Apoptosis-inducing anti-proliferative and quantitative phytochemical profiling with in silico study of antioxidant-rich Leea aequata L. leaves.

Natural products have been important parts of traditional medicine since ancient times, with various promising health effects. Leea aequata (L. aequata), a natural product, has been widely used for treating several diseases due to its promising pharmacological activities. Therefore, the present study aimed to explore the phytochemical profiling and molecular docking of the antioxidant-rich part of L. aequata leaves and its antiproliferative activity. L. aequata leaves were extracted with methanol, followed by fractionation with the respective solvents to obtain the petroleum ether, chloroform, ethyl acetate, and aqueous fractions. The antioxidant activity was evaluated by spectrophotometric methods. The cytotoxic and antiproliferative activities were detected using MTT colorimetric and confocal microscopy methods, respectively. Phytochemical compositions were analyzed using gas chromatography‒mass spectrometry analysis. Computer aided (molecular docking SwissADME, AdmetSAR and pass prediction) analyses were undertaken to sort out the best-fit phytochemicals present in the plant responsible for antioxidant and anticancer effects. Among the fractions, the ethyl acetate fraction was the most abundant polyphenol-rich fraction and showed the highest antioxidant, reducing power, and free radical scavenging activities. Compared to untreated MCF-7 cells, ethyl acetate fraction-treated MCF-7 cells showed an increase in apoptotic characteristics, such as membrane blebbing, chromatin condensation, and nuclear fragmentation, causing apoptosis and decreased proliferation of HeLa and MCF-7 cells. Furthermore, gas chromatography mass spectrometry data revealed that the ethyl acetate fraction contained 16 compounds, including methyl esters of long-chain fatty acids, which are the major chemical constituents. Moreover, hexadecanoic acid, methyl ester; 9-octadecenoic acid (Z)-, methyl ester; 9,12-octadecadienoic acid, methyl ester (Z, Z) and phenol, 2,4-bis(1,1-dimethylethyl) are known to have antioxidant and cytotoxic activity, as confirmed by computer-aided models. A strong correlation was observed between the antioxidant and polyphenolic contents and the anticancer activity. In conclusion, we explored the possibility that L. aequata could be a promising source of antioxidants and anticancer agents with a high phytochemical profile.

Molecular Insight into the Crosstalk of UPS Components and Alzheimer's Disease.

The ubiquitin (Ub)-proteasome system (UPS) targets various cellular proteins for degradation. It has been found that defects in the UPS play a crucial role in the pathogenesis of Alzheimer's disease (AD), as the existence of Ub immunoreactivity in AD-linked neuronal inclusions, including neurofibrillary tangles, is observed in all types of AD cases. Current investigations have shown that components of the UPS can be connected with the early stage of AD, which is characterized by synaptic dysfunction, and to the late phases of the disease, marked by neurodegeneration. Although the significance of UPS in the pathogenesis of AD has been emphasized, targeted treatment at the main components of these pathways has a great perspective in advancing new therapeutic interventions for AD. In this review, we emphasize the relationship between UPS and AD pathology. We also represent the recent therapeutic advancements targeting UPS components in AD.

Corrigendum to "Chemical profiles, pharmacological properties, and in silico studies provide new insights on Cycas pectinata" [Heliyon 6 (6), (June 2020) Article e04061].

[This corrects the article DOI: 10.1016/j.heliyon.2020.e04061.].

Chemical profiles, pharmacological properties, and in silico studies provide new insights on Cycas pectinata.

The current study aimed to qualitatively and quantitatively determine the phytochemical components of Cycas pectinata methanol extract (MECP), along with its antioxidant, anti-inflammatory, thrombolytic, locomotor, anxiolytic, analgesic, and antidiarrheal activities. The in vitro antioxidant activity was evaluated by DPPH scavenging assay and the total phenol and total flavonoid contents, while the anti-inflammatory activity was evaluated by a protein denaturation assay. The in vivo locomotor effects were examined using the open field test and hole-cross test. The anxiolytic effect was examined using the elevated plus maze (EPM) test, hole-board test (HBT), and light-dark test (LDT), while the analgesic activity was investigated using the acetic acid-induced writhing test. The antidiarrheal effect was evaluated by castor oil-induced diarrhea and gastrointestinal motility. Ten bioactive compounds were selected on the basis of their biological activities and further investigated using in silico molecular docking simulation to correlate with the identified pharmacological properties. Additionally, the ADME properties of the compounds were evaluated according to their drug-likeness profile. MECP had a maximum total phenol content of 209.85 ± 3.40 gallic acid equivalents/g extract and a total flavonoid content of 105.17 ± 3.45 quercetin equivalents/g extract, with an IC50 value of 631.44 µg/mL. MECP (62.5-500 µg/mL) elicited 20.96-38.12% decreased protein denaturation compared to diclofenac sodium (65.40-83.50%), while a 35.72% (P < 0.001) clot lysis activity was observed for the 10 mg/mL concentration. MECP induced a dose-dependent reduction in locomotor activity, with a significant anxiolytic effect. In the analgesic test, MECP (200, 400 mg/kg) showed a 45.12% and 58.82% inhibition in analgesia, and the 400 mg/kg dose elicited a 27.5% inhibition in intestinal motility. These findings suggest that MECP might be effective in treating antioxidant, anti-inflammatory, and neuropharmacological defects, but this requires further study.