of Ang II-infused mice and H9c2 cells stimulated with Ang II. In conclusion, gastrodin treatment can mitigate hypertension-induced myocardial apoptosis in hypertensive mice by inhibiting the PRDX2/p53 pathway.

Although neferine exhibits obvious therapeutic effects against hypertension, its effects on cardiac protection remain unknown. This study aimed to investigate its potential cardioprotective effects and associated mechanisms. Spontaneously hypertensive rats (SHRs) were randomly divided into four groups, namely SHR, SHR + Neferine-L (2.5 mg/kg/day), SHR + Neferine-M (5 mg/kg/day), and SHR + Neferine-H (10 mg/kg/day). Wistar Kyoto rats were used as control. Various concentrations of neferine or double distilled water were then administered intragastrically for 10 weeks. Thereafter, cardiac function, pathological changes, cell apoptosis, and reactive oxygen species (ROS) accumulation, as well as their underlying mechanisms, were evaluated in SHRs and/or hypoxia-induced H9c2 cells. Neferine treatment significantly mitigated the decrease in left ventricular ejection fraction and fractional shortening and increase in left ventricular mass, end-systolic volume, and cardiac injury in SHRs. In SHR cardiac tissues, neferine treatment reversed 154 upregulated and 108 and downregulated transcripts. Pathway enrichment analysis found that multiple pathways were commonly enriched, including the apoptosis, PI3K-Akt, MAPK, and HIF-1 pathways. Consistently, neferine treatment significantly mitigated cardiomyocyte apoptosis, restored mitochondrial membrane depolarization, and reduced ROS accumulation. Mechanistically, neferine treatment significantly decreased the phosphorylation of ERK, p38 MAPK, and JNK; the Bax/Bcl-2 ratio; and the expression of HIF-1α, NADPH oxidase 4, and cleaved caspases-3 and -9 but increased the phosphorylation of PI3K and Akt and the expression of CD31. Neferine treatment effectively mitigated hypertensive cardiomyocyte apoptosis and attenuated the abnormal activation of multiple signaling pathways, including the PI3K/Akt, MAPK, and HIF-1 pathways.