Ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry-characterized extract of Aerides odorata Lour alleviates paracetamol-induced hepatotoxicity in animal model evidenced by biochemical, molecular, and computational studies.

BACKGROUND: Many kinds of orchids have significant health benefits although adequate research on their biological functions is yet to be carried out. This study investigated the paracetamol-induced liver damage-protecting effect of epiphytic Aerides odorata methanol extract (AODE). METHODS: The protective effects of AODE were studied by analyzing its effect on liver function parameters, messenger RNA (mRNA) expression, and tissue histopathological architecture. The results were confirmed by ligand-receptor interaction of molecular docking and multitarget interaction of network pharmacological analyses. RESULTS: AODE significantly (p < 0.05) minimized the dose-dependent increase in acid phosphatase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamyl transferase, lactate dehydrogenase, and total bilirubin compared to the reference drug silymarin. Malondialdehyde level decreased, and the antioxidant genes catalase (CAT), superoxide dismutase (SOD), ß-actin, paraoxonase-1 (PON1), and phosphofructokinase-1 (PFK-1) were upregulated in AODE-treated paracetamol-intoxicated rats. A total of 376 compounds comprising phenols and flavonoids were identified using ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-qTOF-MS). The online toxicity assessment using SwissADME and admetSAR exhibited drug-like, nontoxic, and potential pharmacological properties. Additionally, in silico analysis showed that isoacteoside, one of the identified compounds, exhibited the best docking score (-11.42) with the liver protein human pituitary adenylate cyclase-1 (Protein Data Bank ID: 3N94). Furthermore, network pharmacology analysis identified the top 10 hub genes, namely AKT1 (protein kinase B), CTNNB1 (catenin beta-1), SRC (proto-oncogene c-Src), TNF (tumor necrosis factor), EGFR (epidermal growth factor receptor), HSP90AA1 (heat shock protein 90α), MAPK3 (mitogen-activated protein kinase 3), STAT3 (signal transducer and activator of transcription 3), CASP3 (caspase protein), and ESR1 (estrogen receptor 1), which are responsible for hepatoprotective activity. CONCLUSION: The findings demonstrate that AODE could be a novel hepatoprotective target in drug-induced liver damage with a further single compound-based animal study.

Unraveling Tamarindus indica Pulp-Derived Green Magnesium Oxide Nanoparticles for Cardioprotective Potential against Doxorubicin-Induced Cardiomyopathy: A Comprehensive Biochemical and Gene Expression Study.

The present work investigates a sustainable approach to synthesize magnesium oxide nanoparticles (MgO NPs) using an aqueous pulp extract derived from Tamarindus indica. The effective synthesis of MgO NPs was verified by characterizing methods such as UV-vis spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, and scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDX). These nanoparticles possess small crystallite sizes, distinctive surface shapes, specific elemental compositions, and stabilizing and encapsulating constituents. Furthermore, total phenolic content (TPC) and total flavonoid content (TFC) tests revealed the existence of phytochemical components in MgO NPs. Significantly, these MgO NPs demonstrated exceptional antioxidant capabilities, as evidenced by their strong performance in antioxidant assays such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), nitric oxide (NO) scavenging, and iron chelation tests. They also exhibited a notable ability to inhibit red blood cell (RBC) hemolysis and lipid peroxidation. In toxicity assessments using Baby Hamster Kidney fibroblasts (BHK-21) and Vero cell lines, the MgO NPs displayed a safe profile. Additionally, in vivo studies on Doxorubicin (DOX)-induced cardiotoxicity revealed the cardioprotective properties of these NPs, accompanied by a detailed understanding of the underlying mechanisms. Pretreatment with MgO NPs effectively countered DOX-induced alterations in cardiac biomarkers, lipid profiles, cardiac enzymes, and lipid peroxidation. Furthermore, they modulated apoptosis-related markers (caspase-3 and p53), upregulated antiapoptotic (Bcl-2), and antioxidant (SOD) markers, suggesting their potential therapeutic value in addressing DOX-induced cardiomyopathy. In conclusion, this study underscores the promising cardioprotective, hypolipidemic, antioxidant, and antiapoptotic qualities of MgO NPs derived from tamarind pulp, offering valuable insights into their therapeutic applications and underlying biological mechanisms.

Sour Tamarind Is More Antihypertensive than the Sweeter One, as Evidenced by In Vivo Biochemical Indexes, Ligand-Protein Interactions, Multitarget Interactions, and Molecular Dynamic Simulation.

This research investigated the antihypertensive effects of tamarind products and compared their potentials based on an animal model's data verified by molecular docking, multitarget interactions, and dynamic simulation assays. GC-MS-characterized tamarind products were administered to cholesterol-induced hypertensive albino rat models. The two-week-intervened animals were dissected to collect their serum and organs and respectively subjected to analyses of their hypertension-linked markers and tissue architectures. The lead biometabolites of tamarinds interacted with eight target receptors in the molecular docking and dynamic simulation studies and with multitarget in the network pharmacological analyses. The results show that the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), C-reactive protein (CRP), troponin I, and lipid profiles were maximally reinstated by the phenolic-enriched ripened sour tamarind extract compared to the sweet one, but the seed extracts had a smaller influence. Among the tamarind's biometabolites, ϒ-sitosterol was found to be the best ligand to interact with the guanylate cyclase receptor, displaying the best drug-likeliness with the highest binding energy, -9.3 Kcal. A multitargeted interaction-based degree algorithm and a phylogenetic tree of pathways showed that the NR3C1, REN, PPARG, and CYP11B1 hub genes were consistently modulated by ϒ-sitosterol to reduce hypertension and related risk factors. The dynamic simulation study showed that the P-RMSD values of ϒ-sitosterol-guanylate cyclase were stable between 75.00 and 100.00 ns at the binding pocket. The findings demonstrate that ripened sour tamarind extract may be a prospective antihypertensive nutraceutical or supplement target affirmed through advanced preclinical and clinical studies.

Correction: Rashid et al. Natural Compounds of Lasia spinosa (L.) Stem Potentiate Antidiabetic Actions by Regulating Diabetes and Diabetes-Related Biochemical and Cellular Indexes. Pharmaceuticals 2022, 15, 1466.

In the published publication [...].

Quercetin: A Functional Food-Flavonoid Incredibly Attenuates Emerging and Re-Emerging Viral Infections through Immunomodulatory Actions.

Many of the medicinally active molecules in the flavonoid class of phytochemicals are being researched for their potential antiviral activity against various DNA and RNA viruses. Quercetin is a flavonoid that can be found in a variety of foods, including fruits and vegetables. It has been reported to be effective against a variety of viruses. This review, therefore, deciphered the mechanistic of how Quercetin works against some of the deadliest viruses, such as influenza A, Hepatitis C, Dengue type 2 and Ebola virus, which cause frequent outbreaks worldwide and result in significant morbidity and mortality in humans through epidemics or pandemics. All those have an alarming impact on both human health and the global and national economies. The review extended computing the Quercetin-contained natural recourse and its modes of action in different experimental approaches leading to antiviral actions. The gap in effective treatment emphasizes the necessity of a search for new effective antiviral compounds. Quercetin shows potential antiviral activity and inhibits it by targeting viral infections at multiple stages. The suppression of viral neuraminidase, proteases and DNA/RNA polymerases and the alteration of many viral proteins as well as their immunomodulation are the main molecular mechanisms of Quercetin's antiviral activities. Nonetheless, the huge potential of Quercetin and its extensive use is inadequately approached as a therapeutic for emerging and re-emerging viral infections. Therefore, this review enumerated the food-functioned Quercetin source, the modes of action of Quercetin for antiviral effects and made insights on the mechanism-based antiviral action of Quercetin.

Deciphering antidiarrheal effects of Meda pata (Litsea glutinosa (Lour.) C.B.Rob.) leaf extract in chemical-induced models of albino rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Diarrhea is one of the leading causes of preventable death in developing countries, mainly caused by bacterial infections and traditional therapies are very common in diarrheal incidences. Meda Pata (Litsea glutionsa) has a long history of use as traditional medicine for diarrhea, dysentery, and spasm in Bangladesh, India, and some other Asian countries. AIM OF THE STUDY: This research reports the antidiarrheal effects of Meda Pata (Litsea glutinosa leaf extract, LGLEx) in animal models. The work has been supported by in silico molecular docking study to verify the effects. MATERIALS AND METHODS: The antidiarrheal effect of LGLEx was investigated in castor oil-induced diarrhea, magnesium sulfate-induced diarrhea, and gastrointestinal motility test models. Antidiarrheal effects were supported by a molecular docking study through an interaction between LGLEx's GC-MS analyzed imidazole-containing compounds and muscarinic acetylcholine receptor (PDB: 4U14) and 5-HT3 receptor (PDB: 5AIN). RESULTS: LGLEx potentially reduced the diarrheal incidences in in vivo assays reducing gastrointestinal motility. The maximum diarrheal inhibition was obtained in the castor oil-induced model (62.63%) and and BaSO4-induced model (73.14%), which were statistically significant (P < 0.05) when compared to the reference drug loperamide. In the castor-oil and BaSO4-induced models, peristaltic movement was reduced by 25.96% and 32.17%, respectively. Biochemical markers particularly IgE, C-reactive proteins, and serum electrolytes were significantly (P < 0.0) restored in treated groups. A Molecular docking analysis revealed that two compounds (1-Ethyl-2-hydroxymethylimidazole and 1,6-Anhydro-beta-D-glucofuranose demonstrated the highest binding affinity with target receptors muscarinic acetylcholine receptor (PDB: 4U14) and 5-HT3 receptor (PDB: 5AIN) confirming their drug likeliness. The findings indicate a high potential antidiarrheal impact that warrants further investigation for its therapeutic application.

Biosynthesized magnesium oxide nanoparticles from Tamarindus indica seed attenuate doxorubicin-induced cardiotoxicity by regulating biochemical indexes and linked genes.

The phytochemicals of Tamarindus indica seed hydroalcoholic extract were exploited as a biocatalyst for the sustainable synthesis of magnesium oxide nanoparticles (MgO-NPs). This research investigated the cardioprotective effects of biosynthesized magnesium oxide nanoparticle (MgO-NPs). The biosynthesized seed MgO-NPs were characterized by ultraviolet-visible spectroscopy (UV-Vis), X-ray diffraction (XRD), scanning electron microscopy (SEM) with energy-dispersive X-ray diffraction (EDX), and Fourier-transform infrared spectroscopy (FT-IR). These methodological approaches demonstrated their capacity to synthesize crystalline and aggregated MgO-NPs with a size average of 13.38 ± 0.16 nm. The biogenic MgO-NPs were found to have a significant quantity of total phenolic contents (TPC) and total flavonoid contents (TFC), indicating the existence of phenol and flavonoid-like components. The biogenic MgO-NPs demonstrated a significant free radical scavenging effects compared to different standards as measured by the inhibition of free radicals produced in 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS•+), and Nitric oxide (NO) scavenging methods; they also exhibited higher ferric ion reducing capacity in FRAP assay. Moreover, they were found to be non-toxic in cytotoxic assessment. Pretreatment of Wistar Albino rats with seed MgO-NPs resulted in a significant reduction of cardiac biomarkers, i.e., cardiac Troponin-I (cTnI), creatine kinase (CK-MB), and aspartate aminotransferase (AST). The seed MgO-NPs were more successful in reducing lipid levels. The results of the mRNA expression analysis showed that seed MgO-NPs efficiently reduced the expression of the apoptotic genes p53 and Caspase-3 while restoring the expected levels of SOD gene expression. The histopathological observations were primarily focused on the disruption of cardiac fibers and myofibrillar disintegration, which are consistent with the biochemical findings. Therefore, our research suggests that MgO-NPs derived from the seeds of Tamarindus indica as a powerful antioxidant; the administration may be effective in protecting the heart from DOX-induced cardiotoxicity.

Natural Compounds of Lasia spinosa (L.) Stem Potentiate Antidiabetic Actions by Regulating Diabetes and Diabetes-Related Biochemical and Cellular Indexes.

Natural biometabolites of plants have been reported to be useful in chronic diseases including diabetes and associated complications. This research is aimed to investigate how the biometabolites of Lasia spinosa methanol stem (MEXLS) extract ameliorative diabetes and diabetes-related complications. MEXLS was examined for in vitro antioxidant and in vivo antidiabetic effects in a streptozotocin-induced diabetes model, and its chemical profiling was done by gas chromatography-mass spectrometry analysis. The results were verified by histopathological examination and in silico ligand-receptor interaction of characterized natural biometabolites with antidiabetic receptor proteins AMPK (PDB ID: 4CFH); PPARγ (PDB ID: 3G9E); and mammalian α-amylase center (PDB ID: 1PPI). The MEXLS was found to show a remarkable α-amylase inhibition (47.45%), strong antioxidant action, and significant (p < 0.05) decrease in blood glucose level, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein (LDL), urea, uric acid, creatinine, total cholesterol, triglyceride (TG), liver glycogen, creatinine kinase (CK-MB), and lactate dehydrogenase (LDH) and increase in serum insulin, glucose tolerance, and high-density lipoprotein (HDL). Rat's pancreas and kidney tissues were found to be partially recovered in histopathological analyses. Methyl α-d-galactopyranoside displayed the highest binding affinity with AMPK (docking score, −5.764), PPARγ (docking score, −5.218), and 1PPI (docking score, −5.615) receptors. Data suggest that the MEXLS may be an exciting source to potentiate antidiabetic activities affirming a cell-line study.

Quercetin attenuates viral infections by interacting with target proteins and linked genes in chemicobiological models.

Medicinally active compounds in the flavonoid class of phytochemicals are being studied for antiviral action against various DNA and RNA viruses. Quercetin is a flavonoid present in a wide range of foods, including fruits and vegetables. It is said to be efficient against a wide range of viruses. This research investigated the usefulness of Quercetin against Hepatitis C virus, Dengue type 2 virus, Ebola virus, and Influenza A using computational models. A molecular docking study using the online tool PockDrug was accomplished to identify the best binding sites between Quercetin and PubChem-based receptors. Network-pharmacological assay to opt to verify function-specific gene-compound interactions using STITCH, STRING, GSEA, Cytoscape plugin cytoHubba. Quercetin explored tremendous binding affinity against NS5A protein for HCV with a docking score of - 6.268 kcal/mol, NS5 for DENV-2 with a docking score of - 5.393 kcal/mol, VP35 protein for EBOV with a docking score of - 4.524 kcal/mol, and NP protein for IAV with a docking score of - 6.954 kcal/mol. In the network-pharmacology study, out of 39 hub genes, 38 genes have been found to interact with Quercetin and the top interconnected nodes in the protein-protein network were (based on the degree of interaction with other nodes) AKT1, EGFR, SRC, MMP9, MMP2, KDR, IGF1R, PTK2, ABCG2, and MET. Negative binding energies were noticed in Quercetin-receptor interaction. Results demonstrate that Quercetin could be a potential antiviral agent against these viral diseases with further study in in-vivo models. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-022-00132-2.