Search Results (82)

Background: Pancreatic lipase (PL), the principal enzyme catalyzing the hydrolysis of dietary triacylglycerols in the intestinal lumen, is pivotal for efficient lipid absorption and plays a central role in metabolic homeostasis. Enhanced PL activity promotes excessive lipid assimilation and contributes to positive energy balance, key pathophysiological mechanisms underlying the escalating global prevalence of obesity—a complex, multifactorial condition strongly associated with metabolic disorders, including type 2 diabetes mellitus and cardiovascular disease. Inhibition of pancreatic lipase (PL) constitutes a well-established therapeutic approach for attenuating dietary lipid absorption and mitigating obesity. Methods: With the aim to identify putative PL inhibitors, a Structure-Based Virtual Screening (SBVS) of PhytoHub database naturally occurring derivatives was performed. A refined library of 10,404 phytochemicals was virtually screened against a crystal structure of pancreatic lipase. Candidates were filtered out based on binding affinity, Lipinski’s Rule of Five, and structural clustering, resulting in six lead compounds. Results: In vitro, enzymatic assays confirmed theoretical suggestions, highlighting Pinoresinol as the best PL inhibitor. Molecular dynamics simulations, performed to investigate the stability of protein–ligand complexes, revealed key interactions, such as persistent hydrogen bonding to catalytic residues. Conclusions: This integrative computational–experimental workflow highlighted new promising natural PL inhibitors, laying the foundation for future development of safe, plant-derived anti-obesity therapeutics. Full article

Background: Magnolia alejandrae is a tree endemic to Tamaulipas, Mexico, distributed in the forests of the Sierra Madre Oriental. Objective: Our objective was to analyze the secondary metabolite profile of different parts of M. alejandrae and evaluate their antiproliferative activity in vitro. Methods: Different extracts of leaf, bark, and fruit were obtained using conventional and unconventional extraction methods with solvents of different polarity. The extracts were analyzed by Ultra-Performance Liquid Chromatography-Mass Spectra (UPLC-MS), and their antiproliferative activity against cancer cell lines was determined. Results: The primary yields of the extracts obtained from M. alejandrae ranged from 8.32% to 36.19%. Three hundred and twelve secondary metabolites previously reported from the Magnolia genus were detected. The most frequent were magnone A, pinoresinol, and yangambin. Honokiol and magnolol were not detected. Two of the extracts (FSW and BSW) had antiproliferative activity (IC₅₀ < 140 µg/mL) against HeLa, MCF-7, A549, U373, and PC3 cancer cell lines. The higher activity was against the A549 cell line. Conclusions: M. alejandre extracts showed secondary metabolites previously reported and unreported in other species. Interestingly, some extracts had antiproliferative activity against cancer cell lines. Therefore, M. alejandrae is a source of molecules that could be explored to develop new drugs. Full article

Breast cancer (BC) is the most common malignancy and the second-leading cause of cancer-related mortalities in women. Epidemiological studies suggested the reduced BC incidence in Mediterranean populations due to the daily consumption of diets rich in extra-virgin olive oil (EVOO). EVOO secoiridoid phenolics are widely known for their positive outcomes on multiple cancers, including BC. The current study investigates the suppressive effects of individual and combined EVOO phenolics for BC progression and motility. Screening of a small library of EVOO phenolics at a single dose of 10 µM against the viability of the BC cell lines ZR-75-1 (luminal A) and MDA-MB-231 (triple negative BC, TNBC) identified oleocanthal (OC) and ligstroside aglycone (LA) as the most active hits. Screening of EVOO phenolics for BC cells migration inhibition identified OC, LA, and the EVOO lignans acetoxypinoresinol and pinoresinol as the most active hits. Combination studies of different olive phenolics showed that OC combined with LA had the best synergistic inhibitory effects against the TNBC MDA-MB-231 cells migration. A combination of 5 µM of each of OC and LA potently suppressed the migration and invasion of the MDA-MB-231 cells versus LA and OC individual therapies and vehicle control (VC). Animal studies using the ZR-75-1 BC cells orthotopic xenografting model in female nude mice showed significant tumor progression suppression by the combined OC-LA, 5 mg/kg each, ip, 3X/week treatments compared to individual LA and OC treatments and VC. The BC suppressive effects of the OC-LA combination were associated with the modulation of SMYD2–EZH2–STAT3 signaling pathway. A metastasis–clonogenicity animal study model using female nude mice subjected to tail vein injection of MDA-MB-231-Luc TNBC cells also revealed the effective synergy of the combined OC-LA, 5 mg/kg each, compared to their individual therapies and VC. Thus, EVOO cultivars rich in OC with optimal LA content can be useful nutraceuticals for invasive hormone-dependent BC and TNBC progression and metastasis. Full article

Storage conditions significantly impact the quality and functional properties of extra-virgin olive oil (EVOO). This study investigated the impact of light and dark storage on the nutritional quality of Umbrian EVOO and its effectiveness in tissue repair. The research aimed to simulate real-world conditions occurring during transport, retail, and domestic storage. Light exposure accelerated EVOO oxidation, significantly affecting peroxide levels (ranging from 5.19 to 24.30 meq O₂/kg of oil), total antioxidant capacity (measured spectrophotometrically, collectively ranging from 399.47 to 684.63 mg TE/kg of oil), and phenolic compound concentrations, particularly secoiridoids, lignans, and flavonoids (measured by HPLC, collectively ranging from 41.92 to 169.74 mg/kg of oil). Statistically significant differences (p < 0.01) were recorded between the control sample and the others in almost all cases, after storage. For instance, both light and dark exposure over a 24-month period resulted in a marked reduction (p < 0.01) in oleocanthal, pinoresinol, luteolin, and apigenin. Pigment levels were also affected, representing a rapid and cost-effective indicator of product oxidative degradation. The loss of phenolic compounds (especially oleacein and oleocanthal, which showed the most significant reductions of approximately 75% and 60%, respectively), impaired the EVOO’s wound-healing properties, affecting key tissue regeneration processes such as keratinocyte migration, hyaluronic acid synthesis, and angiogenesis. Notably, oleocanthal and oleacein, present at higher concentrations in fresh extracts, emerged as the primary contributors to the observed dermal effects and wound-healing processes, demonstrating a significant highest efficacy (p < 0.0001) in promoting wound closure. These findings underscore the critical role of EVOO storage in preserving its sensory properties and labile components with tissue repair and regeneration functions. Full article

Near-infrared (NIR) spectroscopy, combined with multivariate calibration techniques such as stepwise decorrelation of variables (SELECT) and ordinary least squares (OLS) regression, was used to develop robust, reduced-spectrum regression models for quantifying key phenolic compound markers in various olive oils. These oils included nine extra virgin olive oil (EVOO) varieties, refined olive oil (ROO) blended with virgin olive oil (VOO) or EVOO, and pomace olive oil, both with and without hydroxytyrosol (HTyr) supplementation. Olive oils were analyzed before and after deep frying. The results show that HTyr ranged from 7.28 mg/kg in Manzanilla (lowest) to 21.43 mg/kg in Royuela (highest). Tyrosol (Tyr) varied from 5.87 mg/kg in Royuela (lowest) to 14.86 mg/kg in Hojiblanca (highest). Similar trends were observed in all phenolic fractions across olive oil cultivars before and after deep-frying. HTyr supplementation significantly increased both HTyr and Tyr levels in non-fried and fried supplemented oils, with HTyr rising from single digits in some controls (around 0 mg/kg) to over 300 mg/kg in most of the supplemented samples. SELECT efficiently reduced redundancy by selecting the most vital wavelengths and thus significantly improved the regression models for key phenolic compounds, including HTyr, Tyr, caffeic acid, decarboxymethyl ligstroside aglycone in dialdehyde form (oleocanthal), decarboxymethyl oleuropein aglycone in dialdehyde form (oleacein), homovanillic acid, pinoresinol, oleuropein aglycone in oxidized aldehyde and hydroxylic form (OAOAH), ligstroside aglycone in oxidized aldehyde and hydroxylic form (LAOAH), and total phenolic content (TPC), achieving correlation coefficients (R) of 0.91–0.98. The SELECT-OLS method generated highly predictive models with minimal complexity, using at most 30 wavelengths out of 700. The number of decorrelated predictors varied, at 12, 14, 15, 30, 30, 21, 30, 30, 30, and 18 for HTyr, Tyr, caffeic acid, oleocanthal, oleacein, homovanillic acid, pinoresinol, OAOAH, LAOAH, and TPC, respectively, demonstrating the adaptability of the SELECT-OLS approach to different spectral patterns. These reliable calibration models enabled online and routine quantification of phenolic compounds in EVOO, VOO, ROO, including both non-fried and fried as well as supplemented and non-supplemented samples. They performed well across eight deep-frying conditions (3–6 h at 170–210 °C). Implementing an NIR instrument with optimized variable selection would simplify spectral analysis and reduce costs. The developed models all demonstrated strong predictive performance, with low leave-one-out mean prediction errors (LOOMPEs) with values of 15.69, 8.47, 3.64, 9.18, 16.71, 3.26, 8.57, 13.56, 56.36, and 82.38 mg/kg for HTyr, Tyr, caffeic acid, oleocanthal, oleacein, homovanillic acid, pinoresinol, OAOAH, LAOAH, and TPC, respectively. These results confirm that NIR spectroscopy combined with SELECT-OLS is a feasible, rapid, non-destructive, and eco-friendly tool for the reliable evaluation and quantification of phenolic content in edible oils. Full article

Valerian root extracts are widely used as mild sedatives to promote sleep, with clinical studies confirming their efficacy. Their sleep-promoting effects are associated with the adenosine A1 receptor (A1AR), a key regulator of sleep through neural activity inhibition. Adenosine, a neuromodulator that accumulates during wakefulness, activates A1ARs to facilitate sleep transitions. Using advanced analytics, we detected adenosine at 0.05% in the valerian extract Ze 911, supporting direct A1AR activation in vitro. Additionally, we explored A1ARs’ allosteric sites for modulatory activity. Valerenic acid and pinoresinol, key constituents of Ze 911, were identified as positive allosteric modulators (PAMs) of A1ARs. Valerenic acid exhibited strong PAM activity, with high cooperativity (αβ = 4.79 for adenosine and αβ = 23.38 for CPA) and intrinsic efficacy (τB = 5.98 for adenosine and τB = 3.14 for CPA). Pinoresinol displayed weaker PAM activity, with moderate cooperativity (αβ = 3.42 for adenosine and αβ = 0.79 for CPA) and limited efficacy (τB = 0.93 for adenosine and τB = 1.66 for CPA). The allosteric modulation observed in valerian extract Ze 911 suggests a mechanism of action in which valerenic acid and pinoresinol enhance receptor activation through allosteric interactions, potentially amplifying the effects of endogenous adenosine. By targeting A1ARs’ allosteric sites, valerian extract Ze 911 offers increased therapeutic selectivity and reduced off-target effects, emphasizing its potential for managing sleep disorders. Full article

Background: Renal fibrosis is a common pathological feature of all progressive chronic kidney disease (CKD). Eucommiae cortex (EC) is a valuable economic tree species endemic to China. The microbial fermentation of Chinese medicines can release their active ingredients as effectively as possible or produce new active ingredients with enhanced efficacy and reduced toxic side effects; Methods: The microbial fermentation of EC can produce pinoresinol (Pin) and dehydrodiconiferyl alcohol (DA). In this study, C57 BL/6 mice were fed a diet containing 0.2% adenine, resulting in a model of chronic kidney disease. The effects of EC and EC ferment (ECF) on CKD were explored by the exogenous supplementation of EC and ECF; Results: The results of the study showed that exogenous supplementation with EC and ECF suc-cessfully reduced creatinine and urea nitrogen levels, down-regulated the expression levels of TGF-β1, α-SMA, Smad3, and phospho-Smad3 in the TGF-β1/Smad signaling pathway, and ameliorated renal fibrosis; Conclusions: Both EC and ECF may have reno-protective effects and provide a reference for relevant clinical drug development. Full article

Chemical investigation on the whole herb of Peperomia heyneana Miq. resulted in the isolation of six lignans, including two previously undescribed compounds, named peperomianan A and B (1–2), and four known compounds, 1,2-cyclobutanedicarboxylic acid (3), (+)-medioresinol (4), (+)-pinoresinol (5), and (+)-yangambin (6). Their structures were established by extensive spectroscopic analyses. The absolute configuration of compound 1 was determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Subsequently, the effects of all isolates on BPH-1 cells were evaluated in vitro by MTT assay. Full article

This study examines the chemical composition and antioxidant properties of iron walnut oil (IWO) from different Chinese regions, using ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry for the analysis of phenolic compounds. Regional variations were identified in fatty acid profiles, with elevated α-linolenic acid levels observed in samples from cooler climates (e.g., Liaoning, sample 1) that were 60% higher than in samples from warmer regions (e.g., Sichuan, sample 2). Antioxidant properties, quantified using 1,1-diphenylpicryl phenyl hydrazine (DPPH), 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonate (ABTS), and Ferric ion reducing antioxidant power (FRAP) assays, corresponded to both oil polyphenol content (up to 62.91 mg/kg) and γ-tocopherol concentrations (268.68–525.05 mg/kg). Nineteen phenolic acids and flavonoids were identified, including ellagic acid, gallic acid, p-hydroxybenzoic acid, syringic acid, vanillic acid, quercetin, caffeic acid, ferulic acid, p-coumaric acid, coniferol, and pinoresinol. This comprehensive analysis underscores the nutritional and therapeutic potential of IWO, and delineates the impact of geographic and environmental factors on its quality, providing a scientific foundation for further research and development aimed at enhancing food industry standards and exploring natural product chemistry. Full article

Ischemic stroke ranks as the second leading cause of global mortality. The limited time for effective thrombolytic treatment has prompted the exploration of alternative prevention approaches. Eucommia ulmoides (E. ulmoides) Oliv. bark has shown multiple pharmacological effects, including neuroprotection, anti-inflammation and autophagy modulation. This study aims to elucidate the neuroprotective effects of water extract of E. ulmoides (WEU) supplementation in a middle cerebral artery occlusion (MCAO) mouse model and to further explore the underlying molecular mechanisms. Seven bioactive compounds in WEU—aucubin, chlorogenic acid, geniposidic acid, quercetin, protocatechuic acid, betulin and pinoresinol diglucoside—were identified using HPLC-MS. Our results showed that WEU supplementation significantly decreased infarct volume and ameliorated neurological dysfunction in mice following MCAO/reperfusion (MCAO/R) injury. Furthermore, the administration of WEU significantly attenuated microglia activation induced by cortical ischemia in mice and inhibited the production of pro-inflammatory mediators, including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Importantly, in contrast with the vehicle group, the protein expression levels of Toll-like receptor 4 (TLR4), phospho-p38 (p-p38) and nuclear factor kappa B (NF-κB) were reduced in the WEU group. Therefore, this present study provides evidence that E. ulmoides improves neurological behaviors by suppressing neuroinflammation and inhibiting the activation of the TLR4/ p38 MAPK and NF-κB pathways in mice after ischemia, which indicates that E.ulmoides is a promising candidate for alleviating gray matter ischemic change. Full article

This study explores approaches to enhancing the biostability of extra virgin olive oil (EVOO) supplemented with olive fruit extract (OFE) enriched with hydroxytyrosol (HTyr). The investigation focuses on prolonged deep frying (DF) conditions at 170 °C and 210 °C, over durations ranging from 3 to 48 h, with the aim of improving sensorial attributes, polyphenolic content, and thermal oxidative stability. Parameters, such as acidity, peroxide value (PV), K₂₃₂, K₂₇₀, ΔK, phenolic compounds, and sensory attributes, were monitored. The PV did not exceed the standard limit in HTyr-EVOO at 210 °C/24 h; however, in non-supplemented EVOOs, it remained within the limits only up to 210 °C/18 h. Acidity stayed within the acceptable limit (≤0.8) at 170 °C/24 h in both enriched and non-enriched EVOOs. K₂₃₂ values were ≤2.5 in HTyr-EVOO fried at 170 °C/18 h. K₂₇₀ and ΔK did not exceed the limits in HTyr-EVOO at 170 °C/3 h, whereas they surpassed them in non-supplemented oils. Additionally, HTyr and tyrosol levels were significantly higher (p < 0.05) in HTyr-EVOOs. Phenolic compounds, including verbascoside, pinoresinol, 1-acetoxypinoresinol, and phenolic acids, such as chlorogenic, vanillic, homovanillic, 4-dihydroxybenzoic, and caffeic acids, were detected in HTyr-EVOOs. Oxidized secoiridoid derivatives increased significantly as DF progressed. Moreover, sensory analysis revealed that positive attributes in EVOOs—such as fruity, bitter, and pungent notes—decreased significantly with increasing temperature and frying duration (p < 0.05). Beyond 210 °C/6 h, these attributes were rated at zero. However, HTyr-EVOOs exhibited lower rancidity compared to non-enriched oils under identical conditions, attributed to the protective effect of HTyr. In conclusion, HTyr-EVOOs demonstrated thermal stability up to 210 °C/6 h, retaining desirable sensory qualities, higher phenolic content, and reduced degradation. These findings indicate that natural OFEs have strong potential as food additive in deep fried EVOOs, enhancing sensory properties, health benefits, and overall oil stability. This innovation provides a practical solution for the food industry by improving the biostability and versatility of EVOO. Further research is recommended to investigate various EVOO categories and oils from diverse origins. Full article

Type 2 diabetes mellitus (T2DM), a serious metabolic disorder, is a worldwide health problem due to the alarming rise in prevalence and elevated morbidity and mortality. Chronic hyperglycemia, insulin resistance, and ineffective insulin effect and secretion are hallmarks of T2DM, leading to many serious secondary complications. These include, in particular, cardiovascular disorders, diabetic neuropathy, nephropathy and retinopathy, diabetic foot, osteoporosis, liver damage, susceptibility to infections and some cancers. Polyphenols such as flavonoids, phenolic acids, stilbenes, tannins, and lignans constitute an extensive and heterogeneous group of phytochemicals in fresh fruits, vegetables and their products. Various in vitro studies, animal model studies and available clinical trials revealed that flavonoids (e.g., quercetin, kaempferol, rutin, epicatechin, genistein, daidzein, anthocyanins), phenolic acids (e.g., chlorogenic, caffeic, ellagic, gallic acids, curcumin), stilbenes (e.g., resveratrol), tannins (e.g., procyanidin B2, seaweed phlorotannins), lignans (e.g., pinoresinol) have the ability to lower hyperglycemia, enhance insulin sensitivity and improve insulin secretion, scavenge reactive oxygen species, reduce chronic inflammation, modulate gut microbiota, and alleviate secondary complications of T2DM. The interaction between polyphenols and conventional antidiabetic drugs offers a promising strategy in the management and treatment of T2DM, especially in advanced disease stages. Synergistic effects of polyphenols with antidiabetic drugs have been documented, but also antagonistic interactions that may impair drug efficacy. Therefore, additional research is required to clarify mutual interactions in order to use the knowledge in clinical applications. Nevertheless, dietary polyphenols can be successfully applied as part of supportive treatment for T2DM, as they reduce both obvious clinical symptoms and secondary complications. Full article

Phytochemical investigation of Staehelina uniflosculosa Sibth. & Sm. resulted in the isolation of twenty-two natural products: eleven sesquiterpene lactones, artemorin (1), tamirin (2), tanachin (3), reynosin (4), baynol C (5), desacetyl-β-cyclopyrethrosin (6), 1β-hydroxy-4α-methoxy-5α,7α,6β-eudesm-11(13)-en-6,12-olide (7), 1β,4α,6α-trihydroxyeudesm-11-en-8α,12-olide (8), 1β-hydroxy-arbusculin A (9), methyl-1β,4α,6α-trihydroxy-5α,7αH-eudesm-11(13)-en-12-oate (10) and methyl-1β,6α,8α-trihydroxy-5α,7αH-eudesma-4(15),11(13)-dien-12-oate (11); one lignan, pinoresinol (12); one norisoprenoid, loliolide (13); six flavonoids (four genins and two glycosides), hispidulin (14), nepetin (15), jaceosidin (16), eriodictyol (17), eriodictyol-3′-O-β-D-glucoside (18) and eriodictyol-7-O-β-D-glucuronide (19); and three phenolic derivatives (one phenolic acid and two phenolic glucosides), protocatechuic acid (20), arbutin (21) and nebrodenside A (22). From the isolated compounds, only nepetin (15) has been reported previously from the Staehelina genus and, to the best of our knowledge, it is the first time that compound (18) has been identified in Asteraceae. A number of these substances were tested for (a) inhibition of lipoxygenase and acetylocholinesterase, (b) their antioxidant activity using the DPPH (1,1-Diphenyl-2-picrylhydrazyl) method or/and (c) inhibition of lipid peroxidation. The tested components exhibited low antioxidant activity with the exception of 5 and 22, while the effectiveness of these compounds in the inhibition of acetylocholinesterase is limited. Furthermore, Molinspiration, an online computer tool, was used to determine the bioactivity ratings of the isolated secondary metabolites. The compounds’ bioactivity ratings for potential therapeutic targets were very promising. Full article

Eucommiae Cortex (EC) is frequently used alone or in combination with other active ingredients to treat a range of illnesses. An efficient technical instrument for changing cheap or plentiful organic chemicals into rare or costly counterparts is biotransformation. It combines EC with biotransformation techniques with the aim of producing some novel active ingredients, using different strains of bacteria that were introduced to biotransform EC in an aseptic environment. The high-quality strains were screened for identification after the fermentation broth was found using HPLC, and the primary unidentified chemicals were separated and purified in order to be structurally identified. Strain 1 was identified as Aspergillus niger and strain 2 as Actinomucor elegans; the main transformation product A was identified as pinoresinol (Pin) and B as dehydrodiconiferyl alcohol (DA). The biotransformation of EC utilizing Aspergillus niger and Actinomucor elegans is reported for the first time in this study’s conclusion, resulting in the production of Pin and DA. Full article