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Grape processing generates large amounts of by-products, including seeds rich in hydrophilic and lipophilic antioxidants. This study demonstrates, for the first time, that subjecting grape seeds to a single ultrasound-assisted extraction (UAE) with aqueous ethanolic solutions yields both flavan-3-ols and tocochromanols in the final extract. Notably, the water content in ethanol significantly influences the extractability of tocochromanols more than flavan-3-ols. Solid-to-solvent ratios of 1:50 to 1:2 were tested for both analytical and industrial applications. A sustainable analytical approach for recovering flavan-3-ols and tocochromanols using 60% and 96.4% ethanol extractions was validated and employed to profile nineteen genotypes of lesser-studied interspecific grape crosses (Vitis spp.). Different genotypes showed a wide range of concentrations of tocopherols (1.6-6.3 mg/100 g), tocotrienols (1.0-17.4 mg/100 g), and flavan-3-ols (861-9994 mg/100 g). This indicated that the genetic background and maturity of the plant material are crucial factors from an industrial perspective due to the initial concentration of bioactive compounds. Finally, the study also discussed the fundamental aspects of hydrophobic antioxidant extractability from the lipid matrix with aqueous ethanol solutions and the limitations of the workflow, such as the non-extractable tocochromanols and their esters and the losses of these lipophilic antioxidants during extraction.

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Indoor farming systems enable plant production in precisely controlled environments. However, implementing stable growth conditions and the absence of stress stimulants can weaken plants' defense responses and limit the accumulation of bioactive, health-beneficial phytochemicals. A potential solution is the controlled application of stressors, such as supplemental ultraviolet (UV) light. To this end, we analyzed the efficiency of short-term pre-harvest supplementation of the red-green-blue (RGB, LED) spectrum with ultraviolet B (UV-B) or C (UV-C) light to boost phytochemical synthesis. Additionally, given the biological harm of UV radiation due to high-energy photons, we monitored plants' photosynthetic activity during treatment and their morphology as well as sensory attributes after the treatment. Our analyses showed that UV-B radiation did not negatively impact photosynthetic activity while significantly increasing the overall antioxidant potential of lettuce through enhanced levels of secondary metabolites (total phenolics, flavonoids, anthocyanins), carotenoids, and ascorbic acid. On the contrary, UV-C radiation-induced anthocyanin accumulation in the green leaf cultivar significantly harmed the photosynthetic apparatus and limited plant growth. Taken together, we showed that short-term UV-B light supplementation is an efficient method for lettuce biofortification with healthy phytochemicals, while UV-C treatment is not recommended due to the negative impact on the quality (morphology, sensory properties) of the obtained leafy products. These results are crucial for understanding the potential of UV light supplementation for producing functional plants.

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Mycoplasma genitalium (M. genitalium) poses a significant challenge in clinical treatment due to its increasing antimicrobial resistance. This study investigates alternative therapeutic approaches by targeting the cofactor-independent phosphoglycerate mutase (iPGM) enzyme with phytochemicals derived from ethnobotanical plants. In silico screening identified several promising inhibitors, with 2-carboxy-D-arabinitol demonstrating the highest binding affinity (- 9.77 kcal/mol), followed by gluconic acid (- 9.03 kcal/mol) and citric acid (- 8.68 kcal/mol). Further analysis through molecular dynamics (MD) simulations revealed insights into the binding mechanisms and stability of these phytochemicals within the iPGM active site. The MD simulations indicated initial fluctuations followed by stability, with intermittent spikes in RMSD values. The lowest RMSF values confirmed the stability of the ligand-protein complexes. Key residues, including Ser-61, Arg-188, Glu-62, Asp-397, and Arg-260, were found to play crucial roles in the binding and retention of inhibitors within the active pocket. These findings suggest that the identified phytochemicals could serve as novel antimicrobial agents against M. genitalium by effectively inhibiting iPGM activity.

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Background: Plant-derived drugs are often preferred over synthetic drugs because of their superior safety profiles. Phenolic compounds and flavonoids-major plant components-possess antioxidant properties. Limited research has been conducted on the bioactive compounds and biochemical properties of Bellevalia pseudolongipes (Asparagaceae), an important pharmacological species endemic to Turkey. Therefore, the chemical composition and antioxidant properties of B. pseudolongipes were investigated in this study. Methods: The chemical composition of B. pseudolongipes was analyzed using liquid chromatography-high-resolution mass spectrometry, and radical scavenging and antioxidant activities were evaluated using DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)) tests. Results: Thirty-eight compounds were identified, including trans-cinnamic acid, caffeic acid, vitexin, schaftoside, orientin, and narirutin. B. pseudolongipes showed high antioxidant activity in antioxidant activity tests. Conclusion: These findings provide novel insights into the potential utility of B. pseudolongipes in the pharmaceutical, food, and cosmetics industries, highlighted by its significant antioxidant capacity.

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Argemone mexicana L. is a medicinal plant, but its impact on Alzheimer's disease (AD) is right now undetermined. We intended to investigate the in-vitro anti-AD potential of leaves and flowers of A. mexicana methanol, ethanol, and ethyl extracts and to identify multi-modal anti-AD phytochemicals by computational approaches. Molecular docking of 196 phytochemicals identified three hit phytochemicals (protoberberine, protopine, and codeine) with higher binding affinity and multi-targeting ability toward AChE, BChE, BACE-1, and GSK-3ß. Further MM-GBSA assays confirmed the integrity of these phytochemicals as the hit phytochemicals. However, these phytochemicals demonstrated favorable pharmacokinetics (PK) and drugable properties having no toxicity. Molecular dynamics simulations confirmed the binding strength of the hit phytoconstituents in the active pockets of AChE, BChE, BACE-1, and GSK-3ß with multi-targeting inhibitory activities. All the extracts exhibited dose-dependent antioxidant and anti-cholinesterase activities supporting the in silico results in the context of oxidative stress and cholinergic pathways. Our results offer scientific validation of the anti-AD properties of Argemone mexicana L. and identified protoberberine, protopine, and codeine that could be used for the development of multi-modal inhibitors of AChE, BChE, BACE-1, and GSK-3ß to combat AD. Additional in vivo validation is recommended to ensure a thorough assessment in the present research.

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Opuntia (Cactaceae) species are native to arid and semi-arid regions of Mexico and the southern United States and grow in various climatic zones. Opuntia dillenii is a cactus fruit with many beneficial properties, and it is used as a medicinal plant in various countries. This review paper provides updated information on the phytochemical and pharmacological aspects of O. dillenii. The fruit contains valuable compounds such as flavonoids, phenolics, ascorbic acid, betanin, and essential elements, which have been isolated and identified. The fruit also exhibits diverse pharmacological activities, such as antioxidant, anti-inflammatory, anti-tumor, neuroprotective, hepatoprotective, hypotensive, anti-diabetic, antifungal, and anticancer effects. Moreover, molecular docking and ADMET predictions were performed to evaluate the antibacterial potential of the fruit against Escherichia coli protein. This paper suggests that O. dillenii has significant potential as a complementary therapy for various pathological conditions.

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Doxorubicin (DOX) is a commonly used drug in chemotherapy for cancer treatment. However, it can cause the threatening side effect of cardiotoxicity. This study investigates whether the hydro-alcoholic leaves of Moringa oleifera have any protective potential against DOX-induced cardiotoxicity. The phytochemical analysis showed that the plant extracts contained bioactive compounds with antioxidant activities. The DOX-treated group confirmed a significant increment in cardiac troponin I (cTnI) and proinflammatory cytokine interleukin-6 (IL-6) levels, which indicates damage to the cardiomyocytes and also inflammation. However, treatment with the M. oleifera extracts significantly inhibited DOX-induced cardiomyocyte damage, as indicated by the significantly low cTnI release. Furthermore, treatment with M. oleifera extracts further increased antioxidant activities, thereby decreasing oxidative stress and lipid peroxidation. Moreover, DOX was found to increase the IL-6 level, and treatment with M. oleifera extracts had a significant impact on the inhibition of IL-6 levels. These results indicate that the M. oleifera extracts have a cardioprotective effect and can play a role as an adjunct drug in mitigating DOX-induced cardiotoxicity, thus providing new prospects for the improvement of safety and efficacy in the treatment of cancer.

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Phytochemicals are compounds found in fruits, vegetables, whole grains, nuts and legumes that are non-nutritive but have bioactive properties. A high intake of these compounds is essential for optimal health and disease prevention. No study has investigated the association between Dietary Phytochemical Index (DPI) and polyneuropathy in patients with diabetes. This study aimed to examine the association between DPI and Diabetic Sensory-motor Polyneuropathy (DSPN) in a case-control study. In this case-control study, a total of 185 diabetic patients with DSPN (case group) and 185 sex- and age-matched diabetic patients without neuropathy (control group) were enrolled in this study. Participants were 30-60 years old. A validated food frequency questionnaire was used to measure the dietary intake of all participants. Daily energy derived from phytochemical-rich foods was used to calculate the DPI score. Toronto clinical neuropathy score was applied to define DSPN. Anthropometric data and fasting blood glucose levels were measured using standard methods. The Binary logistic regression was used to estimate Crude and multivariable-adjusted OR (95% CI) for DSPN across tertiles of DPI for the whole population. In the crude model, there was a significant trend across the tertile of DPI (OR highest vs. lowest tertile of DPI = 0.33; 95%CI 0.18, 0.52; P-trend < 0.001). After controlling for age, sex, and energy, a significant reverse association was observed between DPI and DSPN (OR highest vs. lowest tertile of DPI = 0.27; 95%CI 0.15, 0·48; P-trend < 0.001). Moreover, after adjusting for a wide range of confounding variables such as energy intake, physical activity, education, smoking status, and HbA1c, participants in the third tertile of DPI had 75% reduced odds for DSPN (95%CI 0.14, 0.45; P-trend < 0.001). Finally in the full adjusted model, after further adjustment for BMI, observed significant association was remained (OR highest vs. lowest tertile of DPI: 0.24; 95% CI 0.13, 0.14; P-trend < 0.001). Higher intakes of phytochemical-rich foods are associated with lower odds of DSPN.

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Staphylococcus aureus infections present a significant threat to the global healthcare system. The increasing resistance to existing antibiotics and their limited efficacy underscores the urgent need to identify new antibacterial agents with low toxicity to effectively combat various S. aureus infections. Hence, in this study, we have screened T-muurolol for possible interactions with several S. aureus-specific bacterial proteins to establish its potential as an alternative antibacterial agent. Based on its binding affinity and interactions with amino acids, T-muurolol was identified as a potential inhibitor of S. aureus lipase, dihydrofolate reductase, penicillin-binding protein 2a, D-Ala:D-Ala ligase, and ribosome protection proteins tetracycline resistance determinant (RPP TetM), which indicates its potentiality against S. aureus and its multi-drug-resistant strains. Also, T-muurolol exhibited good antioxidant and anti-inflammatory activity by showing strong binding interactions with flavin adenine dinucleotide (FAD)-dependent nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase, and cyclooxygenase-2. Consequently, molecular dynamics (MD) simulation and recalculating binding free energies elucidated its binding interaction stability with targeted proteins. Furthermore, quantum chemical structure analysis based on density functional theory (DFT) depicted a higher energy gap between the highest occupied molecular orbital and lowest unoccupied molecular orbital (EHOMO-LUMO) with a lower chemical potential index, and moderate electrophilicity suggests its chemical hardness and stability and less polarizability and reactivity. Additionally, pharmacological parameters based on ADMET, Lipinski's rules, and bioactivity score validated it as a promising drug candidate with high activity toward ion channel modulators, nuclear receptor ligands, and enzyme inhibitors. In conclusion, the current findings suggest T-muurolol as a promising alternative antibacterial agent that might be a potential phytochemical-based drug against S. aureus. This study also suggests further clinical research before human application.

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Olive trees not only produce olives but also generate a substantial amount of waste and by-products, including leaves, pomace (the solid remains after pressing olives for oil), and wastewater from the olive oil-making process. The waste products, particularly the leaves, contain bioactive compounds, especially phenolic compounds, known for their health benefits, such as high antioxidant potential and the ability to reduce inflammation. These compounds have shown promise in preventing and treating cancer. This review, based on in vitro evidence, provides a detailed description and discussion of the mechanisms through which these compounds from olive leaves can prevent development, the ways they might act against cancer cells, and their potential to increase the sensitivity of tumor cells to conventional anticancer therapy. The possible synergistic effects of these compounds suggest that olive leaf extracts may offer a promising approach for cancer treatment, compared with isolated compounds, thus providing novel possibilities for cancer therapy.

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α-tocopherol (α-T), ß-sitosterol (ß-S), canolol (CA), and sinapic acid (SA) are the four main endogenous lipid phytochemicals (LP) found in Brassica napus L. seed oil, which possess the bioactivity to prevent the risk of several chronic diseases via antioxidant-associated mechanisms. Discovering the enhancer effects or synergies between LP is valuable for resisting oxidative stress and improving health benefits. The objectives of this study were to identify a potentially efficacious LP combination by central composite design (CCD) and cellular antioxidant activity (CAA) and to investigate its protective effect and potential mechanisms against H2O2-induced oxidative damage in HepG2 cells. Our results indicated that the optimal concentration of LP combination was α-T 10 µM, ß-S 20 µM, SA 125 µM, and CA 125 µM, respectively, and its CAA value at the optimal condition was 10.782 µmol QE/100 g. At this concentration, LP combination exerted a greater amelioration effect on H2O2-induced HepG2 cell injury than either antioxidant (tea polyphenols or magnolol) alone. LP combination could reduce the cell apoptosis rate induced by H2O2, lowered to 10.06%, and could alleviate the degree of oxidative damage to cells (ROS↓), lipids (MDA↓), proteins (PC↓), and DNA (8-OHdG↓). Additionally, LP combination enhanced the antioxidant enzyme activities (SOD, CAT, GPX, and HO-1), as well as the T-AOC, and increased the GSH level in HepG2 cells. Furthermore, LP combination markedly upregulated the expression of Nrf2 and its associated antioxidant proteins. It also increased the expression levels of Nrf2 downstream antioxidant target gene (HO-1, SOD-1, MnSOD, CAT, GPX-1, and GPX-4) and downregulated the mRNA expression levels of Keap1. The oxidative-stress-induced formation of the Keap1/Nrf2 complex in the cytoplasm was significantly blocked by LP treatment. These results indicate that LP combination protected HepG2 cells from oxidative stress through a mechanism involving the activation of the Keap1/Nrf2/ARE signaling pathways.

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In the realm of disease vectors and agricultural pest management, insecticides play a crucial role in preserving global health and ensuring food security. The pervasive use, particularly of organophosphates (OPs), has given rise to a substantial challenge in the form of insecticide resistance. Carboxylesterases emerge as key contributors to OP resistance, owing to their ability to sequester or hydrolyze these chemicals. Consequently, carboxylesterase enzymes become attractive targets for the development of novel insecticides. Inhibiting these enzymes holds the potential to restore the efficacy of OPs against which resistance has developed. This study aimed to screen the FooDB library to identify potent inhibitory compounds targeting carboxylesterase, Ha006a from the agricultural pest Helicoverpa armigera. The ultimate objective is to develop effective interventions for pest control. The compounds with the highest scores underwent evaluation through docking studies and pharmacophore analysis. Among them, four phytochemicals-donepezil, protopine, 3',4',5,7-tetramethoxyflavone, and piperine-demonstrated favorable binding affinity. The Ha006a-ligand complexes were subsequently validated through molecular dynamics simulations. Biochemical analysis, encompassing determination of IC50 values, complemented by analysis of thermostability through Differential Scanning Calorimetry and interaction kinetics through Isothermal Titration Calorimetry was conducted. This study comprehensively characterizes Ha006a-ligand complexes through bioinformatics, biochemical, and biophysical methods. This investigation highlights 3',4',5,7-tetramethoxyflavone as the most effective inhibitor, suggesting its potential for synergistic testing with OPs. Consequently, these inhibitors offer a promising solution to OP resistance and address environmental concerns associated with excessive insecticide usage, enabling a significant reduction in their overuse.

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Considerable advancements have been made in breast cancer therapeutics in the past few decades. However, the advent of chemo-resistance and adverse drug reactions coupled with tumor metastasis and recurrence posed a serious threat to combat this lethal disease. Novel anti-cancer agents, as well as new therapeutic strategies, are needed to complement conventional breast cancer therapies. The quest for developing novel anti-cancer drugs caused an upsurge in exploring and harnessing natural compounds, especially phytochemicals. Various research groups have explored and documented the anti-cancer potential of wide variety of phytochemical groups including flavonoids (curcumin, kaempferol, myricetin, quercetin, naringenin, apigenin, genistein epigallocatechin gallate), stilbenes (resveratrol), carotenoids (crocin, lycopene, lutein), and anthraquinone (Emodin). However, low chemical stability, poor water solubility, and short systemic half-life impede their clinical utility. The implication of nano-technological approaches to decode the pharmacokinetic challenges associated with phytochemical usage, as well as selective drug targeting, have markedly enhanced the pre-clinical anti-cancer activity, thus aiding in their clinical translation. This review documented the recent advances in utilizing phytochemicals for breast cancer prevention and lipidbased nanotechnological approaches for circumventing their pharmacokinetic concerns to enhance their systemic availability, cytotoxicity, and targeted delivery against breast cancer alone as well as in combination with conventional therapeutic agents.

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Mosquitoes are considered one of the most lethal creatures on the planet and are responsible for millions of fatalities annually through the transmission of several diseases to humans. Green trash is commonly employed in agricultural fertilizer manufacturing and microbial bioprocesses for energy production. However, there is limited information available on the conversion of green waste into biocides. This study investigates the viability of utilizing green waste as a new biopesticide against Culex pipiens mosquito larvae. The current study found that plant extracts from Punica granatum (98.4 % mortality), Citrus sinensis (92 % mortality), Brassica oleracea (88 % mortality), Oryza sativa (81.6 % mortality), and Colocasia esculenta (53.6 % mortality) were very good at killing Cx. pipiens larvae 24 h post-treatment. The LC50 values were 314.43, 370.72, 465.59, 666.67, and 1798.03 ppm for P. granatum, C. sinensis, B. oleracea, O. sativa, and C. esculenta, respectively. All plant extracts, particularly P. granatum extract (14.93 and 41.87 U/g), showed a significant reduction in acid and alkaline phosphate activity. Additionally, pomegranate extract showed a significant decrease (90 %) in field larval density, with a stability of up to five days post-treatment. GC-MS results showed more chemical classes, such as terpenes, esters, fatty acids, alkanes, and phenolic compounds. HPLC analysis revealed that the analyzed extracts had a high concentration of phenolic and flavonoid components. Moreover, there are many variations among these plants in the amount of each compound. The docking interaction showed a simulation of the atomic-level interaction between a protein and a small molecule through the binding site of target proteins, explaining the most critical elements influencing the enzyme's activity or inhibitions. The study's findings showed that the various phytochemicals found in agro-waste plants had high larvicidal activity and provide a safe and efficient substitute to conventional pesticides for pest management, as well as a potential future in biotechnology.

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A versatile and popular Cucurbitaceous vegetable, pumpkin has recently gained much attention because of its variety of phytochemicals and health advantages. Pumpkins are a type of winter squash, traditionally with large, spherical, orange fruits and a highly nutrient food. Pumpkin by-products comprise various parts, such as seeds, peels, and pulp residues, with their bioactive composition and many potential benefits poorly explored by the food industry. Pumpkin and their by-products contain a wide range of phytochemicals, including carotenoids, polyphenols, tocopherols, vitamins, minerals, and dietary fibers. These compounds in pumpkin by-products exhibit antioxidant, anticancer, anti-inflammatory, anti-diabetic, and antimicrobial properties and could reduce the risk of chronic diseases. This comprehensive review aims to provide a detailed overview of the phytochemicals found in pumpkin and its by-products, along with their extraction methods, health benefits, and diverse food and industrial applications. This information can offer valuable insights for food scientists seeking to reevaluate pumpkin's potential as a functional ingredient. Reusing these by-products would support integrating a circular economy approach by boosting the market presence of valuable and sustainable products that improve health while lowering food waste.

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Postprandial hyperglycemia (PPG) exacerbates endothelial dysfunction and impairs vascular function in diabetes as well in healthy people. Though synthetic drugs are available to regulate PPG, the severe gastrointestinal side effects of those medications have prompted the search for alternative treatments. Recently, some phytochemicals captured the attention because of their inhibitory effects on α-amylase to control diabetes. The aim of this study was to investigate and identify potential alpha-amylase inhibitors in C. indica and W. coagulans. This study also aims to understand one of the possible mechanisms of action of plants for their anti-diabetic activity. A total of 36 phytochemical ligands were subjected for protein-ligand docking analysis. Among the phytochemicals, Taraxerol and Epoxywithanolide-I demonstrated significant binding free energy of - 10.2 kcal/mol and - 11.9 kcal/mol respectively, which was higher than the reference acarbose with - 8.6 kcal/mol. These molecules were subjected for molecular dynamics simulation (MDS) analysis with alpha-amylase protein for a duration of 150 ns. Among the three complexes, Taraxerol and Epoxywithanolide-I complexes demonstrates strong potential as inhibitors of the target protein. MDS results were analyzed via root mean square deviation (RMSD), fluctuation of residues, potential energy, radii of gyration and solvent access surface area analysis. Taraxerol demonstrated a significantly low potential energy of - 1,924,605.25 kJ/mol, and Epoxywithanolide-I demonstrated - 1,964,113.3 kJ/mol of potential energy. RMSD plot shows that Epoxywithanolide-I has much higher stability than the other MDS complexes. Drugability and toxicity studies show that the test ligands are demonstrating strong potential as drug like molecules. The results of the study conclude that, Taraxerol of C. indica and Epoxywithanolide-I of W. coagulans are strong inhibitors of alpha-amylase enzyme and that, this is one of the possible mechanisms of action of the plants for their reported anti-diabetic activities. Further in-vitro analysis is in demand to prove the observed results.

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BACKGROUND: Tribulus terrestris, a plant known for its pharmacological properties, was investigated in this study for its potential anticancer effects against oral cancer cells. The study aimed to explore the phytochemical composition of T. terrestris seed extract and evaluate its cytotoxic, pro-apoptotic, antioxidant, anti-inflammatory, and antimicrobial activities. MATERIALS AND METHODS: Methanolic seed extracts of T. terrestris were obtained and subjected to phytochemical analysis to identify bioactive compounds. The cytotoxic effect of the extract on oral cancer cells was evaluated using the MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay, while pro-apoptotic effects were assessed through dual fluorescent staining. Antioxidant activity was measured using hydrogen peroxide and erythrocyte aggregation assays, while anti-inflammatory activity was evaluated through inhibition of albumin denaturation. RESULTS: Phytochemical analysis revealed the presence of alkaloids, tannins, saponins, flavonoids, and phenols in T. terrestris seed extract. The extract demonstrated concentration-dependent cytotoxicity against oral cancer cells, with 100 µg/mL showing significant growth inhibition. Pro-apoptotic effects were observed, with characteristic morphological changes in cancer cells treated with the extract. Antioxidant activity was demonstrated by the extract, with methanol fraction of a flower (MFF) exhibiting the highest capacity, followed by total trichome fraction (TTF), and a positive correlation between phenolic content and free radical scavenging effectiveness was noted. Antimicrobial activity against various pathogens, including bacteria and fungi, was also observed, with higher concentrations showing increased efficacy. CONCLUSION: The study concludes that methanolic extracts of T. terrestris possess significant anticancer, antioxidant, anti-inflammatory, and antimicrobial activities. These findings highlight the potential of T. terrestris as a candidate for further research and clinical applications, either alone or in combination with other agents, for the treatment of oral cancer and associated conditions.

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As screening strategies employ better biomarkers and genetics to identify individuals at an increased risk of prostate cancer, there are currently no chemotherapeutic prevention strategies. With any chemoprevention strategy, the population will be younger and healthier; therefore, they will be less tolerant of side effects. This study translated findings from screening a natural product library and pre-clinical evaluation of curcumin (CURC) in combination with ursolic acid (UA) in prostate cancer models. After manufacturing capsules for each compound, 18 subjects were enrolled. The study used a 3 × 3 phase 1 clinical trial to evaluate CURC (1200 mg/day) and UA (300 mg/day) alone and in combination over a 2-week period with endpoints of safety, bioavailability, and microbiome alterations. After enrolling six subjects in each arm, we found no grade 3 or 4 events and only minor changes in the safety laboratory values. In the pooled analysis of groups, we noted a statistically significant difference between median serum levels of UA when administered alone vs administered in the combination (2.7 ng/mL vs 43.8 ng/mL, p = 0.03). Individuals receiving the combination also had a favorable impact on gut microbiome status and a reduction in "microbiome score" predictive of prostate cancer risk.

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Tragopogon dubius is commonly consumed as a vegetable and used in traditional medicine for treating inflammatory skin conditions and cutaneous swelling. Despite known pharmacological properties of its leaves and roots, many of its biological characteristics and active phytochemicals remain unexplored. The present study investigates the phytochemical composition, antioxidant, and anticancer properties of methanolic root extracts and isolated fractions (TdRM-1 and TdRM-2) of T. dubius. Utilizing preparative thin-layer chromatography, the crude extract was successfully separated into TdRM-1 and TdRM-2, characterized by GC-MS and FTIR analysis, revealing a diverse range of bioactive compounds including terpenes, flavonoids, and phenolic acids. Qualitative phytochemical screening indicated the presence of carbohydrates, tannins, alkaloids, and other phytoconstituents. Advanced UPLC-ESI-QTOF-MS analysis identified 54 metabolites, significantly contributing to the chemical profiling of the extract. The antioxidant activities of the fractions were quantitatively assessed using ABTS, DPPH, and superoxide radical scavenging assays, where TdRM-2 exhibited superior activity with IC50 values ranging from 51.29 to 60.03 µg/mL. Anticancer potential was evaluated against A549, LN-18, and MCF-7 cancer cell lines, demonstrating that TdRM-2 significantly inhibited cell proliferation with GI50 values as low as 31.62 µg/mL for A549 cells. Additionally, fluorescence microscopy revealed that TdRM-2 induces apoptosis, indicated by changes in nuclear morphology and loss of mitochondrial membrane potential. Annexin V-FITC/PI double staining indicate that the TdRM-2 fractions from T. dubius can significantly inhibit the growth of A-549, LN-18, and MCF-7 cancer cell lines by inducing apoptosis These findings suggest that T. dubius root extracts, particularly the TdRM-2 fraction, hold promising therapeutic potential due to their significant antioxidant and anticancer activities, underpinned by their rich phytochemical composition. This study underscores the importance of T. dubius as a source of natural bioactive compounds with potential health benefits.

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BACKGROUND: Due to the complex pathophysiological mechanisms involved in cancer progression and metastasis, current therapeutic approaches lack efficacy and have significant adverse effects. Therefore, it is essential to establish novel strategies for combating cancer. Phytochemicals, which possess multiple biological activities, such as antioxidant, anti-inflammatory, antimutagenic, immunomodulatory, antiproliferative, anti-angiogenesis, and antimetastatic properties, can regulate cancer progression and interfere in various stages of cancer development by suppressing various signaling pathways. METHODS: The current systematic and comprehensive review was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) criteria, using electronic databases, including PubMed, Scopus, and Science Direct, until the end of December 2023. After excluding unrelated articles, 111 related articles were included in this systematic review. RESULTS: In this current review, the major signaling pathways of cancer metabolism are highlighted with the promising anticancer role of phytochemicals. This was through their ability to regulate the AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) signaling pathway. The AMPK/PGC-1α signaling pathway plays a crucial role in cancer cell metabolism via targeting energy homeostasis and mitochondria biogenesis, glucose oxidation, and fatty acid oxidation, thereby generating ATP for cell growth. As a result, targeting this signaling pathway may represent a novel approach to cancer treatment. Accordingly, alkaloids, phenolic compounds, terpene/terpenoids, and miscellaneous phytochemicals have been introduced as promising anticancer agents by regulating the AMPK/PGC-1α signaling pathway. Novel delivery systems of phytochemicals targeting the AMPK/PGC-1α pathway in combating cancer are also highlighted in this review.

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