Cardiovascular & Haematological Disorders - Drug Targets - Online First

Due to the lack of sufficient studies on the mechanisms of the cardiovascular effects of Berberis vulgaris (B. vulgaris), this study aimed to evaluate the cardiovascular effects of the hydroalcoholic extract of B. vulgaris fruit on nitric oxide (NO) and acute hypertension caused by NG-nitro-L-arginine methyl ester (L-NAME; a NOS inhibitor).

In total, 48 male rats were assigned to six groups (n = 8): the control group, which received saline intraperitoneally (i.p), the L-NAME group, which received L-NAME intravenously (10 mg/kg. i.v), the L-NAME + SNP group, which received sodium nitroprusside (SNP, 50 µg/kg, i.v), followed by L-NAME after 30 min, and three treatment groups, which received the B. vulgaris extract at doses of 100, 200, and 400 mg/kg, followed by L-NAME. The heart rate (HR), mean arterial pressure (MAP), and systolic blood pressure (SBP) were measured up to 30 min after L-NAME injection. Afterward, changes (Δ) in SBP, MAP, and HR were calculated and analyzed.

All doses of the extract attenuated ΔSBP, ΔMAP, and ΔHR; however, these changes in the groups receiving the extract at the doses of 200 and 400 mg/kg were significantly lower than in the group receiving saline (P < 0.05-P < 0.01, respectively). In the L-NAME group, ΔSBP, ΔMAP, and ΔHR were significantly increased (P < 0.01-P < 0.001). In the L-NAME + SNP group, all responses were significantly lower than in the L-NAME group (P < 0.01-P < 0.001). The extract at the doses of 200 and 400 mg/kg significantly reduced ΔHR, ΔMAP, and ΔSBP induced by L-NAME (P < 0.05-P < 0.001). Moreover, these changes at the doses of 100 and 200 were significantly higher than in the L-NAME + SNP group.

In the present study, it was demonstrated that the B. vulgaris extract dose dependently decreased cardiovascular parameters in basal and L-NAME-induced hypertensive conditions. This response suggests that the cardiovascular effect of the hydroalcoholic extract of B. vulgaris is partly mediated by an increase in NO production. Given the vasodilatory effect of NO, it seems that NO reduces vascular resistance and causes a decrease in blood pressure.

NO has a beneficial effect on the cardiovascular system, and the hypotensive effect of B. vulgaris extract is partly mediated by increased NO production.

The present study aimed to investigate the cardioprotective effect of Borago officinalis and its synergistic effect against isoproterenol-induced myocardial infarction in Sprague-Dawley (SD) rats.

Myocardial infarction was experimentally induced in SD rats (Rattus norvegicus) using subcutaneous administration of isoproterenol (ISO) 85 mg/kg/s.c on days 20 and 21. Experimental animals were divided into five groups (5 animals each): normal control (NC), negative control (ISO), test drug Borago officinalis leaf extract (BOL) group, standard drug metoprolol (SDG) group, and combination of test drug Borago officinalis and standard drug metoprolol (BOM) group. Physical (heart grading and heart/body weight ratio), biochemical (CK-MB, LDH, AST, and ALT), troponin, oxidative stress (TBARS), and antioxidant parameters (SOD, CAT, GSH, and GPx) were assessed. Additionally, histopathological analysis of heart tissues was performed.

ISO significantly impaired cardiac function, as indicated by elevated biochemical markers (CK-MB, LDH, AST, and ALT) and oxidative stress markers (TBARS), and by heart tissue damage, with lowered antioxidant parameters (SOD, CAT, GSH, and GPx). Rats pre-treated with BOL, SDG, or their combination, BOM, effectively reduced these effects. Among them, the BOM group showed a significant cardioprotective effect, suggesting a synergistic action that outperformed metoprolol alone.

Rats that were pre-treated with Borago officinalis extract showed significant improvement in biochemical, antioxidant, and histopathological markers compared to the rats in the ISO group. However, the combination of Borago officinalis and metoprolol provided the most pronounced protection, suggesting a synergistic effect.

The findings of the present study highlight the potential of Borago officinalis as a complementary cardioprotective agent.

Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder marked by insulin resistance and impaired insulin secretion. Effective glycemic management is critical for preventing problems, which can be achieved through Oral Hypoglycemic Agents (OHAs). Metformin is the first-line drug due to its insulin-sensitizing effects, while other classes, such as sulfonylureas, meglitinides, DPP-4 inhibitors, SGLT2 inhibitors, thiazolidinediones, and α-glucosidase inhibitors, serve complementary roles. Evolving treatment strategies increasingly favour combination therapies to increase outcomes.

The review involved an extensive search of scientific databases and relevant literature, including studies published to date in PubMed, Science Direct, and Google Scholar. Type 2 Diabetes Mellitus (T2DM), oral hypoglycaemic agents, pharmacoeconomics, insulin sensitivity, SGLT2 inhibitors, and Thiazolidinediones were among the search phrases used. The selected papers were carefully evaluated for methodological soundness and the significance of their results.

There is an increased prescribing of fixed-dose combinations, such as metformin-vildagliptin, which has led to better adherence and control. Regional differences in costs have an impact on the accessibility of drugs. SGLT2 and GLP-1 drugs provide cardiovascular and renal effects, whereas DPP-4 drugs produce limited results. The difference in pharmacokinetics and a certain decline of β-cells may require the prescription of an individualized treatment, combination therapy, or the introduction of insulin over time.

The current inclination to fixed-dose combinations improves compliance and glycemic control. Regional inequity is affected by the differences in costs. Better results in the use of SGLT2 and GLP-1 drugs favor their application in vulnerable patients, whereas the DDP-4 blocking agent is more appropriate in milder patient populations. Individualized treatment programs are a necessity, even with impaired β-cell functioning, which necessitates intensification of the therapy or insulin.

Optimizing T2DM management requires a personalized approach that integrates clinical efficacy, safety, and cost into account. Regular prescription audits and targeted pharmacoeconomic strategies are vital for equitable access and long-term disease control worldwide.

Acute coronary syndrome (ACS) is a leading cause of death, and clopidogrel resistance remains a major challenge in its treatment. This study aims to determine the impact of CYP2C19 genetic variants on clopidogrel resistance (CR) and major adverse cardiovascular events (MACEs) in Vietnamese patients undergoing percutaneous coronary intervention (PCI).

We carried out a descriptive cross-sectional study, supplemented by a prospective longitudinal follow-up, on 113 ACS patients undergoing PCI with drug-eluting stent implantation at the Department of Cardiology, Military Hospital 103, from January 2015 to May 2018. We excluded patients with a decreased platelet count (< 100 × 10^9/L), a decreased estimated glomerular filtration rate (< 15 mL/min), ongoing bleeding, coagulation disorders, planned or recent surgery, or a coexisting malignancy. CR was defined as platelet aggregation ≥ 46%. The Amplification Refractory Mutation System (ARMS)-PCR was used to determine the CYP2C19 genotype and phenotype. Causes leading to patient readmission, such as angina, recurrent acute myocardial infarction, stroke, or death within 30 days, were recorded as MACEs.

The rate of CR was 29.9% (33/113 patients), and the incidence of MACEs was 15.9% (18/113 patients). The frequencies of CYP2C192 and CYP2C193 polymorphisms, as well as the PM CYP2C19 phenotype, were higher in the CR and MACE groups compared to those without these characteristics (p = 0.24, 0.006, and < 0.001, respectively). The PM CYP2C19 phenotype was predictive of 30-day MACEs in ACS patients undergoing PCI with stent implantation (p < 0.001).

Our findings demonstrate a strong association between CYP2C19 PM phenotypes and increased risks of both clopidogrel resistance and 30-day MACEs in Vietnamese ACS patients undergoing PCI. These results underscore the clinical significance of CYP2C19 genotyping in optimizing antiplatelet therapy and enhancing outcomes in this patient population.

PM CYP2C19 phenotypes were associated with an increased risk of CR and MACEs in Vietnamese patients undergoing PCI with stent implantation.