Antihypertensive Activity Research Articles

Unveiling Wide Spectrum Therapeutic Implications and Signaling Mechanisms of Valsartan in Diverse Disorders: A Comprehensive Review.

Valsartan is an orally active non-peptide angiotensin receptor antagonist, an effective and well-tolerated anti-hypertensive drug. Besides its antihypertensive action, it has clinical implications in many other disorders, like heart failure (HF), arrhythmia, chronic kidney disease (CKD), diabetic complications (DM), atherosclerosis, etc. Besides angiotensin receptor blocking activity, valsartan reduces circulating levels of biochemical markers, such as hs-CRP, which is responsible for its anti-inflammatory and anti-oxidant activity. Moreover, valsartan also acts by inhibiting or inducing various signalling pathways, such as inducing autophagy via the AKT/mTOR/S6K pathway or inhibiting the TLR/NF-kB pathway. The current review exhaustively discusses the therapeutic implications of valsartan with specific emphasis on the mechanism of action in various disorders. The article provides a detailed spectrum of the therapeutic profile of valsartan and will likely be very useful to researchers working in the relevant research areas.

Targeting Diabetes with Azole-derived Medicinal Agents.

Azoles have long been regarded as an ideal scaffold for the development of numerous innovative therapeutic agents as well as other incredibly adaptable and beneficial chemicals with prospective uses in a variety of fields, including materials, energetics (explosophores), and catalysis (azole organocatalytic arbitration). Azoles exhibit promising pharmacological activities, including antimicrobial, antidiabetic, antiviral, antidepressant, antihistaminic, antitumor, antioxidant, antiallergic, antihelmintic, and antihypertensive activity. According to a database analysis of U.S. FDAapproved medications, 59% of specific medications are connected to small molecules that have heterocycles having nitrogen atoms. The azole moiety has impressive electron abundance. Azoles promptly attach to various receptors as well as enzymes in the physiological environment via distinct specialized interactions, contributing to their anti-diabetic potential. This review encompasses the recent research progress on potent azole-derived antidiabetic agents that can be used as an alternative for the management of type-2 diabetes.

Mechanistic insights into antihypertensive activity of mushroom-derived protein-peptides via metabolomic and proteomic approaches

Stropharia rugosoannulata mushroom peptides have well-defined sequences, specific structures, and excellent antihypertensive activity. In this study, metabolomic and proteomic analyses revealed the antihypertensive mechanism of mushroom-derived protein-peptides, GQEDYDRLRPL (GL-11P) and KSWDDFFTR (KR-9P), to demonstrate their potential antihypertensive buck-regulation systems and pathways. Protein-peptides were predominantly down-regulated expression of endogenous metabolites in antihypertensive regulation, and bile acid analogs were key endogenous differentially expressed metabolic markers. Antihypertensive treatment with protein-peptides activated the immune and signal transduction systems, affected extracellular regions, metal ion binding, and receptor binding ability. The ECM-receptor interaction pathway, with differentially expressed proteins in antihypertensive treatment, distinguished the protein-peptides from blank control and was also a critical pathway that distinguished the two protein-peptides. Up-regulatory pathways of protein expression dominated by GL-11P's antihypertensive regulation, while down-regulatory pathways of protein expression dominated by KR-9P's antihypertensive regulation. Protein-peptides exerted antihypertensive regulatory effects by enhancing immune responses, up-regulating protein and enzyme binding capacity, and down-regulating inflammatory mediator release. Differentially expressed protein interactions produced in protein-peptides antihypertensive therapy mostly up-regulated the Reactome pathway and were dominated by immune system regulation. This study provided data support for utilizing mushroom-derived protein-peptides in antihypertensive therapy, and enriched the theoretical basis of protein-peptides' antihypertensive regulation mechanisms.

Antioxidant, Antihypertensive, and Anti-Inflammatory Activities of Long-Term Ripened Cheddar Cheese Water-Soluble Extract

Antioxidant, Antihypertensive, and Anti-Inflammatory Activities of Long-Term Ripened Cheddar Cheese Water-Soluble Extract

Cardiovascular Effects of a Glycosylated Flavonoids-Rich Leaf Extract from Brazilian Erythroxylum campestre: A Potential Health Bio-Input

Background: Bioactivity assessments of plant-derived products can benefit human and animal health, especially in regions with vast plant diversity. This study focused on chemical and cardiovascular analyses of Erythroxylum campestre A. St. Hil. leaf extracts. Methods: High-performance liquid chromatography, liquid chromatography coupled with mass spectrometry, and nuclear magnetic resonance spectroscopy were used to elucidate the structures of the flavonoids in E. campestre. The E. campestre methanolic fraction (ECM-ppt-M; at doses of 1, 2, 3, and 6 mg∙kg−1 or vehicle) was administered intravenously to normotensive and spontaneously hypertensive rats (SHRs), and we recorded the mean arterial pressure (MAP), heart rate (HR), renal vascular resistance (RVR), and aortic vascular resistance (AVC). Results: The ECM-ppt-M extract demonstrated significant antihypertensive activity, as evidenced by reductions in MAP, RVR, and AVR, with effects that were particularly pronounced in SHRs. Following the establishment of these cardiovascular effects, phytochemical analysis revealed the presence of glycosylated flavonoids, which are likely contributors to the observed antihypertensive properties of the extract. Conclusions: The notable reductions in MAP and vascular resistance observed with ECM-ppt-M treatment suggest its antihypertensive effect. These findings demonstrate the potential therapeutic value of this extract with regard to the treatment of hypertension. Future studies on ECM may provide a promising therapeutic alternative capable of reducing the risk of toxicity and adverse effects associated with synthetic drugs.

Nyctanthes arbor-tristis Improves Blood Pressure via Endothelial Pathway: In Silico, Ex Vivo, and In Vivo Evidence.

Systemic hypertension, a common metabolic disorder, poses significant health risks despite the availability of antihypertensive drugs. Nyctanthes arbor-tristis has garnered increasing attention for its perceived efficacy and safety, though its mechanisms of action and the bioactive compounds responsible for its antihypertensive effects remain elusive. Therefore, this study aims to elucidate the antihypertensive activity of N. arbor-tristis leaves in rats and explore associated mechanism through in silico, in vitro, ex vivo, and in vivo studies. The methanolic extract of N. arbor-tristis leaves (MENAT) was fractionated and subjected to qualitative and quantitative phytochemical screening, including total phenolic content (Folin-Ciocalteu method), total flavonoid content (Aluminum chloride method), and total alkaloid content (spectrometric method). Antioxidant studies were conducted using DPPH, FRAP, and H2O2 assays. The most promising fraction (WNAT) was analyzed using LC-MS, and the identified compounds were used for molecular docking studies against cGMP and eNOS. Further, aortic ring assays were conducted to assess ex vivo vasorelaxant activity (rat aortic strip assay) and the underlying mechanisms of WNAT. Later, in vivo studies using a DOCA-salt-induced hypertension model in Wistar rats, along with molecular analyses (RT-PCR), were performed to validate the antihypertensive claims of N. arbor-tristis. In vitro studies demonstrated that the water extract of N. arbor-tristis leaves (WNAT) exhibited strong antioxidant activity and contained key phytochemicals. LC-MS analysis revealed the presence of 19 major compounds, including betulinic acid and arbortristosides. Molecular docking studies indicated that arborside C exhibited a strong affinity for both eNOS and cGMP. Ex vivo studies involving rat aortic strips showed that WNAT induced vasodilatory activity, which is associated with parasympathetic and nitric oxide-related pathways. In vivo experiments further supported WNAT's antihypertensive properties through improvements via amelioration of rat blood pressure and histological features, biochemical markers, morphometric parameters, and gene expression in hypertensive rats. In conclusion, WNAT effectively lowers blood pressure through modulation of the endothelial pathway and warrants further studies to attain its clinical utility in hypertensive subjects.

The influence of the daily salt-intake on the antihypertensive action and atrial natriuretic peptide level in patietns with angiotensin receptor neprilysin inhibition

Abstract Background The angiotensin receptor–neprilysin inhibitor (ARNI) is a drug which acts through angiotensin receptor blocking effect and the increase in atrail natriuretic peptide (ANP) through neprilysin inhibitor in hypertension (HT). These combined effects result in a reduced risk of hospitalization for heart failure or death from cardiovascular causes. ANP is also known for its various cardioprotective effects including vasodilator and natriuretic action. Acording to Guyton's pressure-natriuresis curve, the efficacy of angiotensin receptor blocker drugs is diminished in HT cases with high daily salt inatke. However, whether the effect of ARNI on HT is attenuated in patients with high daily salt intake remains unclear. Purpose The present study investigated the influence of a daily salt intake on the antihypertensive action and ANP level in patients with ARNI. Methods Fourty-four consecutive essential HT patients on ARNI were enrolled. Blood pressure and ANP level were measured at baseline (before taking ARNI) and 3 weeks later. ARNI (200mg) was prescribed and maintained during the study. In addtion, the daily salt intake was calculated using creatinine and natrium levels in urine, age, and body weight according to Japanese hypertensive guideline at baseline and 3 weeks later. Results The average age was 70±8 years old. About 50% (N=23) was male. The mean sytolic and diastolic blood pressure was 148±14mmHg and 89±10mmHg, respectively. The mean daily salt intake was 9.5±2.2 g/day at baseline. The mean ANP level was 529±300pg/ml. At follow up (3 weeks later), the mean systolic and diastolic blood pressure significanly went down to 132± 18 mmHg and 70± 9 mmHg, respectively (p=0.03). ANP level also increased from 529±300pg/ml to 793±580pg/ml. However, the mean daily salt intake was almost same as the baseline at 9.4±3.2 g/day. The patients were divided into 2 groups; high daily salt intake (N=20 with mean daily salt intake 10.5±1.7g/day)) and low daily salt intake (N=24 with 8.4±3.1g/day) groups compared to the baseline. The absolute and percentage changes in systolic blood pressure were almost same in the high and low daily salt intake groups (-12.7±15.8mmHg vs -13.7±14.2mmHg, p=0.75; -5.8±6.5% vs.-7.0±9.6%, p=0.58, respectively). However, the change rate in ANP level was significantly higer in the high daily salt intake group than in the low daily salt intake group (155±63 vs. 12±16%, p=0.01). Conclusion ARNI demonstrates effectiveness in lowering the blood pressure even in patients with higher salt intake, unlike angiotensin receptor blocker. In cases with high salt intake, the notable increase in ANP levels may contribute to decreasing blood pressure through vasodilator and natriuretic action.

Bio-Guided Extraction of a Phenolic-Rich Extract from Industrial Peanut Skin with Antioxidant and Hypotensive Potential.

Peanut composition includes phenolic compounds, especially in the skins, which are often not consumed. High blood pressure affects more than one billion people worldwide and is considered a high-risk factor for cardiovascular diseases. Several studies have correlated antihypertensive activity with the total phenolic content present in the plants. This study evaluated the hydroethanolic extraction of phenolic compounds from the industrial residue of peanut skin and evaluated the antioxidant and antihypertensive capacity of these extracts using in vitro models. A rotational central composite design (DCCR) was proposed to study the influence of the variables: (1) the ethanol concentration on the hydroalcoholic extractor solution, and (2) the proportion of solid sample (waste) per liquid in the extraction (mass/volume) in a simple solid-a liquid extraction process. The optimal extraction conditions within this model were 50% ethanol in water, and the proportion of sample to extraction solution (m/v) equaled to 0.2. The extract obtained had significant antioxidant capacity, both in chemical (ORAC) and in cellular models, with potential for free radical scavenging. Significant levels of ACE inhibition were also found, indicating antihypertensive activity.

Identification of Structure-Linked Activity on Bioactive Peptides from Sea Cucumber (Stichopus japonicus): A Compressive In Silico/In Vitro Study.

A sea cucumber (Stichopus japonicus) is an invertebrate rich in high-quality protein peptides that inhabits the coastal seas around East Asian countries. Such bioactive peptides can be utilized in targeted disease therapies and practical applications in the nutraceutical industry. Bioactive peptides were isolated from Stichopus japonicus through ultrafiltration and Sephadex G-10 size exclusion chromatography. The low-molecular-weight fraction (ACSH-III) showed the highest hydroxyl radical scavenging and angiotensin-converting enzyme (ACE) inhibitory activities. Subsequent purification of ACSH-III resulted in four fractions, of which ACSH-III-F3 and ACSH-III-F4 exhibited significant bioactivity. Peptides identified in these fractions, including Phenylalanine-Proline-Threonine-Tyrosine (FPTY) and Tyrosine-Proline-Serine-Tyrosine-Proline-Serine (YPSYPS), were characterized using high-performance liquid chromatography (HPLC) and quadrupole time-of-flight mass spectrometry (QTOF-MS). FPTY demonstrated the most potent antioxidant and antihypertensive activities among these peptides, with IC50 values of 0.11 ± 0.01 mg/mL for hydroxyl radicals and 0.03 ± 0.01 mg/mL for ACE inhibition. Docking simulations revealed strong binding affinities of these peptides to the active site of the ACE, with FPTY displaying interactions similar to those of the synthetic inhibitor lisinopril. These findings suggest that the identified peptides, particularly FPTY, have potential applications as natural antioxidants and functional foods.

Improved Antioxidant, Antihypertensive, and Antidiabetic Activities and Tailored Emulsion Stability and Foaming Properties of Mixture of Corn Gluten and Soy Protein Hydrolysates Via Enzymatic Processing and Fractionation

ABSTRACTBioactive peptides and protein hydrolysates have gained considerable attention in the food industry and functional food markets due to their diverse health effects, including antioxidant, antihypertensive, and antidiabetic properties. This study aimed to produce combined soy and corn protein hydrolysates using Alcalase (Al), modification of Al‐hydrolysates through sequential hydrolysis using Flavourzyme (Al‐FL), cross‐linking of Al‐hydrolysates using microbial transglutaminase (MTGase) (Al‐TG), and fractionation of Al‐hydrolysates by ultrafiltration (UF) with molecular weight (MW) cut‐off of 100 (Al‐F4), 30 (Al‐F3), 10 (Al‐F2), and 2 kDa (Al‐F1). Notably, the < 2 kDa fraction (Al‐F1) showcased exceptional biological activities, including antioxidant (81.54% DPPH, 98.02% ABTS), antihypertensive (95.45%), and antidiabetic effects (44.72% α‐glucosidase, 77.52% α‐amylase), linked to its high hydrophobic amino acid content and low molecular weights (111 and 263 Da). Conversely, the higher molecular weight fraction (Al‐TG) excelled in emulsion and foam stability, attributed to its balanced amino acid profile and larger peptides (1385–7057 Da). Our findings reveal that specific protein hydrolysate fractions, particularly Al‐F1 and Al‐TG, are promising for applications in food and pharmaceutical formulations due to their enhanced biological and functional properties.

Ameliorative Effects of Phyto-estrogen ‘Genistein’, Homeopathic Combination ‘R-85’and Captopril on Body Weight, Organ Weight, Feed and Water Intake in L-NAME Induced Hypertensive Wistar Rats

Hypertension is associated with the development and progression of severe damage to organs. Meager studied has been found on the effect of Phyto-estrogen ‘genistein’ and homeopathic combination ‘R-85’ as antihypertensive action which may aid in main therapy of hypertension. Thus, present study aims to evaluate the effect of ‘genistein’, ‘R-85’ and ‘captopril’ on body weight, organ weight feed and water intake in Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) induced hypertensive male wistar rats. After acclimatization, the male wistar rats were divided into 5 groups of 5 rats in each group. The rats except control group (group-I) were treated with L-NAME (@50mg/kg, in drinking water, group-II), L-NAME + Genistein (@50mg/kg, per os, group-III), L-NAME + R-85 (@ 5 drops, twice daily, group-IV) and L-NAME + Captopril (@50 mg/kg, per os, group-V) daily for 42 days. The study was conducted for a period of 42 days. During the experimental period, weight of rats, feed intake and water intake was measured weekly. At the end of the experimental period, rats were sacrificed andheart, kidneys and liver were weighed. After treatment with genistein, R-85 and captopril an increase in body weight was found as compared to L-NAME group. On similar treatment there was an increase in feed intake per 100 g of rat was found compared to L-NAME hypertensive group per week. Unlike feed intake, treatments decrease the water intake per 100 g of rat compared to L-NAME group per week. A significant increase in the relative weights of the liver and kidney was found in L-NAME group compared to control. Whereas, treatment with R-85 and captopril significantly decreased the relative weight of liver and kidney as compared to L-NAME group. Thus finding of the present study discloses ameliorative effect of genistein, R-85 and captopril on hypertensive rats.

HPTLC method to support formulation development and quality control of the tablets prepared from fruit extracts of Piper longum

Alcoholic extract of fruits of Piper longum is reported to have antihypertensive activity, significantly due to presence of alkaloids like piperine, piperlongumine, piperlonguminine and pipernonaline. A sensitive and specific HPTLC method was developed and validated for simultaneous estimation of piperine, piperlongumine and piperlonguminine in fruit extracts with a purpose to provide the analytical support during the development of formulation as well as to serve as a quality control tool for optimised formulation. Developed method was validated with respect to ICH (International Council for Harmonisation) Q2(R1) and found to be accurate, precise, sensitive, specific and robust for estimation of piperine, piperlongumine and piperlonguminine. Method was successfully applied for assay of dry powdered extract and optimised tablet formulation in terms of content of piperine, piperlongumine and piperlonguminine as well as to study the dissolution profiles of formulation batches during development stage.

Murraya koenigii (Curry Tree): A review of its Phytochemistry, Ethnomedicinal uses, and Pharmacology with Respect to Molecular Mechanisms

Abstract: Medicinal plants have significant therapeutic value and are a gift to humanity in pursuing healthy living. The discovery of numerous rejuvenating compounds that can stop or reduce the pathology of many diseases will be a crucial advancement in the coming years. Synthetic compounds can cause health issues and side effects, necessitating the development of molecules derived from plants and other natural resources as viable substitutes for synthetic compounds. Several plant phytochemicals and extracts have been found to have significant effects on traditional medical therapy. Murraya koenigii (M. Koenigii) is a member of the Rutaceae family, well-known in the Ayurvedic system of medicine as a therapeutically important herb of Indian origin. M. Koenigii has been used in several ancient systems of medicine, including Siddha and Unani, as a multi-potential medicinal plant. Previous research has shown that this plant's bark, roots, and leaves are abundant sources of carbazole alkaloids, which have beneficial pharmacological and biological effects. These include antioxidant, antibacterial, antidiabetic, anti-inflammatory, antihypertensive, antifungal, antiprotozoal, hepatoprotective, antihypercholesterolemic, antiulcer, cytotoxic, antidiarrheal, phagocytic, neuroprotective, and antitumor activities. The key components of the M. koenigii plant and their pharmacological activities against various diseases using preclinical models are discussed in this review. Exhaustive studies on the molecular mechanism of action of M. koenigii are needed to validate the effectiveness of curry tree and their constituents as potent therapeutic agents. However, serious efforts are required to identify, isolate and evaluate the chemical components for nutritional and medicinal potentials.

Molecular Targets of Valeric Acid: A Bioactive Natural Product for Endocrine, Metabolic, and Immunological Disorders.

Postbiotics produced by gut microbiota have exhibited diverse pharmacological activities. Valeric acid, a postbiotic material produced by gut microbiota and some plant species like valerian, has been explored to have diverse pharmacological activities. This narrative review aims to summarise the beneficial role of valeric acid for different health conditions along with its underlying mechanism. In order to get ample scientific evidence, various databases like Science Direct, PubMed, Scopus, Google Scholar and Google were exhaustively explored to collect relevant information. Collected data were arranged and analyzed to reach meaningful a conclusion regarding the bioactivity profiling of valeric acid, its mechanism, and future prospects. Valeric acid belongs to short-chain fatty acids (SCFAs) compounds like acetate, propionate, butyrate, pentanoic (valeric) acid, and hexanoic (caproic) acid. Valeric acid has been identified as one of the potent histone deacetylase (HDAC) inhibitors. In different preclinical in -vitro and in-vivo studies, valeric acid has been found to have anti-cancer, anti-diabetic, antihypertensive, anti-inflammatory, and immunomodulatory activity and affects molecular pathways of different diseases like Alzheimer's, Parkinson's, and epilepsy. These findings highlight the role of valeric acid as a potential novel therapeutic agent for endocrine, metabolic and immunity-related health conditions, and it must be tested under clinical conditions to develop as a promising drug.

Endothelin receptor B is required for the blood pressure-lowering effect of G protein-coupled estrogen receptor 1 in ovariectomized rats.

Activation of G protein-coupled estrogen receptor 1 (GPER1) elicits antihypertensive actions in different animal models. The endothelin-1 signaling system plays a fundamental role in blood pressure regulation. Lack of functional endothelin receptor B (ETB) evokes hypertension and salt sensitivity. GPER1 and ETB interact to promote urinary sodium excretion in female rats. We hypothesized that activation of GPER1 protects against hypertension and salt sensitivity induced by ETB antagonism in female rats. Female Sprague-Dawley rats were implanted with radiotelemetry. Animals were then subjected to ovariectomy and simultaneously implanted with minipumps to deliver either the GPER1 agonist G1 or its corresponding vehicle. Two weeks post surgery, we initiated treatment of rats with the ETB antagonist A-192621. Animals were maintained on a normal-salt diet and then challenged with a high-salt diet for an additional 5 days. Assessment of mean arterial blood pressure revealed an increase in vehicle-treated, but not G1-treated, rats in response to ovariectomy. A-192621 increased blood pressure in normal-salt diet-fed vehicle- and G1-treated rats. G1 improved the circadian blood pressure rhythms that were disrupted in A-192621-treated ovariectomized rats. Thus, although systemic GPER1 activation did not protect ovariectomized rats from hypertension and salt sensitivity induced by ETB antagonism, it maintained circadian blood pressure rhythms. Functional ETB is required to elicit the antihypertensive actions of GPER1. Additional studies are needed to improve our understanding of the interaction between G protein-coupled receptors in regulating circadian blood pressure rhythm.NEW & NOTEWORTHY Systemic G protein-coupled estrogen receptor 1 (GPER1) activation in rats prevents the increase in blood pressure evoked by ovariectomy. Blockade of endothelin receptor B negates the blood pressure-lowering impact of GPER1 in ovariectomized rats. Endothelin receptor B plays an important role in mediating the blood pressure-lowering action of GPER1 activation in female rats.

Food processing drives the toxic lectin reduction and bioactive peptide enhancement in Pinellia ternata

Processing can change the properties and flavors of food. Many plants in the Araceae family can be used as food or medicine, but their raw materials are usually toxic, such as Pinellia ternata tuber (PTT). After processing (processed PTT, PPTT), its toxicity is reduced. However, the mechanism remains unclear. In this study, a novel approach integrating liquid chromatography-mass spectrometry, feature-based molecular networking (FBMN), de novo sequencing, and protein database searching was applied to rapidly discover and characterize peptides in PPTT. Potential antihypertensive peptides were screened using in silico methods, angiotensin I-converting enzyme (ACE) inhibitory assay, and molecular docking analysis. A significant decrease was observed in toxic lectins after processing. Meanwhile, a total of 1,954 mass spectral nodes were discovered in PPTT, of which 130 were annotated as peptides by FBMN. These peptides, ranging from 2 to 21 amino acids, were rapidly identified using PEAKS. Notably, 98 peptides were derived from lectins, most of which increased after processing. Approximately 30% of identified peptides were screened for potential high antihypertensive activity in silico. Five peptides exhibited inhibitory effects on ACE, with two showing IC50 values of 131 and 185 μM. Dynamic profiling indicated that 7 to 9 days of processing is optimal for reducing toxicity and enhancing efficacy. More importantly, these peptides were also found in commercial PPTT, confirming their bioactivity contributions. These findings provide insights into the mechanism by which food processing drives the toxic lectin reduction and bioactive peptide enhancement in PTT, providing a novel approach to rapidly discover bioactive peptides, which can be extended to other foods in Araceae family.

Novel bioactive peptides with antihypertensive activity generated from beef muscle during fermentation with Lactobacillus rhamnosus FERM P-15120

Novel bioactive peptides with antihypertensive activity generated from beef muscle during fermentation with Lactobacillus rhamnosus FERM P-15120

The Combination of Gastrodin and Gallic Acid Synergistically Attenuates AngII-Induced Apoptosis and Inflammation via Regulation of Sphingolipid Metabolism.

Hypertension (HTN) is closely related to endothelial damage. While tianma (TM) and gouqizi (GQZ) have the potential to be effective in the treatment of HTN in traditional Chinese medicine, their main active ingredients and whether its exert synergistic effects and the underlying mechanisms of synergistic effects are still unclear. This study screened the active ingredients of TM and GQZ, investigated the synergistic effects of the active ingredients and explored possible mechanisms. The potential targets and mechanisms of TM and GQZ were screened using network pharmacology, and gastrodin (GAS) and gallic acid (GA) were identified as compounds with significant antihypertensive activity. The synergistic effects of the combination of GAS and GA was assessed by measuring biomarkers of AngII-induced human umbilical vein endothelial cell (HUVECs) dysfunction model. Furthermore, the anti-apoptotic and anti-inflammatory effects were evaluated by measuring inflammatory cytokine secretion, and apoptosis-related markers. Finally, key targets of the sphingolipid signaling pathway were experimentally validated by Western blotting. In network pharmacology, the herb-pair exerted a synergetic effect by regulating sphingolipid pathways. The GAS and GA exerted synergistic protective effects in AngII-induced HUVECs injury by improving Nitric Oxide Content (NO) levels, alleviating lactate Endothelin-1 (ET-1), and Thromboxane B2 (TX-B2) release, reducing the secretion of inflammatory factors like interleukin-6 (IL-6), interleukin-1β (IL-1β), Tumor Necrosis Factor Alpha (TNF-α)), decreasing the pro-apoptotic protein BAX, and increasing the anti-apoptotic protein BCL-2. Furthermore, the results showed that the GAS and GA combination could elevate the level of S1PR1 and inhibit the expression of ROCK2 and the phosphorylation of NF-κB, which are key targets involved in sphingolipid pathways. Our study revealed that the combination of GAS and GA could suppress inflammation and apoptosis, which are highly correlated with sphingolipid signaling pathways, making it a potential candidate for the treatment of HTN.

Evaluation of anti-hypertensive activity of Quercus leucotrichophora A. camus methanolic extract on DOCA-salt induced hypertensive rats

Quercus leucotrichophora A. camus, commonly known as Banj oak or Ban tree, belongs to the Fagaceae family and is abundantly found in the regions of Shimla, Kullu-Manali, and upper Mandi in Himachal Pradesh. This study explores the medicinal properties of plant seeds, known for their antioxidant and diuretic activity, traditionally utilized in the treatment of hypertension and hypolipidemic, hepatoprotective conditions. PurposeTo investigate the antihypertensive effect of methanolic extract of Quercus leucotrichophora A. camus seeds in DOCA sat induced rats. Material and methodsGround seeds of Quercus leucotrichophora A. camus were stored in an airtight container. A total of 100 gs of dried seed powder were subjected to extraction using 250 ml of methanol and a Soxhlet extractor maintained at 60–65 °C for five hours. The resulting dried extract (5 gs) was stored in an airtight container in a refrigerator at low temperature and administered by rats to test its antihypertensive impact. The assessment of obtained extract impact on hypertension induced by DOCA-salt was conducted through blood pressure measurement and biochemical analysis. ResultsOur study revealed that the methanolic extract of Quercus leucotrichophora A. camus seeds exerted blood pressure-lowering effects, associated with an increase in serum Nitric Oxide (NO) levels. The attenuation of hypertension by extract was further linked to the normalization of serum Na+ and K+concentrations, indicating an improvement in electrolyte imbalance. Additionally, the antioxidant properties of Quercus leucotrichophora A. camus were evident through increased activities of Glutathione (GSH), Glutathione Peroxidase (GHPx), Superoxide Dismutase (SOD), and decrease activity of Thiobarbituric acid reactive substances (TBARS). ConclusionThe findings of our investigation suggest that the antihypertensive action of Quercus leucotrichophora A. camus is correlated with enhanced endothelial nitric oxide synthase (eNOS) activation and an augmented antioxidant defense system. This sheds light on the potential therapeutic benefits of plant under investigation in managing hypertension, emphasizing its role in promoting cardiovascular health. Further research is warranted to elucidate the underlying mechanisms and to explore the full pharmacological potential of Quercus leucotrichophora A. camus in the field of cardiovascular medicine.

Co-delivery of novel valsartan and hydrochlorothiazide pH-responsive electrospun polymeric nanofibers for improved oral delivery

Valsartan (VAL) and Hydrochlorothiazide (HCTZ) as a fixed-dose combination are widely used for the management of hypertension. To enhance the dissolution and oral delivery of VAL (BCS class II drug) and HCTZ (BCS class IV drug), nanofibers containing both drugs were prepared using an electrospinning technique. VAL/HCTZ-loaded NFs were prepared using Eudragit L100-55 (EUD L100-55) and Poly (ethyne oxide) (PEO) polymer mixture and the formulation process was optimized through three process variables of polymer composition, polymer concentration, and spinning voltage. VAL/HCTZ-loaded NFs were characterized for their size, surface morphology, entrapment efficiency (%EE), drug-polymer interaction, in vitro drug release, ex-vivo permeation, and in vivo studies. Smooth, beadles and uniform drug-loaded NFs were successfully fabricated using optimum polymer composition (EUD L100-55/PEO 3:1), concentration (12 % w/v), and applied voltage (30 KV). The optimum formula (F9) showed a low average nanosize of 300 nm and a high drug loading of > 90 % was achieved. In vitro, release results showed a pH-dependent drug release, with minimum drug released at pH lower than 4.5, but a significant and complete release of both drugs was achieved at pH 6.5. The EUD L100-55/PEO improved the dissolution of VAL and HCTZ compared to free drugs at the intestinal site of absorption. Differential Scanning calorimetry and Fourier Transform Infra-Red studies showed both drugs’ amorphization and compatibility between drugs and polymers. Permeability behavior for the VAL/HCTZ-loaded NFs was found to be significantly higher than free drug suspensions of both drugs which indicated the improvement of VAL and HCTZ permeability through the intestinal membrane. The in vivo study proved the enhanced oral anti-hypertensive action of drugs-loaded NFs compared to free drug suspensions. The superior in vitro release, ex-vivo permeation, and in vivo anti-hypertensive effect indicate that drug-loaded nanofibers have the potential to improve the biological activity and hence oral delivery of the fixed-drug combination.