Analyzing the potential mechanism of Buyang Huanwu decoction for the treatment of salt-sensitive hypertension based on network pharmacology and in vivo experiments

Background:Buyang Huanwu decoction(BHD)is a traditional Chinese medicine herbal formula used for treating hypertension,particularly in the later stages of hypertension when it is associated with intracerebral hemorrhage.This study aims to investigate the treatment mechanism of BHD to provide a basis for its clinical application in hypertension treatment.Methods:Network pharmacology analysis and cell culture experiments were performed to explore the potential proteins and mechanisms of action of BHD against hypertension.Bioactive compounds related to BHD were screened,and relevant targets associated with hypertension and BHD were retrieved.Molecular docking technology was used to identify the effective signaling pathway based on the Kyoto Encyclopedia of Genes and Genomes and protein-protein interaction network cores.Lastly,the effects and mechanisms of BHD on salt-sensitive hypertensive endothelial cells were investigated.Results:Ninety-three potential therapeutic targets for BHD and salt-sensitive hypertension were found to be closely associated with the PI3K/Akt/eNOS signaling pathway and oxidative stress.Cell experiments further indicated the pivotal role of endothelial cells in hypertension,and validation analysis showed that BHD significantly preserved cell morphology,suppressed oxidative stress reactions,activated the PI3K/Akt/eNOS signaling pathways,preserved normal endothelial cell function,and reduced cell apoptosis.Conclusion:BHD effectively activates the PI3K/Akt/VEGF signaling pathway,attenuates oxidative stress-induced injury in endothelial cells exposed to high salt levels,and mitigates apoptosis,supporting the use of traditional Chinese medicine BHD in the treatment of salt-sensitive hypertension.

Low Salt Diet in Pregnant Mothers Is Associated with Enhanced Salt Appetite in Their Offspring of Dahl Salt-Sensitive Rats

Objectives: We investigated an influence of salt intake during gestation or lactation in salt preference of weaning Dahl salt sensitive (Dahl S) strain. Material and Methods: Nine-week-old female Dahl S rats, after mated with the male, were divided into 1) high-salt group fed a 4% NaCl diet (high-salt mother) or 2) low-salt group fed a 0.3% NaCl diet (low-salt mother) during gestation or lactation periods. Using 0.4%, 0.6% and 0.8% (w/v) saline solutions, we assessed salt preference in their offspring after weaning. Systolic blood pressure (SBP) was determined by tail cuff method. Results: Both the male and female offspring from low-salt mothers during gestation consumed equal amounts of any saline solution. However, the amount of each saline solution was higher in the offspring of low-salt mothers than those of high-salt mothers. This resulted in a significant increase of salt intake in both the male and female offspring of low-salt mothers compared with those of high-salt mothers. In contrast, both the male and female offspring from low-mothers during lactation rather preferred the lower concentration of saline solution, and this resulted in less salt intake in the offspring of low-salt mothers than those of high-salt mothers. Conclusions: We demonstrated that low salt diet in pregnant mothers increased salt intake of their offspring. The offspring of mothers fed a low salt diet during lactation had less salt than those of high-salt mothers. The influence of salt intake of mothers in their offspring varies along with the growth stage of their babies.

Study on the Difference of Body Mass Index and Insulin Sensitivity Index in Salt-sensitive Hypertension Patients of Different Traditional Chinese Medicine Syndrome Types

OBJECTIVE: To explore the difference of body mass index(BMI) and insulin sensitivity index(ISI) in saltsensitive hypertension patients of different traditional Chinese medicine(TCM) syndrome types, so as to elucidate the effect of the distribution of each syndrome on the degree of insulin resistance in salt-sensitive hypertension patients. METHODS: A total of 131 patients with salt-sensitive hypertension were included in the study. Factor analysis and cluster analysis were used to study the characteristics of TCM viscera, syndrome elements and syndrome differentiation. Furthermore, the following parameters were observed and corresponding differences were analyzed, including BMI, waist circumference, abdominal circumference, neck circumference and insulin sensitivity index among group s of different TCM syndrome types. RESULTS: There were 131 cases of saltsensitive hypertension. The results of factor analysis showed that the total variance contribution of F1-5 common factors was 75.8%. According to the pattern differentiation of zang-fu organs, a basic theory of traditional Chinese medicine(TCM), the main zang-fu organs involved in the five common factors are: liver, spleen, and kidney.The main syndrome factors that had been extracted include yin de?ciency, ?re, qi stagnation, yang hyperactivity,dampness, phlegm, qi reversal, heat, retained fluid, essence deficiency, qi descending, qi deficiency, and yang deficiency. Among them, factor 1 accounted for 18.32%, factor 2 accounted for 21.37%, factor 3 accounted for20.43%, factor 4 accounted for 20.61%, and factor 5 accounted for 22.14%. The proportion of zang-fu organs involvement was: 21.37% of the spleen, 17.56% of the kidney, 18.32% of the liver and spleen, and 42.75% of the spleen and kidney. Syndrome elements: yin de?ciency 18.32%, phlegm-dampness 21.37%, qi stagnation 39.69%, qi de?ciency 42.75%, retained ?uid 20.61%, yang de?ciency 60.31%, essence de?ciency 17.56%, qi sinking 17.56%,heat 21.37%, qi reversal 21.37%. Results of cluster analysis: there were 3 categories when the distance variance was 20-Category 1: Factor 1; Category 2: Factor 2; Category 3: Factor 3, Factor 4, Factor 5. Combined with the clinical practice of TCM, the classi?cation based on TCM syndromes was:Category 1, yin de?ciency and yang hyperactivity pattern(accounting for 18.32%); Category 2, excessive accumulation of phlegm-dampness(accounting for 21.37%); Category 3, spleen-kidney yang de?ciency and pattern of water-rheum collecting internally(accounting for 60.31%), including 24 cases of yin-de?ciency and yang-hyperactivity(YDYH), 28 cases of excessive phlegmdampness syndrome(EPDS), 79 cases of spleen and kidney yang-de?ciency and ?uid retention stagnating in the interior(SKFR). There was no difference in the distribution of age and sex among groups. In addition, no signi?cant difference was found regarding BMI, waist circumference, abdominal circumference, neck circumference among groups of salt-sensitive hypertension of different TCM syndrome types. Meanwhile, ISI was signi?cantly lower in cases of spleen and kidney yang-de?ciency and ?uid retention stagnating in the interior than in the other 2 groups,with statistical difference. CONCLUSION: Insulin resistance is the most serious in salt-sensitive hypertension patients with spleen and kidney yang-de?ciency and ?uid retention stagnating in the interior. Besides, obesity is not a critical factor in determining the distribution of TCM syndrome types in patients with salt-sensitive hypertension.

SYNTHESIS AND CHARACTERIZATION OF AMPHOTERIC HYDROGELS BASED ON N-CARBOXYETHYLCHITOSAN

New amphoteric hydrogels based on carboxyethylchitosans (CECH) with various degrees of substitution (DS) were prepared using different amounts of epichlorohydrin (ECH) as the crosslinking agent. The equilibrium swelling ratio (SW) was determined as functions of pH and salt concentration. The hydrogels show typical amphoteric character responding to pH change of the external medium. At isoelectric point (IEP), the hydrogels shrink. The DS value has important effect on the swelling properties of the hydrogels. When the DS of N-carboxyethylchitosan increases from 0.32 to 0.72, the equilibrium swelling ratio (SW) of the hydrogel changes from 76 to 290 at pH 7.3 and from 117 to 499 at pH 11.3. A marked volume decrease was observed in hydrogels with increasing salt concentration in the surrounding solution. The viscoelastic properties of the hydrogels were studied by oscillatory shear measurements under small-deformation conditions. The elastic modulus G' of all the samples has no dependence on frequency and is one order of magnitude larger than the loss modulus G '', corresponding to a strong gel behavior.

High salt-induced weakness of anti-oxidative function of natriuretic peptide receptor-C and podocyte damage in the kidneys of Dahl rats

Background:Atrial natriuretic peptide(ANP)and its natriuretic peptide receptors A(NPR-A)and C(NPR-C)are involved in the regulation of physiological and pathophysiological process of blood pressure.The present study aimed to determine the role of NPR-C in the development of salt-sensitive hypertension.Methods::The Dahl salt-sensitive(DS)and salt-resistant(DR)rats were used in this study.Animals were matched according to their age and weight,and then placed on either a high-salt(HS,8%)or a normal-salt(NS,0.4%)diet for 6 weeks randomly using random number table.The systolic blood pressure(SBP),plasmatic sodium concentration(PL Na),urinary sodium excretion(UV Na),and serum creatinine concentration(Scr)were measured.The concentration of ANP in blood and tissues(heart and kidney)was detected by enzyme-linked immunosorbent assay.The expression of ANP,NPR-A,and NPR-C in kidney was evaluated with western blot analysis.Regarding renal redox state,the concentration changes in malondialdehyde(MDA),lipofuscin,nicotinamide adenine dinucleotide phosphate(NADPH)oxidase(Nox),and nitric oxide synthase(NOS)in kidney were detected by a spectrophotometric method.The kidney damage was evaluated using pathological techniques and the succinodehydrogenase(SDHase)examination.Furthermore,after an intra-peritoneal injection of C-atrial natriuretic peptide(ANP)4-23(C-ANP 4-23),an NPR-C receptor agonist,the SBP,biochemical values in blood and urine,and renal redox state were evaluated.The paired Student’s t test and analysis of variance followed by the Bonferroni test were performed for statistical analyses of the comparisons between two groups and multiple groups,respectively.Results::The baseline SBP in all groups was within the normal range.At the end of the 6-week experiment,HS diet significantly increased the SBP in DS rats from 116.63±2.90 mmHg to 162.25±2.15 mmHg(t=-10.213,P<0.001).The changes of SBP were not significant in DS rats on an NS diet and DR rats on an NS diet or on an HS diet(all P>0.05).The significant increase of PL Na,UV Na,and Scr related to an HS diet was found in both DS and DR rats(all P<0.05).However,significant changes in the concentration(t=-21.915,P<0.001)and expression of renal ANP(t=-3.566,P=0.016)and the expression of renal NPR-C(t=5.864,P=0.002)were only observed in DS hypertensive rats.The significantly higher desmin immunochemical staining score(t=-5.715,P=0.005)and mitochondrial injury score(t=-6.325,P=0.003)accompanied by the lower SDHase concentration(t=3.972,P=0.017)revealed mitochondrial pathologic abnormalities in podocytes in DS rats with an HS diet.The distinct increases of MDA(t=-4.685,P=0.009),lipofuscin(t=-8.195,P=0.001),and Nox(t=-12.733,P<0.001)but not NOS(t=-0.328,P=0.764)in kidneys were also found in DS hypertensive rats.C-ANP 4-23 treatment significantly decreased the SBP induced by HS in DS rats(P<0.05),which was still higher than NS groups with the vehicle or C-ANP 4-23 treatment(P<0.05).Moreover,the HS-induced increase of MDA,lipofuscin,Nox concentrations,and Nox4 expression in DS rats was significantly attenuated by C-ANP 4-23 treatment as compared with those with HS diet and vehicle injection(all P<0.05).Conclusions::The results indicated that the renal NPR-C might be involved in the salt-sensitive hypertension through the damage of mitochondria in podocytes and the reduction of the anti-oxidative function.Hence,C-ANP 4-23 might serve as a therapeutic agent in treating salt-sensitive hypertension.