Anti-inflammatory Bioactivities Research Articles

A Pharmacokinetic and Bioavailability Study of Ecklonia cava Phlorotannins Following Intravenous and Oral Administration in Sprague–Dawley Rats

This study examines the pharmacokinetics and bioavailability of phlorotannins from Ecklonia cava in rats following intravenous and oral administration. Known for their potent antioxidant, anti-inflammatory and many other bioactivities, these phlorotannins, particularly dieckol, 8,8′-bieckol, and phlorofucofuroeckol-A (PFF-A), were analyzed using high-performance liquid chromatography coupled with tandem mass spectrometry. Intravenous administration at 10 mg/kg allowed detectability in plasma for up to 36 h for dieckol and 8,8′-bieckol, but only 2 h for PFF-A. Oral administration at doses of 100 mg/kg and 1000 mg/kg showed limited detectability, indicating low bioavailability and rapid clearance, particularly for PFF-A. The pharmacokinetic data suggest non-linear increases in the maximum plasma concentration (Cmax) and area under the curve (AUC) with increasing doses, pointing to significant challenges in achieving systemic availability of these eckols through oral administration. This study underscores the necessity for advanced formulation strategies and alternative routes of administration to enhance systemic bioavailability. At the same time, this result also suggests their effects may be through non-systemic pathways such as gut microbiome modulation or lipid-rich tissue targeting. The findings lay a crucial foundation for the further development of Ecklonia cava phlorotannins as therapeutic agents, offering insights into their pharmacokinetic behavior and informing enhancements in future clinical utility.

Preparation of safflower fermentation solution and study on its biological activity

IntroductionSafflower, a traditional Chinese medicine, is rich in chemical components including flavonoids, polysaccharides, and alkaloids. It exhibits pharmacological effects such as antioxidant, anti-inflammatory, anti-tumor, and anti-thrombosis properties, making it a valuable resource in the medical field. Furthermore, due to its antioxidant and anti-inflammatory effects, safflower is increasingly being utilized in the cosmetics industry.MethodsIn this study, yeast was employed to ferment safflower, and the optimal fermentation conditions were established through single-factor experiments and response surface methodology. Subsequently, the antioxidant and anti-inflammatory efficacy of the safflower fermentation solution was assessed using both cellular and zebrafish models. Finally, the safety of the safflower fermentation solution was evaluated through a cosmetic eye irritation test.ResultsFrom a total of 20 yeast strains, YF-5 was identified as the dominant strain for safflower fermentation. By optimizing the fermentation conditions, it was established that the optimal parameters for YF-5 fermentation of safflower are as follows: a fermentation temperature of 36.55°C, a material-to-liquid ratio of 1:20.46, a fructose concentration of 6.20%, a fermentation duration of 72 h, and an inoculum volume of 4%. The biological activities of safflower, including its antioxidant and anti-inflammatory properties, were enhanced through yeast fermentation. In HaCaT cell and zebrafish oxidative damage assays, safflower fermentation solution inhibits the production of malondialdehyde (MDA) and increases superoxide dismutase (SOD) activity as well as total antioxidant capacity (T-AOC). In the RAW264.7 cell inflammatory damage assays, a 20% safflower fermentation solution was found to inhibit the release of TNF-α and NO in the inflammatory model, with inhibition rates of 30.94 and 28.86%, respectively. In the zebrafish inflammatory damage assays, the quantity of fluorescent neutral proteins in the 5% safflower fermentation solution was 0.7 times that observed in the dexamethasone (0.1 mg/mL) positive control group, indicating that its anti-inflammatory activity is comparable to that of dexamethasone (0.1 mg/mL). In the chicken embryo chorionic membrane experiment, it was observed that the safflower fermentation solution did not cause significant damage to the blood vessels of the chorionic allantoic membrane (CAM). This finding demonstrates that the safflower fermentation solution possesses a certain degree of safety.DiscussionSafflower fermentation solution has antioxidant and anti-inflammatory bioactivities, and it has passed cosmetic safety evaluations. It can be used as a new natural cosmetic ingredient added to cosmetic products.

Mentha aquatica (Water Mint) as a Source of ActivePharmaceutical and Cosmetic Ingredients: ACriticalReview.

Mentha aquatica L., or water mint, is an important member of the Mentha genus, and has long been used in traditional medicine, mainly to treat respiratory diseases such as the common cold. Nevertheless, although over the years many studies have shown that it's potential grows beyond this use, a review that highlights M. aquatica L.'s true potential is still lacking. Thus, the main purpose of the present article is to provide a thorough and multidisciplinary critical review of M. aquatica L., including its phytochemical characterization, main bioactivities, and current marketed cosmetic products. Many compounds have been identified as part of M. aquatica L. composition, such as terpenes, phenolic acids, phenols, and terpenoids, which have been linked to a vast therapeutic potential, namely anti-inflammatory, antioxidant, antibacterial, antifungal, antiobesity, and hepatoprotection bioactivities, with additional anticancer potential for several types of tumors (breast, lung, and skin), and psycho and neuroactive potential in depression, or Alzheimer's or Parkinson's disease. Additionally, it has been proven to be suitable for cosmetic application since several cleansing, hydrating, protecting, and/or odor masking products containing it are already available, with the main functions attributed to M. aquatica including refreshing/cooling effects, calming/soothing/relaxing effects, and purifying effects, properties closely related to its anti-inflammatory and antioxidant bioactivities. Hence, M. aquatica is an extremely versatile plant, with its extracts and essential oils having great therapeutic and cosmetic potential. With many marketed cosmetic products, future studies should focus on this plant's medicinal aspects, so that 1 day it can be part of therapeutic regimens.

Engineering surfactant-free pickering double emulsions gels with different structures as low-calorie fat analogues: Tunable oral perception, inhibiting lipid digestion, and potent co-delivery for lycopene and epigallocatechin gallate

Structural design has been as a transformative strategy to create clean-label and well-nourished fat-based foods. Herin, surfactant-free, plant-based oil-in-water-in-oil (O/W/O) and water-in-oil-in-water (W/O/W) emulsions gels (EGs) were designed using protein microgels and fat crystals formed in situ, which achieved dual-interface Pickering stabilization. The suitability and difference of O/W/O and W/O/W EGs as fat analogues in maintaining fat texture, inhibiting lipid digestion, target release and bioactivity of co-loading epigallocatechin gallate (EGCG) and lycopene were examined. O/W/O and W/O/W EGs displayed own unique characteristics, and could be tailored to optimize their performance. O/W/O EGs provided smoother oral perception similar to butter. The multi-structure and interface modulation for double EGs achieved inhibiting lipid digestion, fat phase position mainly controlled the digestive process. Co-delivery systems exhibited synchronous release profiles, allowing a more obvious in-time sustained release of lycopene in O/W/O and EGCG in W/O/W EGs. Both co-delivery O/W/O and W/O/W showed anti-inflammatory bioactivity.

Intestinal-level anti-inflammatory bioactivities of whole wheat: Rationale, design, and methods of a randomized, controlled, crossover dietary trial in adults with prediabetes

Randomized controlled trials (RCT) demonstrate that whole wheat consumption improves glycemia. However, substantial inter-individual variation is often observed, highlighting that dietary whole grain recommendations may not support the health of all persons. The objective of this report is to describe the rationale and design of a planned RCT aimed at establishing the gut microbiota and metabolome signatures that predict whole wheat-mediated improvements in glucose tolerance in adults with prediabetes. It is hypothesized that a controlled diet containing wheat bread (WHEAT; 160 g/day) compared with refined bread (WHITE) will improve glucose tolerance in a gut microbiota-mediated manner. Biospecimens will be collected before and after each 2-week study arm. Testing for oral glucose tolerance and gastrointestinal permeability will be performed post-intervention. Assessments will include oral glucose tolerance (primary outcome) and secondary outcomes including gut microbiota, targeted and untargeted metabolomics of fecal and plasma samples, intestinal and host inflammatory responses, and intestinal permeability. WHEAT is predicted to alleviate glucose intolerance by shifting microbiota composition to increase short-chain fatty acid-producing bacteria while reducing populations implicated in intestinal inflammation, barrier dysfunction, and systemic endotoxemia. Further, benefits from WHEAT are anticipated to correlate with gut-level and systemic metabolomic responses that can help to explain the expected inter-individual variability in glucose tolerance. Thus, knowledge gained from integrating multi-omic responses associating with glucose tolerance could help to establish a precision nutrition-based framework that can alleviate cardiometabolic risk. This framework could inform novel dietary whole grain recommendations by enhancing our understanding of inter-individual responsiveness to whole grain consumption.

Alkaloids from Anacyclus pyrethrum

Twelve undescribed alkaloids, including eight pyrrolo[3,2-g]isoquinoline alkaloids (+)/(−)-anacyquinoline A (1a/1b), (±)-anacyquinoline B (2), (+)/(−)-anacyquinoline C (3a/3b), (±)-anacyquinoline D (4), (±)-anacyquinoline E (5), and (±)-anacyquinoline F (6), together with four pyrrolo[2,3-g]quinoline alkaloids (+)/(−)-anacyquinoline G (7a/7b), (±)-anacyquinoline H (8), and (±)-anacyquinoline I (9), were isolated from the roots of Anacyclus pyrethrum (L.) DC. Their structures were determined via spectroscopic analyses (UV, IR, NMR), HRESIMS, quantum chemical calculations of ECD, DP4+ analysis, and single-crystal X-ray diffraction analysis (Cu Kα). Furthermore, in bioassay, (+)/(−)-anacyquinoline G (7a/7b) and (±)-anacyquinoline H (8) showed inhibition on nitric oxide production in lipopolysaccharide -induced RAW 264.7 cells with IC50 values of 41.4, 44.1, and 31.4 μM, respectively, indicating their potential anti-inflammatory bioactivity.

Klotho: molecular mechanisms and emerging therapeutics in central nervous system diseases.

Klotho is recognized as an aging-suppressor protein that is implicated in a variety of processes and signaling pathways. The anti-inflammatory, anti-apoptotic, anti-oxidant, and anti-tumor bioactivities of klotho have extended its application in neurosciences and made the protein popular for its lifespan-extending capacity. Furthermore, it has been demonstrated that klotho levels would reduce with aging and numerous pathologies, particularly those related to the central nervous system (CNS). Evidence supports the idea that klotho can be a key therapeutic target in CNS diseases such as amyotrophic lateral sclerosis, Parkinson's disease, stroke, and Alzheimer's disease. Reviewing the literature suggests that the upregulation of klotho expression regulates various signaling pathways related to autophagy, oxidative stress, inflammation, cognition, and ferroptosis in neurological disorders. Therefore, it has been of great interest to develop drugs or agents that boost or restore klotho levels. In this regard, the present review was designed and aimed to gather the delegated documents regarding the therapeutic potential of Klotho in CNS diseases focusing on the molecular and cellular mechanisms.

Extracellular vesicles from the microalga Tetraselmis chuii are biocompatible and exhibit unique bone tropism along with antioxidant and anti-inflammatory properties

Extracellular vesicles (EVs) are membrane-enclosed bio-nanoparticles secreted by cells and naturally evolved to transport various bioactive molecules between cells and even organisms. These cellular objects are considered one of the most promising bio-nanovehicles for the delivery of native and exogenous molecular cargo. However, many challenges with state-of-the-art EV-based candidates as drug carriers still exist, including issues with scalability, batch-to-batch reproducibility, and cost-sustainability of the final therapeutic formulation. Microalgal extracellular vesicles, which we named nanoalgosomes, are naturally released by various microalgal species. Here, we evaluate the innate biological properties of nanoalgosomes derived from cultures of the marine microalgae Tetraselmis chuii, using an optimized manufacturing protocol. Our investigation of nanoalgosome biocompatibility in preclinical models includes toxicological analyses, using the invertebrate model organism Caenorhabditis elegans, hematological and immunological evaluations ex vivo and in mice. We evaluate nanoalgosome cellular uptake mechanisms in C. elegans at cellular and subcellular levels, and study their biodistribution in mice with accurate space-time resolution. Further examination highlights the antioxidant and anti-inflammatory bioactivities of nanoalgosomes. This holistic approach to nanoalgosome functional characterization demonstrates that they are biocompatible and innate bioactive effectors with unique bone tropism. These findings suggest that nanoalgosomes have significant potential for future therapeutic applications.

Mitigative Effects of Topical Norfloxacin on an Imiquimod-Induced Murine Model of Psoriasis.

Psoriasis is a chronic, inflammatory dermatosis characterized by thickened, reddened, and scaly skin lesions. Norfloxacin is a fluoroquinolone antibiotic with enhanced antioxidant, anti-inflammatory, and immunomodulatory bioactivities. The aim of this study was to figure out the possible impact of topical norfloxacin on an imiquimod-induced model of psoriasis in mice. Thirty albino-type mice were split into five distinct groups of six animals each. The control group included healthy mice that had not received any treatment. The induction group was given the vehicle 2 h after the topical imiquimod, once daily for 8 days. Two hours after receiving topical imiquimod, the treatment groups including calcipotriol, norfloxacin 2.5%, and norfloxacin 5% were given topical ointments containing calcipotriol 0.005%, norfloxacin 2.5%, and norfloxacin 5%, for 8 days. Topical norfloxacin ointment significantly reduced the severity of imiquimod-exacerbated psoriatic lesions including erythema, shiny-white scaling, and acanthosis and fixed histological abnormalities. Furthermore, imiquimod-subjected mice treated with a higher concentration of norfloxacin ointment exhibited dramatically lower skin levels of inflammation-related biomarkers like IFN-γ, TNF-α, IL-6, IL-17A, IL-23, and TGF-β but higher levels of IL-10. They also demonstrated a notable decrease in angiogenesis parameters such as VEGF and IL-8, a substantial reduction in oxidative indicators like MDA and MPO, and a considerable rise in antioxidant enzymes like SOD and CAT. This study offers novel evidence that norfloxacin may assist in controlling inflammatory dermatoses like psoriasis by minimizing the severity of psoriatic plaques, correcting histological alterations, and diminishing the production of inflammatory, oxidative, and angiogenetic parameters.

In Situ Hydrogel-Forming Powders Containing Eutectic Mixture of Curcumin-Arginine as a Multi-Drug Delivery System for Wound Healing Applications

Background: Curcumin (CUR) has antimicrobial, anti-inflammatory, and antioxidant bioactivities and is a promising molecule to treat chronic wounds. However, CUR shows limited oral bioavailability due to low aqueous solubility and dissolution, chemical instability, and rapid metabolism in the gastrointestinal tract and liver. Therefore, topical delivery seems to provide therapeutic concentrations of CUR in a controlled manner. Arginine (ARG) promotes the wound healing process. CUR and ARG form a eutectic mixture (EMCA) that can be used for simultaneous improvement of dissolution of CUR and combinational wound therapy. Here, we have formulated in situ hydrogel-forming powders of EMCA using hydrophilic carriers. Methods: EMCA was prepared by liquid-assisted grinding and analyzed by powder X-ray diffraction (PXRD) and Fourier transform infrared (FT-IR) methods. The formulations were prepared by mixing EMCA with sodium carboxy methyl cellulose, sodium alginate, and polyethylene glycol. Optical microscopy, flow property, dissolution rate, water uptake, hydrogel forming ability, release profile, and antioxidant activity of the formulated powders were measured and compared with raw CUR. Results: The solid-state analyses revealed the formation of EMCA. Photographs showed that EMCA exhibited a lower particle size than raw CUR and ARG. The formulation content significantly affected fluid uptake, hydrogel-forming ability, and dissolution rate. The optimized formulation (FEP5) showed a considerable enhancement in the dissolution rate of CUR and could control the release. FEP5 also demonstrated promising characteristics including high fluid uptake and suitable hydrogel-forming ability. FEP5 enhanced the antioxidant activity of CUR from 9% to 50%. Additionally, FEP5 exhibited improved flow properties compared to raw CUR, which is crucial for practical applications in wound therapy. Conclusion: Current work highlighted the potential of EMCA formulated as a hydrogel-forming powder as a novel formulation with improved dissolution, rapid fluid uptake, inexpensive components, feasible method of preparation, and easy application and removal for combinational wound therapy

Anoectochilus roxburghii polysaccharide reduces D-GalN/LPS-induced acute liver injury by regulating the activation of multiple inflammasomes.

Acute liver injury (ALI) is a serious syndrome with a high mortality rate due to viral infection, toxic exposure, and autoimmunity, and its severity can range from mildly elevated liver enzymes to severe liver failure. Activation of the nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is closely associated with the development of ALI, and the search for an inhibitor targeting this pathway may be a novel therapeutic option. Anoectochilus roxburghii polysaccharide (ARP) is a biologically active ingredient extracted from Anoectochilus roxburghii with immunomodulatory, antioxidant, and anti-inflammatory bioactivities and pharmacological effects. In this study, we focused on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury by ARP through inhibition of NLRP3 inflammasome. An inflammasome activation model was established in bone marrow-derived macrophages (BMDMs) to investigate the effects of ARP on caspase-1 cleavage, IL-1β secretion, and ASC oligomerization in inflammasomes under different agonists. We used the D-GalN/LPS-induced acute liver injury model in mice, intraperitoneally injected ARP or MCC950, and collected liver tissues, serum, and intraperitoneal lavage fluid for pathological and biochemical indexes. ARP effectively inhibited the activation of the NLRP3 inflammasome and had an inhibitory effect on non-classical NLRP3, AIM2, and NLRC4 inflammasomes. It also effectively inhibited the oligomerization of apoptosis-associated speck-like protein (ASC) from a variety of inflammatory vesicles. Meanwhile, ARP has good therapeutic effects on acute liver injury induced by D-GaIN/LPS. The inhibitory effect of ARP on a wide range of inflammasomes, as well as its excellent protection against acute liver injury, suggests that ARP may be a candidate for acute liver injury.

Avocado and Its By-Products as Natural Sources of Valuable Anti-Inflammatory and Antioxidant Bioactives for Functional Foods and Cosmetics with Health-Promoting Properties

Avocado (Persea americana) is a unique fruit with exceptional nutritional and technological characteristics, as well as proposed health benefits. Moreover, the commercial utilization of avocado to make guacamole and/or to extract its oil for several applications generates massive amounts of avocado bio-wastes, including peels and seeds by-products, which further impact the environment and waste management costs. Within this article, the proposed health benefits of moderate avocado consumption, as a functional component of a balanced diet against inflammation-related chronic disorders, and its potential applications are fully addressed. The numerous bioactive compounds present in avocado fruit and its by-products, such as its bioactive phenolics, dietary fiber, and lipid bioactives like unsaturated fatty acids and polar lipids, are also thoroughly outlined. The functional anti-inflammatory, antithrombotic, and antioxidant properties of each of these bioactives and avocado extracts, are then thoroughly reviewed. Emphasis is given to these avocado-derived bioactives and extracts that have the potential to be utilized in various industrial applications, such as in functional foods, supplements, nutraceuticals, and cosmetics related health-promoting applications. The limitations and future perspectives of these applications based on avocado bioactives are also discussed.

A Comprehensive Review on the Antioxidant and Anti-Inflammatory Bioactives of Kiwi and Its By-Products for Functional Foods and Cosmetics with Health-Promoting Properties

Kiwi’s increased popularity as a healthy fruit with several agro-food applications has increased the amount of bio-waste produced like leaf, peel, and seed by-products, usually combined to form a kiwi pomace, which increases the environmental footprint of kiwi fruit and waste management costs. The aim of the present study is to thoroughly review and outline the nutritional content and bioactive components of both kiwi fruit and its by-products, as well as the innovative approaches to obtain and valorize kiwi’s bioactives, phytochemicals, vitamins, and nutrients in several functional food products, nutraceuticals, and cosmetics applications with health-promoting properties. The antioxidant and anti-inflammatory properties and mechanisms of action of the extracted polyphenols, flavonoids, flavones, organic acids, and other bioactive components in both the fruit and in its functional products are also elucidated. Emphasis is given to those bioactive ingredients and extracts from kiwi by-products that can be valorized in various functional foods, supplements, nutraceuticals, nutricosmetics, cosmeceuticals, and cosmetics-related applications, with antioxidant and anti-inflammatory health-promoting properties. Characteristic examples with reported health benefits are the functional kiwi fruit jelly (FKJ),fermented kiwi fruit products like wine, starchy kiwi fruit flour (SKF), and kiwi-derived functional protein bars, cheese and flour, as well as several nutraceuticals and functional cosmetics with kiwi bioactives improving their antioxidant, antiaging, and photoprotective properties, collagen synthesis, skin density, hydration, elasticity, and the wound healing process, while beneficially reducing skin roughness, wrinkles, hyperpigmentation, keratinocyte death, and DNA and cell damage. The limitations and future perspectives for these kiwi bioactive-based applications are also discussed.

Anti-Inflammatory and Antithrombotic Potential of Metal-Based Complexes and Porphyrins

Inflammation and thrombosis are implicated in several chronic disorders. Recent studies have outlined the way in which several compounds can offer protection against inflammation. Within this comprehensive review the so-far reported anti-inflammatory health-promoting effects of several metal-based complexes, both in vitro and in vivo, are thoroughly presented. These metal-based compounds usually interfere with various biochemical processes associated with the inflammatory response and thrombus formation and become capable of inhibiting these biochemical pathways with proposed health benefits. Emphasis is given to the multifaceted actions of metal-based complexes that have exhibited potent anti-inflammatory and antithrombotic activities against the inflammatory mediator, platelet-activating factor (PAF), and its thrombo-inflammatory signaling, as well as on their anti-platelet and antitumor health promoting properties. Furthermore, the enhancement of the anti-inflammatory potency of well-established bioactive compounds by their incorporation as ligands in several metal-based complexes is discussed. Metal-based complexes bearing natural anti-inflammatory bioactives are also outlined. Characteristic examples of both free and metal-based porphyrins are explored. These compounds are recognized to have anti-inflammatory and antithrombotic assets, in addition to other pleiotropic advantages including antibacterial or anticancer actions. Additionally, applications of metal complexes in various models of inflammatory and thrombotic complications are demonstrated. The combined results of this study show that further research is required towards the preparation of several metal-based complexes with improved pharmacological profiles. Finally, restrictions on the application of these metal-based compounds are also covered, along with their prospects for the future and the need for additional study in order to improve their efficacy and safety.

Effect of silk fibroin protein hydrolysis on biochemistry, gelation kinetics, and NF-kB bioactivity in vitro

Fibroin is a structural protein derived from silk cocoons, which may be used in a variety of biomedical applications due to its high biocompatibility and controllable material properties. Conversely, fibroin solution is inherently unstable in solution, which limits its potential utility. Fibroin hydrolysates possess enhanced aqueous solubility and stability, with known anti-inflammatory bioactivity. Here, silk-derived protein (SDP) was produced through controlled time, temperature, and pressure conditions to generate a novel and reproducible hydrolysate population. Both regenerated fibroin and SDP solution stability were characterized for MWD, amino acid content, solubility, viscosity, surface interaction, secondary structure formation, and in vitro assessment of NF-kB pathway activity. Mechanistic studies indicate that hydrolysis processing is required to enhance material stability by abolishing fibroin's ability to self-associate. In vitro assays using HCLE cells indicate SDP has dose dependent potency for inhibiting NF-kB driven gene expression of TNF-α and MMP-9. Collectively, the results support SDP's use as an anti-inflammatory wetting agent compatible with a wide range of both biomedical and industrial applications. Furthermore, the conditions used to generate SDP hydrolysates are readily accessible, produce a highly consistent material from batch-to-batch, and permit widespread investigation of this novel population for these purposes.

Prevotella histicola ameliorates DSS-induced colitis by inhibiting IRE1α-JNK pathway of ER stress and NF-κB signaling

Inflammatory bowel disease (IBD) is a chronic and recurrent gastrointestinal inflammation regulated by intricate mechanisms. Recently, prebiotics is considered as promising nutritional strategy for the prevention and treatment of IBD. Prevotella histicola (P. histicola), an emerging probiotic, possesses apparently anti-inflammatory bioactivity. However, the role and underlying mechanism of P. histicola on IBD remain unclear. Hence, we probe into the effect of P. histicola on dextran sulfate sodium (DSS)-induced colitis and clarified the potential mechanism. Our results revealed that DSS-induced colonic inflammatory response and damaged epithelial barrier in mice were attenuated by oral administration of P. histicola. Moreover, supplementary P. histicola significantly enriched short-chain fatty acid (SCFA)-producing bacteria (Lactobacillus, and Bacillus) and reduced pathogenic bacteria (Erysipelotrichaceae, Clostridium, Bacteroides) in DSS-induced colitis. Notably, In DSS-treated mice, endoplasmic reticulum stress (ERS) was persistently activated in colonic tissue. Conversely, P. histicola gavage suppressed expansion of endoplasmic reticulum, downregulated PERK-ATF4-CHOP and IRE1α-JNK pathway. In vitro, the P. histicola supernatant eliminated LPS-induced higher production of pro-inflammatory cytokines regulated by NF-κB and impairment of epithelial barrier by inhibiting IRE1α-JNK signaling in Caco-2 cell. In summary, our study indicated that P. histicola mitigated DSS-induced chronic colitis via inhibiting IRE1α-JNK pathway and NF-κB signaling. These findings provide the new insights into the promotion of gut homeostasis and the application potential of P. histicola as a prebiotic for IBD in the future.

Bioassay-guided isolation of anti-inflammatory and antinociceptive metabolites among three Moroccan Juniperus leaves extract supported with in vitro enzyme inhibitory assays

Ethnopharmacological relevanceHerbs of the genus Juniperus (family Cupressaceae) have been commonly used in ancestral folk medicine known as “Al'Araar” for treatment of rheumatism, diabetes, inflammation, pain, and fever. Bioassay-guided isolation of bioactives from medicinal plants is recognized as a potential approach for the discovery of novel drug candidates. In particular, non-addictive painkillers are of special interest among herbal phytochemicals. Aim of the studyThe current study aimed to assess the safety of J. thurifera, J. phoenicea, and J. oxycedrus aqueous extracts in oral treatments; validating the traditionally reported anti-inflammatory and analgesic effects. Further phytochemical investigations, especially for the most bioactive species, may lead to isolation of bioactive metabolites responsible for such bioactivities supported with in vitro enzyme inhibition assays. Materials and methodsFirstly, the acute toxicity study was investigated following the OECD Guidelines. Then, the antinociceptive, and anti-inflammatory bioactivities were evaluated based on chemical and mechanical trauma assays and investigated their underlying mechanisms. The most active J. thurifera n-butanol fraction was subjected to chromatographic studies for isolating the major anti-inflammatory metabolites. Moreover, several enzymatic inhibition assays (e.g., 5-lipoxygenase, protease, elastase, collagenase, and tyrosinase) were assessed for the crude extracts and isolated compounds. ResultsThe results showed that acute oral administration of the extracts (300–500 mg/kg, p. o.) inhibited both mechanically and chemically triggered inflammatory edema in mice (up to 70% in case of J. thurifera) with a dose-dependent antinociceptive (tail flick) and anti-inflammatory pain (formalin assay) activities. This effect was partially mediated by naloxone inhibition of the opioid receptor (2 mg/kg, i. p.). In addition, 3-methoxy gallic acid (1), quercetin (2), kaempferol (3), and ellagic acid (4) were successfully identified being involved most likely in J. thurifera extract bioactivities. Nevertheless, quercetin was found to be the most potent against 5-LOX, tyrosinase, and protease with IC50 of 1.52 ± 0.01, 192.90 ± 6.20, and 399 ± 9.05 μM, respectively. ConclusionJ. thurifera extract with its major metabolites are prospective drug candidates for inflammatory pain supported with inhibition of inflammatory enzymes. Interestingly, antagonism of opioid and non-opioid receptors is potentially involved.

Digestion of whey peptide induces antioxidant and anti-inflammatory bioactivity on glial cells: Sequences identification and structural activity analysis

Whey derived peptides have shown potential activity improving brain function in pathological condition. However, there is little information about their mechanism of action on glial cells, which have important immune functions in brain. Astrocytes and microglia are essential in inflammatory and oxidative defense that take place in neurodegenerative disease. In this work we evaluate antioxidant and anti-inflammatory potential bioactivity of whey peptide in glial cells. Peptides were formed during simulated gastrointestinal digestion (Infogest protocol), and low molecular weight (<5kDA) peptides (WPHf) attenuated reactive oxygen species (ROS) production induced by hydrogen peroxide stimulus in both cells in dose-dependent manner. WPHf induced an increase in the antioxidant glutathione (GSH) content and prevented GSH reduction induced by lipopolysaccharides (LPS) stimulus in astrocytes cells in a cell specific form. An increase in cytokine mRNA expression (TNFα and IL6) and nitric oxide secretion induced by LPS was attenuated by WPHf pre-treatment in both cells. The inflammatory pathway was dependent on NFκB activation. Bioactive peptide ranking analysis showed positive correlation with hydrophobicity and negative correlation with high molecular weights. The sequence identification revealed 19 peptides cross-referred with bioactive database. Whey peptides were rich in leucine, valine and tyrosine in the C-terminal region and lysine in the N-terminal region. The anti-inflammatory and antioxidant potential of whey peptides were assessed in glia cells and its mechanisms of action were related, such as modulation of antioxidant enzymes and anti-inflammatory pathways. Features of the peptide structure, such as molecular size, hydrophobicity and types of amino acids present in the terminal region are associated to bioactivity.

Procuring the polysaccharides with anti-inflammatory bioactivity from Russula vinosa Lindblad by citric acid extraction

Russula vinosa Lindblad is a wildly edible fungus that has been used as the health food due to its high content of bioactive constituents. This study investigated the anti-inflammatory bioactivity of two kinds of low-molecular-weight polysaccharides (CA-S and CA-L) extracted by citric acid (CA) from Russula vinosa Lindblad. The structure of CA-S and CA-L were identified using different characterization techniques. Structural characterization revealed that both CA-S and CA-L possessed a similar structure for the backbone but differed in the substitution sites and residues. CA-S and CA-L demonstrated the ability to ameliorate the damage of intestinal tissue in dextran sulfate sodium (DSS)-induced ulcerative colitis mice in vivo, the DAI values of CA-S and CA-L fed mice decreased by 36.84% and 31.58% respectively. This might be attributed to CA-S's higher Mw, increased content of OH groups, and an enriched mannose fraction. Immuno-analysis revealed that CA-S better reduced inflammation and oxidative-state-related stress by scavenging the endogenous reactive oxygen species through the activation of Nrf2 and suppression of the NFκB signaling pathways.

Garlic oil supplementation blocks inflammatory pyroptosis-related acute lung injury by suppressing the NF-κB/NLRP3 signaling pathway via H2S generation.

Acute lung injury (ALI) is a major cause of acute respiratory failure with a high morbidity and mortality rate, and effective therapeutic strategies for ALI remain limited. Inflammatory response is considered crucial for the pathogenesis of ALI. Garlic, a globally used cooking spice, reportedly exhibits excellent anti-inflammatory bioactivity. However, protective effects of garlic against ALI have never been reported. This study aimed to investigate the protective effects of garlic oil (GO) supplementation on lipopolysaccharide (LPS)-induced ALI models. Hematoxylin and eosin staining, pathology scores, lung myeloperoxidase (MPO) activity measurement, lung wet/dry (W/D) ratio detection, and bronchoalveolar lavage fluid (BALF) analysis were performed to investigate ALI histopathology. Real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay were conducted to evaluate the expression levels of inflammatory factors, nuclear factor-κB (NF-κB), NLRP3, pyroptosis-related proteins, and H2S-producing enzymes. GO attenuated LPS-induced pulmonary pathological changes, lung W/D ratio, MPO activity, and inflammatory cytokines in the lungs and BALF. Additionally, GO suppressed LPS-induced NF-κB activation, NLRP3 inflammasome expression, and inflammatory-related pyroptosis. Mechanistically, GO promoted increased H2S production in lung tissues by enhancing the conversion of GO-rich polysulfide compounds or by increasing the expression of H2S-producing enzymes in vivo. Inhibition of endogenous or exogenous H2S production reversed the protective effects of GO on ALI and eliminated the inhibitory effects of GO on NF-κB, NLRP3, and pyroptotic signaling pathways. Overall, these findings indicate that GO has a critical anti-inflammatory effect and protects against LPS-induced ALI by suppressing the NF-κB/NLRP3 signaling pathway via H2S generation.