Venoms contain a wide range of biologically active peptides with multiple pharmacological properties, making them important for novel therapeutic development. This study involves in silico and in vitro approaches to evaluate the anti-inflammatory potential of a small oligopeptide derived from jellyfish Chironex fleckeri toxin CfTX-A. Using computational methods, structural modeling, and ADMET screening, the active peptides were identified based on their physicochemical properties, enzymatic stability, and predicted interaction with key inflammation-associated proteins such as NLRP3, caspase-1, xanthine oxidase (XO), and IL-1β. Molecular docking predicted high-affinity binding of peptide WPNY to active sites within these targets, suggesting its potential dual role in modulating inflammatory and uric acid pathways. The peptide further demonstrated potent XO inhibition (47.98 ± 12.41%) which was comparable to allopurinol (Alp) drug control. In LPS/MSU-stimulated fibroblast cells, CfTX-A peptide at 125µM maintained high cytocompatibility (97.23 ± 3.83%), significantly suppressed NLRP3 inflammasome activation (1.23 ± 0.07), NO (15.35 ± 1.77μM) and IL-1β (26.86 ± 3.01pg/ml) production, NF-κB phosphorylation (1.52 ± 0.06), and downstream inflammatory mediators including iNOS (2.88 ± 0.10), COX-2 (6.24 ± 0.67), TNF-α (2.85 ± 0.16), and MMP-9 (4.06 ± 0.38). It also reduced intracellular ROS levels, retained thermal stability, and showed efficient uptake within the cells. These findings suggest the peptide’s dual role as an anti-inflammatory and antioxidant agent. Further, it demonstrates the utilization of venom-derived peptides and in silico-driven platforms in accelerating peptide drug discovery. Future in vivo investigations in arthritis models are essential to establish therapeutic relevance.
Background Colorectal cancer is a highly prevalent neoplasm worldwide. In experimental models, colorectal carcinogenesis can be induced by 1,2-dimethylhydrazine (DMH), resulting in preneoplastic lesions, oxidative stress, and inflammation. Beyond local effects, systemic consequences of carcinogenesis may impact distant intestinal segments. This study investigated neuroimmune alterations in the ileum of rats with DMH-induced colorectal carcinogenesis and evaluated the effects of microencapsulated quercetin and Bifidobacterium animalis. Methods Twenty-five 50-day-old male Wistar rats were randomly assigned to five groups: control (C); colorectal carcinogenesis (CR); colorectal carcinogenesis treated with microencapsulated quercetin (CQ); colorectal carcinogenesis treated with Bifidobacterium animalis (CB); and colorectal carcinogenesis treated with the combination of microencapsulated quercetin and Bifidobacterium animalis (CQB). Colonic tissue was collected for histopathological analysis, and ileal samples were processed for the evaluation of enteric neurons and glial cells in the myenteric and submucosal plexuses, as well as glial and immune cells in the intestinal mucosa. CD45- and CD68-immunoreactive immune cells were also quantified. Key findings Colorectal carcinogenesis induced significant quantitative and morphological changes in enteric neurons. These changes included a reduction in the neuronal population and an increase in glial cell morphology. The changes were accompanied by increased glial activation and immune cell infiltration in the ileal mucosa. Treatment with microencapsulated quercetin and Bifidobacterium animalis, when administered alone or in combination, partially attenuated these neuroimmune alterations. Significance DMH-induced colorectal carcinogenesis promotes enteric neuroinflammation in the ileum, and microencapsulated quercetin and Bifidobacterium animalis exert protective effects on enteric glial and immune cells, likely mediated by their antioxidant and anti-inflammatory properties.
Persistent hyperglycemia is the hallmark of diabetes mellitus, and it involves complex metabolic and neuro-enteric disturbances that challenge single-target therapies. Fermentation of Musa paradisiaca (plantain) fruit pulp has previously been reported as a means of enhancing its bioactivity, which may exert multifaceted nutraceutical benefits, including metabolic regulation. We tested the hypothesis that fermented M. paradisiaca fruit pulp methanolic extract (f-PUME) normalises body weight and fasting glycaemia, attenuates dyslipidaemia, preserves pancreatic β-cell mass and function via antioxidant and anti-inflammatory actions, and maintains the integrity of hypothalamic and jejunal morphology. Thirty adult male Sprague–Dawley rats were randomised into five groups: control, STZ-only, STZ + glibenclamide (5 mg/kg), STZ + unfermented extract (100 mg/kg), and STZ + fermented extract (100 mg/kg). Hyperglycemia was induced with a single i.p. STZ injection, followed by 42 days of daily oral treatment. Body weight, glucose regulatory, coronary, and atherogenic indices, oxidative stress biomarkers, pancreatic proinflammatory cytokines, brain, jejunal, and pancreatic organosomatic indices, and their histomorphometry were assessed. By Day 14, f-PUME reversed STZ-induced weight loss and fasting hyperglycaemia. f-PUME modestly lowered total cholesterol and triglycerides while preserving HDL-c, normalising Castelli and atherogenic indices. In the pancreas, f-PUME restored organ weight, boosted insulin secretion, reactivated antioxidant enzyme activities, and suppressed MDA and proinflammatory cytokine levels, thereby preserving islet architecture and β-cell granule density. f-PUME also reversed hypothalamic- and jejunal- vacuolation and pyknotic nuclei and repaired jejunal crypt morphology. f-PUME exhibits a marked anti-hyperglycemic effect via antioxidant, glucose and lipid metabolic normalisation, organoprotection, and entero-neuronal morphological and functional restoration.
Objectives This study investigated the renoprotective effects of methylsulfonylmethane (MSM) against diclofenac (DIC)-induced acute kidney injury (AKI) in rats and examined its association with oxidative stress (OS), inflammation, ferroptosis-related changes, mitochondrial dysfunction, and autophagy. Methods Twenty-four male Sprague-Dawley rats were randomly allocated into four groups: control, DIC, MSM200 + DIC, and MSM400 + DIC. MSM was administered by oral gavage for seven consecutive days before a single intraperitoneal injection of DIC (100 mg/kg). Renal function biomarkers, KIM-1, NGAL, OS markers, inflammatory mediators, ferroptosis- and mitochondrial biogenesis-related markers, autophagy-associated proteins, miR-34a expression, histopathological examination, and immunohistochemistry were evaluated. Results DIC markedly impaired renal function, increased serum creatinine, blood urea nitrogen, proteinuria, KIM-1, and NGAL, and induced OS, inflammatory responses, DNA damage, histopathological injury, and alterations in ferroptosis-, mitochondrial biogenesis-, and autophagy-related markers. MSM pretreatment significantly ameliorated these abnormalities in a dose-dependent manner, with the 400 mg/kg dose providing greater protection than the 200 mg/kg dose. Conclusions MSM demonstrated significant renoprotective effects against DIC-induced AKI, which were associated with attenuation of OS and inflammation together with modulation of ferroptosis-, mitochondrial biogenesis-, and autophagy-related pathways. Further mechanistic and translational studies are warranted to confirm these associations.
The brown mussel, Perna indica (Kuriakose & Nair, 1976), native to the western Indian Ocean is widely consumed as a rich source of nutritious delicacy. In this study, the polysaccharide (PIP) isolated from the brown mussel, built in with glucose and glucuronic acid units, demonstrated significant immunomodulatory activity. PIP exhibited anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and THP-1 human cells by regulating inflammatory mediators. In LPS-induced RAW cells, treatment with 10–50 μg/mL of PIP resulted in a dose-dependent decrease in levels of interleukin-6 (IL-6) by 23–50% and tumor necrosis factor-alpha (TNF-α) by 19–35%. The gene expression studies revealed that treatment with 10–50 μg/mL of PIP inhibited IL-6 by 41–64% and IL-1β by 60–98%. In LPS-stimulated THP-1 cells, exposure to 50 μg/mL of PIP led to a 48–54% reduction in the mean fluorescence intensity of TNF-α, IL-1β, and IL-12, as assessed using confocal microscopy. Similarly, PIP decreased IL-6 and inducible nitric oxide synthase (iNOS) expressions by 69% and 62%, respectively. Furthermore, PIP downregulated mRNA expression of interferon-γ (IFN-γ) and IL-2 by 30% and 55%, respectively. The therapeutic potential of PIP is primarily attributed to functional groups, such as carboxylic acid, sulfate, and hydroxyl, thereby facilitating receptor interactions through non covalent interactions and ultimately modulating key metabolic pathways. These findings highlight PIP sourced from brown mussel as a promising candidate for functional food applications aimed at managing inflammatory disorders.
Natural products remain an important source for the discovery of new therapeutic agents. This review critically discusses the traditional practices, phytochemical constituents, nutritional value, and pharmacological potential of Prinsepia utilis Royle (Rosaceae), a medicinal shrub traditionally used in the Himalayan regions for the treatment of skin conditions, inflammation, and wound healing. Quantitative data reveal that the seeds produce 30-35% oil with a high concentration of unsaturated fatty acids (65.2-87.17%), primarily oleic acid (28.11-37.3%) and linoleic acid (16.4-59.06%), establishing its nutritional and cardioprotective role. The plant is rich in various bioactive compounds such as flavonoids, phenolics, tocopherols, and phytosterols, establishing its pharmacological properties. The plant exhibits potent antioxidant activity with DPPH IC50 values of 2.35-2.57 mu g/mL for fruit flavonoids and ABTS IC50 values of 21.13-23.01 mu g/mL for flower extracts, along with high total phenolic content (44-50 mu g GAE/mg). Antimicrobial activity is established with inhibition zones of 10-12.9 mm and minimum inhibitory concentrations of 0.9-1.7 mg/mL for both Gram-positive and Gram-negative bacteria. Toxicological analysis reveals a positive safety profile with no mortality at oral doses of up to 5000 mg/kg for leaf extracts and 2000 mg/kg for seed oil. Although these results are encouraging, there is a lack of validation and analysis of metabolomics and toxicity. P. utilis is a versatile bioresource that has great potential as a nutraceutical/pharmaceutical agent and thus requires further research.
Functional foods, defined as foods that provide health benefits beyond basic nutrition, are gaining global popularity because of their potential role in maintaining health and preventing chronic diseases. However, regulations differ considerably across countries, affecting market entry, labeling practices, and claim approval. This narrative review, based on the analysis of recent regulatory documents and policy frameworks, provides a comparative overview of functional food regulations in the United States, European Union, Japan, and India. In the United States, the Food and Drug Administration (FDA) generally classifies functional foods as conventional foods or dietary supplements, with health claims regulated under the Dietary Supplement Health and Education Act (DSHEA). In the European Union, the European Food Safety Authority (EFSA) follows a rigorous scientific evaluation process for health claims under European Commission Regulation (EC) No. 1924/2006. Japan has established an innovative regulatory pathway through the Foods for Specified Health Uses (FOSHU) system, which requires structured approval supported by clinical evidence. In India, the Food Safety and Standards Authority of India (FSSAI) regulate functional foods and nutraceuticals through dedicated guidelines that align with international safety standards while addressing domestic market needs. Key challenges include inconsistent definitions, variable evidence requirements for health claims, and limited global harmonization. A more harmonized approach could streamline approvals, support responsible innovation, and facilitate international trade. This review highlights the need for a balanced regulatory framework that integrates scientific rigor with practical market accessibility.
Diabetes remains a major global health problem, with traditional treatments often showing delayed effects and unwanted side effects. In response, curcumin (a bioactive compound from turmeric) has gained increasing interest for its potential antidiabetic properties. This scoping review aims to compile current evidence on how curcumin works to combat diabetes, focusing on its effects on key cellular processes such as inflammation, oxidative stress, apoptosis, and lipid metabolism. Notably, recent advances in nano-formulated curcumin have significantly improved its bioavailability, opening new possibilities for clinical use. Although early preclinical results look promising, gaps still exist in understanding curcumin's clinical effectiveness and optimal dosing. Future research should prioritize large-scale clinical trials and integrated treatment approaches to confirm curcumin's potential as a complementary therapy for diabetes mellitus (T2DM in particular). Overall, these findings highlight curcumin's therapeutic potential and identify important areas that need further investigation.
The gut microbiota is increasingly recognized as a metabolic descriptor that shapes host physiology through amino acid utilization and its metabolites. This review integrates the roles of proteolytic, tryptophan-utilizing, and glutamate-metabolizing bacteria with host nutrient-sensing pathways (GCN2/eIF2α-ATF4 and mTORC1), emphasizing their influence on metabolism, immunity, and neurobehavioral function. Particular attention is given to how microbial metabolites, including short-chain fatty acids, bile acids, and indole derivatives, interact with host signaling pathways and inform translational strategies, such as dietary modulation, prebiotics, probiotics, postbiotics, and emerging engineered microbiome-based interventions. By mapping microbial pathways to clinical endpoints, we outlined how dietary and microbiome-based interventions can reduce the risk of chronic diseases. This bench-to-bedside perspective underscores the therapeutic potential of gut metabolites in personalized nutrition and in precision medicine. This review provides an integrated mechanistic perspective linking amino acid–metabolizing microbial communities to host nutrient-sensing pathways that regulate metabolism and immunity. Microbial metabolites have been highlighted as modifiable regulators with clear relevance to personalized nutrition and precision medicine by directly connecting these molecular interactions to dietary, postbiotic, and emerging microbiome-based interventions.
Resveratrol is a polyphenolic stilbenoid found in various plants like peanuts, grapes, berries and has gained significant attention for its diverse therapeutic properties. It is synthesized as a natural defence against UV light and fungal infection. This review article explores chemical structure, pharmacokinetics, beneficial health properties along with formulations and clinical data related to resveratrol. Chemically resveratrol exists in its two isomeric forms, trans and cis among which trans form is the most stable and active form. The resveratrol has complex pharmacokinetics with rapid absorption form GIT and extensive first pass metabolism in liver and intestines. It has low solubility with limited bioavailability thus several novel formulations have been discovered in order to overcome this limitation. Its absorption is influenced directly by presence of food, gut microbiota and dosage form with peak plasma concentrations occurring in 1-2 h after ingestion. However, the plasma half-life of the parent (unconjugated) resveratrol is relatively short (approximately 1-3 h) due to rapid phase II metabolism, while longer persistence in circulation is mainly attributed to conjugated metabolites. Mechanistically, resveratrol suppresses NF-kappa B-mediated inflammatory pathways and frequently activates sirtuin signalling, especially SIRT1, to produce numerous benefits. Its extensive metabolic, anti-inflammatory, cardioprotective, and anticancer effects reported in preclinical and clinical research are explained by these convergent pathways. Resveratrol has been shown to reduce variety of illnesses including cardiovascular, age related, cancer and these all are covered in detail further in this review. Although, clinical trial studies have demonstrated its effectiveness in the treatment of several diseases yet, further research is required to understand the pharmacokinetics, pharmacodynamics and long-term effects of resveratrol.
Purpose of review: Metabolic dysfunction-associated liver disease (MASLD) is presently the most common chronic liver disorder globally. Flavonoids, a broad array of polyphenolic plant chemicals, have emerged as multitarget therapeutic agents owing to their potent antioxidant, anti-inflammatory, and lipid-modulating activities. This review synthesizes current understanding of the mechanisms by which flavonoids alleviate MASLD, highlighting their impact on oxidative stress, inflammation, and de novo lipogenesis (DNL) pathways, while providing a critical assessment of preclinical and clinical evidence supporting their effectiveness. Principal results: Extensive preclinical and epidemiological research demonstrates that flavonoids, such as quercetin, kaempferol, and silymarin provide substantial protective benefits against hepatic steatosis, inflammation, and oxidative injury. Flavonoids suppress hepatic DNL by regulating transcription factors, including SREBP-1c and ChREBP, reducing the expression of essential lipogenic enzymes (FAS, ACC, SCD1), and promoting fatty acid oxidation via AMPK activation. They diminish the synthesis of pro-inflammatory cytokines (TNF-alpha, IL6, IL-1(3) and obstruct central inflammatory pathways, such as NF-kappa B and TLR4 signaling, while augmenting intrinsic antioxidant defenses through the activation of Nrf2, SOD, CAT, and GPx. Major conclusion: Although their safety and extensive mechanistic activity are well-documented, further research should concentrate on enhancing delivery systems, confirming clinical efficacy, while incorporating personalized medicine strategies.
A hormonal imbalance that causes infertility in women is called polycystic ovarian syndrome, or PCOS. Among the causes of PCOS are genetics, lipid imbalance, insulin resistance, and oxidative stress. Recently, a number of pharmacological treatments for PCOS have been proposed. However, the negative consequences of these treatments differ. Only a few of them can restore a significant amount of metabolic and hormonal imbalances. Aspirin's metabolite, gentisic acid (GA), is a naturally occurring compound extracted from Gentiana species roots. Under a range of chemical and physical stressors, gentisic acid has been demonstrated to behave as an antiinflammatory, free radical scavenger, and antioxidant. Thus, the present study elucidated the potential protective effects of GA against PCOS in rats administered letrozole (LTZ) to induce PCOS. Reproductive and metabolic dysfunctions were significantly reduced by GA administration. Additionally, GA had a hepatoprotective benefit against PCOS-associated unfavourable responses. These results imply that GA's antiandrogenic and metabolicregulating properties may help control PCOS symptoms. Consequently, GA might be a viable option for treating metabolic and reproductive issues in PCOS patients.
Different types of depression are a major global health issue and many patients don't respond to standard treatments. It has been showed that there is a link between neuroinflammation and depression. Experiencing stressful events in initial life like maternal separation (MS) stress negatively affects the brain and behavior. Anethole is a core constituent of the essential oils found in anise, fennel, and dill and has anti-inflammatory and neuroprotective possessions. This study intended to evaluate the anti-depressant effect of anethole in a MS model in mice whereas also probing its impact on proinflammatory gene expression and histological deviations in the CA3 region of the hippocampus. Twenty-four NMRI male mice were divided into four distinct groups. Three MS groups were received normal saline (10 ml/kg) or anethole (50 mg/kg or 100 mg/kg) for 7 continous days. The control group received 10 ml/kg of normal saline. Forced swimming test (FST), open field test (OFT), and splash test (ST) were conducted. Also, gene expression of IL-1 beta and TNF-alpha in addition to histological changes of the CA3 area in the hippocampus were assessed. Outcomes displayed that the MS triggered depressive-like behavior, such as an rise in immobility period in the FST and a reduction in the grooming time in the ST. In contrast, treatment with anethole decreased depressive-like behaviors. Furthermore, the qPCR revealed that MS augmented the gene expression of IL-1 beta while anethole at 100 mg/kg reduced it. Histologically, MS caused cell disruption and decreased pyramidal cells in the CA3 region of the hippocampus, while anethole treatment mitigated these effects. We determined that anethole, probably at least, via modulation of neuroinflammatory response and improvement in the structure of the CA3 area in the hippocampus led to antidepressant-like effects in the MS paradigm in mice.
Green coffee bean extract (GCBE) from Coffee arabica has gathered attention due to its potential antiinflammatory benefits and polyphenol-enriched content. This study explores the potential of GCBE and its phytoconstituents in mitigating airway inflammation via inhibiting NF-kappa B signaling in ovalbumin (OVA)-induced in Balb/c mice, a model for allergic asthma. Electrospray ionization-mass spectrometry (ESI-MS) was utilized to qualitatively analyze GCBE, confirming that chlorogenic acid (CAC) and trigonelline (TRG) are major bioactive components. Balb/c mice were sensitized with OVA to induce airway inflammation and subsequently treated with GCBE, CAC, and TRG at varying doses. The study evaluated the suppression of pro-inflammatory cytokines and NF-kappa B activation. Histopathological assessments measured eosinophil infiltration, goblet cell hyperplasia, and mucus production. Biochemical markers, including myeloperoxidase, malondialdehyde, and total protein, were quantified in lung tissue homogenates. Treatment with GCBE, CAC, and TRG significantly reduced levels of IL-1 beta, IL6, and TNF-alpha. Histopathological analysis revealed a marked decrease in eosinophil infiltration, goblet cell hyperplasia, and mucus production. Biochemical markers were notably elevated in OVA-challenged mice but were significantly suppressed by GCBE at 300 mg kg-1 and the combination of CAC and TRG at 50 mg kg-1 each. The fixed dose combination (CAC 50 mg kg-1 + TRG 50 mg kg-1) exhibited increased anti-inflammatory effect than the individual doses of the two compounds used in the experiment. GCBE and its phytoconstituents, particularly in combination, demonstrate potent anti-inflammatory effects by inhibiting NF-kappa B, reducing pro-inflammatory cytokines, and attenuating histopathological features of airway inflammation. These findings highlight their potential as therapeutic agents for managing allergic asthma.
Excessive fructose intake is increasingly recognized as a contributor to metabolic dysfunction and associated neurobehavioral disturbances, including pain and emotional alterations. This study investigated whether metformin could mitigate the metabolic, nociceptive, and emotional impairments induced by chronic fructose consumption in female Swiss mice. Animals received a 30% fructose solution in their drinking water for 14 weeks, and a subset was treated with metformin (4 mg/mL in the drinking solution) during the final four weeks. Fructose-fed mice developed marked metabolic dysfunction, characterized by fasting hyperglycemia, glucose intolerance, and increased plasma cholesterol, accompanied by mechanical allodynia, cold allodynia and cold hyperalgesia, and depressive-and anxiety-like behaviors. Metformin treatment effectively improved glycemic control but failed to reverse nociceptive hypersensitivity or emotional disturbances. These findings indicate that, under the present experimental conditions, metabolic improvement induced by metformin was not accompanied by detectable improvement in neurobehavioral outcomes.
Niacin, the most traditional lipid-lowering agent, was gradually replaced after the discovery of statins. Statins have a clear hypolipidemic effect and can improve atherosclerosis, but they are ineffective in some patients with hyperlipidaemia, and their long-term use may cause serious adverse effects. The complexity of the pathogenesis of atherosclerotic cardiovascular disease makes lipid-lowering therapy alone ineffective. In addition to being a participant in lipid metabolism, niacin can be processed into NAD. Some scholars have even redefined the position of niacin in cardiovascular disease as an NAD precursor. More than that, the pleiotropy exhibited by niacin in cardiovascular diseases has given it a new lease of life as new mechanisms of action and targets have been proposed. The present study attempts to integrate as well as abandon the cardiovascular effects of niacin itself by focusing on niacin and prying new directions in the study of atherosclerotic cardiovascular diseases from multiple perspectives such as lipid action, NAD consuming enzymes, HDL, GPR109A receptor and gut microbiota.
Gene expression (GEX) analysis, often assessed using real-time PCR (qPCR), is a key genotypic method. Studying the health benefits of probiotics at the GEX level offers advantages, such as greater accuracy and time efficiency, compared to phenotypic and other PCR-based evaluations. The present manuscript discusses potential mechanisms of up- or down-regulating GEX of probiotics associated with their health-promoting benefits (HPBs) and related challenges. In addition, this paper presents a comprehensive study of the use of the qPCR technique to evaluate HPBs of probiotics on the GEX scale recently published in the literature. Anti-pathogenicity, anti-cancer, immune-regulatory, and anti-inflammatory capabilities are the main HPBs of probiotics studied using qPCR. MicroRNA interfering and structural changes of the 60S subunit of the ribosome have been verified as important mechanisms for down-regulating GEX activities of probiotics. Moreover, increased mRNA stability and inducing expression of transcription factors are the main action modes in up-regulating the activities of these beneficial microorganisms.
