Inhibition of ACE is considered as one of the main strategies to reduce hypertension. ACE inhibitors derived from Suaeda salsa (S. salsa) present a novel antihypertensive agent source. This study employed 3D-QSAR pharmacophore, metabolomics, docking-based screening, and molecular dynamics simulations to identify ACE inhibitors from S. salsa. A set of 53 known molecules was chemically diverse to construct a 3D-QSAR model for predictive purposes. S. salsa was characterized using UPLC-QqQ-MS/MS and UPLC-Q-TOF-LC-MS techniques, 211 and 586 kinds of bioactive metabolites were identified, respectively. A total of 680 compounds were collected for database construction and virtual screening. An ADMET assessment was conducted to evaluate drug-likeness and pharmacokinetics parameters. Moreover, molecular docking results show that six top hit compounds bind to ACE tightly. Specially, diosmin could interact with ACE by hydrogen bond, Pi-cation bond, and metal bond. Molecular dynamics (MD) simulation and MMPBSA calculations were subsequently employed to elucidate complex stability and the interaction between diosmin and ACE, indicating it a strong ACE inhibitory activity. In conclusion, this study suggests that S.salsa represents a potential source of antihypertensive agents.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s40203-024-00233-0.

BACKGROUND: Colorectal cancer (CC) is the fourth most common type of cancer that causes illness and death. Medicines like ACE inhibitors and ARBs, usually used for heart problems, have shown they might help with the growth and development of CC.
BACKGROUND: An analysis of ACE inhibitors and colon cancer is conducted in this comprehensive review. The main goal is to see how ACEIs/ARBs affect the chances of getting cancer and dying in patients with CC.
METHODS: A systematic literature search was conducted to identify relevant studies. Inclusion criteria encompassed studies that evaluated the use of ACEIs/ARBs in patients with CC and reported outcomes related to new cancer incidence and mortality. Data from selected studies were extracted and analyzed using appropriate statistical methods.
RESULTS: The study showed that fewer cancer cases occurred in patients who took ACEIs/ARBs compared to those who did not (RR 0.962, 95% CI 0.934-0.991, p = 0.010). Furthermore, patients with CC who utilized ACEIs/ARBs exhibited a decreased mortality rate compared to non-users (HR 0.833, 95% CI 0.640-1.085, p = 0.175).
CONCLUSIONS: This review suggests that using ACEIs/ARBs medicine could help people with CC live longer and lower their chances of dying. These results highlight the potential benefits of utilizing ACE inhibitors in the management of CC, warranting further investigation and consideration in clinical practice.

BACKGROUND: Sacubitril-valsartan, an inhibitor of the angiotensin receptor neprilysin (ARNi), has been purported to exhibit superiority over angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in individuals diagnosed with heart failure.
OBJECTIVE: This paper gives an updated meta-analysis comparing the efficacy and safety of sacubitril-valsartan to that of standard treatment for different types of heart failure.
RESULTS: The meta-analysis comprised a total of nine randomized controlled trials (RCTs), incorporating data from a substantial sample size of 15 939 patients. The study observed a decrease in overall mortality and mortality related to cardiovascular causes among patients in the heart failure with reduced ejection fraction (HFrEF) category who were treated with sacubitril-valsartan. However, no statistically significant variation in this outcome was seen among patients with heart failure with preserved ejection fraction and HFmrEF. Patients who were administered sacubitril-valsartan had a notably elevated likelihood of experiencing hypotension. Nevertheless, no significant disparities were observed in terms of other adverse events among the various treatment groups.
CONCLUSIONS: Current meta-analysis provide support for use of sacubitril-valsartan in decreasing mortality in patients with HFrEF. However, more numbers of studies are required to draw a definite conclusion on other benefits associated with sacubitril-valsartan use over standard treatment of ACE inhibitors and ARBs.

Studies have shown that angiotensin converting enzyme inhibitors (ACEIs) are superior in primary and secondary prevention for cardiac mortality and morbidity to angiotensin receptor blocker (ARBs). One of the common side effects from ACEI is dry cough. The aims of this systematic review, and network meta-analysis are to rank the risk of cough induced by different ACEIs and between ACEI and placebo, ARB or calcium channel blockers (CCB). We performed a systematic review, and network meta-analysis of randomized controlled trials to rank the risk of cough induced by each ACEI and between ACEI and placebo, ARB or CCB. A total of 135 RCTs with 45,420 patients treated with eleven ACEIs were included in the analyses. The pooled estimated relative risk (RR) between ACEI and placebo was 2.21 (95% CI: 2.05-2.39). ACEI had more incidences of cough than ARB (RR 3.2; 95% CI: 2.91, 3.51), and pooled estimated of RR between ACEI and CCB was 5.30 (95% CI: 4.32-6.50) Moexipril ranked as number one for inducing cough (SUCRA 80.4%) and spirapril ranked the least (SUCRA 12.3%). The order for the rest of the ACEIs are as follows: ramipril (SUCRA 76.4%), fosinopril (SUCRA 72.5%), lisinopril (SUCRA 64.7%), benazepril (SUCRA 58.6%), quinapril (SUCRA 56.5%), perindopril (SUCRA 54.1%), enalapril (SUCRA 49.7%), trandolapril (SUCRA 44.6%) and, captopril (SUCRA 13.7%). All ACEI has the similar risk of developing a cough. ACEI should be avoided in patients who have risk of developing cough, and an ARB or CCB is an alternative based on the patient\'s comorbidity.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells via receptor angiotensin-converting enzyme 2 (ACE2) and co-receptor transmembrane serine protease 2 (TMPRSS2). However, patients with SARS-CoV-2 infection receiving ACE1 inhibitors had higher ACE2 expression and were prone to poorer prognostic outcomes. Until now, information on the expression of ACE1, ACE2, and TMPRSS2 in human endometrial tissues, and the effects of ACE inhibitors on embryo implantation are limited. We found human endometria expressed ACE1, ACE2, and TMPRSS2 transcripts and proteins. Lower ACE1, but higher ACE2 transcripts were found at the secretory than in the proliferative endometria. ACE1 proteins were weakly expressed in endometrial epithelial and stromal cells, whereas ACE2 and TMPRSS2 proteins were highly expressed in luminal and glandular epithelial cells. However, ACE1 and TMPRSS4 were highly expressed in receptive human endometrial epithelial (Ishikawa and RL95-2) cells, but not in non-receptive AN3CA and HEC1-B cells. Treatment of human endometrial epithelial cells with ACE1 (Captopril, Enalaprilat, and Zofenopril) or ACE2 (DX600) inhibitors did not significantly alter the expression of ACE1, ACE2 and TMPRSS2 transcripts and spheroid (blastocyst surrogate) attachment onto Ishikawa cells in vitro. Taken together, our data suggest that higher ACE2 expression was found in mid-secretory endometrium and the use of ACE inhibitors did not alter endometrial receptivity for embryo implantation.

Dihydropyridine calcium channel blockers (DHPCCBs) are widely used to treat hypertension and chronic coronary artery disease. One common adverse effect of DHPCCBs is peripheral edema, particularly of the lower limbs. The side effect could lead to dose reduction or discontinuation of the medication. The combination of DHPCCBs and renin-angiotensin system blockers has shown to reduce the risk of DHPCCBs-associated peripheral edema compared with DHPCCBs monotherapy. We performed the current systematic review and network meta-analysis of randomized controlled trials (RCTs) to estimate the rate of peripheral edema with DHPCCBs as a class and with individual DHPCCBs and the ranking of the reduction of peripheral edema. The effects of renin-angiotensin system blockers on DHPCCBs network meta-analysis were created to analyze the ranking of the reduction of peripheral edema. A total of 3312 publications were identified and 71 studies with 56,283 patients were included. Nifedipine ranked highest in inducing peripheral edema (SUCRA 81.8%) and lacidipine (SUCRA 12.8%) ranked the least. All DHPCCBs except lacidipine resulted in higher relative risk (RR) of peripheral edema compared with placebo. Nifedipine plus angiotensin receptor blocker (SUCRA: 92.3%) did not mitigate peripheral edema and amlodipine plus angiotensin-converting enzyme inhibitors (SUCRA: 16%) reduced peripheral edema the most. Nifedipine ranked the highest and lacidipine ranked the lowest amongst DHPCCBs for developing peripheral edema when used for cardiovascular indications. The second or higher generation of DHPCCBs combination with ACEIs or ARBs or diuretics lowered the chance of peripheral edema development compared to single DHPCCB treatment.

OBJECTIVE: Angiotensin-converting enzyme inhibitors (ACEIs) are widely used in the treatment of scleroderma renal crisis (SRC), and their use prior to the onset of SRC in patients with systemic sclerosis (SSc) has received wide attention in recent years. We undertook an evidence-based approach to identify whether the use of ACEIs prior to the onset of SRC is beneficial for patients with SSc.
METHODS: We searched PubMed and Embase for any published studies produced between database inception and 22 October 2021. Articles obtained after using appropriate keywords were selected independently by two reviewers according to the established inclusion and exclusion criteria.
RESULTS: Nine studies were included. Pooled results indicated that using ACEIs prior to SRC was associated with a higher incidence of SRC than no ACEIs prior to SRC (RR 2.05, 95% confidence interval 1.08-3.91, p = 0.03). Compared with patients who did not use ACEIs prior to the onset of SRC, a higher proportion of patients with SRC who used ACEIs prior to its onset had a poorer prognosis (RR 1.46, 95% confidence interval 1.20-1.78, p < 0.01). The difference in mortality between patients who used ACEIs prior to SRC onset and those who did not was not statistically significant (RR 1.12, 95% confidence interval 0.76-1.65, p = 0.57).
CONCLUSIONS: We recommend against using ACEIs prior to SRC in SSc patients. The use of ACEIs prior to SRC is associated with a higher incidence of SRC and poorer prognosis, especially in patients with progressive SSc or SSc-related renal vasculopathy (SSc-related hypertension and proteinuria).

Angiotensin-converting enzyme-2 (ACE2) is the receptor for SARS-CoV-2. Animal studies suggest that renin-angiotensin-aldosterone system (RAAS) blockers might increase the expression of ACE2 and potentially increase the risk of SARS-CoV-2 infection.
The effect of ACE inhibitor (ACEI) treatment on the pneumonia incidence in non-COVID-19 patients (25 studies, 330 780 patients) was associated with a 26% reduction of pneumonia risk (odds ratio [OR]: 0.74, P < .001). Pneumonia-related death cases in ACEI-treated non-COVID-19 patients were reduced by 27% (OR: 0.73, P = .004). However, angiotensin II receptor blockers (ARB) treatment (10 studies, 275 621 non-COVID-19 patients) did not alter pneumonia risk in patients. Pneumonia-related death cases in ARB-treated non-COVID-19 patients was analysed only in 1 study and was significantly reduced (OR, 0.47; 95% confidence interval, 0.30 to 0.72). Results from 11 studies (8.4 million patients) showed that the risk of getting infected with the SARS-CoV-2 virus was reduced by 13% (OR: 0.87, P = .014) in patients treated with ACEI, whereas analysis from 10 studies (8.4 million patients) treated with ARBs showed no effect (OR, 0.92, P = .354). Results from 34 studies in 67 644 COVID-19 patients showed that RAAS blockade reduces all-cause mortality by 24% (OR = 0.76, P = .04).
ACEIs reduce the risk of getting infected with the SARS-CoV-2 virus. Blocking the RAAS may decrease all-cause mortality in COVID-19 patients. ACEIs also reduce the risk of non-COVID pneumonia. All-cause mortality due to non-COVID pneumonia is reduced by ACEI and potentially by ARBs.

Quinoa protein has been paid more and more attention because of its nutritional properties and beneficial effects. With the development of bioinformatics, bioactive peptide database and computer-assisted simulation provide an efficient and time-saving method for the theoretical estimation of potential bioactivities of protein. Therefore, the potential of quinoa protein sequences for releasing bioactive peptides was evaluated using the BIOPEP database, which revealed that quinoa protein, especially globulin, is a potential source of peptides with dipeptidyl peptidase-IV (DPP-IV) and angiotensin-I-converting enzyme (ACE) inhibitory activities. Three plant proteases, namely papain, ficin, and stem bromelain, were employed for the in silico proteolysis of quinoa protein. Furthermore, four tripeptides (MAF, NMF, HPF, and MCG) were screened as novel promising bioactive peptides by PeptideRanker. The bioactivities of selected peptides were confirmed using chemical synthesis and in vitro assay. The present work suggests that quinoa protein can serve as a good source of bioactive peptides, and in silico approach can provide theoretical assistance for investigation and production of functional peptides.

The critical role of the intrarenal renin-angiotensin system (RAS) in the development of kidney disease has been well demonstrated in animal and cell-culture experiments, but evidence from human kidney tissues is lacking. In this study, we screened 438 patients with IgA nephropathy (IgAN) and analyzed their clinical characteristics. Renal biopsy revealed the expression of angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), and MAS receptor (MASR) in the tissues of 260 patients not treated with RAS inhibitors, 32 patients treated with angiotensin-converting enzyme inhibitors (ACEIs), and 89 patients treated with angiotensin receptor blockers (ARBs). The correlations in expression among these three receptors and the results of Oxford typing were analyzed, together with the ability of ACEIs and ARBs to reduce proteinuria and the effects of ARBs on AT1R and AT2R expression. The results showed significantly higher AT1R, AT2R, and MASR expression in the M1 group (mesangial score > 0.5) than in the M0 group (mesangial score < 0.5), significantly higher AT1R expression in the S1 group (presence of segmental glomerulosclerosis) than in the S0 group (absence of segmental glomerulosclerosis); AT1R expression in the C2 group (crescent formation > 25%) was significantly higher than in the C0 (crescent formation = 0) and C1 (crescent formation < 25%) groups. Patients treated with an ARB for < 6 months had significantly lower urinary protein levels than those taking these drugs for > 6 months. These findings imply that overexpression of AT1R on the mesangial cells of IgAN patients is associated with mesangial cell proliferation, glomerular segmental sclerosis, and crescent formation. In addition, long-term administration of ARB may decrease the efficacy of these medications in terms of reducing proteinuria.