Study of an inhibitory effect of plant polyphenolic compounds against digestive enzymes using bench-working experimental evidence predicted by molecular docking and dynamics.

The substantial nutritional content and diversified biological activity of plant-based nutraceuticals are due to polyphenolic chemicals. These chemicals are important and well-studied plant secondary metabolites. Their protein interactions are extensively studied. This relationship is crucial for the logical development of functional food and for enhancing the availability and usefulness of polyphenols. This study highlights the influence of protein types and polyphenols on the interaction, where the chemical bindings predominantly consist of hydrophobic interactions and hydrogen bonds. The interaction between polyphenolic compounds (PCs) and digestive enzymes concerning their inhibitory activity has not been fully studied. Therefore, we have examined the interaction of four digestive enzymes (α-amylase, pepsin, trypsin, and α-chymotrypsin) with four PCs (curcumin, diosmin, morin, and 2',3',4'-trihydroxychalcone) through in silico and in vitro approaches. In vitro plate assays, enzyme kinetics, spectroscopic assays, molecular docking, and simulations were performed. We observed all these PCs have significant docking scores and preferable interaction with the active site of the digestive enzymes, resulting in the reduction of enzyme activity. The enzyme-substrate binding mechanism was determined using the Lineweaver Burk plot, indicating that the inhibition occurred competitively. Among four PCs diosmin and morin has the highest interaction energy over digestive enzymes with IC50 value of 1.13 ± 0.0047 and 1.086 ± 0.0131 µM. Kinetic studies show that selected PCs inhibited pepsin, trypsin, and chymotrypsin competitively and inhibited amylase in a non-competitive manner, especially by 2',3',4'-trihydroxychalcone. This study offers insights into the mechanisms by which the selected PCs inhibit the enzymes and has the potential to enhance the application of curcumin, diosmin, morin, and 2',3',4'-trihydroxychalcone as natural inhibitors of digestive enzymes.

Effectiveness of Rabeprazole and Other Proton Pump Inhibitors in Managing GERD with Varying Severity: A Retrospective, Real-world EMR-based Study (POWER GERD Study).

Purpose: To evaluate the effectiveness of rabeprazole and other proton pump inhibitors (PPIs) in providing symptomatic relief in patients with varying severity of gastroesophageal reflux disease (GERD). Methods: In this multicenter retrospective study, electronic medical records (EMRs) of GERD patients prescribed with PPIs at two Indian clinics/hospitals were reviewed (2016-2020). Rabeprazole's effectiveness was assessed at different follow-up visits and compared with other PPIs. Results: Overall, 269 patients (moderate and severe GERD: 84.39%) were included in three groups, viz rabeprazole, pantoprazole, and esomeprazole groups. A significant proportion of patients experienced quick and complete symptomatic relief at visit 1 with rabeprazole compared to the baseline visit, which gradually increased till visit 4 for both daytime [viz heartburn (38.78-93.88%; p < 0.001)] and nocturnal symptoms [viz sleep disturbances (62.92-97.75%; p < 0.001)]. Rabeprazole provided quick relief at visit 1 when compared with pantoprazole for daytime heartburn (38.78 vs 5.56%; p = 0.01), daytime epigastric pain (66.04 vs 12.12%; p = 0.049), and nocturnal water brash (60.71 vs 16.13%; p = 0.015), and when compared with esomeprazole for nocturnal nausea (82.61 vs 20.00%; p = 0.013). Further, the proportion of patients exhibiting complete treatment response was relatively higher in the rabeprazole group (83.33%) than in the pantoprazole (62.07%) and esomeprazole (65.67%) groups at visit 4. Conclusion: Rabeprazole was effective in providing quick and sustained relief for both daytime and nocturnal GERD symptoms in patients with moderate and severe GERD. Rabeprazole also demonstrated greater effectiveness when compared with pantoprazole and esomeprazole in reducing the severity of multiple GERD symptoms. How to cite this article: Lawate P, Jilawar N, Vyas K, et al. Effectiveness of Rabeprazole and Other Proton Pump Inhibitors in Managing GERD with Varying Severity: A Retrospective, Real-world EMR-based Study (POWER GERD Study). J Assoc Physicians India 2023;71(10):37-44.

Impact of newer direct-acting antiviral drugs based on quality-adjusted life years: A prospective pharmacoeconomic study in hepatitis C patients.

CONTEXT: The Indian government is dispensing newer direct-acting antiviral (DAA) drugs, which may have impact on hepatitis C virus (HCV) patients' quality of life (QoL). AIMS: To evaluate different DAA regimens and impact on QoL in terms of quality-adjusted life year (QALY) in HCV patients and to measure cost-effectiveness. METHODS: This prospective, observational study was carried out on patients who were diagnosed with HCV. Recruited patients were followed up until 12-24 weeks. Patients were recruited following the selection criteria. Along with demographic and drug details, the regimens used were analyzed and evaluated for cost minimization, cost-effectiveness, and cost-utility analysis. For health quality check, the Chronic Liver Disease questionnaire (CLDQ) was used which was also used for QALY assessment. Data were entered into MS Excel 2016. Difference in between the regimens for total cost was done using unpaired t-test and ANOVA test using SPSS 25.0. Overall cost-effectiveness, cost minimization, cost utility and cost of illness analysis was also calculated. P < 0.05 was considered statistically significant. RESULTS: A total of 31 patients were enrolled. A total of five drugs, namely, sofosbuvir, daclatasvir, ribavirin, velpatasvir, and ledipasvir were widely used. Sofosbuvir was most common (46.25%)component of drug combination in our study. A total of five types of regimen were used according to the genotype of patients. With 44,260.13 ± 15,884.92 INR of the total drug cost, 70.97% of patients spent around 30,000-40,000 INR for the whole pharmacotherapy. The total indirect cost was 2768.39 ± 3916.13 INR with the total direct cost of 48,660.90 ± 15,356.39 INR. The total cost including direct as well as indirect cost spent during 6-month therapy by 61.29% of patients was 40,000-50,000 INR. Based on the CLDQ score, QoL was 64.1 ± 25. Regimen 2 (sofosbuvir + velpatasavir) stood out with the lowest cost. Regimen 5 (ribavirin [200 mg] + sofosbuvir [400 mg] + velpatasvir [100 mg]) was found to be the most cost-effective. Considering 1 life year with good health after treatment, QALY was 0.31. CONCLUSIONS: Ribavirin (200 mg) + sofosbuvir (400 mg) + velpatasvir (100 mg) was found to be the cost-effective and cost-saving regimen among DAAs.

Assessment of portal hemodynamics by ultrasound color Doppler and laser Doppler velocimetry in liver cirrhosis.

BACKGROUND: Color Doppler is a noninvasive method for assessing portal hemodynamics. Laser Doppler velocimetry is useful in assessment of microcirculatory abnormalities in portal hypertensive gastropathy (PHG). AIMS: To study portal hemodynamics by color Doppler and gastric mucosal blood flow (GMBF) by laser Doppler velocimetry in patients with cirrhosis. METHODS: Twenty-eight patients with cirrhosis of liver (24 men) and 10 healthy subjects (7 men) were studied. Portal venous blood flow (PVBF) and portal flow velocity (PFV) were assessed by color Doppler at the level where the hepatic artery crosses the portal vein, and GMBF was measured by laser Doppler velocimetry. RESULTS: PVBF (379.5 [102.9] mL/min), PFV (5.3 [1.1] cm/sec) and GMBF (3.5 [0.8] volts) were significantly lower in patients with cirrhosis than in controls. PVBF and PFV were significantly lower in patients in Child class B and C than those in class A. Patients with ascites had significantly lower PVBF, PFV and GMBF than those without; values were also lower in patients with PHG than in those without. History of bleeding had no relation with PVBF and PFV. GMBF showed good correlation with PVBF (r=0.58, p<0.001) and with PFV (r=0.48, p<0.01). CONCLUSIONS: In cirrhosis of liver, PVBF, PFV and GMBF are significantly lower, and the changes increase with increasing severity of liver disease.