In-silico study unveils potential phytocompounds in Andrographis paniculata against E6 protein of the high-risk HPV-16 subtype for cervical cancer therapy.

Despite therapeutic advancements, cervical cancer caused by high-risk subtypes of the human papillomavirus (HPV) remains a leading cause of cancer-related deaths among women worldwide. This study aimed to discover potential drug candidates from the Asian medicinal plant Andrographis paniculata, demonstrating efficacy against the E6 protein of high-risk HPV-16 subtype through an in-silico computational approach. The 3D structures of 32 compounds (selected from 42) derived from A. paniculata, exhibiting higher binding affinity, were obtained from the PubChem database. These structures underwent subsequent analysis and screening based on criteria including binding energy, molecular docking, drug likeness and toxicity prediction using computational techniques. Considering the spectrometry, pharmacokinetic properties, docking results, drug likeliness, and toxicological effects, five compounds-stigmasterol, 1H-Indole-3-carboxylic acid, 5-methoxy-, methyl ester (AP7), andrographolide, apigenin and wogonin-were selected as the potential inhibitors against the E6 protein of HPV-16. We also performed 200 ns molecular dynamics simulations of the compounds to analyze their stability and interactions as protein-ligand complexes using imiquimod (CID-57469) as a control. Screened compounds showed favorable characteristics, including stable root mean square deviation values, minimal root mean square fluctuations and consistent radius of gyration values. Intermolecular interactions, such as hydrogen bonds and hydrophobic contacts, were sustained throughout the simulations. The compounds displayed potential affinity, as indicated by negative binding free energy values. Overall, findings of this study suggest that the selected compounds have the potential to act as inhibitors against the E6 protein of HPV-16, offering promising prospects for the treatment and management of CC.

Increased lipid peroxidation, depleted non-enzymatic antioxidant, and variability in trace elements concentration in serum are correlated with Bangladeshi end-stage renal disease population.

INTRODUCTION: End-stage renal disease (ESRD) is an abnormality where the kidneys are not usually working. This case-control study was planned to determine the extent of serum lipid peroxidation, non-enzymatic antioxidant (vitamin c), and trace elements in 50 patients with ESRD as cases and 50 normal healthy individuals as controls. METHODS: Determination of lipid peroxidation was carried out by ascertaining concentration of malondialdehyde (MDA) and vitamin C in serum using UV spectrophotometry whereas atomic absorption spectroscopy was used for trace elements estimation. The statistical analysis was conducted via the independent t-test samples and Pearson correlation test. RESULTS: The blood serum study has shown substantially higher MDA values than the control level and lowers vitamin C levels in the patient population (P < .001). A negative correlation was found between the vitamin C in serum with BMI and MDA for both patients (r = -0.017 and r = -0.132, respectively) and the control group (r = -0.014 and r = -0.229, respectively) after Pearson's correlation analysis. Regarding trace elements, significantly (P < .001) lower concentrations of zinc, copper, and manganese were found in the patient group than control subjects. Inter-element-relationship established a strong positive harmonization between these studied elements in both the cases of patients and control subjects. CONCLUSION: Our results indicate strong associations of the pathogenesis of ESRD with depleted non-enzymatic antioxidant, increased lipid peroxidation, and inconsistency in trace elements concentration in serum, which may provide a prognostic tool for the treatment of this concerning the disease.

Elevated Serum Lipid Peroxidation and Reduced Vitamin C and Trace Element Concentrations Are Correlated With Epilepsy.

BACKGROUND: Epilepsy is one of the chronic and heterogeneous epidemic neurological disorders leading to substantial mortality. The aim of the present study was to investigate the serum levels of malondialdehyde (MDA), vitamin C, and trace elements namely zinc (Zn), copper (Cu), and manganese (Mn) in epileptic patients of Bangladesh and to establish if there are any pathophysiological correlations. METHODS: This was a case-control study with 40 generalized epileptic patients and 40 healthy subjects as controls. Epilepsy was determined by the presence of seizure events with an abnormal electroencephalography and magnetic resonance imaging report of brain. RESULTS: Anthropometric parameters highlighted that age is a major risk factor of epilepsy and men are more prone to epilepsy than women. Blood serum analysis demonstrated significantly ( P < .001) higher values of MDA and lower level of vitamin C in the patient group (4.41 ± 0.76 µmol/mL and 18.31 ± 0.84 µmol/L, respectively) compared with control (1.81 ± 0.70 µmol/mL and 29.72 ± 1.06 µmol/L, respectively). Pearson's correlation analysis revealed a negative correlation between the serum level of MDA and vitamin C for both patient ( r = -0.023, P = .887) and control group ( r = -0.142, P = .383). This study also revealed that the trace elements (Zn, Cu) were significantly ( P < .05) lower in epileptics (68.32 ± 4.59 and 50.81 ± 2.54 µg/dL, respectively) where the level of Mn in patients (187.71 ± 9.04 µg/dL) was almost similar to that of the control group ( P > .05). The univariate analysis demonstrated that zinc <70 µg/dL (odds ratio = 3.56, P < .05) and copper <50 µg/dL were associated (odds ratio = 14.73, P < .001) with an increased risk of epilepsy. Establishment of interelement relationship strongly supported that there was a disturbance in the element homeostasis of epileptic patients. CONCLUSIONS: The study results strengthen the role of lipid peroxidation, antioxidants and trace elements in the pathogenesis and warrant larger studies to investigate the association of these biochemical parameters with epilepsy.

Investigation of total phenolic content and antioxidant activities of Azadirachta indica roots.

OBJECTIVE: The present study was an attempt to study total phenolic content and antioxidant property of the crude ethanolic extract of the roots of Azadirachta indica (A. indica). MATERIALS AND METHODS: To evaluate the antioxidant properties of the crude extract, some complementary test systems, namely DPPH free radical scavenging assay, reducing power assay, and ferrous ion chelating ability and determination of total phenolic content were conducted. RESULTS: In DPPH free radical scavenging test, IC50 value of the crude extract was found to be fairly significant (13.81±0.06 µg/ml) while compared with that of the reference standards, ascorbic acid and BHA (2.12±0.02 and 4.87±0.05 µg/ml, respectively). In reducing power assay, the maximum absorbance for the extract was found to be 1.523±0.026 at100 µg/ml compared with standard ascorbic acid and BHA (2.811±0.013 µg/ml and 2.031±0.019 µg/ml, respectively). The IC50 value of the extract as percentage of Fe(++) ion chelating ability was determined as 19.01±0.024 µg/ml where EDTA showed 8.87±0.035 µg/ml. The total phenolic amount was also calculated quite high in the extract (238.81±0.98 mg/g of gallic acid equivalent). CONCLUSION: The assays showed the presence of significant antioxidant properties of the crude sample, which would justify its traditional use. However, it would be very interesting to investigate the possible causes and their mechanisms responsible for the antioxidant property of the plant A. indica.