Large Cardamom Extract Enhances Ramipril's Vasoprotective Action in the Aorta by Modulating Endothelial Redox Biology. An Evaluation based on In-silico and In-vitro Research.

BACKGROUND: The mechanisms that cause a patient's blood pressure to rise are diverse. Controlling blood pressure with monotherapy acting through a single pathway may be unachievable. Combining a clinically used medication with herbal medicine can result in an antihypertensive effect that is two to five times greater than monotherapy. METHOD: This study examined the effects of aqueous extracts of large cardamom and ramipril on the redox biology of nitric oxide and vascular reactivity in the isolated aorta incubated with a nitro-L-arginine methyl ester. Molecular docking study was performed to predict the affinity of constituents of large cardamom extracts with the NOX 2 gene. RESULTS: Nitric oxide (NO) levels, disordered antioxidant enzymes (glutathione and catalase), NADPH oxidase and lipid peroxidation were recovered when aqueous extract of large cardamom and ramipril were combined. A gradual increase in the percentage relaxation of acetylcholine in phenylephrine pre-contracted aorta indicates that the combination therapy prevents endothelial damage. The molecular docking study reveals the important phytoconstituents present in the large cardamom that can effectively bind with the NADPH oxidase for its antioxidant activity. Consculsion: According to our findings, it was evidenced that the large cardamom extract's vasoprotective action was mostly related to its ability to restore endothelial redox biology by suppressing NADPH oxidase activity. Our findings suggest that ramipril's direct impact on the eNOS/NO system, along with the antioxidant properties of AELC, could have a synergetic benefit in the treatment of hypertension, as well as lessen ramipril's existing side effects.

Renin-angiotensin system modulators in COVID-19 patients with hypertension: friend or foe?

Background: ACE2, a component of the non-classic renin-angiotensin system (RAS), acts as a functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) spike protein, which enables the entry of the virus into the host cells. Non-classical ACE2 is one of two types of ACE2 that has a protective effect on vascular and respiratory cells. RAS modulators like angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are among the first-line treatment for hypertensive patients. An upregulation in ACE2 levels with RAS modulators was observed in few preclinical studies, which raised concerns regarding possible increased infectivity among patients treated with RAS modulators.Method: For shortlisting the outcome effects, open-ended, English-restricted databases, published literature, and various clinical studies performed utilizing RAS modulators in COVID 19 patients were considered. Conclusion: Current evidence reveals no increased risk of COVID-19 infection among hypertensive patients on ACEIs/ARBs compared to other antihypertensive medications. Several studies have demonstrated no detrimental effects of RAS modulators on clinical severity, hospital/intensive care unit stay, ventilation and mortality.  Hence, we can conclude that neither ARBs nor ACEIs treatment will cause any side effects or undesirable interactions in COVID-19 infected hypertensive patients.

Aqueous extract of large cardamom inhibits vascular damage, oxidative stress, and metabolic changes in fructose-fed hypertensive rats.

PURPOSE: Since metabolic abnormalities such as elevated glucose level and imbalanced lipid profiles increase the risk for hypertension and cause endothelial dysfunction, we evaluated the effect of aqueous extract of large cardamom (AELC) on fructose-induced metabolic hypertension and oxidative stress. METHODS: The male Sprague-Dawley rats were divided into 6 groups with 5 rats in each group, and each group was fed with 10% fructose in drinking water for 8 weeks. Starting from week 5, animals were treated with 50, 100, and 200 mg/kg/day AELC or Losartan (10 mg/kg/day). Systolic, diastolic, and mean arterial blood pressure was measured once in every seven days using the tail-cuff method. Vascular function, plasma nitric oxide (NO), glucose, lipid profiles, serum biochemical, and anti-oxidant parameters were also evaluated. RESULTS: Rats fed with fructose showed higher blood pressure, serum cholesterol, and triglyceride levels, but decreased in the AELC or Losartan treatment group. Treatments with AELC prevented exaggerated plasma glucose and oxidative stress and restored the nitric oxide level in fructose-fed rats. Besides, it also reduced vascular proliferation and improved the relaxation response of acetylcholine in the aorta pre-contracted with phenylephrine. CONCLUSION: In summary, the obtained results suggest that AELC can prevent and reverse the high blood pressure induced by fructose, probably by restoring nitric oxide level and by improving altered metabolic parameters.

Antioxidant and vasorelaxant effects of aqueous extract of large cardamom in L-NAME induced hypertensive rats.

PURPOSE: The present work aimed to study the effect of aqueous extract of large cardamom (AELC) to prevent vascular remodeling and oxidative stress in Nω-Nitro-L-arginine methyl ester (L-NAME)-induced hypertension. METHOD: Male Wistar rats were administered with L-NAME 40 mg/kg/day for 28 days by oral gavage. The treatments included captopril (20 mg/kg/day) or AELC (100, 200 and 400 mg/kg/day) along with L-NAME administration. RESULTS: L-NAME treated rats showed high systolic, diastolic and mean arterial pressure, decreased nitric oxide level, increased level of malondialdehyde in plasma, heart, aorta and kidney, hypertrophy of the vascular wall and reduced vascular response to acetylcholine in phenylephrine-precontracted aorta. Treatment with AELC markedly reduced the blood pressure, restored the nitric oxide level, reduced the malondialdehyde level, alleviated the hypertrophy in L-NAME-induced hypertensive rats. Additionally, it also improved the vascular response to acetylcholine in phenylephrine pre-contracted aorta. CONCLUSION: In conclusion, our results demonstrate the preventive effect of AELC in L-NAME-induced hypertensive model, which is possibly related to antioxidant activities and restoration of nitric oxide level.

Effectiveness of zolpidem and sleep hygiene counseling in the treatment of insomnia in solid tumor patients.

OBJECTIVE: To study the effectiveness of zolpidem and sleep hygiene counseling in managing insomnia in solid tumor patients. METHODS: Cancer patients with a Pittsburgh Sleep Quality Index score ≥ 5 were grouped into two. Both groups received treatment for insomnia in the form of either zolpidem 5 mg for 7 days or sleep hygiene counseling. RESULT: At baseline, zolpidem and counseling group had a mean Pittsburgh Sleep Quality Index score of 14.82 ± 2.61 and 11.67 ± 3.32, respectively. The difference in mean Pittsburgh Sleep Quality Index score was found to be 4.03 in patients using zolpidem and 1.5 in counseled patients (p = 0.003). The components of Pittsburgh Sleep Quality Index namely difficulty falling asleep within 30 min (sleep latency), overall sleep quality, trouble staying awake during daytime and trouble staying motivated to get things done showed statistically significant improvement after treatment with zolpidem. Following sleep hygiene counseling, the proportion of patients with sleep latency > 30 min reduced considerably. Waking up to use the bathroom was the most common problem reported by approximately 94% patients in both groups before treatment which remained the most prevalent problem even after treatment. Night or early morning awakenings seemed to decrease significantly in patients taking zolpidem (p = 0.039) while it did not show any improvement with counseling. Counseling seemed to get patients to sleep within 30 min. CONCLUSION: Patients on zolpidem showed a reduction in their Pittsburgh Sleep Quality Index scores thereby suggesting it as a treatment for insomnia in solid tumor patients. Sleep hygiene counseling, though not as effective as zolpidem, made a slight difference in the overall sleep.