Search Results (238)

Background/Objectives: Ginger (Zingiber officinale Roscoe) is a flowering plant widely used as a spice and natural medicine for millennia. Ginger demonstrates multiple protective effects, regulates cholesterol, and may reduce the risk of cancer and colitis. However, little attention has been paid to its potential to cause herb–drug interactions (HDIs). The aim of this study was to investigate the interaction of ginger extract and its major components [⁶]-gingerol and [⁶]-shogaol with clinically relevant uptake and efflux transporters in vitro. Methods: Transporter-overexpressing cell lines of 25 uptake transporters and inside-out membrane vesicles containing 8 efflux transporters were employed to measure potential interactions. Results: Zingiber officinale extract at 150 µg/mL interacted with 17 of 33 transporters examined. These were further investigated for interactions with the purified active components. Seven and 16 transporters interacted with pure [⁶]-gingerol (100 µM) and [⁶]-shogaol (100 µM), respectively. To evaluate the risk of in vivo inhibition, IC₅₀ values were determined for the affected transporters. Based on standard risk assessment calculations, we confirmed previously reported inhibitory effects of ginger components on MDR1 (67.64 µM) and BCRP (9.931 µM), and revealed novel potential interactions with renal OAT3 (0.956 µM) and URAT1 (5.887 µM), hepatic OCT1 (4.287 µM) and BSEP (25.45 µM), and the ubiquitously expressed ENT1 (11.62 µM) ([⁶]-shogaol IC₅₀ values are shown in parentheses). Strong and isoform-selective inhibition of OAT3 by [⁶]-shogaol is particularly intriguing. Additionally, via cell viability experiments on a set of human cervical, breast, and oropharyngeal cancer cell lines, we demonstrated the antiproliferative effect of [⁶]-shogaol in vitro. Conclusions: Prolonged consumption of high-dose ginger supplements may pose a risk of transporter-mediated HDIs when consumed concomitantly with conventional medications. Our study encourages follow-up of the suspected effects in vivo. Full article

Background/Objectives: Flavonoids are widely used as lead structures in drug discovery, and their pharmacological and metabolic properties are strongly influenced by structural features such as positional isomerism. This study aimed to compare the metabolic profiles and underlying mechanisms of two isoflavone-based positional isomers, ACF-02 (2-(4-hydroxy-3-methoxyphenyl)-6,7-dimethoxy-3-(4-methoxyphenyl)-4H-chromen-4-one) and ACF-03 (2-(3-hydroxy-4-methoxyphenyl)-6,7-dimethoxy-3-(4-methoxyphenyl)-4H-chromen-4-one). Methods: The metabolic pathways of synthetically prepared ACF-02 and ACF-03 were investigated using an in vitro incubation system with human liver microsomes (HLMs) supplemented with an NADPH-regenerating system, followed by liquid chromatography–high-resolution tandem mass spectrometry (LC–HRMS/MS) analysis. Metabolites were identified based on LC–HRMS/MS data and molecular networking-based node connectivity with the parent compounds. Major metabolites were further characterized by CYP phenotyping using recombinant CYP450 isoforms, and the potential for drug–drug interactions of ACF-03 was evaluated using a CYP probe substrate cocktail approach. Results: HLM incubation of ACF-02 and ACF-03 produced both hydroxylated and O-demethylated metabolites, with O-demethylation as the predominant pathway; notably, the most abundant O-demethylated metabolite differed in an isomer-dependent manner, occurring at the B₂ ring for ACF-02 and at the A ring for ACF-03, with distinct CYP isoform involvement. Molecular networking supported the relationships between the parent compounds and their metabolites, and both compounds exhibited relatively high metabolic stability with limited CYP inhibition. Conclusions: Despite differing only in the position of a single methyl substituent, ACF-02 and ACF-03 exhibited distinct isomer-dependent metabolic profiles. These findings demonstrate that even subtle positional isomerism can significantly influence metabolic behavior and should be carefully considered during lead optimization and drug design. Full article

Zebrafish is emerging as a model animal for phenotype-based drug screening. Drugs screened from the zebrafish platform have advanced into clinical trials, underscoring their translational potential. Amyotrophic lateral sclerosis is a progressive motor neurons (MN) degenerative disease with few approved drugs. Previously, supplementation with exogenous recombinant phosphoglycerate kinase 1 (Pgk1) was found to improve MN growth through its interaction with receptor Eno2. To bypass the high complexity and cost of full-length Pgk1 production, a short segment within Pgk1 (M08) was predicted as the key motif interacting with Eno2, and a zebrafish phenotypic screening platform was established to find the most neurotrophic compound(s) among M08 and its mutants. We first found that M08-injected zebrafish embryos significantly increased branched caudal primary MNs (CaPMNs). However, compared to M08 (59.20 ± 1.80%), M039, among 17 mutants further screened, showed even more improvement of branched CaPMNs, up to 74.54 ± 3.73%. Next, when we administered the M039 peptide to C9ORF72-knockdown ALS-like zebrafish embryos, it improved axonal growth and swimming ability. Then, we employed a cellular model as a secondary screen, and M039 exhibited improved neurite outgrowth of MN (NOMN) and reduced p-Cofilin in NSC34 neural cells grown in ALS-like condition. Therefore, by using a zebrafish MN phenotype as a primary screening platform, we identified a mutated short peptide M039 having the most pronounced positive effect on improving neurite growth among all 17 mutants in comparison to parental M08, demonstrating the feasibility of zebrafish screening as a cost-effective strategy for finding promising neuroprotective short peptides that serve as neurotherapeutic potentials. Full article

Background: The role of digoxin in atrial fibrillation, particularly in patients with heart failure, has long been debated. Observational studies reporting higher mortality have fueled skepticism, yet growing evidence suggests that these findings largely reflect prescription bias, confounding by indication, and inadequate adjustment for serum-level rather than intrinsic toxicity. Objective: To reassess digoxin’s role in atrial fibrillation with heart failure using contemporary evidence and to propose a physiology-based, personalized monitoring framework. Evidence review: We reevaluated the studies that initially linked digoxin to excess mortality and reassessed these associations through three analytic pillars: randomized evidence, bias deconstruction, and exposure–response relationships. Across datasets, low serum digoxin concentrations were consistently associated with stable resting rate control without increasing mortality. Key findings: Low-dose, continuously administered digoxin is a viable second-line option for atrial fibrillation rate control in patients who are hypotensive or intolerant of β-blockers. Safety is concentration-dependent; adverse outcomes increase at higher serum digoxin concentration (≥1.2 ng/mL). Resting heart rate can serve as a contextual surrogate of exposure: persistent HR > 100 bpm in stable patients usually reflects underexposure rather than digoxin toxicity, whereas bradycardia should prompt immediate serum digoxin concentration testing. Proposal: A probability-based monitoring model that integrates heart rate, renal function, dosage, electrolytes, and drug–drug interactions to guide when serum digoxin concentration measurement is warranted. As a future direction, a supervised “pill-in-the-pocket” supplemental dose strategy could be evaluated for transient tachycardia in selected, stable patients. Conclusions: When properly dosed and contextually monitored, digoxin remains a safe, effective, and individualized rate-control option in atrial fibrillation with heart failure. Prospective validation of probability-guided monitoring and evaluation of a “pill-in-the-pocket” approach could simplify digoxin management while maintaining safety. Full article

Personalizing therapy using medical marijuana (MM) is based on understanding the pharmacogenomics (PGx) and drug–drug interactions (DDIs) involved, as well as identifying potential epigenetic risk markers. In this work, the evidence regarding the role of variants in phase I (CYP2C9, CYP2C19, CYP3A4/5) and II (UGT1A9/UGT2B7) genes, transporters (ABCB1), and selected neurobiological factors (AKT1/COMT) in differentiating responses to Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD) has been reviewed. Data indicating enzyme inhibition by CBD and the possibility of phenoconversion were also considered, which highlights the importance of a dynamic interpretation of PGx in the context of current pharmacotherapy. Simultaneously, the results of epigenetic studies (DNA methylation, histone modifications, and ncRNA) in various tissues and developmental windows were summarized, including the reversibility of some signatures in sperm after a period of abstinence and the persistence of imprints in blood. Based on this, practical frameworks for personalization are proposed: the integration of PGx testing, DDI monitoring, and phenotype correction into clinical decision support systems (CDS), supplemented by cautious dose titration and safety monitoring. The culmination is a proposal of tables and diagrams that organize the most important PGx–DDI–epigenetics relationships and facilitate the elimination of content repetition in the text. The paper identifies areas of implementation maturity (e.g., CYP2C9/THC, CBD-CYP2C19/clobazam, AKT1, and acute psychotomimetic effects) and those requiring replication (e.g., multigenic analgesic signals), indicating directions for future research. Full article

Background: Individualized care in veterinary practice optimizes pharmaceutical dose regimens, facilitates disease prevention, and supports animal health by considering the animal’s individual profile. Three-dimensional (3D) printing is a suitable technology for manufacturing both tailored drugs and supplements with enhanced efficacy and reduced adverse reactions. Zinc is used to correct deficiencies, support growth, boost the immune system, and treat specific conditions like zinc-responsive dermatosis in dogs. The purpose of the study was to develop and analyze tailored zinc-loaded filaments for the design of custom-made 3D-printed shapes. Methods: Zinc oxide (ZnO) and artificial beef flavor were incorporated into hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC), respectively, to produce tailored 5% or 10% ZnO-containing filaments for 3D printing. The obtained filaments and 3D-printed forms were characterized using sieve analysis, moisture determination, melting point, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction analysis. Results: The characterization of two placebo and four custom-made 3D-printed ZnO supplements suggested that HPMC is a polymer with poor processability, whereas HPC is suitable for incorporating artificial beef flavor and ZnO. FTIR analysis indicated no interaction between the components. Conclusion: The HPC and 10% flavor mixture can be applied as a matrix for manufacturing 3D-printed forms with ZnO for individualized animal care. Full article

(1) Background: How to reduce respiratory diseases in animals is a matter of great concern, and this study aimed to investigate the effect of maternal administration with all-trans retinoic acid (ATRA) on the lung health of neonatal pigs. (2) Methods: Fifteen sows were randomly allotted to one of five ATRA groups (0, 4, 8, 16, and 32 mg/kg diet), respectively; on average, from days 12 to 95 after insemination, lung samples of neonatal pigs were harvested for HE staining, 16S DNA sequencing, and transcriptomic analysis. (3) Results: Compared to neonatal pigs from the ATRA0 group, neonatal pigs from the ATRA4 group had an increased (p > 0.05) alveolar number and the thinner (p < 0.05) alveolar septum, higher (p < 0.05) abundance of Akkermansia and unidentified_Mitochondria, and a lower (p < 0.05) abundance of Acinetobacter, Cutibacterium, Stenotrophomonas, Enterobacter, Saccharomonospora, and Alistipes in the lungs. Maternal supplementation of ATRA at 4 mg/kg diet had the benefits of reducing pathogen virulence and drug resistance, but it poses the risk of increasing the resistance to β-lactam antibiotics. In addition, it reduced (p < 0.05) the virulence, drug resistance, and stress tolerant capacity of potential pathogens (Proteobacteria, Acinetobacter, Cupriavidus, and Pseudomonas), enriched the highest number of genes in neuroactive ligand–receptor interaction pathway, and decreased gene expression of CCL11 and IL9 in the asthma pathway. (4) Conclusions: Maternal supplementation of ATRA at 4 mg/kg diet can strengthen the lung health of neonatal pigs by improving alveolar development, decreasing the number and virulence of pathogens, and down-regulating the expression of asthma-related genes. Full article

Background: Unfractionated heparin (UFH) is the standard anticoagulant during cardiopulmonary bypass (CPB). A clinically relevant subset develops heparin resistance (HR)—failure to reach adequate anticoagulation with usual UFH—raising thrombotic risk and complicating perioperative care. Objectives: To synthesize contemporary evidence on the mechanisms, clinical implications, and perioperative management of HR in adult cardiac surgery with CPB. Methods: This narrative review synthesizes contemporary evidence on the epidemiology, mechanisms, recognition, and management of HR in adult cardiac surgery with CPB, emphasizing clinically actionable points. Results: Incidence varies across centers and definitions. Mechanisms include antithrombin (AT) deficiency or consumption and AT-independent drivers such as systemic inflammation or sepsis, protein-loss states, thrombocytosis, hyperfibrinogenemia, obesity, prior heparin exposure, and drug interactions. Sole reliance on activated clotting time (ACT) may misestimate anticoagulant effect; anti–factor Xa (anti-Xa) assays or heparin titration systems improve assessment when available. Management is stepwise: UFH dose escalation; targeted AT supplementation (or fresh frozen plasma where concentrates are unavailable); and transition to direct thrombin inhibitors when HR persists or UFH is contraindicated. Protocolized pathways and multidisciplinary coordination reduce delays and adverse events. Conclusions: HR is a multifactorial, common challenge in CPB. Pre-bypass risk assessment, multimodal monitoring, and an algorithm prioritizing UFH optimization, AT repletion, and timely use of direct thrombin inhibitors provide a pragmatic framework to limit thrombosis and bleeding. Harmonized definitions and comparative trials remain priorities. Full article

Acetylcholinesterase (AChE) is a key enzyme responsible for terminating cholinergic neurotransmission by hydrolyzing acetylcholine. While clinically approved AChE inhibitors such as donepezil, rivastigmine, and galantamine are used in the symptomatic treatment of Alzheimer’s disease and related dementias, little is known about the modulatory effects of common dietary compounds on AChE activity. In this study, we investigated the influence of creatine (CR) and taurine (TA)—two widely consumed nutritional supplements with reported neuroprotective and cognitive-enhancing properties—on AChE. Enzyme kinetics were evaluated using a modified Ellman’s method, and Lineweaver–Burk analyses revealed that both CR and TA act as competitive inhibitors. Calculated parameters (Km, Vmax), inhibition constants (Ki), and half maximal inhibitory concentrations (IC₅₀) consistently indicated stronger potency for CR (IC₅₀ = 0.0056 ± 0.00018 mM) compared to TA (IC50 = 0.0097 ± 0.00035 mM). To complement the experimental data, molecular docking was performed using two crystal structures of human AChE. Docking confirmed that both ligands preferentially occupy the active-site region in a manner consistent with competitive inhibition, with CR showing more favorable binding scores than TA. Although markedly weaker than clinical drugs, these findings provide the first biochemical and in silico evidence that CR and TA directly interact with AChE, suggesting subtle cholinergic modulation relevant to cognitive function and neuroprotection. Full article

Background/Objective: American tegumentary leishmaniasis is a neglected tropical disease with limited therapeutic options characterized by high toxicity and poor tolerability. Drug repurpose offers a pragmatic strategy to accelerate the development of safer treatments. This study evaluated the antileishmanial activity of three clinically approved acetylcholinesterase (AChE) inhibitors—donepezil hydrochloride (DH), rivastigmine tartrate (RT), and galantamine hydrobromide (GH), tested individually and in combination with amphotericin B (AmpB) against Leishmania species relevant to tegumentary leishmaniasis. Methods: Antileishmanial activity was assessed against Leishmania (Leishmania) amazonensis promastigotes and intracellular amastigotes and Leishmania (Viannia) braziliensis promastigotes and axenic amastigotes. Cytotoxicity was evaluated in mammalian cell lines. The synergy with AmpB was analyzed at different proportions. Mechanistic studies included morphological analysis using light and scanning electron microscopy, flow cytometry, AChE activity assays, choline supplementation experiments, and membrane fluidity measurements. Results: All three AChE inhibitors demonstrated antileishmanial activity with selectivity indices > 1. DH emerged as the most promising candidate (IC₅₀ = 16.82 μM against promastigotes; SI = 10.25), with superior potency compared to other repurposed drugs. Strong synergistic interactions with AmpB were observed for all inhibitors (χΣFIC ≤ 0.17), with DH-AmpB displaying the most robust synergy (χΣFIC = 0.09), reducing the IC ₅₀ of AmpB by nearly 90-fold. DH induced distinct morphological alterations and acted through non-cholinergic mechanisms. The DH-AmpB combination retained maximal efficacy against L. (V.) braziliensis, with enhanced activity against clinically relevant amastigotes. Conclusions: Repurposed AChE inhibitors, particularly donepezil hydrochloride, are highly promising therapeutic candidates for tegumentary leishmaniasis. The robust synergistic effect with amphotericin B, together with their favorable safety profiles and non-antimicrobial mechanisms, positions these drugs as viable partners in dose-sparing combination regimens that could improve treatment adherence and reduce toxicity in endemic areas. Full article

Cardiovascular diseases (CVDs) remain a leading cause of mortality worldwide. According to the WHO, every year, there is an increase in the rate of death globally due to CVDs, stroke, and myocardial infarction. Several risk factors contribute to the development of CVDs, one of which is hypoxia, defined as a reduction in oxygen levels. This major stressor affects aerobic species and plays a crucial role in the development of cardiovascular disease. Research has uncovered the “hypoxia-inducible factors (HIFs) switch” and investigated the onset, progression, acute and chronic effects, and adaptations of hypoxia, particularly at high altitudes. The hypoxia signalling pathways are closely linked to natural rhythms such as the circadian rhythm and hibernation. In addition to genetic and evolutionary factors, epigenetics also plays an important role in postnatal cardiovascular responses to hypoxia. Oxidized LDL-C initiates atherosclerosis amidst oxidative stress, inflammation, endothelial dysfunction, and vascular remodelling in CVD pathogenesis. Anti-inflammatory and antioxidant biomarkers are needed to identify individuals at risk of cardiovascular events and enhance risk prediction. Among these, C-reactive protein (CRP) is a recognized marker of vascular inflammation in coronary arteries. Elevated pro-atherogenic oxidized LDL (oxLDL) expression serves as an antioxidant marker, predicting coronary heart disease in apparently healthy men. Natural antioxidants and anti-inflammatory molecules protect the heart by reducing oxidative stress, enhancing vasodilation, and improving endothelial function. For instance, the flavonoid quercetin exerts antioxidant and anti-inflammatory effects primarily by activating the Nrf2/HO-1 signaling pathway, thereby enhancing cellular antioxidant defense and reducing reactive oxygen species. Carotenoids, such as astaxanthin, exhibit potent antioxidant activity by scavenging free radicals and preserving mitochondrial integrity. The alkaloid berberine mediates cardiovascular benefits through activation of AMO-activated protein kinase (AMPK) and inhibition of nuclear factor kappa B [NF-kB] signalling, improving lipid metabolism and suppressing inflammatory cytokines. Emerging evidence highlights microRNAs (miRNAs) as potential regulators of oxidative stress via endothelial nitric oxide synthase (eNOS) and silent mating-type information regulation 2 homolog (SIRT1). While the exact mechanisms remain unclear, their benefits are likely to include antioxidant and anti-inflammatory effects, notably reducing the susceptibility of low-density lipoproteins to oxidation. Additionally, the interactions between organs under hypoxia signalling underscore the need for a comprehensive regulatory framework that can support the identification of therapeutic targets, advance clinical research, and enhance treatments, including FDA-approved drugs and those in clinical trials. Promising natural products, including polysaccharides, alkaloids, saponins, flavonoids, and peptides, as well as traditional Indian medicines, have demonstrated anti-hypoxic properties. Their mechanisms of action include increasing haemoglobin, glycogen, and ATP levels, reducing oxidative stress and lipid peroxidation, preserving mitochondrial function, and regulating genes related to apoptosis. These findings emphasise the importance of anti-hypoxia research for the development of effective therapies to combat this critical health problem. A recent approach to controlling CVDs involves the use of antioxidant and anti-inflammatory therapeutics through low-dose dietary supplementation. Despite their effectiveness at low doses, further research on ROS, antioxidants, and nutrition, supported by large multicentre trials, is needed to optimize this strategy. Full article

Background/Objectives: Vitamin D deficiency is highly prevalent worldwide and is associated with multiple comorbidities and pharmacological treatments that may interfere with its metabolism. Evidence on the effect of supplementation across different drug user groups remains limited. Methods: A prospective study was conducted across community pharmacies over twelve months. Baseline socio-demographic, serum 25(OH)D concentration, quality of life (QoL), lifestyle habits, and medication use were collected. Participants received vitamin D supplementation for 12 months. Changes in vitamin D status and QoL were analyzed according to medication use. Logistic regression identified predictors of achieving adequate serum vitamin D levels (>30 ng/mL). Statistical significance was set at p < 0.05. Results: At baseline, 87.2% of 210 participants had insufficient or deficient vitamin D levels. After supplementation, mean serum vitamin D increased significantly from 21.3 ± 8.2 to 32.1 ± 12.6 ng/mL (p < 0.001), and QoL scores improved from 68.6 ± 18.7 to 77.8 ± 18.5 (p < 0.001). Dietary intake of vitamin D–rich foods and outdoor activity also increased. Supplementation improved vitamin D status among users of benzodiazepines, proton pump inhibitors, beta-blockers, statins, levothyroxine, metformin, and angiotensin-converting enzyme inhibitors, but not among corticosteroid, nonsteroidal anti-inflammatory drugs, or vitamin K antagonist. Multivariate analysis confirmed adherence as a strongest predictor of vitamin D adequacy (OR = 15.31, 95% CI = 2.90–80.75), while corticosteroid therapy, diabetes, and hypercholesterolemia were negatively associated. Conclusions: Vitamin D supplementation effectively corrected deficiency and improved QoL, but its efficacy varied according to comorbidities and medication use. Personalized supplementation strategies, emphasizing adherence and considering pharmacological profiles, may optimize outcomes. Further studies should explore mechanistic drug–nutrient interactions and long-term clinical implications. Full article

Although traditionally contraindicated, the coadministration of tamoxifen and estradiol may hold clinical relevance in specific contexts, particularly in breast cancer survivors with premature menopause and a high risk of osteoporosis, thereby justifying the need to re-evaluate this therapeutic combination. This study presents an innovative physiologically based pharmacokinetic (PBPK) modeling approach to evaluate the coadministration of tamoxifen and estradiol in women with breast cancer and a high risk of osteoporosis. Using GastroPlus^® software, PBPK models were developed and validated for both drugs, based on physicochemical and kinetic data obtained from the literature and, where necessary, supplemented by estimates generated in ADMET Predictor^®. The simulations considered different hormonal profiles (pre and postmenopausal) and therapeutic regimens, evaluating potential interactions mediated by the CYP3A4 enzyme. Analysis of the pharmacokinetic parameters (F, C_max, T_max and AUC) revealed strong agreement between the simulated and experimental values, with prediction errors of less than twofold. The drug interaction studies, carried out in dynamic and stationary modes, indicated that estradiol does not significantly alter the pharmacokinetics of tamoxifen, even at increasing doses or in enlarged virtual populations. These results represent the first in silico evidence that, under certain conditions, the concomitant use of estradiol does not compromise the pharmacokinetic efficacy of tamoxifen. Although the study is computational, it provides a solid scientific basis for re-evaluating this therapeutic combination and proposes a pioneering model for personalized strategies in complex oncological contexts. All simulations assumed average enzyme abundance/activity without CYP polymorphism parameterization; findings are restricted to parent-tamoxifen pharmacokinetics and do not infer metabolite (e.g., endoxifen) exposure or phenotype effects. Full article

Background/Objectives: Polygoni Cuspidati Rhizoma et Radix (PCRR) is an herb and a source of a resveratrol-containing dietary supplement. Breast cancer resistance protein (BCRP) is an ATP-binding cassette transporter involved in numerous drug-related pharmacokinetic interactions. This study used both in vivo and in vitro models to investigate the modulation effect of PCRR ingestion on BCRP. Methods: Three groups of rats were orally administered methotrexate (MTX), a probe substrate of BCRP, without and with PCRR at 1.0 g/kg and 2.0 g/kg in a parallel design, and the MTX pharmacokinetics were compared among three treatments. The modulation effects of PCRR and its serum metabolites (PCRRM) on BCRP were assayed by in vitro models. Results: PCRR at 1.0 g/kg and 2.0 g/kg significantly decreased the area under the serum level–time curve from 0 to 240 min (AUC_0-240) of MTX by 31% and 58%, respectively; 2.0 g/kg of PCRR markedly increased the area under the serum level–time curve from 240 to 2880 min (AUC_240-2880) and the mean residence time (MRT) of MTX by 39% and 74%, respectively. The results of in vitro assays indicated that PCRR enhanced the function of BCRP by 33~48%; on the contrary, PCRRM reduced the function of BCRP by 200~209%. Conclusions: PCRR activated BCRP, whereas PCRRM inhibited BCRP, thereby the coadministration of PCRR reduced both the absorption and excretion of MTX in rats. In clinical practice, the concurrent use of PCRR with critical BCRP substrate drugs should be avoided. Full article

Natural bioactive chemicals sourced from marine species have attracted growing interest due to their immunomodulatory, antioxidant, and gut microbiota-regulating characteristics. These chemicals, especially peptides, offer therapeutic approaches for addressing inflammation, immunological dysfunction, and intestinal barrier disturbance, which are frequently observed in conditions such as inflammatory bowel disease (IBD). This review centers on current discoveries about marine-derived peptides from octopus, sea conch, and scallop. These substances have demonstrated a considerable ability to restore intestinal integrity, regulate immune cell function, reduce pro-inflammatory cytokines, and rebalance dysbiotic gut microbiota. We consider several in vivo scenarios, encompassing dextran sulphate sodium (DDS)-induced colitis and cyclophosphamide-induced immunosuppression. These compounds raise the expression of tight junction proteins (including ZO-1 and occludin), boost the production of mucin, and encourage the growth of good bacteria such as Lactobacillus and Lachnospiraceae. Their effects are mechanistically associated with the inhibition of critical inflammatory pathways (e.g., Nuclear factor-κB (NF-κB), Toll-like receptor 4 (TLR-4)) and the modulation of both innate and adaptive immune responses. These versatile bioactives can serve as dietary supplements or complementary therapies for gastrointestinal and cancer-related issues. This review emphasizes the therapeutic potential of marine peptides, concentrating on gut–immune–microbiota interactions, as well as exploring future avenues for clinical translation and drug development Full article