Mediterranean diet in the targeted prevention and personalized treatment of chronic diseases: evidence, potential mechanisms, and prospects.

The prevalence of chronic diseases is currently a major public health issue worldwide and is exploding with the population growth and aging. Dietary patterns are well known to play a important role in our overall health and well-being, and therefore, poor diet and malnutrition are among the most critical risk factors for chronic disease. Thus, dietary recommendation and nutritional supplementation have significant clinical implications for the targeted treatment of some of these diseases. Multiple dietary patterns have been proposed to prevent chronic disease incidence, like Dietary Approaches to Stop Hypertension (DASH) and Diabetes Risk Reduction Diet (DRRD). Among them, the MedDiet, which is one of the most well-known and studied dietary patterns in the world, has been related to a wide extent of health benefits. Substantial evidence has supported an important reverse association between higher compliance to MedDiet and the risk of chronic disease. Innovative strategies within the healthcare framework of predictive, preventive, and personalized medicine (PPPM/3PM) view personalized dietary customization as a predictive medical approach, cost-effective preventive measures, and the optimal dietary treatment tailored to the characteristics of patients with chronic diseases in primary and secondary care. Through a comprehensive collection and review of available evidence, this review summarizes health benefits of MedDiet in the context of PPPM/3PM for chronic diseases, including cardiovascular disease, hypertension, type 2 diabetes, obesity, metabolic syndrome, osteoporosis, and cancer, thereby a working hypothesis that MedDiet can personalize the prevention and treatment of chronic diseases was derived.

Phenylboronic acid functionalized dextran loading curcumin as nano-therapeutics for promoting the bacteria-infected diabetic wound healing.

Chronic bacterial infections, excessive inflammation, and oxidative stress significantly hinder diabetic wound healing by prolonging the inflammatory phase and complicating the healing process. In this study, phenylboronic acid functionalized dextran (PODP) was developed to encapsulate curcumin, referred to as PODP@Cur. Experimental results indicate that PODP significantly improves the water solubility of curcumin and exhibits synergistic biological activity both in vitro and in vivo. PODP@Cur is capable of accelerating drug release under the pathological microenvironment with ROS accumulation. Furthermore, phenylboronic acid (PBA) has demonstrated potential for targeted bacterial drug delivery, enhancing antibacterial efficacy and trapping free LPS/PGN from dead bacteria to reduce undesirable inflammation. In a diabetic mouse model, PODP@Cur exhibits an excellent antibacterial, anti-inflammatory and antioxidant activities to ultimately promote the efficient and safe wound healing. Due to the specific interaction between PBA and LPS, PODP@Cur could enhance antibacterial activity against bacteria, reduce toxic side effects on normal cells, and alleviate the LPS-mediated pro-inflammatory pathological microenvironment. Therefore, PODP@Cur is capable of being exploited as an efficient and safe candidate for promoting the bacteria-infected diabetic wound healing.

Unraveling the parahormetic mechanism underlying the health-protecting effects of grapeseed procyanidins.

Proanthocyanidins (PACs), the predominant constituents within Grape Seed Extract (GSE), are intricate compounds composed of interconnected flavan-3-ol units. Renowned for their health-affirming properties, PACs offer a shield against a spectrum of inflammation associated diseases, such as diabetes, obesity, degenerations and possibly cancer. While monomeric and dimeric PACs undergo some absorption within the gastrointestinal tract, their larger oligomeric and polymeric counterparts are not bioavailable. However, higher molecular weight PACs engage with the colonic microbiota, fostering the production of bioavailable metabolites that undergo metabolic processes, culminating in the emergence of bioactive agents capable of modulating physiological processes. Within this investigation, a GSE enriched with polymeric PACs was employed to explore in detail their impact. Through comprehensive analysis, the present study unequivocally verified the gastrointestinal-mediated transformation of medium to high molecular weight polymeric PACs, thereby establishing the bioaccessibility of a principal catabolite termed 5-(3',4'-dihydroxyphenyl)-γ-valerolactone (VL). Notably, our findings, encompassing cell biology, chemistry and proteomics, converge to the proposal of the notion of the capacity of VL to activate, upon oxidation to the corresponding quinone, the nuclear factor E2-related factor 2 (Nrf2) pathway-an intricate process that incites cellular defenses and mitigates stress-induced responses, such as a challenge brought by TNFα. This mechanistic paradigm seamlessly aligns with the concept of para-hormesis, ultimately orchestrating the resilience to stress and the preservation of cellular redox equilibrium and homeostasis as benchmarks of health.

Study on the Biotransformation and Activities of Astragalosides from Astragali Radix In Vitro and In Vivo.

Astragalosides (AGs), as one of the main active ingredients in Astragali Radix (AR), have a series of biological activities. Previous studies have only qualitatively identified the metabolites of AGs in AR, resulting in a lack of quantification. In the present study, the original material was selected from 12 origins based on the levels of 4 AGs by high-performance liquid chromatography (HPLC). The prototype components and metabolites of total AGs (TAGs) in feces, urine, and plasma samples of rats were thoroughly screened and characterized by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). The fermentation reaction and metabolites were verified by human fecal TAG fermentation in vitro. The metabolites of AG I, II, and IV transformed by human feces at different times were identified using UHPLC-HRMS, and the partial metabolites were quantified by HPLC. Furthermore, the anti-inflammatory and antioxidant activities of the metabolites were evaluated based on 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells in vitro. In total, 13 AGs and 170 metabolites were identified in TAGs as well as in the plasma, urine, and feces of Sprague-Dawley (SD) rats by UHPLC-HRMS, including 28, 36, and 170 metabolites in the plasma, urine, and feces, respectively. The metabolites included the products of deglycosylation, demethylation, hydroxylation, glucuronidation, sulfation, and cysteine-binding reactions. Moreover, the TAG fermentation results in vitro showed great similarity. The human fecal incubation experiments for AG I, II, and IV demonstrated that the metabolic reaction of TAGs mainly occurred in intestinal feces and that deglycosylation, demethylation, and hydroxylation were the main pathways of their metabolism. HPLC quantitative analysis of the transformation solution at different time points showed that AGs were transformed into secondary glycosides [cycloastragenol-6-glucoside (CAG-6-glucoside)] and aglycones [cycloastragenol (CAG)] through a deglycosylation reaction. Analysis of the pharmacological activity showed that the anti-inflammatory and antioxidant activities of the metabolites were associated with the levels of the corresponding aglycones. Further, metabolic profiles of the TAGs were constructed. Overall, this study revealed the metabolic process of AGs in the intestine, providing guidance for the metabolism and pharmacological effects of other saponins.

Glucagon-Like Peptide-1 Inhibits the Progression of Abdominal Aortic Aneurysm in Mice: The Earlier, the Better.

OBJECTIVES: Glucagon-like peptide-1 (GLP-1) has a cardiovascular protective effect by preventing abdominal aortic aneurysm (AAA) formation. However, it is unclear at what point the agent should be administered to achieve the optimal effect. In this study, we aimed to determine whether administering the GLP-1 receptor agonist liraglutide during the earlier stages would more efficiently inhibit AAA progression in mice. METHODS: Depending on the group, mice were given a daily dose of 300 µg/kg liraglutide for 28 days at 7, 14, and 28 days after aneurysm induction. The morphology of the abdominal aorta was monitored using 7.0 T magnetic resonance imaging (MRI) during the administration of liraglutide. After 28 days of administration, the AAA dilatation ratio was calculated, and histopathological examination was performed. Oxidative stress levels were evaluated by the expression of malondialdehyde (MDA) and matrix metalloproteinases (MMPs). The inflammatory response was also evaluated. RESULTS: Liraglutide treatment led to a decrease in AAA formation, including a reduction in abdominal aorta expansion, elastin degradation in the elastic laminae, and vascular inflammation caused by leukocyte infiltration. The expression of MDA and the activity of MMPs (MMP-2, MMP-9) also decreased. Notably, administering liraglutide during the early stages resulted in a significant reduction in the dilatation rate of the aortic wall, as well as in MDA expression, leukocyte infiltration, and MMP activity in the vascular wall. CONCLUSIONS: The GLP-1 receptor agonist liraglutide was found to inhibit AAA progression in mice by exerting anti-inflammatory and antioxidant effects, particularly during the early stages of AAA formation. Therefore, liraglutide may represent a potential pharmacological target for the treatment of AAA.

Protein-spatiotemporal partition releasing gradient porous scaffolds and anti-inflammatory and antioxidant regulation remodel tissue engineered anisotropic meniscus.

Meniscus is a wedge-shaped fibrocartilaginous tissue, playing important roles in maintaining joint stability and function. Meniscus injuries are difficult to heal and frequently progress into structural breakdown, which then leads to osteoarthritis. Regeneration of heterogeneous tissue engineering meniscus (TEM) continues to be a scientific and translational challenge. The morphology, tissue architecture, mechanical strength, and functional applications of the cultivated TEMs have not been able to meet clinical needs, which may due to the negligent attention on the importance of microenvironment in vitro and in vivo. Herein, we combined the 3D (three-dimensional)-printed gradient porous scaffolds, spatiotemporal partition release of growth factors, and anti-inflammatory and anti-oxidant microenvironment regulation of Ac2-26 peptide to prepare a versatile meniscus composite scaffold with heterogeneous bionic structures, excellent biomechanical properties and anti-inflammatory and anti-oxidant effects. By observing the results of cell activity and differentiation, and biomechanics under anti-inflammatory and anti-oxidant microenvironments in vitro, we explored the effects of anti-inflammatory and anti-oxidant microenvironments on construction of regional and functional heterogeneous TEM via the growth process regulation, with a view to cultivating a high-quality of TEM from bench to bedside.

The potential of glycyrrhizin and licorice extract in combating COVID-19 and associated conditions.

Background: Several recent studies have stated that glycyrrhizin and licorice extract are present in most traditional Chinese medicine formulas used against SARS-CoV-2 in China. Significant data are showing that glycyrrhizin and licorice extract have multiple beneficial activities in combating most features of SARS-CoV-2. Purpose: The aim of current review was to highlight recent progresses in research that showed the evidence of the potential use of glycyrrhizin and licorice extract against COVID-19. Methodology: We have reviewed the information published from 1979 to October 2020. These studies demonstrated the effects , use and safety of glycyrrhizin and icorice extract against viral infections,bacterial infections, inflammatory disorders of lung ( in vitro and in vivo).  These studies were collated through online electronic databases research (Academic libraries as PubMed, Scopus, Web of Science and Egyptian Knowledge Bank). Results: Pooled effect size of articles provides information about the rationale for using glycyrrhizin and licorice extract to treat COVID-19. Fifty studies demonstrate antiviral activity of glycyrrhizin and licorice extract. The most frequent mechanism of the antiviral activity is due to disrupting viral uptake into the host cells and disrupting the interaction between receptor- binding domain (RBD) of SARS-COV2 and ACE2 in recent articles. Fifty studies indicate that glycyrrhizin and licorice extract have significant antioxidant, anti-inflammatory and immunomodulatory effects. Twenty five studies provide evidence for the protective effect of glycyrrhizin and licorice extract against inflammation-induced acute lung injury and cardiovascular disorders. Conclusion: The current study showed several evidence regarding the beneficial effects of glycyrrhizin and licorice extract in combating COVID-19. More randomized clinical trials are needed to obtain a precise conclusion.

An anti-inflammatory salmachroman from the sea urchin Salmacis bicolor: a prospective duel inhibitor of cyclooxygenase-2 and 5-lipoxygenase.

An isochroman derived polyketide, salmachroman characterized as methyl 153(11-(10-hydroxy-12-oxo-6-pent-63-en-61-yl)isochroman-10-yl)-13-oxotetrahydrofuran-15-yl was isolated from the organic extract of the Echinodermata sea urchin Salmacis bicolor (family Temnopleuridae) through chromatographic fractionation. The structure of the compound was identified by detailed spectroscopic techniques. Salmachroman demonstrated significant duel inhibition potential against pro-inflammatory enzymes, cyclooxygense-2 (IC50 1.29 mM) and 5-lipoxygenase (IC50 1.39 mM). The compound exhibited significantly greater anti-inflammatory selectivity index (1.03) than that displayed by the anti-inflammatory agent ibuprofen (0.43). The isochroman analogue exhibited greater antioxidant activities against 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (IC50 1.19 mM) and 2,2-diphenyl-1-picrylhydrazyl (IC50 1.24 mM) than the standard antioxidative agent α-tocopherol (IC50 > 1.50 mM). The binding properties of the compound with the active site of cyclooxygense-2 and 5-lipoxygenase enzymes, combined with its higher electronic parameters as attributed by the structure-activity relationship accounted for its significant anti-inflammatory properties.

Hyrtioscalaranes A and B, two new scalarane-type sesterterpenes from Hyrtios erectus with anti-inflammatory and antioxidant effects.

Two new scalarane-type sesterterpenes, hyrtioscalaranes A and B, were isolated from the organic extract of the Demosponge Hyrtios erectus through extensive chromatographic purification. Hyrtioscalarane A exhibited significantly greater attenuation property against cyclooxygense-2 (IC50 0.83 mM) than that displayed by hyrtioscalarane B (IC50 0.98 mM). The greater selectivity index of hyrtioscalaranes (> 1) than that exhibited by the commercial anti-inflammatory agent ibuprofen (0.43) further supported the higher selectivity of the former towards pro-inflammatory cyclooxygenase-2. Hyrtioscalarane A exhibited greater antioxidant activities as determined by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (IC50 0.77 mM) and 2,2-diphenyl-1-picrylhydrazyl (IC50 0.81 mM) free radical quenching properties than those displayed by hyrtioscalarane B (IC50 > 0.83 mM) and the antioxidative agent α-tocopherol (IC50 1.51 mM). The greater binding energy (-14.32 kcal/mol) and docking score (15.22 kcal/mol) of hyrtioscalarane A at the active site of cyclooxygenase-2 along with the higher electronic parameters and balanced hydrophobicity could attribute its potential anti-inflammatory activity.

L-linalool exerts a neuroprotective action on hemiparkinsonian rats.

Linalool (LIN) is a monoterpene, responsible for the aroma of essential oils in some species. It presents a sedative and anxiolytic potential, enhancing GABAergic currents and behaving as a benzodiazepine-type of drug. The objectives of the present work were to study the neuroprotective effects of LIN on a model of Parkinson's disease. For that, male Wistar rats were divided into the following groups: sham-operated (SO), 6-OHDA-lesioned, and 6-OHDA-lesioned and treated with LIN (25, 50, and 100 mg/kg, p.o.) for 2 weeks. Afterwards, the animals were subjected to behavioral tests (apomorphine-induced rotations, open field, and forced swimming tests). Then, the animals were euthanized, and the striatum, hippocampus, and prefrontal cortex were processed for neurochemistry (nitrite and lipoperoxidation measurements) and immunohistochemistry (TH and DAT) assays. The results were analyzed by ANOVA and Tukey's test for multiple comparisons and considered significant at p < 0.05. LIN significantly improved the behavioral alterations of the 6-OHDA-lesioned group, as evaluated by the apomorphine-induced rotations, open field, and forced swimming tests. In addition, LIN partially reversed the decreased DA, DOPAC, and HVA contents observed in the 6-OHDA-lesioned striatum. The untreated 6-OHDA group presented increased nitrite contents and lipoperoxidation in all the brain areas studied, and these changes were completely reversed after LIN treatments. Finally, LIN significantly prevented the reduction in TH and DAT expressions demonstrated in the right 6-OHDA-lesioned striatum. All these data strongly suggest that LIN presents a neuroprotective action in hemiparkinsonian rats, probably related to the drug anti-inflammatory and antioxidant activities.

Polyphenolic Fraction from Olive Mill Wastewater: Scale-Up and in Vitro Studies for Ophthalmic Nutraceutical Applications.

The valorization of food wastes is a challenging opportunity for a green, sustainable, and competitive development of industry. Approximately 30 million m3 of olive mill wastewater (OMWW) are produced annually in the world as a by-product of the olive oil extraction process. In addition to being a serious environmental and economic issue because of their polluting load, OMWW can also represent a precious resource of high-added-value molecules such as polyphenols that show acclaimed antioxidant and anti-inflammatory activities and can find useful applications in the pharmaceutical industry. In particular, the possibility to develop novel nutraceutical ophthalmic formulations containing free radical scavengers would represent an important therapeutic opportunity for all inflammatory diseases of the ocular surface. In this work, different adsorbents were tested to selectively recover a fraction that is rich in polyphenols from OMWW. Afterward, cytotoxicity and antioxidant/anti-inflammatory activities of polyphenolic fraction were evaluated through in vitro tests. Our results showed that the fraction (0.01%) had no toxic effects and was able to protect cells against oxidant and inflammatory stimulus, reducing reactive oxygen species and TNF-α levels. Finally, a novel stable ophthalmic hydrogel containing a polyphenolic fraction (0.01%) was formulated and the technical and economic feasibility of the process at a pre-industrial level was investigated.

Phytochemical study and anti-inflammatory and antioxidant potential of Spondias mombin leaves

Abstract Spondias mombin L., Anacardiaceae, is a plant native of Brazil, where it is known as "cajá". In order to find a potential application for this native species, the anti-inflammatory and antioxidant effects were investigated. The anti-inflammatory activity was evaluated using the in vivo model carrageenan-induced peritonitis in mice. The in vitro antioxidant potential as well the cytotoxicity against 3T3 fibroblast cells also were evaluated. Through High Performance Liquid Chromatography-diode array detector analysis, an analytic method was developed and validated. It allowed the identification and quantification of ellagic acid and chlorogenic acid in hydroethanolic extract of S. mombin leaves. This extract showed anti-inflammatory effect at 100, 200, 300 and 500 mg/kg, however, the ethyl acetate fraction, at 200 mg/kg, showed the highlighted results. Ellagic acid and chlorogenic acid (2.5, 5 and 10 mg/kg) also inhibited the leukocyte migration to the site of inflammation. The extract, fractions and compounds showed significant antioxidant potential when evaluated in different assays. The results shown in this work suggest the anti-inflammatory potential of the leaf extract of S. mombim on peritonitis model induced by carrageenan, it was also observed antioxidant properties associated with an absence of cytotoxicity in cell culture. Further in vivo studies are required to confirm the anti-inflammatories action of S. mombin and its possible anti-inflammatory mechanisms of action.