Alzheimer's diseases in America, Europe, and Asian regions: a global genetic variation.

Background: Alzheimer's disease (AD) is one of the multifaceted neurodegenerative diseases influenced by many genetic and epigenetic factors. Genetic factors are merely not responsible for developing AD in the whole population. The studies of genetic variants can provide significant insights into the molecular basis of Alzheimer's disease. Our research aimed to show how genetic variants interact with environmental influences in different parts of the world. Methodology: We searched PubMed and Google Scholar for articles exploring the relationship between genetic variations and global regions such as America, Europe, and Asia. We aimed to identify common genetic variations susceptible to AD and have no significant heterogeneity. To achieve this, we analyzed 35 single-nucleotide polymorphisms (SNPs) from 17 genes (ABCA7, APOE, BIN1, CD2AP, CD33, CLU, CR1, EPHA1, TOMM40, MS4A6A, ARID5B, SORL1, APOC1, MTHFD1L, BDNF, TFAM, and PICALM) from different regions based on previous genomic studies of AD. It has been reported that rs3865444, CD33, is the most common polymorphism in the American and European populations. From TOMM40 and APOE rs2075650, rs429358, and rs6656401, CR1 is the common investigational polymorphism in the Asian population. Conclusion: The results of all the research conducted on AD have consistently shown a correlation between genetic variations and the incidence of AD in the populations of each region. This review is expected to be of immense value in future genetic research and precision medicine on AD, as it provides a comprehensive understanding of the genetic factors contributing to the development of this debilitating disease.

Bioactive compounds from Ocimum tenuiflorum and Poria cocos: A novel natural Compound for insomnia treatment based on A computational approach.

Insomnia, a widespread public health issue, is associated with substantial distress and daytime functionality impairments and can predispose to depression and cardiovascular disease. Cognitive Behavioral Anti-insomnia therapies including benzodiazepines often face limitations due to patient adherence or potential adverse effects. This study focused on identifying novel bioactive compounds from medicinal plants, aiming to discover and develop new therapeutic agents with low risk-to-benefit ratios using computational drug discovery methods. Through a systematic framework involving compound library preparation, evaluation of drug-likeness and pharmacokinetics, toxicity prediction, molecular docking, and molecular dynamic simulations, two natural compounds such as 2-(4-hydroxy-3-methoxyphenyl)-8-methoxy-6-prop-2-enyl-3,4-dihydro-2H-chromen-3-ol from Ocimum tenuiflorum and 7-(2-hydroxypropan-2-yl)-1,4a-dimethyl-9-oxo-3,4,10,10a-tetrahydro-2H-phenanthrene-1-carboxylic acid from Poria cocos exhibited high binding affinity with orexin receptor type 1 (OX1R) and type 2 (OX2R), surpassing commercial drugs used in insomnia treatment. Additionally, they showed interactions with critical amino acid residues within the receptors that play crucial roles in competitive inhibitor activity, like commercial drugs such as Suvorexant, Lemborexant, and Daridorexant. Further, molecular dynamics simulations of the protein-ligand complexes under conditions that mimic the in vivo environment revealed both compounds' sustained and robust interactions with the OX1R and OX2R, reinforcing their potential as effective therapeutic candidates. Furthermore, upon evaluating both compounds' drug-likeness, pharmacokinetics, and toxicity profiles, it was discerned that they displayed considerable drug-like properties and favorable pharmacokinetics, along with diminished toxicity. The research provides a solid foundation for further exploring and validating these compounds as potential anti-insomnia therapeutics.

Exploring the antioxidant and antimicrobial potential of three common seaweeds of Saint Martin's Island of Bangladesh.

Antioxidants, which have long been deemed an indispensable guardian of human health, play a pivotal role in bolstering the body's defense against a plethora of diseases. Three well-recognized seaweeds in Bangladesh, including Caulerpa racemosa, Padina tetrastromatica, and Hypnea musciformis, were subjected to meticulous analysis to reveal their phytochemical composition, antioxidant activity, and antimicrobial efficacy using advanced spectroscopic and disc diffusion methods. Intriguingly, we observed that C. racemosa emerges as frontrunners, possessing a substantial arsenal of phenol (143.08 ± 18.51 mg gallic acid equivalent g─1) and flavonoid (63.79 ± 2.16 mg rutin equivalent g─1). More fundamentally, C. racemosa exhibits a notable enrichment in the content of tannin (73.58 mg RE g─1) and chlorophyll (13.50 mg g─1), as well as, antioxidant capacity (4457.67 µg g─1). P. tetrastromatica, on the other hand, displayed commendable effectiveness in scavenging the DPPH radical, with percentages ranging from 53.98 to 62.17%. In terms of hydroxyl radical (OH•) scavenging activity, C. racemosa exhibited the highest efficacy at 400 g mL─1. Fascinatingly, C. racemosa exhibited an impressive antioxidant potential, as evidenced by its exceptionally low IC50 value of 5.58 µg mL-1 for OH• scavenging, whereas P. tetrastromatica showed impressively low value of 0.96 µg mL-1 for DPPH scavenging. Although the three seaweeds demonstrated limited efficacy against a spectrum of five human pathogenic bacteria, their potential as abundant sources of antioxidants remains unscathed. Notably, heatmap and PCA analysis revealed that C. racemosa and P. tetrastromatica emerge as the leading contender for studied antioxidant compounds, demonstrating their proclivity for antioxidant extraction, a trait that could be exploited for large-scale production of these valuable compounds.

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.

A Critical Review of the Neuropharmacological Effects of Kratom: An Insight from the Functional Array of Identified Natural Compounds.

Kratom (Mitragyna speciosa Korth. Havil) has been considered a narcotic drug for years, barred by the law in many parts of the world, while extensive research over the past few decades proves its several beneficial effects, some of which are still in ambiguity. In many countries, including Thailand, the indiscriminate use and abuse of kratom have led to the loss of life. Nonetheless, researchers have isolated almost fifty pure compounds from kratom, most of which are alkaloids. The most prevalent compounds, mitragynine and 7-hydroxy mitragynine, are reported to display agonist morphine-like effects on human µ-opioid receptors and antagonists at κ- and δ-opioid receptors with multimodal effects at other central receptors. Mitragynine is also credited to be one of the modulatory molecules for the Keap1-Nrf2 pathway and SOD, CAT, GST, and associated genes' upregulatory cascades, leading it to play a pivotal role in neuroprotective actions while evidently causing neuronal disorders at high doses. Additionally, its anti-inflammatory, antioxidative, antibacterial, and gastroprotective effects are well-cited. In this context, this review focuses on the research gap to resolve ambiguities about the neuronal effects of kratom and demonstrate its prospects as a therapeutic target for neurological disorders associated with other pharmacological effects.

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.

Tea tree oil, a vibrant source of neuroprotection via neuroinflammation inhibition: a critical insight into repurposing Melaleuca alternifolia by unfolding its characteristics. / èŒ¶æ ‘æ²¹æŠ‘åˆ¶ç¥žç»ç‚Žç—‡å¹¶æä¾›ç¥žç»ä¿æŠ¤­­æŽ¢ç´¢äº’花千层的潜力.

Over the past few decades, complementary and alternative treatments have become increasingly popular worldwide. The purported therapeutic characteristics of natural products have come under increased scrutiny both in vitro and in vivo as part of efforts to legitimize their usage. One such product is tea tree oil (TTO), a volatile essential oil primarily obtained from the native Australian plant, Melaleuca alternifolia, which has diverse traditional and industrial applications such as topical preparations for the treatment of skin infections. Its anti-inflammatory-linked immunomodulatory actions have also been reported. This systematic review focuses on the anti-inflammatory effects of TTO and its main components that have shown strong immunomodulatory potential. An extensive literature search was performed electronically for data curation on worldwide accepted scientific databases, such as Web of Science, Google Scholar, PubMed, ScienceDirect, Scopus, and esteemed publishers such as Elsevier, Springer, Frontiers, and Taylor & Francis. Considering that the majority of pharmacological studies were conducted on crude oils only, the extracted data were critically analyzed to gain further insight into the prospects of TTO being used as a neuroprotective agent by drug formulation or dietary supplement. In addition, the active constituents contributing to the activity of TTO have not been well justified, and the core mechanisms need to be unveiled especially for anti-inflammatory and immunomodulatory effects leading to neuroprotection. Therefore, this review attempts to correlate the anti-inflammatory and immunomodulatory activity of TTO with its neuroprotective mechanisms.

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 [...].

Therapeutic potentials of Adenostemma lavenia (L.) O.Kuntze evidenced into an array of pharmacological effects and ligand-receptor interactions.

This study constructed the phytochemical profiles of Adenostemma lavenia (L) methanol extract (MEAL) and investigated its anti-nociceptive, anti-diarrheal, antipyretic, thrombolytic and anthelmintic effects. The GC-MS characterized MEAL had undergone an in vivo antipyretic effect assayed on Swiss albino mice adopting the yeast-induced pyrexia model, antinociceptive activity tested following acetic acid-induced writhing and formalin-induced licking paw models, anti-diarrheal effect in castor oil-induced diarrhea, castor oil-induced enteropooling, and charcoal-induced intestinal transit tests, in vitro thrombolytic effect using clot-lysis model and anthelmintic effects assayed on Tubifex tubifex nematode. The MEAL biometabolites and associated proteins of target diseases were interacted with computational analysis. The MEAL showed a significant dose-dependent percentage of inhibition in acetic acid-induced writhing and formalin-induced paw licking displaying inhibition of 80.40% in acetic acid-induced writhing and 36.23% and 58.21% in the second phase of the formalin-induced model. The MEAL inhibition of 34.37%, 35.29%, and 42.95% in castor oil-induced diarrhea, castor oil-induced enteropooling, and charcoal-induced gastrointestinal motility, respectively. The MEAL significantly reduced yeast-induced pyrexia. Its biometabolites showed remarkable (-4.1 kcal/mol to 7.4 kcal/mol) binding affinity with the protein receptors. Caryophyllene and Cyclobarbital yielded the best binding scores in this research. Results suggest that pure compounds-based pharmacological investigations are necessary to affirm the therapeutic effects.

Green-synthesized nanoparticles of the polyherbal extract attenuate the necrosis of pancreatic ß-cell in a streptozotocin-induced diabetic model.

Plant-based nanoformulation is one of the novel approaches for therapeutic benefits. This research synthesized a silver nanoparticle from the polyherbal combination of four plants/seeds (Momordica charantia, Trigonella foenum-graecum, Nigella sativa, and Ocimum sanctum) and investigated its antidiabetic effects in streptozotocin-induced Wistar albino rat model. The polyherbal extract (PH) was extracted by the Soxhlet-solvent extraction method and the resulting crude extract was undergone for silver nanoparticle synthesis. The PH extract was subjected to a four-week intervention in fructose-fed streptozotocin-induced Wistar Albino rats' models and in vitro antioxidative tests. Experimental animals (age: 6-7 weeks, male, body weight: 200-220 g), were divided into five groups including normal control (NC), reference control (RC), diabetic control (DC), and treatment groups PH200, PH100, and PHAgNP20. After three weeks of intervention, body weight, weekly blood glucose level, oral glucose tolerance test, AST, ALT, alkaline phosphatase, total cholesterol, triglycerides, uric acid, urea, and creatinine level of PH200 were found to be significantly (P < 0.05) improved compared to the diabetic control. The same dose demonstrated better regeneration of damaged pancreatic and kidney tissues. In vitro antioxidant assay manifested promising IC50 values of 86.17 µg/mL for DPPH, 711.04 µg/mL for superoxide free radical, and 0.48 mg/mL for Iron chelating activity of the polyherbal extract. GC-MS analysis impacted the major volatile compounds of the PH. The data demonstrate that the PH and its nanoparticles could be a novel source of antidiabetic therapeutics through an advanced dose-response study in the type 2 diabetic model.

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.

The Protective Effect of Lasia spinosa (Linn.) Dissipates Chemical-Induced Cardiotoxicity in an Animal Model.

Lasia spinosa (L.) Thwaites is a medicinal plant of enormous traditional use with insufficient scientific evidence. This research screened the antioxidative effect of L. spinosa extracts by measuring the total phenolic content, total flavonoid content, DPPH free radical scavenging activity, ABTS scavenging activity, Iron-chelating activity, and Ferric reducing power followed by an evaluation of in vivo cardioprotective effect in doxorubicin-induced Wistar Albino rats. Phytochemical characterization was made by Gas Chromatography-Mass Spectroscopic analysis. L. spinosa showed an excellent antioxidative effect while methanol leaf extract (LSM) was found to be more potent than ethyl acetate leaf extract (LSE) in scavenging the free radicals. Intraperitoneal injection of doxorubicin caused a significant (P < 0.001) increase in lactate dehydrogenase (LDH), creatine kinase (CK-MB), C-reactive protein (CRP), and Cardiac troponin I. Pretreatment with orally administrated (LSM100 and LSM200 mg/kg b.w.) daily for 10 days showed a decrease in the cardiac markers, lipid profiles, especially triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), and an increase of high-density lipoprotein (HDL) compared to the disease control group. LSM200 was found to significantly (P < 0.05) decrease the levels of CK-MB and LDH. It also restored TC, TG, and LDL levels compared to the doxorubicin-induced cardiac control group. The protective role of LSM was further confirmed by histopathological examination. This study thus demonstrates that L. spinosa methanol extract could be approached as an alternative supplement for cardiotoxicity, especially in the chemical-induced toxicity of cardiac tissues.

Mechanistic insight into immunomodulatory effects of food-functioned plant secondary metabolites.

Medicinally important plant-foods offer a balanced immune function, which is essential for protecting the body against antigenic invasion, mainly by microorganisms. Immunomodulators play pivotal roles in supporting immune function either suppressing or stimulating the immune system's response to invading pathogens. Among different immunomodulators, plant-based secondary metabolites have emerged as high potential not only for immune defense but also for cellular immunoresponsiveness. These natural immunomodulators can be developed into safer alternatives to the clinically used immunosuppressants and immunostimulant cytotoxic drugs which possess serious side effects. Many plants of different species have been reported to possess strong immunomodulating properties. The immunomodulatory effects of plant extracts and their bioactive metabolites have been suggested due to their diverse mechanisms of modulation of the complex immune system and their multifarious molecular targets. Phytochemicals such as alkaloids, flavonoids, terpenoids, carbohydrates and polyphenols have been reported as responsible for the immunomodulatory effects of several medicinal plants. This review illustrates the potent immunomodulatory effects of 65 plant secondary metabolites, including dietary compounds and their underlying mechanisms of action on cellular and humoral immune functions in in vitro and in vivo studies. The clinical potential of some of the compounds to be used for various immune-related disorders is highlighted.

Upregulation of Antioxidative Gene Expression by Lasia spinosa Organic Extract Improves the Predisposing Biomarkers and Tissue Architectures in Streptozotocin-Induced Diabetic Models of Long Evans Rats.

Plants are an entity essential to the function of the biosphere as well as human health. In the context of human health, this research investigated the effect of Lasia spinosa (Lour) leaf methanolic extracts (LSML) on antioxidative enzymes and gene expression as well as biochemical and histological markers in a streptozotocin (STZ)-induced diabetes model. Fructose-fed streptozotocin (STZ)-induced diabetic animals were subjected to a four-week intervention followed by the assessment of the animal's blood and tissues for enzymatic, biochemical, histological, and genetic changes. LSML-treated groups were shown to decrease plasma glucose levels and improve body and organ weights compared to the untreated group in a dose-dependent manner. At the doses of 125 and 250 mg/kg b.w., LSML were able to normalize serum, hepatic, and renal biochemical parameters and restore the pancreas, kidney, liver, and spleen tissue architectures to their native state. A considerable increase (p < 0.01) of liver antioxidant enzymes CAT, SOD, GSH, and a decrease of MDA level in LSML-treated groups were found at higher doses. The improved mRNA expression level of antioxidant genes CAT, SOD2, PON1, and PFK1 was also found at the doses of 125 mg/kg and 250 mg/kg BW when compared to untreated control groups. The results demonstrate that LSML impacts the upregulation of antioxidative gene expressions, thus improving the diabetic complications in animal models which need to be affirmed by compound-based antioxidative actions for therapeutic development.

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.

Incredible affinity of Kattosh with PPAR-γ receptors attenuates STZ-induced pancreas and kidney lesions evidenced in chemicobiological interactions.

Since ancient times, plants have been used as green bioresources to ensure a healthier life by recovering from different diseases. Kattosh (Lasia spinosa L. Thwaites) is a local plant with various traditional uses, especially for arthritis, constipation and coughs. This research investigated the effect of Kattosh stem extract (LSES) on streptozotocin-induced damage to the pancreas, kidney, and liver using in vitro, in vivo and in silico methods. In vitro phytochemical, antioxidative and anti-inflammatory effects of LSES were accomplished by established methods followed by antidiabetic actions in in vivo randomized controlled intervention in STZ-induced animal models for four weeks. In an in silico study, LSES phytocompounds interacted with antidiabetic receptors of peroxisome proliferator-activated receptor-gamma (PPAR, PDB ID: 3G9E), AMP-activated protein kinase (AMPK, PDB ID: 4CFH) and α-amylase enzyme (PDB ID: 1PPI) to verify the in vivo results. In addition, LSES showed promising in vitro antioxidative and anti-inflammatory effects. In contrast, it showed a decrease in weekly blood glucose level, normalized lipid profile, ameliorated liver and cardiac markers, managed serum AST and ALT levels, and increased glucose tolerance ability in the animal model study. Restoration of pancreatic and kidney damage was reflected by improving histopathological images. In ligand-receptor interaction, ethyl α-d-glucopyranoside of Kattosh showed the highest affinity for the α-amylase enzyme, PPAR, and AMPK receptors. Results demonstrate that the affinity of Kattosh phytocompounds potentially attenuates pancreatic and kidney lesions and could be approached as an alternative antidiabetic source with further clarification.