Search Results (2,255)

Objectives: Paratubal cysts (PTCs) are embryological remnants and are potentially hormonally responsive. Since hyperandrogenism (HA) is representative of polycystic ovary syndrome (PCOS), we examined whether biochemical hyperandrogenism is associated with PTCs in women with PCOS and if body mass index (BMI) and insulin resistance (IR) mediate this association. Methods: This retrospective study included 577 women diagnosed with PCOS at a tertiary academic center from 2010 to 2018. Clinical data included age at diagnosis, BMI, and diagnoses of hypertension, non-alcoholic fatty liver disease, and metabolic syndrome. Laboratory measures included total testosterone, sex hormone-binding globulin, anti-Müllerian hormone, luteinizing hormone, fasting glucose, insulin, and triglycerides (TG). Derived indices included a free androgen index (FAI), homeostasis model assessment of insulin resistance (HOMA-IR), and fasting glucose-to-insulin ratio. PTCs were identified through imaging or surgical findings. Structural equation modeling (SEM) assessed direct and indirect relationships between FAI, BMI, HOMA-IR, and PTCs, while adjusting for diagnostic age. Results: PTCs were identified in 2.77% of participants. BMI, FAI, TG, and IR indices were significantly higher for women with PTCs than those without PTCs. SEM revealed significant indirect effects of FAI on PTCs via BMI and HOMA-IR. The direct effect was negative, resulting in a non-significant total effect. A sensitivity model using HOMA-IR as the predictor showed a significant direct effect on PTCs without mediation via FAI. Conclusions: Biochemical HA may influence PTC development in PCOS through metabolic pathways, establishing the need to consider metabolic context when evaluating adnexal cysts in hyperandrogenic women. Full article

TRPV1 regulates neuronal and vascular function mediated by NO and CGRP. Systemic arterial hypertension (SAH) induces an imbalance in vascular mediators NO and CGRP by altering the transport of Ca²⁺ ions through TRPV1, generating cellular damage. We studied the effect of topical capsaicin (CS) treatment on cardiac mechanical work, oxidative stress (CAT, NO, BH4, and BH2), cellular damage (MDA, MTO, and 8HO2dG), and inflammation (IL-6 and TNFα), generated by SAH, which was induced by L-NAME, in male Wistar rats. CS was added to a moisturizing cream and applied to the abdomen of animals for two weeks. Experimental groups were as follows: (1) Control, (2) Control + Cream, (3) Hypertensive, and (4) Hypertensive + Cream. Hearts were exposed to ischemia-reperfusion (I-R) using the Langendorff technique to study the potential cardioprotection of CS. Expression of SOD1, SOD2, catalase, eNOS, pNOS, TRPV1, and CGRP in cardiac tissue was evaluated. In the Hypertensive group, TRPV1 activation by CS (Hypertensive + Cream) reduced oxidative stress (OS), decreasing cellular damage and inflammation and increasing CAT, modulating biochemical and tissue alterations induced by OS generated by SAH. In parallel, an increase in tissue levels and the expression of CGRP, TRPV1, and eNOS, induced by CS, was observed. These findings indicate that pretreatment with CS attenuates cardiac I-R and SAH injury in rats. The cardioprotective mechanism may be based on TRPV1-mediated CGRP overexpression. Full article

Cardiovascular disease (CVD) is the leading cause of death worldwide, with pathophysiological mechanisms often involving platelet activation and chronic inflammation. While antiplatelet agents targeting adenosine diphosphate (ADP)-mediated pathways are well established in CVD management, less is known about drug interactions with the platelet-activating factor (PAF) pathway, a key mediator of inflammation. This study aimed to evaluate the effects of several commonly used cardiovascular and anti-inflammatory drug classes—including clopidogrel, non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin II receptor blockers (ARBs), β-blockers, and analgesics—on platelet function via both the ADP and PAF pathways. Using human platelet-rich plasma (hPRP) from healthy donors, we assessed platelet aggregation in response to these two agonists in the absence and presence of graded concentrations of each of these drugs or of their usually prescribed combinations. The study identified differential drug effects on platelet aggregation, with some agents showing pathway-specific activity. Clopidogrel and NSAIDs demonstrated expected antiplatelet effects, while some (not all) antihypertensives exhibited additional anti-inflammatory potential. These findings highlight the relevance of evaluating pharmacological activity beyond traditional targets, particularly in relation to PAF-mediated inflammation and thrombosis. This dual-pathway analysis may contribute to a broader understanding of drug mechanisms and inform the development of more comprehensive therapeutic strategies for the prevention and treatment of cardiovascular, hypertension, and inflammation-driven diseases. Full article

Background/Objectives: Nelumbo nucifera Gaertn. (lotus) seeds have traditionally been used to treat hypertension, though their mechanisms remain unclear. This study investigated the antihypertensive effects of lotus seed extract (LSE) and its mechanisms in rats with N^ω-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Methods: Male Sprague Dawley rats received L-NAME (40 mg/kg/day) in drinking water and were treated orally with LSE (5, 10, or 100 mg/kg/day), captopril (5 mg/kg/day), or a combination of LSE and captopril (2.5 mg/kg/day each) for 5 weeks. Hemodynamic parameters and histological changes in the left ventricle and aorta were assessed. Mechanistic studies included measurements of plasma nitric oxide (NO) metabolites, malondialdehyde (MDA), superoxide dismutase (SOD) activity, angiotensin II (Ang II), angiotensin-converting enzyme (ACE) activity, and protein expression via western blot. Results: L-NAME elevated systolic blood pressure and induced cardiovascular remodeling, oxidative stress, and renin-angiotensin system activation. LSE treatment reduced blood pressure, improved antioxidant status, increased NO bioavailability, and downregulated gp91^phox and AT₁R expression. The combination of low-dose LSE and captopril produced stronger effects than LSE alone, with efficacy comparable to captopril. Conclusions: These findings suggest that LSE exerts antihypertensive effects via antioxidant activity and inhibition of the renin-angiotensin system, supporting its potential as an adjunct therapy for hypertension. Full article

Hypertension is a major pathogenic contributor to cardiovascular diseases, primarily mediated through activation of the angiotensin-converting enzyme (ACE) system. Food-derived ACE-inhibitory peptides represent a promising alternative to synthetic drugs due to their favorable safety profile and minimal side effects. ACE-inhibitory peptides have been extensively identified from various foods, with their antihypertensive activity and molecular mechanisms comprehensively characterized through in vitro and in vivo studies. ACE-inhibitory peptides can be prepared by methods such as natural extraction, enzymatic hydrolysis, and fermentation. The production process significantly modulates structural characteristics of the polypeptides including peptide chain length, amino acid composition, and sequence, consequently determining their functional activity. To comprehensively elucidate the gastrointestinal stability and mechanisms action of ACE-inhibitory peptides, integrated experimental approaches combining both in vitro and in vivo methodologies are essential. This review systematically examines current advances in food-derived ACE-inhibitory peptides in terms of sources, production, structure, in vivo and in vitro activities, and bioavailability. Full article

Background: Ingestion of dietary fibers (DFs) is a safe and accessible intervention associated with reductions in blood pressure (BP) and cardiovascular mortality. However, the mechanisms underlying the antihypertensive effects of DFs remain poorly defined. This systematic review and meta-analysis evaluates how DFs influence BP regulation by modulating gut microbial composition and enhancing short-chain fatty acid (SCFA) production. Methods: MEDLINE and EMBASE were systematically searched for interventional studies published between January 2014 and December 2024. Eligible studies assessed the effects of DFs or other prebiotics on systolic BP (SBP) and diastolic BP (DBP) in addition to changes in gut microbial or SCFA composition. Results: Of the 3010 records screened, nineteen studies met the inclusion criteria (seven human, twelve animal). A random-effects meta-analysis was conducted on six human trials reporting post-intervention BP values. Prebiotics were the primary intervention. In hypertensive cohorts, prebiotics significantly reduced SBP (−8.5 mmHg; 95% CI: −13.9, −3.1) and DBP (−5.2 mmHg; 95% CI: −8.5, −2.0). A pooled analysis of hypertensive and non-hypertensive patients showed non-significant reductions in SBP (−4.5 mmHg; 95% CI: −9.3, 0.3) and DBP (−2.5 mmHg; 95% CI: −5.4, 0.4). Animal studies consistently showed BP-lowering effects across diverse etiologies. Prebiotic interventions restored bacterial genera known to metabolize DFs to SCFAs (e.g., Bifidobacteria, Akkermansia, and Coprococcus) and increased SCFA levels. Mechanistically, SCFAs act along gut–organ axes to modulate immune, vascular, and neurohormonal pathways involved in BP regulation. Conclusions: Prebiotic supplementation is a promising strategy to reestablish BP homeostasis in hypertensive patients. Benefits are likely mediated through modulation of the gut microbiota and enhanced SCFA production. Full article

Background/Objectives: The novel compound 221s (2,9), derived from danshensu and ACEI-active proline, exhibits antihypertensive effects (50/35 mmHg SBP/DBP reduction in SHRs) with potential cough mitigation. However, its excretion kinetics remain unstudied. This study investigates 221s (2,9) elimination in rats to bridge this knowledge gap. Methods: Excretion of unchanged 221s (2,9) was quantified in urine, feces, and bile of Sprague-Dawley rats after oral administration (30 mg/kg). Concentrations of unchanged 221s (2,9) in all matrices were quantified using developed UPLC-MS/MS that underwent methodological validation. Excretion amount, excretion velocity, and accumulative excretion rate of 221s (2,9) were calculated. Results: Urinary excretion exhibited rapid elimination kinetics, reaching peak cumulative excretion rates (138.81 ± 15.56 ng/h) at 8 h post-dosing and plateauing by 48 h (cumulative excretion: 1479.81 ± 155.7 ng). Fecal excretion displayed an accelerated elimination phase between 4 and 8 h (excretion rate: 7994.29 ± 953.75 ng/h), followed by a sustained slow-release phase, culminating in a cumulative output of 36,726.31 ± 5507 ng at 48 h. Biliary excretion was minimal and ceased entirely by 24 h. Notably, total recovery of unchanged drug across all matrices remained below 1% (urine: 0.020 ± 0.021%; feces: 0.73 ± 0.069%; bile: 0.00044 ± 0.00002%) at 72 h. Conclusions: This study provides the first definitive excretion data for 221s (2,9). Quantitative analysis via a validated UPLC-MS/MS method revealed that fecal excretion is the principal elimination pathway for unchanged 221s (2,9) in rats, with direct excretion of the parent compound accounting for <1% of the administered dose over 72 h. Future studies will employ extended pharmacokinetic monitoring and concurrent UPLC-MS/MS analysis of the parent drug and phase II conjugates to resolve the observed mass imbalance and elucidate contributions to total elimination. Full article

Background: Cardiovascular diseases, particularly hypertension, and gastrointestinal disorders represent major public health concerns in Mexico. Although a range of pharmacological treatments exists, their use is associated with adverse effects, highlighting the need for safer therapeutic alternatives. Species of the Ipomoea genus are widely employed in Mexican traditional medicine (MTM) for their purgative, anti-inflammatory, analgesic, and sedative properties. Particularly, Ipomoea purpurea is traditionally used as a diuretic and purgative; its leaves and stems are applied topically for their anti-inflammatory and soothing effects. This study aimed to determine their phytochemical composition and to evaluate the associated vasodilatory activity, modulatory effects on intestinal smooth-muscle motility, and toxicological effects of the methanolic (ME-Ip) and dichloromethane (DE-Ip) extracts obtained from the aerial parts of I. purpurea. Methods: The phytochemical composition of the ME-Ip and DE-Ip extracts of I. purpurea was assessed using UPLC-QTOF-MS and GC-MS, respectively. For both extracts, the vasodilatory activity and effects on intestinal smooth muscle were investigated using ex vivo models incorporating isolated rat aorta and ileum, respectively, whereas acute toxicity was evaluated in vivo. Results: Phytochemical analysis revealed, for the first time, the presence of two glycosylated flavonoids within the Ipomoea genus; likewise, constituents with potential anti-inflammatory activity were detected. The identified compounds in I. purpurea extracts may contribute to the vasodilatory, biphasic, and purgative effects observed in this species. The EC₅₀ values for the vasodilatory effects of the methanolic (ME-Ip) and dichloromethane (DE-Ip) extracts were 0.80 and 0.72 mg/mL, respectively. In the initial phase of the experiments on isolated ileal tissues, both extracts induced a spasmodic (contractile) effect on basal motility, with ME-Ip exhibiting higher potency (EC₅₀ = 27.11 μg/mL) compared to DE-Ip (EC₅₀ = 1765 μg/mL). In contrast, during the final phase of the experiments, both extracts demonstrated a spasmolytic effect, with EC₅₀ values of 0.43 mg/mL for ME-Ip and 0.34 mg/mL for DE-Ip. In addition, both extracts exhibited low levels of acute toxicity. Conclusions: The phytochemical profile and the vasodilatory and biphasic effects of the I. purpurea extracts explain, in part, the use of I. purpurea in MTM. The absence of acute toxic effects constitutes a preliminary step in the toxicological safety assessment of I. purpurea extracts and demonstrates their potential for the development of phytopharmaceutic agents as adjuvants for the treatment of cardiovascular and gastrointestinal disorders. Full article

Background: Hypertension is a serious global health issue affecting over one billion adults and leading to severe complications if left unmanaged. Despite medical advancements, only a fraction of patients effectively have their hypertension under control. Among the factors that hinder adherence to hypertensive drugs are the debilitating side effects of the drugs. The lack of adherence results in poorer patient outcomes as patients opt to live with their condition, instead of having to deal with the side effects. Hence, there is a need to discover new hypertension drug molecules with better side effects to increase patient treatment options. To this end, computational methods such as artificial intelligence (AI) have become an exciting option for modern drug discovery. AI-based computational drug discovery methods generate numerous new lead antihypertensive drug molecules. However, predicting their potential side effects remains a significant challenge because of the complexity of biological interactions and limited data on these molecules. Methods: This paper presents a machine learning approach to predict the potential side effects of computationally synthesised antihypertensive drug molecules based on their molecular properties, particularly functional groups. We curated a dataset combining information from the SIDER 4.1 and ChEMBL databases, enriched with molecular descriptors (logP, PSA, HBD, HBA) using RDKit. Results: Gradient Boosting gave the most stable generalisation, with a weighted F1 of 0.80, and AUC-ROC of 0.62 on the independent test set. SHAP analysis over the cross-validation folds showed polar surface area and logP contributing the largest global impact, followed by hydrogen bond counts. Conclusions: Functional group patterns, augmented with key ADMET descriptors, offer a first-pass screen for identifying side-effect risks in AI-designed antihypertensive leads. Full article

Background: Chronic Kidney Disease (CKD) is a major global health issue, with diabetes being its primary cause and cardiovascular disease contributing significantly to patient mortality. Recently, two classes of medications—sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs)—have shown promise in protecting both kidney and heart health beyond their effects on blood sugar control. Methods: We conducted a narrative review summarizing the findings of different clinical trials and mechanistic studies evaluating the effect of SGLT2i and GLP-1 RAs on kidney function, cardiovascular outcomes, and overall disease progression in patients with CKD and DKD. Results: SGLT2i significantly mitigate kidney injury by restoring tubuloglomerular feedback, reducing intraglomerular hypertension, and attenuating inflammation, fibrosis, and oxidative stress. GLP-1 RAs complement these effects by enhancing endothelial function, promoting weight and blood pressure control, and exerting direct anti-inflammatory and anti-fibrotic actions on renal tissues. Landmark trials—CREDENCE, DAPA-CKD, and EMPA-KIDNEY—demonstrate that SGLT2i reduce the risk of kidney failure and renal or cardiovascular death by 25–40% in both diabetic and non-diabetic CKD populations. Likewise, trials such as LEADER, SUSTAIN, and AWARD-7 confirm that GLP-1 RAs slow renal function decline and improve cardiovascular outcomes. Early evidence suggests that using both drugs together may offer even greater benefits through multiple mechanisms. Conclusions: SGLT2i and GLP-1 RAs have redefined the therapeutic landscape of CKD by offering organ-protective benefits that extend beyond glycemic control. Whether used individually or in combination, these agents represent a paradigm shift toward integrated cardiorenal-metabolic care. A deeper understanding of their mechanisms and clinical utility in both diabetic and non-diabetic populations can inform evidence-based strategies to slow disease progression, reduce cardiovascular risk, and improve long-term patient outcomes in CKD. Full article

Mauritia flexuosa, commonly known as “canangucha,” holds significant nutritional and economic value in the Amazon region. While its pulp is widely utilized in local food products, the seed or kernel is largely underutilized. This study investigated the proximal and phytochemical composition of M. flexuosa, alongside its biological properties, specifically focusing on the hypoglycemic activity of an ethanolic extract from M. flexuosa seeds (MFSs). Proximal analysis revealed that MFSs are a notable source of crude fiber (28.4%) and a moderate source of protein (9.1%). Phytochemical screening indicated a high total polyphenol content (123.4 mg gallic acid equivalents/100 mg dry weight) and substantial antiradical capacity against the ABTS radical (IC₅₀ = 171.86 µg/mL). Notably, MFS ethanolic extracts exhibited significant in vitro antihyperglycemic activity via inhibiting α-amylase and α-glucosidase enzymes, demonstrating comparable inhibition to acarbose at higher concentrations. This hypoglycemic effect was further corroborated in an in vivo rat model with induced diabetes, where the administration of 100 mg/kg of MFS ethanolic extract significantly reduced blood glucose levels compared to the diabetic control group (p < 0.05). A moderate antihypertensive effect was observed at a concentration of 150 mg/kg, correlating with ACE inhibition. High-performance liquid chromatography–mass spectrometry (UHPLC-ESI-HRMS) analysis of the seed extract identified phenolic compounds including ellagic, p-coumaric, and chlorogenic acids, as well as flavonoids such as quercetin, myricetin, and epicatechin. This study provides the first evidence of the hypoglycemic activity of MFSs, offering valuable insights into their phytochemistry and potential therapeutic applications. Full article

The study aimed to evaluate how different production methods and fermentation processes using two different lactic acid bacteria (LAB) affect the chemical composition and bioactive properties of pistachio beverages. The beverages were prepared with two varieties of pistachios, one from Argentina and the other from Italy. The pistachios were processed with two technologies: a domestic processor and a colloidal mill. For the fermentation, pistachio beverages were inoculated with two different LAB strains and incubated at 28 °C for 24 h. The beverages were analyzed for proximal composition (including protein, fat, fiber, and minerals) and bioactive properties such as antioxidant activity, angiotensin-converting enzyme inhibition (ACE-I), and dipeptidyl peptidase-4 inhibition (DPP-4). The colloidal milling allowed the inclusion of the whole pistachio nut, resulting in beverages with higher solid content and no waste. Beverages treated with colloidal milling exhibited higher acidity, improved microbial fermentation performance, and generally showed higher bioactivity compared to those obtained by the domestic processor. Bioactivity varied according to the pistachio variety, the processing method and LAB strains used. Lactic acid bacteria fermentation decreased antioxidant properties of the beverages by ~40% but improved anti-hypertensive and hypoglycaemic activities. Fermented pistachio-based beverages showed promising health-promoting properties, indicating their potential as functional foods. Full article

Background and Objectives: A commonly observed phenomenon in outpatient oncological patients is the appearance of hypotension not attributable to other causes in hypertensive patients undergoing oncological treatment. Once antihypertensive treatment is discontinued, patients remain normotensive after the oncological treatment ends. The objective of this research is to analyze our experience with this phenomenon and try to provide an explanation. Materials and Methods: A retrospective case-control study was conducted with a total sample of 302 hypertensive oncological patients, with cases presenting symptomatic hypotension and controls not. Descriptive and inferential statistics were performed, with the latter focusing on studies by Odds Ratio, Chi-square, Z test for comparison of two proportions, and multivariate regression. Results: Regarding the results obtained, it is noteworthy that in both the univariate and multivariate models, treatment with cisplatin showed statistical significance (Univariate, OR 3.06 (CI 1.82–5.11). Z 4.45, p < 0.0001; multivariate, p < 0.001, Nagelkerke R2 74.8%). Cisplatin treatment and the study phenomenon were correlated with magnesium levels (Chi-square 8.2, p = 0.017), relating hypotension to hypertensive patients with low magnesium levels. Conclusions: CDDP treatment is associated with hypotension or normotension in previously hypertensive cancer patients. This may be related to peripheral vascular fragility induced by oncological drugs, leading to reduced vascular resistance. Although magnesium deficiency is generally linked to hypertension, chemotherapy-related shifts in magnesium levels due to impaired renal handling may play a role. These findings may help improve the understanding of blood pressure regulation in oncology patients. Full article

In order to innovatively develop high-activity ACE inhibitory peptides from edible fungi, the conditions for a double-enzymatic hydrolysis preparation of ACE inhibitory peptides from Flammulina velutipes were optimized by response surface methodology. After purification by macroporous resin, gel chromatography, and RP-HPLC, a crude peptide fraction was obtained; its ACE inhibition rate was 85.73 ± 0.95% (IC₅₀ = 0.83 ± 0.09 mg/mL). Based on LC-MS/MS sequencing, the four novel peptides, namely, FAGGP, FDGY, FHPGY, and WADP, were screened by computer analysis and molecular docking technology. The four peptides exhibited a binding energy between −9.4 and −10.3 kcal/mol, and formed hydrogen bonds with Tyr523, Ala354, and Glu384 in the S1 pocket, Tyr520 and His353 in the S2 pocket, and His383 in the HEXXH zinc-coordinating motif of ACE, indicating their good affinity with the ACE active site. The IC₅₀ values of the four ACE inhibitory peptides were 29.17, 91.55, 14.79, and 41.27 μM, respectively, suggesting that these peptides could potentially contribute to the development of new antihypertensive products. Full article

Captopril, a well-established angiotensin-converting enzyme (ACE) inhibitor, has garnered attention for its cardioprotective effects in preventing heart remodeling and maintaining cardiac function, significantly improving life quality. However, recent studies have revealed that in addition to known hemodynamic alterations, captopril exhibits significant antioxidant, anti-inflammatory, and immunomodulatory effects that may underlie its protective mechanisms. Although it appeared to be overlooked in clinical practice, in recent years, additional efforts have been made to uncover the mechanisms of all drug effects, as recent research studies predict a wide spectrum of diseases beyond the recommended indications. This review thoroughly examines the mechanisms by which captopril mediates its protective effects, bridging basic biochemical observations with applied clinical investigation, especially during ischemic reperfusion (I/R) injury, hypertension, and heart failure (HF). Evidence points to captopril as a promising agent for modulating oxidative and inflammatory pathways that are crucial for cardiovascular medicine. Directions for future research are defined to determine the molecular targets of captopril further and to optimize its clinical utility in the management of cardiovascular and possibly other diseases. Full article