Elucidating the anti-cancer potential of Cinnamomum tamala essential oil against non-small cell lung cancer: A multifaceted approach involving GC-MS profiling, network pharmacology, and molecular dynamics simulations

Heliyon, Journal Year: 2024, Volume and Issue: 10(6), P. e28026 - e28026

Published: March 1, 2024

Cinnamomum tamala (Buch.-Ham.) T.Nees & Eberm., or Indian Bay Leaf, is a well-known traditional ayurvedic medicine used to treat various ailments. However, the molecular mechanism of action essential oil (CTEO) against non-small cell lung cancer (NSCLC) remains elusive. The present study aims decipher targets and CTEO in treating NSCLC. GC-MS analysis detected 49 constituents; 44 successfully passed drug-likeness screening were identified as active compounds. A total 3961 4588 anti-NSCLC-related acquired. JUN, P53, IL6, MAPK3, HIF1A, CASP3 determined hub genes, while cinnamaldehyde, ethyl cinnamate acetophenone core Enrichment revealed that mainly involved apoptosis, TNF, IL17, pathways MAPK signalling pathways. mRNA expression, pathological stage, survival analysis, immune infiltrate correlation genetic alteration genes carried out. Kaplan-Meier overall (OS) curve HIF1A are linked worse Lung Adenocarcinoma (LUAD) patients compared normal patients. Ethyl cinnamaldehyde showed high binding energy with MAPK3 formed stable interactions during dynamic simulations for 100 ns. MM/PBSA van der Waals (VdW) contributions predominantly account significant portion compound within pocket MAPK3. Density functional theory most reactive least compound. exhibited selective cytotoxicity by inhibiting proliferation A549 cells sparing HEK293 cells. triggered apoptosis arresting cycle, increasing ROS accumulation, causing mitochondrial depolarisation, elevating caspase-3, caspase-8 caspase-9 levels above provides insights into pharmacological mechanisms treatment, suggesting its potential an adjuvant therapy.

Language: Английский

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Waste to Wealth: Dynamics and metabolic profiles of the conversion of jackfruit flake into value-added products by different fermentation methods

Food Chemistry X, Journal Year: 2024, Volume and Issue: 21, P. 101164 - 101164

Published: Jan. 30, 2024

Thus far, little is known about whether jackfruit flake, a byproduct of jackfruit, can be used as fermentation substrate to obtain value-added products through microbial fermentation. Here, flake puree was fermented by three different ways: spontaneous (JF), inoculated with LAB (JFL), co-fermentation and yeast (JFC). In contrast JF, the total polyphenol flavonoid content syndrome-associated enzyme inhibition are significantly increased in JFC at end Electronic tongue analysis revealed that lower astringency higher bitterness. 41 volatile compounds were identified during HS-SPME-GC-MS, richer honey, rose, fruity flavors. A 290 screened for discriminative pre- post-fermentation differential metabolites non-target metabolomics analysis. These results provide potential reference conversion waste into functional using

Language: Английский

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Exploring the therapeutic mechanism of potential phytocompounds from Kalanchoe pinnata in the treatment of diabetes mellitus by integrating network pharmacology, molecular docking and simulation approach

Saudi Pharmaceutical Journal, Journal Year: 2024, Volume and Issue: 32(5), P. 102026 - 102026

Published: March 13, 2024

Since ancient times, bioactive phytocompounds from different parts of medicinal plants have been used to heal various disease ailments and they are now regarded as a valuable source prevention globally. Kalanchoe pinnata is member the Crassulaceae family; it has long history usage in traditional ayurvedic treatment. Analysis compounds for their potential anti-type-2 diabetes mellitus (T2DM) mechanism along with in-vitro in-silico approaches was studied present research. The alpha-amylase alpha-glucosidase inhibitory activity methanolic extract (α-amylase: IC50 29.50 ± 0.04 μg/ml; α-glucosidase 32.04 0.35 μg/ml) exhibit high degree similarity standard drug acarbose (IC50 35.82 0.14 μg/ml). Different biological databases were list plant, ADME analysis using swissADME carried out screen that obeyed Lipinski rule 5 employed further. STRING KEGG pathway performed gene enrichment followed by network pharmacology identify key target proteins involved DM. AMY2A, NOX4, RPS6KA3, ADRA2A, CHRM5, IL2 identified core targets luteolin, kaempferol, alpha amyrin, stigmasterol modulating neuroactive ligand interaction, P13-AKT, MAPK, PPAR signaling pathways. Molecular docking study binding affinity among K. against aldose reductase, alpha-amylase, alpha-glucosidase, dipeptidyl peptidase IV. Alpha-amylase-friedelin [FRI] alpha-amylase-acarbose [STD] complexes subjected molecular simulation 200 ns duration depicted stability proteins. In current study, employing dual approach enzyme assays yielded comprehensive strong understanding its therapeutic properties, making significant step towards development novel anti-diabetic

Language: Английский

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Screening for potential novel probiotic Levilactobacillus brevis RAMULAB52 with antihyperglycemic property from fermented Carica papaya L.

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: June 20, 2023

Probiotics are live microorganisms with various health benefits when consumed in appropriate amounts. Fermented foods a rich source of these beneficial organisms. This study aimed to investigate the probiotic potential lactic acid bacteria (LAB) isolated from fermented papaya (Carica L.) through vitro methods. The LAB strains were thoroughly characterized, considering their morphological, physiological, fermentative, biochemical, and molecular properties. strain's adherence resistance gastrointestinal conditions, as well its antibacterial antioxidant capabilities, examined. Moreover, tested for susceptibility against specific antibiotics, safety evaluations encompassed hemolytic assay DNase activity. supernatant isolate underwent organic profiling (LCMS). primary objective this was assess inhibitory activity α-amylase α-glucosidase enzymes, both silico. Gram-positive that catalase-negative carbohydrate fermenting selected further analysis. exhibited bile (0.3% 1%), phenol (0.1% 0.4%), simulated juice (pH 3-8). It demonstrated potent abilities kanamycin, vancomycin, methicillin. strain showed autoaggregation (83%) adhesion chicken crop epithelial cells, buccal HT-29 cells. Safety assessments indicated no evidence hemolysis or DNA degradation, confirming isolates. isolate's identity confirmed using 16S rRNA sequence. Levilactobacillus brevis RAMULAB52, derived papaya, promising significant inhibition (86.97%) (75.87%) enzymes. In silico studies uncovered hydroxycitric acid, one acids isolate, interacted crucial amino residues target Specifically, formed hydrogen bonds key residues, such GLU233 ASP197 α-amylase, ASN241, ARG312, GLU304, SER308, HIS279, PRO309, PHE311 α-glucosidase. conclusion, possesses properties exhibits an effective remedy diabetes. Its abilities, different cell types, enzymes make it valuable candidate research application field probiotics diabetes management.

Language: Английский

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Fermented sugarcane juice-derived probiotic Levilactobacillus brevis RAMULAB54 enhances lipid metabolism and glucose homeostasis through PPAR-γ activation

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 29, 2025

The gut microbiota plays a significant role in metabolic disorders such as diabetes and obesity, with the peroxisome proliferator-activated receptor gamma (PPAR-γ) being key regulator adipogenesis glucose metabolism. This study is novel approach that explores antihyperglycemic antihyperlipidemic effects of Levilactobacillus brevis RAMULAB54 (LB13243), isolated from fermented sugarcane juice. LB13243 was cultured for SEM imaging, its supernatant (LBR54) analyzed. Organic acid interactions PPAR-γ were evaluated via molecular docking, while cytotoxicity adipocyte differentiation 3T3-L1 cells tested using MTT assays, Oil Red O staining, triglyceride quantification, qRT-PCR. In vivo , male Wistar rats hyperlipidemic streptozotocin-induced hyperglycemic models treated 4 weeks, followed by analysis food intake, body weight, serum glucose, lipids, histopathology. inhibited carbohydrate-hydrolyzing enzymes showed an organic profile. silico hydroxycitric had similar binding to PPARγ rosiglitazone (binding energy:−8.4 kcal/mol vs.−8.3 kcal/mol), greater stability (RMSD: 1.2 Å vs. 1.7 Å). Pharmacokinetics indicated moderate GI absorption (20%) low toxicity acid. LBR54 did not affect cell viability but reduced lipid accumulation 13% triglycerides ≤ 44 mg/dL. qRT-PCR revealed upregulation C/EBP-α, downregulation FAS, suggesting modulation adipogenesis. weight gain, normalized organ weights rats, improving levels profiles models. Histopathology improved tissue structure, indicating LB13243's potential reduce hyperglycemia hyperlipidemia modulating metabolism inflammation. suggests it promising natural option managing hyperlipidemia. also highlights distinctive capability modulate through acids, particularly acid, providing insights into therapeutic potential.

Language: Английский

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Combined in vitro and in silico approach to define alangimarckine from Thunbergia mysorensis leaves as a potential inhibitor of α-glucosidase

Journal of Biomolecular Structure and Dynamics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 20

Published: March 6, 2025

The current work investigated biocomputational methodologies for α-glucosidase inhibition to examine the antidiabetic potential of methanolic extract T. mysorensis leaves (MeL). MeL intensely impeded yeast-glucosidase, which is vital treating postprandial hyperglycemia (IC50 = 5.76 ± 0.10 μg/mL) in comparison an acarbose control 7.98 0.23 μg/mL). affected by phytochemical profiling employing LC-MS, GC-MS, and HPLC analysis determine bioactive components responsible activity. specified phytocompounds were employed silico research following profiling, where they docked into inhibitor binding site α-glucosidase. Molecular docking simulations, molecular dynamics free energy inquiries utilized clarify mechanism block Alangimarckine a glucocorticoid that used treat nasal symptoms. inhibited target enzyme with greater efficiency (-9.7 kcal/mol) than (-8.6 during docking. Concerning simulation studies, Alangimarckine-α-glucosidase complex was found be stable inside protein, compared -α-glucosidase complex. Additionally, alangimarckine at IC50 5.32 0.19 μg/mL vitro α-glucosidase, efficient both acarbose. Therefore, our suggests from may function as potent medications. could vivo clinical investigations specify its properties inhibition.

Language: Английский

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Green jackfruit flour ameliorates MASH and development of HCC via the AMPK and MAPK signaling pathways in experimental model systems

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 9, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a serious public health concern. Given the paucity of approved therapeutic strategies for this lifestyle disorder, dietary interventions may prove effective. We evaluated mechanisms how green jackfruit flour (JF) ameliorates metabolic-dysfunction-associated steatohepatitis (MASH) and halts progression to hepatocellular carcinoma (HCC). The study used murine models MASH MASH-HCC that closely mimic human MASLD. C57Bl/6 male mice were fed with chow or western diet normal sugar water 12 weeks, then randomized receive either 5 kcal% an equal volume placebo (PB). JF significantly reduced body weight, injury, insulin resistance, alleviated obesity, steatosis, inflammation, fibrosis, tumor development in WDSW WDSW/CCl4 compared placebo. Furthermore, activated AMPK (AMP-activated protein kinase) inhibited MAPK (mitogen-activated signaling pathways models, respectively. Sodium propionate treatment, primary short-chain fatty acid entering from JF's soluble fiber microbial fermentation, further supported these mechanistic insights. Hence, our findings present strong evidence potential attenuating MASH-HCC, warranting investigation efficacy as intervention clinical trials.

Language: Английский

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Inhibition of carbohydrate hydrolyzing enzymes by a potential probiotic Levilactobacillus brevis RAMULAB49 isolated from fermented Ananas comosus

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: June 14, 2023

The research aimed to explore the potential probiotic characteristics of Levilactobacillus brevis RAMULAB49, a strain lactic acid bacteria (LAB) isolated from fermented pineapple, specifically focusing on its antidiabetic effects. importance probiotics in maintaining balanced gut microbiota and supporting human physiology metabolism motivated this research. All collected isolates underwent microscopic biochemical screenings, those exhibiting Gram-positive characteristics, negative catalase activity, phenol tolerance, gastrointestinal conditions, adhesion capabilities were selected. Antibiotic susceptibility was assessed, along with safety evaluations encompassing hemolytic DNase enzyme activity tests. isolate's antioxidant ability inhibit carbohydrate hydrolyzing enzymes examined. Additionally, organic profiling (LC-MS) silico studies conducted tested extracts. RAMULAB49 demonstrated desired such as Gram-positive, hydrophobicity (65.71%), autoaggregation (77.76%). Coaggregation against Micrococcus luteus, Pseudomonas aeruginosa, Salmonella enterica serovar Typhimurium observed. Molecular characterization revealed significant ABTS DPPH inhibition rates 74.85% 60.51%, respectively, at bacterial cell concentration 109 CFU/mL. cell-free supernatant exhibited substantial α-amylase (56.19%) α-glucosidase (55.69%) vitro. In supported these findings, highlighting inhibitory effects specific acids citric acid, hydroxycitric malic which displayed higher Pa values compared other compounds. These outcomes underscore promising pineapple. Its properties, including antimicrobial autoaggregation, contribute therapeutic application. activities further support anti-diabetic properties. analysis identified that may observed isolate derived holds promise an agent for managing diabetes. Further investigations should focus evaluating efficacy vivo consider application diabetes management.

Language: Английский

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Quinoline- and Isoindoline-Integrated Polycyclic Compounds as Antioxidant, and Antidiabetic Agents Targeting the Dual Inhibition of α-Glycosidase and α-Amylase Enzymes

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(9), P. 1222 - 1222

Published: Aug. 30, 2023

Novel analogs of quinoline and isoindoline containing various heterocycles, such as tetrazole, triazole, pyrazole, pyridine, were synthesized characterized using FT-IR, NMR, mass spectroscopy, their antioxidant antidiabetic activities investigated. The previously compound 1 was utilized in conjugation with ketone-bearing tetrazole isoindoline-1,3-dione to synthesize Schiff’s bases 2 3. Furthermore, hydrazide treated aryledines provide pyrazoles 4a–c. Compound 5 obtained by treating potassium thiocyanate, which then cyclized a basic solution afford triazole 6. On the other hand, pyridine derivatives 7a–d 8a–d 2-(4-acetylphenyl)isoindoline-1,3-dione via one-pot condensation reaction aryl aldehydes active methylene compounds. From studies, 7d showed significant activity an EC50 = 0.65, 0.52, 0.93 mM free radical scavenging assays (DPPH, ABTS, superoxide anion radicals). It also displayed noteworthy inhibitory against both enzymes α-glycosidase (IC50: 0.07 mM) α-amylase (0.21 compared acarbose (0.09 0.25 for α-amylase), higher than During silico assays, exhibited favorable binding affinities towards (−10.9 kcal/mol) (−9.0 (−8.6 kcal/mol −6.0 α-amylase). stability demonstrated molecular dynamics simulations estimations energy throughout simulation session (100 ns).

Language: Английский

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Scavenger Receptors: Different Classes and their Role in the Uptake of Oxidized Low-Density Lipoproteins

Biomedical & Pharmacology Journal, Journal Year: 2024, Volume and Issue: 17(2), P. 699 - 712

Published: June 25, 2024

Oxidation of lipoproteins marks a fundamental early phase in atherosclerosis development, condition distinguished by plaque build-up the arteries. It is widely accepted that oxidation low-density lipoprotein (LDL) plays pivotal role progression. Oxidized LDL (Ox-LDL) exhibits numerous atherogenic characteristics, leading to endothelial dysfunction, creation foam cells, and inflammation arterial wall. The crucial interaction between Ox-LDL specific receptors on cells key initiating these processes. In this article, we're going delve into various play part uptake metabolism LDL, emphasizing their significance development atherosclerosis. Cochrane database, Embase, PubMed, Scopus, Google Scholar, Ovid, other databases were thoroughly searched for works addressing scavenger explore how both native (nLDL) engage with receptors, facilitating formation progression atherosclerotic plaques. We'll then proceed more detailed examination complex internalization oxidized (Ox-LDL), vital onset diseases. review will further cover identification, categorization, roles along molecular mechanisms. Grasping complexity receptor-ligand interactions critical focused treatments fight against pathologic conditions such as its related health scenarios.

Language: Английский

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