Cardiovascular and Hematological Agents in Medicinal Chemistry最新文献

Objective: Salvia miltiorrhiza (SM) contains four major aqueous active ingredients, which have been isolated, purified and identified as danshensu (DSS), salvianolic acid A (Sal-A), salvianolic acid B (Sal-B) and protocatechuic aldehyde (PAL), A mixture of these four ingredients is called SABP. Although aqueous extract from Salvia miltiorrhiza has been traditionally used to treat cardiovascular diseases, the efficacy and function of the optimal ratio of SABP in preventing and treating cardiovascular diseases remain unknown. This study aims to explore the antiinflammatory mechanisms underlying the attenuation of atherosclerosis development by aqueous extract from Salvia miltiorrhiza.

Methods: Male ApoE^-/- mice (6 weeks) were randomly allocated into three groups: the model group (Model), the SABP group (SABP), and the rosuvastatin calcium group (RC). Male C57BL/6 mice (6 weeks) were used as a control group. All mice were fed with an ordinary diet. After 8 weeks of treatment, the lipid profiles in serum and the lactate dehydrogenase (LDH) and creatine kinase (CK) in heart tissue were measured using an automatic biochemical analyzer. Alterations of the thoracic aorta and the heart were assessed using Hematoxylin and eosin staining. The protein expression of Toll-like receptor 4 (TLR4), TGF beta-activated kinase 1 (TAK1), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the heart tissue were determined though immunohistochemistry and western blotting analysis.

Results: The serum low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) levels were increased, and the high-density lipoprotein cholesterol (HDL-C) level was decreased in ApoE^-/- mice. SABP significantly decreased serum lipid levels and improved histopathology in the thoracic aorta. In addition. SABP treatment inhibited the expression of TLR4, TAK1, NF-κB, IL-6 and TNF-α in the heart in ApoE^-/- mice. The LDH and CK in the heart did not differ significantly among different groups, and the heart did not have obvious pathological changes.

Conclusion: These findings indicated that SABP may exert an anti-atherosclerotic effect by lowering blood lipids and inhibiting inflammatory response via TLR4/ NF-κB signaling pathway.

Aims: The study aimed to investigate the effect of Euphorbia cheiradenia on blood pressure.

Background: Euphorbia cheiradenia is a medicinal plant with several medicinal properties.

Objective: This study aimed to study the vasorelaxant and antihypertensive capacity of the aqueous extract of Euphorbia cheiradenia (E. cheiradenia), and to evaluate its effect on angiotensinconverting enzyme 2 (ACE2).

Methods: The antihypertensive ability of aerial parts of the aqueous extract of E. cheiradenia (AEEC) was investigated in L-NAME-induced hypertensive rats, and its vasorelaxant effect was performed on the isolated thoracic rat aorta. In addition, the possible inhibitory effect of AEEC on ACE2 was also studied.

Results: AEEC lowered blood pressure parameters in hypertensive rats. The study of the vasorelaxant activity revealed that AEEC partially relaxed the aortic rings through activation of the KATP channel and inhibition of the β-adrenergic pathway. Whereas pretreatment of aortic rings with nifedipine, indomethacin, L-NAME, and methylene blue did not attenuate AEEC-induced vasorelaxation. However, AEEC did not affect ACE2 in isolated rat aortas.

Conclusion: The study showed that aqueous E. cheiradenia extract exhibits significant antihypertensive activity in hypertensive rats.

Background: Ammodaucus leucotrichus is a medicinal plant used in traditional medicine to treat various ailments, including hypertension.

Aims: The study aimed to determine the antihypertensive activity of Ammodaucus leucotrichus.

Objective: The study aimed to investigate the antihypertensive and vasorelaxant activities of the aqueous extract of Ammodaucus leucotrichus fruits (ALAE) in rats.

Methods: ALAE was prepared to study its antihypertensive effect in L-NAME (Nω-L-arginine methyl ester)-induced hypertensive rats and its vasorelaxant activity in isolated thoracic aortas of rats. The acute and subchronic effects of ALAE on systolic, diastolic, mean arterial pressure, and heart rate (HR) were evaluated after oral administration of ALAE (60 and 100 mg/kg body weight) for 6 h for the acute experiment and over 7 days for the subchronic test. Isolated thoracic aortic rings were prepared to examine the vasorelaxant action of ALAE. Several common pharmacological agents were used to test potential pathways implicated in vasorelaxant action.

Results: The results showed that ALAE reduced blood pressure parameters (systolic, mean, and diastolic blood pressure) in L-NAME-induced hypertension rats after repeated oral treatment over seven days without affecting normotensive rats. Furthermore, in thoracic aortic rings pre-contracted with epinephrine (EP) (10 μM) or KCl (80 mM), ALAE (0.250-1.625 mg/ml) showed a vasorelaxant effect. In isolated rat thoracic aortas, blockage of soluble guanylyl cyslase with blue methylene (P < 0.01) partially decreased this vasorelaxant effect. In addition, blockage of the prostaglandin synthesis pathway with indomethacin (P<0.05) also reduced the vasorelaxant activity of ALAE. Pretreatment of aortic rings with glibenclamide, propanolol, L-NAME, MLN-4760, or nifedipine did not affect ALAE-induced vasorelaxation.

Conclusion: Ammodaucus leucotrichus is a prescient medicinal plant, able to act as an antihypertensive agent. Moreover, the results suggest that the extract increased cGMP in NO-independent manner.

Cardiospecific troponins are specifically localized in the troponin-tropomyosin complex and the cytoplasm of cardiac myocytes. Cardiospecific troponin molecules are released from cardiac myocytes upon their death (irreversible damage in acute coronary syndrome) or reversible damage to cardiac myocytes, for example, during physical exertion or the influence of stress factors. Modern high-sensitive immunochemical methods for detecting cardiospecific troponins T and I are extremely sensitive to minimal reversible damage to cardiac myocytes. This makes it possible to detect damage to cardiac myocytes in the early stages of the pathogenesis of many extra-cardiac and cardiovascular diseases, including acute coronary syndrome. So, in 2021, the European Society of Cardiology approved diagnostic algorithms for the acute coronary syndrome, which allow the diagnosis of acute coronary syndrome in the first 1-2 hours from the moment of admission of the patient to the emergency department. However, high-sensitive immunochemical methods for detecting cardiospecific troponins T and I may also be sensitive to physiological and biological factors, which are important to consider in order to establish a diagnostic threshold (99 percentile). One of the important biological factors that affect the 99 percentile levels of cardiospecific troponins T and I are sex characteristics. This article examines the mechanisms underlying the development of sex-specific serum levels of cardiospecific troponins T and I and the importance of sexspecific cardiospecific troponin concentrations in diagnosing acute coronary syndrome.

Radiation-induced heart disease (RIHD) is a significant cause of morbidity in breast and other mediastinal cancers. The many molecular and cellular patho-mechanisms that have a role in RIHD are not completely understood. Endothelial injury, oxidative stress, and inflammation, as well as endoplasmic reticulum and mitochondrial damage, are considered the primary causes of RIHD. Ferroptosis is a newly discovered type of cell death that results from irondependent lipid peroxide accumulation. As ferroptosis plays an important role in the pathogenesis of cardiovascular diseases, it seems that it has a significant effect on RIHD. It was recently shown that ionizing radiation (IR) generates severe ferroptosis, which is a critical component of Radiotherapy-mediated normal cell toxicity. These findings support the use of a ferroptosis inhibitor to reduce RIHD. In this perspective review, we summarize the role of ferroptosis in pathogens of cardiovascular disease and radiation toxicity, and we will introduce ferroptosis inhibitors as a new strategy to prevent or reduce RIHD.

Background: Thrombotic disease is still a major killer. Aspirin, Ticagrelor, Clopidogrel, etc. are the most widely used conventional antiplatelet drugs. The significant number of patients who are resistant to this drug shows a poor outcome.

Objective: Developing a new antiplatelet agent with a stable antiplatelet effect and minimal bleeding risk is required for a patient who is resistant to antiplatelet drugs.

Methods: Protein-ligand docking was performed using Autodock Vina 1.1.2 to study the interaction of 67LR with different Polyphenols.

Results: Among the 18 polyphenols, thearubigin has the highest binding affinity towards 67LR and gallic acid shows the lowest binding affinity. Among the 18 molecules, the top 4 molecules from the highest to lowest binding affinity range from-10.6 (thearubigin) to -6.5 (Epigallocatechin).

Conclusion: Polyphenols may inhibit platelet aggregation through 67 LR and can be an alternative treatment for Thrombotic Disease. Moreover, it will be interesting to know whether polyphenols interfere with the same pathways as aspirin and clopidogrel. Effective polyphenols could help prototype the compound development of novel antiplatelet agents.

Aim: This study investigates the prevalence of non-malignant lesions of the cervix among various biopsy samples.

Methods: This case study consists of 50 cases of cervical biopsy over almost two years. The case history and clinical details of the patients were obtained.

Results: 60% of the cases that participated in this study reported white discharge per vaginum as a common clinical symptom. 4 cases (8%) showed koilocytic changes specific to the human papillomavirus during the study. Only 2% of the non-specific cervicitis showed lymphoid aggregates. Endocervical changes projected papillary endocervicitis with 9 cases (18%), squamous metaplasia with 7 cases (14%), and nabothian follicle cyst with 3 cases (6%).

Conclusion: It has been concluded that 50 cases were studied histologically, which had adequate representation of both ecto and endocervical tissue. Moreover, 31-40 years of age of patients showed the highest percentage of non-neoplastic lesions of the cervix when compared to other age groups.

Aims: The work aimed to study the antihypertensive ability of Haloxylon scoparium.

Background: Haloxylon scoparium Pomel is used to treat various diseases, including hypertension.

Objective: This study aimed to evaluate the antihypertensive effect of Haloxylon scoparium (H. scoparium) in hypertensive rats, and to evaluate its probable vasorelaxant activity.

Materials and methods: The aqueous extract of Haloxylon scoparium (AEHS) was prepared and used to investigate its antihypertensive ability in L-NAME(Nω-L-arginine methyl ester)-induced hypertensive rats, and its vasorelaxant activity was studied on the isolated thoracic aorta of rats. The acute and subchronic effects of (AEHS) on blood pressure parameters were evaluated after oral administration of AEHS (60 and 100 mg/kg body weight) for 6 h for the acute experiment and for 7 days for the subchronic test.

Results: The results indicated that AEHS decreased blood pressure parameters (systolic, mean, and diastolic blood pressure) after repeated oral administration in hypertensive rats without affecting normal rats. In addition, AEHS (375-1250 μg/mL) revealed a vasorelaxant effect in thoracic aortic rings precontracted with norepinephrine (NE) (10 μM) or KCl (80 mM). This effect was partially decreased in the presence of nifedipine by inhibition of the vascular calcium channel pathway in isolated rat thoracic aorta.

Conclusion: The study demonstrates the beneficial effect of Haloxylon scoparium as an antihypertensive agent. Moreover, this plant exerts vasorelaxant activity via the blockade of Ca²⁺ channels.

Background: Human factor XIIa (FXIIa) is a plasma serine protease that plays a significant role in several physiological and pathological processes. Animal models have revealed an important contribution of FXIIa to thromboembolic diseases. Remarkably, animals and patients with FXII deficiency appear to have normal hemostasis. Thus, FXIIa inhibition may serve as a promising therapeutic strategy to attain safer and more effective anticoagulation. Very few small molecule inhibitors of FXIIa have been reported. We synthesized and investigated a focused library of triazol-1-yl benzamide derivatives for FXIIa inhibition.

Methods: We chemically synthesized, characterized, and investigated a focused library of triazol- 1-yl benzamide derivatives for FXIIa inhibition. Using a standardized chromogenic substrate hydrolysis assay, the derivatives were evaluated for inhibiting human FXIIa. Their selectivity over other clotting factors was also evaluated using the corresponding substrate hydrolysis assays. The best inhibitor affinity to FXIIa was also determined using fluorescence spectroscopy. Effects on the clotting times (prothrombin time (PT) and activated partial thromboplastin time (APTT)) of human plasma were also studied.

Results: We identified a specific derivative (1) as the most potent inhibitor in this series. The inhibitor exhibited nanomolar binding affinity to FXIIa. It also exhibited significant selectivity against several serine proteases. It also selectively doubled the activated partial thromboplastin time of human plasma.

Conclusion: Overall, this work puts forward inhibitor 1 as a potent and selective inhibitor of FXIIa for further development as an anticoagulant.