Anti-inflammatory Bioactivities Research Articles

Portulaca Oleracea L. (Purslane) Extract Protects Endothelial Function by Reducing Endoplasmic Reticulum Stress and Oxidative Stress through AMPK Activation in Diabetic Obese Mice.

Portulaca oleracea L. (purslane) is a food and a traditional drug worldwide. It exhibits anti-inflammatory, anti-oxidative, anti-tumor, and anti-diabetic bioactivities; but its activity on diabetic-associated endothelial dysfunction is unknown. This study aimed to investigate the effect of purslane on endothelial function and the underlying mechanisms. Male C57BL/6 mice had 14-week ad libitum access to a high-fat rodent diet containing 60% kcal% fat to induce obesity and diabetes whereas purslane extract (200 mg/kg/day) was administered during the last 4 weeks via intragastric gavage. Primary rat aortic endothelial cells and isolated mouse aortas were cultured with a risk factor, high glucose or tunicamycin, together with purslane extract. By ESI-QTOF-MS/MS, flavonoids and their glycoside products were identified in the purslane extract. Exposure to high glucose or tunicamycin impaired acetylcholine-induced endothelium-dependent relaxations in aortas and induced endoplasmic reticulum (ER) stress and oxidative stress with the downregulation of 5' AMP-activated protein kinase (AMPK)/ endothelial nitric oxide synthase (eNOS) signaling. Co-incubation with purslane significantly ameliorated these impairments. The effects of purslane were abolished by Compound C (AMPK inhibitor). Four-week purslane treatment ameliorated aortic relaxations, ER stress, and oxidative stress in diabetic obese mice. This study supported that purslane protected endothelial function, and inhibited ER stress and oxidative stress in vasculature through AMPK/eNOS activation, revealing its therapeutic potential against vascular complications in diabetes.

Undescribed indole lactones from Alstonia scholaris protecting hepatic cell damage

Six previously undescribed rigidly monoterpenoid indole alkaloids, alstolactines F–K (1−6), were isolated from Alstonia scholaris. Among them, a pair of cage-like epimers, 1 and 2, featuring a rare 6/5/6/6/7 ring system, represent the first example of C5→C20-olide, while compound 3 possesses unique degraded C18 and C19. The structures of the isolates were established by multiple spectroscopic analyses, quantum computational chemistry methods, and X-ray diffraction. Furthermore, the expression levels of proteins including NLRP3, TLR4, P-p65, NF-ĸB, Notch-2, IL-18, P-p38, and p38 in LPS-induced human normal hepatocyte (LO2) cells could be significantly downregulated by compounds 1−6, which showed potent anti-inflammatory bioactivity.

Salvianolic acid B protects against pulmonary fibrosis by attenuating stimulating protein 1-mediated macrophage and alveolar type 2 cell senescence.

Idiopathic pulmonary fibrosis (IPF), as the most common idiopathic interstitial pneumonia, is caused by a complex interaction of pathological mechanisms. Interestingly, IPF frequently occurs in the middle-aged and elderly populations but rarely affects young people. Salvianolic acid B (SAB) exerts antioxidant, antiinflammatory, and antifibrotic bioactivities and is considered a promising drug for pulmonary disease treatment. However, the pharmacological effects and mechanisms of SAB on cellular senescence of lung cells and IPF development remain unclear. We used bleomycin (BLM)-induced pulmonary fibrosis mice and different lung cells to investigate the antisenescence impact of SAB and explain its underlying mechanism by network pharmacology and the Human Protein Atlas database. Here, we found that SAB significantly prevented pulmonary fibrosis and cellular senescence in mice, and reversed the senescence trend and typical senescence-associated secretory phenotype (SASP) factors released from lung macrophages and alveolar type II (AT2) epithelial cells, which further reduced lung fibroblasts activation. Additionally, SAB alleviated the epithelial-mesenchymal transition process of AT2 cells induced by transforming growth factor beta. By predicting potential targets of SAB that were then confirmed by chromatin immunoprecipitation-qPCR technology, we determined that SAB directly hampered the binding of transcription factor stimulating protein 1 to the promoters of SASPs (P21 and P16), thus halting lung cell senescence. We demonstrated that SAB reduced BLM-induced AT2 and macrophage senescence, and the subsequent release of SASP factors that activated lung fibroblasts, thereby dual-relieving IPF. This study provides a new scientific foundation and perspective for pulmonary fibrosis therapy.

Identification of Bioactive Solutions of Corn Silk (Zea mays L.) Extract and Biological Activity Test By Bioinformatics

Corn silk (Zea mays L.) is an agricultural by-product that is discarded as agricultural waste. Corn silk has secondary metabolite compounds that have the potential to become useful bioactive compounds. The purpose of this study is to recognize the bioactive potential of corn hair through compound identification and biological activity. The method used is preparation and extraction by maceration method followed by identification of compounds through LC-MS analysis method and Phytochemical test, bioinformatic PASS test based on data through PubChem, ChemSpider, and way2drug web. The results obtained from corn silk have a group of active compounds, including alkaloids, flavonoids, saponins, steroids and triterpenoids. Analysis of potential bioactivity received Acaciin compounds have high antioxidant bioactivity with a Pa value of 0.815, 2-arachidonoylglycerol has high potential antiinflammatory bioactivity with a Pa value of 0.736 and 1,2-di-O-methyl-4-[(2R)-2,4-dihydro butyramide shows moderate possible antibacterial activity with a Pa value of 0.643. This study concludes that corn silk has high bioactive potential as an antioxidant, anti-inflammatory and antibacterial.

Glycyrrhizin alleviates varicellovirus bovinealpha 1-induced oxidative stress, inflammation, and apoptosis in MDBK cells by inhibiting NF-κB/NLRP3 axis through the Nrf2 signalling pathway.

Varicellovirus bovinealpha 1 (BoAHV-1) is one of the crucial pathogens of bovine respiratory diseases, and its pathogenic mechanism involves oxidative stress, inflammation response, and apoptosis. Glycyrrhizin (GLY) possesses powerful antiviral, antioxidant, anti-inflammatory, and anti-apoptotic bioactivities. However, the anti-BoAHV-1 activity of GLY and its role in BoAHV-1-induced oxidative stress, inflammation, and apoptosis remain unclear. Therefore, the current study investigated the anti-BoAHV-1 effect of GLY and its ability to alleviate BoAHV-1-induced oxidative stress, inflammation, and apoptosis using an in vitro model (MDBK cells). Our results showed that BoAHV-1 titers significantly increased in MDBK cells after infection, and GLY reduced the BoAHV-1 titers in MDBK cells exposed to it. Furthermore, Interleukin (IL)-1β, IL-8, tumor necrosis factor (TNF)-α, phosphorylated NF-κB p65 (p-NF-κB p65), the NLR pyrin domain containing 3 (NLRP3), Caspase-1, and Cleaved Caspase-3 levels were significantly upregulated when MDBK cells were challenged with BoAHV-1. In BAY 11-7085 (a specific NF-κB inhibitor) treated MDBK cells, IL-1β, IL-8, TNF-α, p-NF-κB p65, NLRP3, Caspase-1, and Cleaved Caspase-3 levels were downregulated. Notably, GLY treatment had the same trend as the BAY 11-7085 treatment. Thus, these results suggested that GLY exerted anti-inflammatory and anti-apoptotic activities by blocking NF-κB/NLRP3 axis. In addition, after BoAHV-1 infection, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and p-NF-κB p65 and apoptosis rate were increased, and catalase (CAT) and glutathione peroxidase (GSH-Px) enzyme activities, as well as NF-E2-related nuclear factor erythroid-2 (Nrf2) protein expression were repressed. Compared with BoAHV-1-infected MDBK cells, GLY treatment significantly downregulated intracellular ROS, MDA, and p-NF-κB p65 levels and apoptotic rates and significantly increased intracellular CAT and GSH-Px enzyme activities and Nrf2 expression. Additionally, ML385 (a specific Nrf2 inhibitor) abolished the enhancing effect of GLY on Nrf2 and the attenuating effect on ROS, p-NF-κB p65, and apoptosis. These results suggested that GLY had an anti-BoAHV-1 effect and could mitigate BoAHV-1-induced oxidative stress, inflammation, and apoptosis by activating the Nrf2 signalling and restraining NF-κB/NLRP3 axis.

Apigenin's Therapeutic Potential Against Viral Infection.

Several antiviral drugs are clinically approved to treat influenza that is a highly prevalent acute respiratory disease. However, emerging drug-resistant virus strains undermine treatment efficacy, highlighting the exigency for novel antiviral drugs to counter these drug-resistant strains. Plants and their derivates have been historically utilized as medicinal remedies, and extensive studies have evidenced the antiviral potential of phytochemicals. Notably, apigenin is a predominant flavonoid with minimal toxicity and substantial therapeutic effects in various disease models. Despite its many anti-inflammatory, anti-oxidant, anti-cancer, anti-bacterial, and other beneficial bioactivities, existing reviews have yet to focus on apigenin's antiviral effects. Therefore, this review elucidates apigenin's therapeutic and antiviral properties in vitro and in vivo, discussing its mode of action and future prospects. Apigenin's remarkable inhibition by modulating multiple mechanisms against viruses has promising potential for novel plant-derived antiviral drugs and further clinical study developments.

Penidihydrocitrinins A-C: New Polyketides from the Deep-Sea-Derived Penicillium citrinum W17 and Their Anti-Inflammatory and Anti-Osteoporotic Bioactivities.

Three new polyketides (penidihydrocitrinins A-C, 1-3) and fourteen known compounds (4-17) were isolated from the deep-sea-derived Penicillium citrinum W17. Their structures were elucidated by comprehensive analyses of 1D and 2D NMR, HRESIMS, and ECD calculations. Compounds 1-17 were evaluated for their anti-inflammatory and anti-osteoporotic bioactivities. All isolates exhibited significant inhibitory effects on LPS-stimulated nitric oxide production in murine brain microglial BV-2 cells in a dose-response manner. Notably, compound 14 displayed the strongest effect with the IC50 value of 4.7 µM. Additionally, compounds 6, 7, and 8 significantly enhanced osteoblast mineralization, which was comparable to that of the positive control, purmorphamine. Furthermore, these three compounds also suppressed osteoclastogenesis in a dose-dependent manner under the concentrations of 2.5 μM, 5.0 μM, and 10 μM.

Bioavailability of bioactive compounds in Hibiscus sabdariffa beverage as a potential anti-inflammatory

The absorption and metabolism of bioactive compounds (BCs) in a Hibiscus sabdariffa drink (HbD) were evaluated by the in vivo bioavailability of organic acids (OA) and phenolic compounds (PC’s). An acute single-blind clinical study in humans was conducted. Twelve volunteers consumed a HbD and a control drink (CD). Urine and plasma samples were taken after consuming both beverages. OA and PC’s of the beverages (HbD and CD) and the biological samples (urine and plasma) were characterized by HPLC-DAD-MS. Thirthy-eight compounds in HbD and four CD were detected and quantified, equivalent to 937.37 mg and 1.22 mg per 60 mL, respectively. Hibiscus acid was the most abundant OA in both drinks.Additionally, hydroxycinnamic acids, flavonoids, anthocyanins, and anthocyanidins were also detected in HbD, although their amount represented 10% of the total BCs. 25 different metabolites were identified, 15 in urine and 23 in plasma. The microbiota extensively biotransformed PCs and their amount was lower than organic acids, particularly hibiscus acid and hydroxycitric acid. The colonic metabolites derived from PCs and organic acids would be behind the anti-inflammatory bioactivity described for Hibiscus sabdariffa L. (Malvaceae family). However, further studies are necessary to evaluate the metabolites responsible for their anti-inflammatory activity.

Review of bioactive components property of Malaysian propolis: A review

Over the past few decades, traditional medicinal products have grown in popularity. It is estimated that 80% of patients worldwide use them for basic health treatment. Due to its extraordinary bioactive properties, propolis is a bee product commonly utilised in alternative medicines. Propolis is a complicated mixture of substances, procured by bees from diverse vegetations and mix them with beeswax and bee saliva enzymes. Propolis bioactivities have been examined and reported in the treatments of numerous chronic diseases. Given the differences in pharmacological activity and compound markup of propolis, huge variation exists due to numerous hive localities. This study intends to define and explore the bioactive qualities of propolis in Malaysia. Information on the antibacterial, antioxidant, anti-inflammatory, and other bioactivity properties from studies conducted on Malaysian propolis have been consolidated in this review. This research would result in an enhanced understanding of the safe consumption of Malaysian propolis and may spur the development of novel and more affordable treatments for various infections.

A biofunctional review of C-reactive protein (CRP) as a mediator of inflammatory and immune responses: differentiating pentameric and modified CRP isoform effects.

C-reactive protein (CRP) is an acute phase, predominantly hepatically synthesized protein, secreted in response to cytokine signaling at sites of tissue injury or infection with the physiological function of acute pro-inflammatory response. Historically, CRP has been classified as a mediator of the innate immune system, acting as a pattern recognition receptor for phosphocholine-containing ligands. For decades, CRP was envisioned as a single, non-glycosylated, multi-subunit protein arranged non-covalently in cyclic symmetry around a central void. Over the past few years, however, CRP has been shown to exist in at least three distinct isoforms: 1.) a pentamer of five identical globular subunits (pCRP), 2.) a modified monomer (mCRP) resulting from a conformational change when subunits are dissociated from the pentamer, and 3.) a transitional isoform where the pentamer remains intact but is partially changed to express mCRP structural characteristics (referred to as pCRP* or mCRPm). The conversion of pCRP into mCRP can occur spontaneously and is observed under commonly used experimental conditions. In careful consideration of experimental design used in published reports of in vitro pro- and anti-inflammatory CRP bioactivities, we herein provide an interpretation of how distinctive CRP isoforms may have affected reported results. We argue that pro-inflammatory amplification mechanisms are consistent with the biofunction of mCRP, while weak anti-inflammatory mechanisms are consistent with pCRP. The interplay of each CRP isoform with specific immune cells (platelets, neutrophils, monocytes, endothelial cells, natural killer cells) and mechanisms of the innate immune system (complement), as well as differences in mCRP and pCRP ligand recognition and effector functions are discussed. This review will serve as a revised understanding of the structure-function relationship between CRP isoforms as related to inflammation and innate immunity mechanisms.

Synthetic Strategies for Quinoline Based Derivatives as Potential Bioactive Heterocycles.

Quinoline derivatives are an important class of heterocyclic compounds and possess various applications in synthetic organic chemistry, medicinal chemistry, material chemistry and natural product chemistry. This review article describes the different quinoline derivatives having antimalarial, analgesic, anti-inflammatory, antineoplastic, antibacterial, antifungal, antiviral, anthelmintic, antiprotozoal, cardiovascular, CNS and other useful bioactivities. We have delineated the general synthetic routes for the synthesis of many bioactive quinoline based heterocycles. In addition to this, we have also discussed the crucial synthetic routes as well as their mechanistic paths for the formation of bioactive quinoline derivatives. The study shows that substitution at the 4 and 8- position of quinoline is more crucial for bioactivity as compared to other positions.

The Impact of Elevated Atmospheric Carbon Dioxide Exposure on Magic Tomatoes' Nutrition-Health Properties.

The release of carbon dioxide (CO2) into the atmosphere has accelerated during the last two decades. Elevated atmospheric CO2 concentration (eCO2) is known as an agent that improves plant photosynthesis. However, eCO2 was also correlated with alterations in the macronutrient and micronutrient compositions of various dietary crops. In order to explore the effect of eCO2 on the nutritional and health properties of tomatoes, three parental lines of the Magic population, which includes a large part of the genetic diversity present in large fruit varieties, were used as models. The plants were grown in growth chambers under ambient (400 ppm) or eCO2 (900 ppm) conditions. The macronutrient and micronutrient contents were measured. The anti-oxidant and anti-inflammatory bioactivities were assessed in vitro on activated macrophages. These analyses highlighted that the carbohydrate content was not affected by the eCO2, whereas the protein, carotenoid, lycopene, and mineral contents decreased. Regarding the anti-oxidant properties, no influence of eCO2 exposure was observed. Similarly, the anti-inflammatory properties were not affected by the eCO2. These data are in contrast with previous studies conducted on different plant species or accessions, indicating that the effect of eCO2 on crops' nutrition and health properties is based on complex mechanisms in which growth conditions and genetic backgrounds play a central role.

Sarcococca saligna fabricated gold nanoparticles alleviated in vitro oxidative stress and inflammation in human adipose-derived stem cells.

Oxidative stress is a destructive phenomenon that affects various cell structures including membranes, proteins, lipoproteins, lipids, and DNA. Oxidative stress and inflammation owing to lifestyle changes may lead to serious diseases such as Cancers, Gout, and Arthritis etc. These disorders can be prevented using different therapeutic strategies including nanomedicine. Biosynthesized gold nanoparticles (GNPs) because of their anti-inflammatory and antioxidant bioactivities can be key player in reversal of these ailments. This study was carried out to evaluate the anti-inflammatory and antioxidant potential of bio fabricated GNPs with Sarcococca saligna (S. saligna) extract on injured human adipose-derived Mesenchymal stem cells (hADMSCs). GNPs were characterized by ultraviolet-visible (UV-Vis) spectroscopy, Scanning Electron Microscopy (SEM), x-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and energy dispersive x-ray (EDS). Phytochemical screening of biosynthesized GNPs exhibited a significant release of polyphenols, that is, total phenolic content (TPC) and total flavonoid content (TFC). GNPs priming amended the in vitro injury caused by Monosodium Iodoacetate (MIA) as exhibited by improved cell viability, wound closure response and superoxide dismutase activity (SOD). The anti-inflammatory conduct assessed through NF-κB pathway and other associated inflammatory markers reported down-regulation of TNF-α (0.644 ± 0.045), IL-1β (0.694 ± 0.147) and IL-6 (0.622 ± 0.112), apoptosis causing genes like Caspase-3 (0.734 ± 0.13) and BAX (0.830 ± 0.12), NF-κB pathway, p65 (0.672 ± 0.084) and p105 (0.539 ± 0.083) associated genes. High SOD activity (95 ± 5.25%) revealed by treated hADMSCs with GNPs also supported the antioxidant role of GNPs in vitro model. This study concludes that S. saligna bio fabricated GNPs priming may improve the therapeutic potential of hADMSCs against chronic inflammatory problems by regulating NF-κB pathway.

High performance anion exchange chromatography purification of probiotic bacterial extracellular vesicles enhances purity and anti-inflammatory efficacy.

Bacterial extracellular vesicles (BEVs), including outer membrane vesicles, have emerged as a promising new class of vaccines and therapeutics to treat cancer and inflammatory diseases, among other applications. However, clinical translation of BEVs is hindered by a current lack of scalable and efficient purification methods. Here, we address downstream BEV biomanufacturing limitations by developing a method for orthogonal size- and charge-based BEV enrichment using tangential flow filtration (TFF) in tandem with high performance anion exchange chromatography (HPAEC). The data show that size-based separation coisolated protein contaminants, whereas size-based TFF with charged-based HPAEC dramatically improved purity of BEVs produced by probiotic Gram-negative Escherichia coli and Gram-positive lactic acid bacteria (LAB). Escherichia coli BEV purity was quantified using established biochemical markers while improved LAB BEV purity was assessed via observed potentiation of anti-inflammatory bioactivity. Overall, this work establishes orthogonal TFF + HPAEC as a scalable and efficient method for BEV purification that holds promise for future large-scale biomanufacturing of therapeutic BEV products.

Multitargeted pharmacokinetics, molecular docking and network pharmacology-based identification of effective phytocompounds from Sauropus androgynus (L.) Merr for inflammation and cancer treatment

According to worldwide health data, cancer, and inflammatory illnesses are on the rise and are among the most common causes of death. Across the world, these types of health problems are now considered top priorities for government health organizations. Hence, this study aimed to investigate medicinal plants’ potential for treating cancer and inflammatory disorders. This network pharmacology analysis aims to learn more about the potential targets and mechanisms of action for the bioactive ingredients in Sauropus androgynus (L.) Merr L. The compound-target network and protein-protein interaction analysis were built using the STRING database. Using Network Analyst, Gene Ontology, and Kyoto Encyclopaedia of Genes and Genomes, pathway enrichment was performed on the hub genes. 1-hexadecanol was shown to inhibit drug-metabolizing enzymes in a pharmacokinetic investigation. Those samples of 1-hexadecanol were found to be 1-hexadecanol (BBB 0.783), GI High, Pgp Substrate Yes, CYP2C19 Inhibitor Yes, CYP2D6 Yes, and HI −89.803. The intermolecular binding energies for 1-hexadecanol (4-DRI, −8.2 kcal/mol) are evaluated. These results from a study on S. androgynus used molecular docking and network pharmacology to gain insight into the prime target genes and potential mechanisms identified for AKT1, mTOR, AR, PPID, FKBP5, and NR3C1. The PI3K-Akt signalling pathway has become an important regulatory node in various pathological processes requiring coordinated actions. Stability and favourable conformations have been resolved by considering nonbonding interactions such as electrostatic and hydrogen bonds in MD simulations of the perfect molecules using the Desmond package. Thus, using an appropriate platform of network pharmacology, molecular docking, and in vitro experiments, this study provides for the first time a clearer knowledge of the anti-cancer and anti-inflammatory molecular bioactivities of S. androgynus. Further in vitro and in vivo confirmations are strongly needed to determine the efficacy and therapeutic effects of 1-hexadecanol in the biological process. Communicated by Ramaswamy H. Sarma

Curcumin and colon cancer: from preclinical to clinical studies

In the US, colon cancer has the third most mortality. Though new managements have reported upgraded prognosis, the five-year survival rates of patients with general or metastatic colon cancer are still unsatisfied at 64.7% and 20%, respectively. As a result, more innovative therapies or drugs with high efficacy should be developed. Curcumin, a natural chemical compound, is now in the spotlight of both preclinical and clinical trials on colon cancer. It not only exerts exceptional anti-cancer effects, but also anti-inflammatory and antiviral bio-activities. However, curcumin shows low bioavailability when orally administered. To resolve this issue, nanoparticles have been widely utilized. In this review, we precisely summarize the effects of curcumin on colon cancer in both preclinical and clinical studies. In vitro studies, curcumin could arrest cell cycle at the G2/M phase as well as part of the G1 phase, and induce cell apoptosis by binding to targeted molecules. Except for this, epigenetic alterations could also induce colon cancer. Both in vitro and in vivo studies have proved that curcumin could remarkably influence the prognosis. Moreover, genetically designed murine models which were orally administered with curcumin demonstrated satisfactory effects on colon cancer induced by different factors. More importantly, curcumin alone or as an adjuvant showed satisfactory results in numerous clinical trials. In conclusion, curcumin demonstrated outstanding anti-cancer activity against colon cancer.

Single-Component Self-Healing Antibacterial Anti-Inflammatory Intracellular-Antioxidative Poly(itaconic acid-pluronic) Hydrogel for Rapid Repair of MRSA-Impaired Wound.

The rapid healing and repair of multidrug-resistant bacteria infected wound is still a challenge in the field of wound surgery. It is an effective strategy to develop multifunctional bioactive biomaterials with anti-infection therapy and promoting tissue regeneration. However, most of conventional multifunctional wound healing biomaterials possess the complicated composition and fabrication procedure, which may limit their clinical transformation. Herein, we report a single-component multifunctional bioactive self-healing scaffold (itaconic acid-pluronic-itaconic acid) (FIA) with robust antibacterial antioxidant anti-inflammatory bioactivity for treating methicillin-resistant Staphylococcus aureus (MRSA) impaired wound. FIA scaffolds exhibited the temperature-responsive sol-gel behavior, good injectability, and broad-spectrum antibacterial activity (100% inhibition rate against S. aureus, E. coli, and MRSA). FIA possessed favorable hemocompatibility and cell compatibility and even stimulated the cellular proliferation. FIA could efficiently scavenge the intracellular reactive oxygen species (ROS), decrease the inflammation factors expression, promote endotheliocyte migration and blood tube formation, and reduce the M1 phenotype of macrophages in vitro. FIA could significantly clear the MRSA infection, speed up the MRSA-infected wound healing and rapid formation of the normal epithelial layer and skin appendages. This work may provide a simple and efficient multifunctional bioactive biomaterial strategy for overcoming the challenge of the MRSA-impaired wound.

Induced Pluripotent Stem Cell-Derived Extracellular Vesicles Promote Wound Repair in a Diabetic Mouse Model via an Anti-Inflammatory Immunomodulatory Mechanism.

Extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) have recently been explored in clinical trials for treatment of diseases with complex pathophysiologies. However, production of MSC EVs is currently hampered by donor-specific characteristics and limited ex vivo expansion capabilities before decreased potency, thus restricting their potential as a scalable and reproducible therapeutic. Induced pluripotent stem cells (iPSCs) represent a self-renewing source for obtaining differentiated iPSC-derived MSCs (iMSCs), circumventing both scalability and donor variability concerns for therapeutic EV production. Thus, it is initially sought to evaluate the therapeutic potential of iMSC EVs. Interestingly, while utilizing undifferentiated iPSC EVs as a control, it is found that their vascularization bioactivity is similar and their anti-inflammatory bioactivity is superior to donor-matched iMSC EVs in cell-based assays. To supplement this initial in vitro bioactivity screen, a diabetic wound healing mouse model where both the pro-vascularization and anti-inflammatory activity of these EVs would be beneficial is employed. In this in vivo model, iPSC EVs more effectively mediate inflammation resolution within the wound bed. Combined with the lack of additional differentiation steps required for iMSC generation, these results support the use of undifferentiated iPSCs as a source for therapeutic EV production with respect to both scalability and efficacy.

The evaluation of stability and bioactivity of xanthone nanoemulsion

The α-mangostin, a lipophilic xanthone derivative, has a low bioavailability. It was, however, isolated from mangosteen rind, which has antioxidant and antimicrobial activity. Oil in water (O/W) Nanoemulsion as drug delivery can stabilize lipophilic drug into core and increase bioavailability. The α-mangostin nanoemulsion (MN) was formulated with various surfactant (Tween 20, Tween 80, Span 20 and Span 80), co-surfactant (Span 20 and Span 80) and oil (Jojoba oil (JO), as well as evening primrose oil (EO), EMOGREENTM19 (E19) and EMOGREENTM15 (E15)). It was found that at 7.5–10% by weight of Tween 80 as surfactant was appropriate for MN formulation. The type of oil influenced droplet size and pH value of MN. The result showed that MN droplet size is bigger in vegetable oil than in hydrocarbon oil. However, its pH value is lower in vegetable oil than that in hydrocarbon oil. For three months, all MN droplet sizes were increased. Interestingly, MN using tween 80 as surfactant can provide good stability during that time. Moreover, MN exhibits anti-oxidant (SC50, 23.07 ± 0.84 μg/mL) and anti-inflammatory (IC50, 12.06 ± 0.99 μg/mL) bioactivities.

Antioxidant Capacity and NF-kB-Mediated Anti-Inflammatory Activity of Six Red Uruguayan Grape Pomaces.

Grape pomaces have a wide and diverse antioxidant phenolics composition. Six Uruguayan red grape pomaces were evaluated in their phenolics composition, antioxidant capacity, and anti-inflammatory properties. Not only radical scavenging methods as DPPH· and ABTS·+ were employed but also ORAC and FRAP analyses were applied to assess the antioxidant potency of the extracts. The antioxidant reactivity of all extracts against hydroxyl radicals was assessed with ESR. The phenol profile of the most bioactive extract was analyzed by HPLC-MS, and a set of 57 structures were determined. To investigate the potential anti-inflammatory activity of the extracts, Nuclear Factor kappa-B (NF-κB) modulation was evaluated in the human colon cancer reporter cell line (HT-29-NF-κB-hrGFP). Our results suggest that Tannat grapes pomaces have higher phenolic content and antioxidant capacity compared to Cabernet Franc. These extracts inhibited TNF-alpha mediated NF-κB activation and IL-8 production when added to reporter cells. A molecular docking study was carried out to rationalize the experimental results allowing us to propose the proactive interaction between the NF-κB, the grape extracts phenols, and their putative anti-inflammatory bioactivity. The present findings show that red grape pomace constitutes a sustainable source of phenolic compounds, which may be valuable for pharmaceutical, cosmetic, and food industry applications.