Bioactive Compounds with Application Potentials in Nutraceuticals and Nutricosmetics: Focus on Mechanism of Action and Application Science

High nutritional value and antioxidant properties make chickpea flour a valuable substitute for wheat flour, although its texture-forming abilities are different. The aim of this study was to investigate the possibility of increasing the content of bioactive compounds and antioxidant properties of shortbread cookies by simple partial or complete replacement of wheat flour with chickpea flour without considerable changes in texture, color, sensory properties, or acceptability. Shortbread cookies were made from wheat flour (0% of chickpea flour), wheat flour and chickpea flour (replacement of 25%, 50%, and 75%), and chickpea flour (100%). Generally, the increase in chickpea flour share resulted in an increase in protein, fat, and ash content, as well as antioxidant properties. Polyphenol content, flavonoid content, and antioxidant activities increased three- to sixfold in shortbread cookies containing chickpea flour in comparison to wheat cookies. The level of proteins increased about 50% and the antioxidant properties were three to six times higher than in wheat cookies. Cookies containing up to 75% chickpea flour were assessed as very good or good quality, while only cookies without wheat flour were assessed as sufficient quality. It could be concluded that part of the wheat flour content in shortbread cookies can be replaced by chickpea flour. Application of a 25% proportion of chickpea flour increases physicochemical properties without changes in sensory properties. Sensory quality was up to 75% lower, but antioxidant properties were increased. However, complete replacement of wheat flour in shortbread cookies without changing the recipe resulted in a product of slightly lower sensory quality. Full article

Alpinia officinarum Hance is rich in carbohydrates and is flavored by natives. The polysaccharide fraction 30 is purified from the rhizome of A. officinarum Hance (AOP30) and shows excellent immunoregulatory ability when administered to regulate immunity. However, the effect of AOP30 on the intestinal epithelial barrier is not well understood. Therefore, the aim of this study is to investigate the protective effect of AOP30 on the intestinal epithelial barrier using a lipopolysaccharide (LPS)-induced intestinal epithelial barrier dysfunction model and further explore its underlying mechanisms. Cytotoxicity, transepithelial electrical resistance (TEER) values, and Fluorescein isothiocyanate (FITC)–dextran flux are measured. Simultaneously, the protein and mRNA levels of tight junction (TJ) proteins, including zonula occludens-1 (ZO-1), Occludin, and Claudin-1, are determined using Western blotting and reverse-transcription quantitative polymerase chain reaction methods, respectively. The results indicate that AOP30 restores the LPS-induced decrease in the TEER value and cell viability. Furthermore, it increases the mRNA and protein expression of ZO-1, Occludin, and Claudin-1. Notably, ZO-1 is the primary tight junction protein altered in response to LPS-induced intestinal epithelial dysfunction. Additionally, AOP30 downregulates the production of TNFα via the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway. Collectively, the findings of this study indicate that AOP30 can be developed as a functional food ingredient or natural therapeutic agent for addressing intestinal epithelial barrier dysfunction. It sheds light on the role of AOP30 in improving intestinal epithelial function. Full article

Red yeast rice dietary supplements have been proven to ameliorate hyperglycemia, but the mechanism was unclear. In this work, ankaflavin (AK) and monascin (MS), as typical pigments derived from red yeast rice, were found to exert noteworthy inhibitory ability against α-glucosidase, with an IC₅₀ of 126.5 ± 2.5 and 302.6 ± 2.5 μM, respectively, compared with acarbose (IC₅₀ = 341.3 ± 13.6 μM). They also exhibited mixed-type inhibition of α-glucosidase in vitro and caused fluorescence quenching through the static-quenching process. Molecular-docking studies indicated that AK and MS bind to amino acid residues outside the catalytic center, which induces structural changes in the enzyme, thus influencing its catalytic activity. The anti-glycation ability of Monascus-fermented products was evaluated, and they exhibited a high inhibition rate of 87.1% in fluorescent advanced glycation end-product formation at a concentration of 0.2 mg mL⁻¹, while aminoguanidine showed a rate of 75.7% at the same concentration. These results will be significant in broadening the application scope of Monascus pigments, especially AK and MS, in treating type 2 diabetes. Full article

Resveratrol and caffeic acid are some of the most consumed antioxidants during the day, so their importance as sources and their benefits need to be evaluated and updated. This survey aimed not only to analyze whether young Romanian consumers are informed about the benefits of antioxidants in general, and resveratrol and caffeic acid in particular, but also to observe the degree of nutritional education of these participants. Young consumers know the concept of antioxidants relatively well; they managed to give examples of antioxidants and indicate their effects. The majority of those chosen drink wine and coffee, but many are unaware of their health advantages and antioxidant properties. Students are less familiar with the antioxidant chemicals resveratrol and caffeic acid. It is advised to have a thorough understanding of these significant antioxidants and their nutritional content as they are present in our regular diets, and further studies on different kinds of antioxidants are required to increase the awareness of people concerning their importance in daily life. Full article

Coffee silverskin (CS), a by-product of the coffee roasting process, has high protein content (16.2−19.0%, w/w), making it a potential source for plant protein and bioactive peptide production. This study aims to develop innovative extraction methods for phenolic compounds and proteins from CS. The conditions for hydrothermal (HT) extraction of phenolic compounds from CS were optimized by varying CS loading (2.5−10%, w/v), temperature (110−130 °C), and time (5−30 min) using a one-factor-at-a-time (OFAT) approach. The highest TPC of 55.59 ± 0.12 µmole GAE/g _CS was achieved at 5.0% (w/v) CS loading and autoclaving at 125 °C for 25 min. Following hydrothermal extraction, CS protein was extracted from HT-extracted solid fraction by microwave-assisted alkaline extraction (MAE) using 0.2 M NaOH at 90 W for 2 min, resulting in a protein recovery of 12.19 ± 0.39 mg/g _CS. The CS protein was then subjected to enzymatic hydrolysis using protease from Bacillus halodurans SE5 (protease_SE5). Protease_SE5-derived CS protein hydrolysate had a peptide concentration of 0.73 ± 0.09 mg/mL, with ABTS, DPPH, and FRAP values of 15.71 ± 0.10, 16.63 ± 0.061, and 6.48 ± 0.01 µmole TE/mL, respectively. Peptide identification by LC-MS/MS revealed several promising biological activities without toxicity or allergenicity concerns. This study’s integrated approach offers a sustainable and efficient method for extracting valuable compounds from CS, with potential applications in the food and pharmaceutical industries. Full article

(1) Background: The elderly suffer from functional constipation (FC), whose causes are not fully known, but nutritional factors may play a role. The aim of the present study was to assess the effect of a low FODMAP diet supplemented with L-tryptophan (TRP) on its metabolism and symptoms of functional constipation in elderly patients. (2) Methods: This study included 40 people without abdominal complaints (Group I, controls) and 60 patients with FC, diagnosed according to the Rome IV Criteria (Group II). Two groups were randomly selected: Group IIA (n = 30) was qualified for administration of the low FODMAP diet, and the diet of patients of Group IIB (n = 30) was supplemented with 1000 mg TRP per day. The severity of abdominal symptoms was assessed with an abdominal pain index ranging from 1 to 7 points (S-score). The concentration of TRP and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), and 3-indoxyl sulfate (3-IS) in urine were determined using the LC-MS/MS method. (3) Results: In Group II, 5-HIAA concentration in urine was lower, and KYN and 3-IS concentrations were higher than in the control group. A negative correlation was found between the S-score and urinary concentration of 5-HIAA (p < 0.001), and 3-IS concentration was positively correlated with the S-score. However, the correlation between the S-score and 3-IS concentration was negative (p < 0.01). After a dietary intervention, 5-HIAA concentration increased in both groups, and the severity of symptoms decreased, but the decrease was more pronounced in Group IIB. (4) Conclusion: A low FODMAP diet supplemented with L-tryptophan has beneficial effects in elderly patients suffering from functional constipation. Full article

Obesity is a global health concern. Recent research has suggested that the development of anti-obesity ingredients and functional foods should focus on natural products without side effects. We examined the effectiveness and underlying mechanisms of Brassica juncea extract (BJE) in combating obesity via experiments conducted in both in vitro and in vivo obesity models. In in vitro experiments conducted in a controlled environment, the application of BJE demonstrated the ability to suppress the accumulation of lipids induced by MDI in 3T3-L1 adipocytes. Additionally, it downregulated adipogenic-related proteins peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-α (C/EBP-α), adipocyte protein 2 (aP2), and lipid synthesis-related protein acetyl-CoA carboxylase (ACC). It also upregulated the heat generation protein peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and fatty acid oxidation protein carnitine palmitoyltransferase-1 (CPT-1). The oral administration of BJE decreased body weight, alleviated liver damage, and inhibited the accumulation of lipids in mice with diet-induced obesity resulting from a high-fat diet. The inhibition of lipid accumulation by BJE in vivo was associated with a decreased expression of adipogenic and lipid synthesis proteins and an increased expression of heat generation and fatty acid oxidation proteins. BJE administration improved obesity by decreasing adipogenesis and activating heat generation and fatty acid oxidation in 3T3-L1 cells and in HFD-induced obese C57BL/6J mice. These results suggest that BJE shows potential as a natural method for preventing metabolic diseases associated with obesity. Full article

Recent studies have demonstrated that the interaction of dietary constituents with taste and olfactory receptors and nociceptors expressed in the oral cavity, nasal cavity and gastrointestinal tract regulate homeostasis through activation of the neuroendocrine system. Polyphenols, of which 8000 have been identified to date, represent the greatest diversity of secondary metabolites in plants, most of which are bitter and some of them astringent. Epidemiological studies have shown that polyphenol intake contributes to maintaining and improving cardiovascular, cognitive and sensory health. However, because polyphenols have very low bioavailability, the mechanisms of their beneficial effects are unknown. In this review, we focused on the taste of polyphenols from the perspective of sensory nutrition, summarized the results of previous studies on their relationship with bioregulation and discussed their future potential. Full article

Jujube is a plant native to China that could be used in medicine and food. Its dried fruit is a superior herb commonly used in traditional Chinese medicine formulations for its calming effect and for nourishing the blood and strengthening the spleen and stomach. Jujube contains numerous active components including polysaccharides, phenols, and triterpene acids, which show a diverse array of pharmacological activities such as neuroprotection and the prevention and treatment of cardiovascular diseases. In this paper, the research status of jujube over the past two decades has been statistically evaluated. Meanwhile, by tracking the latest research advances, the pharmacological efficacy and molecular mechanisms of jujube are exhaustively expounded to provide specific and systematic references for further research on the pharmacological effects of jujube and its application in the food and pharmaceutical industries. Full article

The research purpose was to investigate the effects and the underlying molecular mechanisms of bovine bone gelatin peptides (BGP) on myocardial hypertrophy in spontaneously hypertensive rats (SHR). BGP relieved myocardial hypertrophy and fibrosis in SHR rats in a dose-dependent manner by reducing the left ventricular mass index, myocardial cell diameter, myocardial fibrosis area, and levels of myocardial hypertrophy markers (atrial natriuretic and brain natriuretic peptide). Label-free quantitative proteomics analysis showed that long-term administration of BGP changed the left ventricle proteomes of SHR. The 37 differentially expressed proteins in the high-dose BGP group participated in multiple signaling pathways associated with cardiac hypertrophy and fibrosis indicating that BGP could play a cardioprotective effect on SHR rats by targeting multiple signaling pathways. Further validation experiments showed that a high dose of BGP inhibited the expression of phosphoinositide 3-kinase (Pi3k), phosphorylated protein kinase B (p-Akt), and transforming growth factor-beta 1 (TGF-β1) in the myocardial tissue of SHR rats. Together, BGP could be an effective candidate for functional nutritional supplements to inhibit myocardial hypertrophy and fibrosis by negatively regulating the TGF-β1 and Pi3k/Akt signaling pathways. Full article

Obesity and Western-like diet consumption leads to gut microbiome dysbiosis, which is associated with the development of cardio-metabolic diseases and poor health outcomes. The objective of this study was to reduce Western diet-mediated gut microbial dysbiosis, metabolic dysfunction, and systemic inflammation through the administration of a novel combined intervention strategy (oral probiotic bacteria supplements and muscadine grape extract (MGE)). To do so, adult female C57BL/6 mice were fed a low-fat control or Western-style diet and sub-grouped into diet alone, probiotic intervention, antibiotic treatments, MGE supplementation, a combination of MGE and probiotics, or MGE and antibiotics for 13 weeks. Mouse body weight, visceral adipose tissue (VAT), liver, and mammary glands (MG) were weighed at the end of the study. Fecal 16S rRNA sequencing was performed to determine gut bacterial microbiome populations. Collagen, macrophage, and monocyte chemoattractant protein-1 (MCP-1) in the VAT and MG tissue were examined by immunohistochemistry. Adipocyte diameter was measured in VAT. Immunohistochemistry of intestinal segments was used to examine villi length, muscularis thickness, and goblet cell numbers. We show that dietary interventions in Western diet-fed mice modulated % body weight gain, visceral adiposity, MG weight, gut microbial populations, and inflammation. Intervention strategies in both diets effectively reduced VAT and MG fibrosis, VAT and MG macrophages, adipocyte diameter, and VAT and MG MCP-1. Interventions also improved intestinal health parameters. In conclusion, dietary intervention with MGE and probiotics modulates several microbial, inflammatory, and metabolic factors reducing poor health outcomes associated with Western diet intake. Full article

Hydrolysates of coix seed prolamins (CHPs) have an excellent hypoglycemic effect and can effectively inhibit α-glucosidase, which is the therapeutic target enzyme for type 2 diabetes mellitus. However, its hypoglycemic components and molecular mechanisms remain unclear, and its stability in food processing needs to be explored. In this study, four potential α-glucosidase inhibitory peptides (LFPSNPLA, FPCNPLV, HLPFNPQ, LLPFYPN) were identified and screened from CHPs using LC-MS/MS and virtual screening techniques. The results of molecular docking showed that the four peptides mainly inhibited α-glucosidase activity through hydrogen bonding and hydrophobic interactions, with Pro and Leu in the peptides playing important roles. In addition, CHPs can maintain good activity under high temperatures (40~100 °C) and weakly acidic or weakly alkaline conditions (pH 6.0~8.0). The addition of glucose (at 100 °C) and NaCl increased the inhibitory activity of α-glucosidase in CHPs. The addition of metal ions significantly decreased the inhibitory activity of α-glucosidase by CHPs, and their effects varied in magnitude with Cu²⁺ having the largest effect followed by Zn²⁺, Fe³⁺, K⁺, Mg²⁺, and Ca²⁺. These results further highlight the potential of CHPs as a foodborne hypoglycemic ingredient, providing a theoretical basis for the application of CHPs in the healthy food industry. Full article

The prevalence of people being overweight and obese has increased globally over the past decades. The use of omega-3 fatty acids—a compound usually primarily found in fish oil—has been known to improve the metabolic profile of obese patients. As the demand for eels increases, the number of waste products from the eels increases and creates environmental problems. This study was conducted to investigate the effect of a newly discovered Indonesian Shortfin eel by-product oil supplementation on the Homeostasis Model Assessment-Estimated Insulin Resistance (HOMA-IR) and lipid profiles of obese male (Lee index ≥ 0.3) Wistar rats (Rattus norvegicus). The oil was extracted from waste products (heads). Fifteen obese rats were divided into three groups and were administered NaCl (C), commercial fish oil (CO), and Indonesian shortfin eel by-product oil (EO). All groups had statistically significant differences in total cholesterol, LDL, and triglyceride levels (p < 0.05). The CO and EO group showed a significant decrease in total cholesterol, LDL, and triglyceride after treatment. However, no significant difference was found in HDL levels and HOMA-IR. The supplementation of Indonesian shortfin eel by-product oil significantly improved lipid profile while effectively mitigating environmental challenges. Full article

There is growing interest in the investigation of ketogenic diets as a potential therapy for bipolar disorder. The overlapping pharmacotherapies utilized for both bipolar disorder and seizures suggest that a mechanistic overlap may exist between these conditions, with fasting and the ketogenic diet representing the most time-proven therapies for seizure control. Recently, preliminary evidence has begun to emerge supporting a potential role for ketogenic diets in treating bipolar disorder. Notably, some patients may struggle to initiate a strict diet in the midst of a mood episode or significant life stressors. The key question addressed by this pilot clinical trial protocol is if benefits can be achieved with a less restrictive diet, as this would allow such an intervention to be accessible for more patients. Recent development of so-called ketone esters, that once ingested is converted to natural ketone bodies, combined with low glycemic index dietary changes has the potential to mimic two foundational components of therapeutic ketosis: high levels of ketones and minimal spiking of glucose/insulin. This pilot clinical trial protocol thus aims to investigate the effect of a ‘ketogenic-mimicking diet’ (combining supplementation of ketone esters with a low glycemic index dietary intervention) on neural network stability, mood, and biomarker outcomes in the setting of bipolar disorder. Positive findings obtained via this pilot clinical trial protocol may support future target engagement studies of ketogenic-mimicking diets or related ketogenic interventions. A lack of positive findings, in contrast, may justify a focus on more strict dietary interventions for future research. Full article

Ginseng is one of the traditional herbal medicines for tonic. Gintonin is a new material derived from white/red ginseng and its lysophosphatidic acids (LPAs) play as a ligand for G protein-coupled LPA receptors. Korean red ginseng marc (KRGM) is a by-product after the KRG processes. We developed a low-cost/high-efficiency method for KRGM gintonin production. We further studied the KRGM gintonin-mediated anti-skin aging effects under UVB exposure using human dermal fibroblasts (HDFs). KRGM gintonin yield is about 8%. KRGM gintonin contains a high amount of LPA C_18:2, lysophosphatidylcholine (LPC), and phosphatidylcholine (PC), which is similar to white ginseng gintonin. KRGM gintonin induced [Ca²⁺]_i transient via LPA1/3 receptors and increased cell viability/proliferation under UVB exposure. The underlying mechanisms of these results are associated with the antioxidant action of KRGM gintonin. KRGM gintonin attenuated UVB-induced cell senescence by inhibiting cellular β-galactosidase overexpression and facilitated wound healing. These results indicate that KRGM can be a novel bioresource of KRGM gintonin, which can be industrially utilized as new material for skin nutrition and/or skin healthcare. Full article

(1) Background: Numerous meta-analyses have shown that a high intake of dietary fiber plays a protective role in preventing the development of various types of cancer. However, previous studies have been limited by focusing on a single type of dietary fiber and variations in outcome measures, which may not be effectively applied to provide dietary guidance for the general population. (2) Object: We summarized the meta-analysis of dietary fiber and cancer, and provided references for residents to prevent cancer. (3) Methods: Systematic search of relevant meta-analyses on the association between dietary fiber and cancer occurrence in PubMed, Web of Science and other databases was conducted from the time of database construction to February 2023. The method logical and evidence quality assessments were performed by applying the criteria in the “A Measurement Tool to Assess Systematic Reviews-2” (AMSTAR2) scale and the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Expert Report, respectively. (4) Results: Our analysis included 11 meta-analyses, and the AMSTAR 2 assessment revealed that the overall methodological quality was suboptimal, with two key items lacking sufficient information. Nonetheless, our findings indicate that a high intake of dietary fiber is associated with a reduced risk of several types of cancer, including esophageal, gastric, colon, rectal, colorectal adenoma, breast, endometrial, ovarian, renal cell, prostate, and pancreatic cancers. The majority of these associations were supported by a “probable” level of evidence. (5) Conclusions: Dietary fiber intake has different protective effects on different cancers. Full article

Plant-derived secondary metabolites (polyphenols/terpenes/alkaloids) and microbial exometabolites/membrane components of fermented tropical fruits are known as highly bioavailable biomolecules causing skin and hair improvement effects (wound healing, anti-inflammatory, antioxidant, antidiabetic, antiacne, skin/hair microbiota balancing, hair growth-promoting, and hair loss-inhibiting). Caffein is considered as a hair growth promoter. A randomized placebo- and caffein-controlled clinical trial on the efficacy of fermented papaya (FP) plus fermented mangosteen (FM) towards human hair quality and loss was conducted. Shampoo and lotion hair care products containing FP, FM, and caffein as active agents were developed and applied to 154 subjects of both sexes with clinically confirmed androgenic or diffuse alopecia for 3 months. Their clinical efficacy was assessed subjectively by questionnaires filled in by dermatologists/trichologists, and by the objective trichomicroscopical calculations. Hair and scalp skin quality was determined by microbiota pattern and ATP, SH-groups, protein, and malonyl dialdehyde quantification. Comparative clinical data showed that the experimental hair care cosmetics significantly inhibited hair loss, increased hair density/thickness, and improved hair follicle structure versus placebo and caffein controls. The cosmetics with FP and FM substantially normalized the microbiota pattern and increased ATP content in hair follicle, while inhibiting lipid peroxidation in the scalp skin, and SH-group formation in the hair shaft. Full article

Shikonin, a natural ingredient produced by Lithospermum erythrorhizon, has anti-inflammatory, anti-cancer, and anti-obesity effects. It also inhibits adipocyte differentiation; however, the underlying molecular and epigenetic mechanisms remain unclear. We performed RNA-sequencing of shikonin-treated 3T3-L1 cells. Gene ontology and gene set enrichment analysis showed that shikonin is significantly associated with genes related to adipogenesis, histone modification, and PPARγ. Shikonin treatment downregulated the mRNA expression of PPARγ-responsive genes and rosiglitazone-induced transcriptional activity of PPARγ. Microscale thermophoresis assays showed a K_D value 1.4 ± 0.13 μM for binding between shikonin and PPARγ. Glutathione S-transferase pull-down assays exhibited that shikonin blocked the rosiglitazone-dependent association of PPARγ with its coactivator CBP. In addition, shikonin decreased the enrichment of the active histone code H3K4me3 and increased the repressive code H3K27me3 of PPARγ target promoters. Shikonin is a PPARγ antagonist that suppresses adipogenesis by regulating the enrichment of histone codes during adipogenesis. Therefore, it may be used to treat obesity-related disorders via epigenetic changes. Full article

Nutritional biomarkers can be used as important indicators of nutritional status and play crucial roles in the prevention as well as prognosis optimization of various metabolism-related diseases. Measuring dietary with the deployment of biomarker assessments provides quantitative nutritional information that can better predict the health outcomes. With the increased availability of nutritional biomarkers and the development of assessment tools, the specificity and sensitivity of nutritional biomarkers have been greatly improved. This enables efficient disease surveillance in nutrition research. A wide range of biomarkers have been used in different types of studies, including clinical trials, observational studies, and qualitative studies, to reflect the relationship between diet and health. Through a comprehensive literature search, we reviewed the well-established nutritional biomarkers of vitamins, minerals, and phytonutrients, and their association with epidemiological studies, to better understand the role of nutrition in health and disease. Full article

Mannuronate oligosaccharide (MOS) is α-D-mannuronic acid polymer with 1,4-glycosidic linkages that possesses beneficial biological properties. The aim of this study was to investigate the hypouricemic effect of MOS in hyperuricemic mice and demonstrate the possible protective mechanisms involved. In this research, 200 mg/kg/day of MOS was orally administered to hyperuricemic mice for four weeks. The results showed that the MOS treatment significantly reduced the serum uric acid (SUA) level from 176.4 ± 7.9 μmol/L to 135.7 ± 10.9 μmol/L (p < 0.05). MOS alleviated the inflammatory response in the kidney. Moreover, MOS promoted uric acid excretion by regulating the protein levels of renal GLUT9, URAT1 and intestinal GLUT9, ABCG2. MOS modulated the gut microbiota in hyperuricemic mice and decreased the levels of Tyzzerella. In addition, research using antibiotic-induced pseudo-sterile mice demonstrated that the gut microbiota played a crucial role in reducing elevated serum uric acid of MOS in mice. In conclusion, MOS may be a potential candidate for alleviating HUA symptoms and regulating gut microbiota. Full article

In this study, we investigated the transport mechanism of immune-active peptide fragments isolated from casein gastrointestinal hydrolysates via a Caco-2 monolayer. The casein gastrointestinal hydrolysates could stimulate B-lymphocyte proliferation and reduce the TNF-α level. Then, we identified the bioactive peptide fragments derived from casein gastrointestinal hydrolysis using LC-MS/MS. Our results demonstrated that the transport mechanism of five immune-active peptides at the cell level was bypass transport. In addition, the majority of peptide RYPLGYL was transported through the monolayer cell membrane as an intact form for playing immune-active functions. The KHPIK and FFSDK were mainly degraded into small fragments, except for a small amount passing through Caco-2 cells in an entire form. Overall, these results suggested that casein or its immune-active peptides might play a role in regulation of the intestinal immune system. Full article

Novel constructed bioactive mixed-ligand complexes (1b) [Cu^II(L)₂(phen)] and (2b) [Zn^II(L)₂(phen)] {where, L = 2-(4-morpholinobenzylideneamino)phenol), phen = 1,10-phenanthroline} have been structurally analysed by various analytical and spectroscopic techniques, including, magnetic moments, thermogravimetric analysis, and X-ray crystallography. Various analytical and spectral measurements assigned showed that all complexes appear to have an octahedral geometry. Agar gel electrophoresis’s output demonstrated that the Cu(II) complex (1b) had efficient deoxyribonucleic cleavage and complex (2b) demonstrated the partial cleavage accomplished with an oxidation agent, which generates spreadable OH^● through the Fenton type mechanism. The DNA binding constants observed from viscosity, UV–Vis spectral, fluorometric, and electrochemical titrations were in the following sequence: (1b) > (2b) > (HL), which suggests that the complexes (1b–2b) might intercalate DNA, a possibility that is supported by the biothermodynamic measurements. In addition, the observed binding constant results of BSA by electronic absorption and fluorometric titrations indicate that complex (1b) revealed the best binding efficacy as compared to complex (2b) and free ligand. Interestingly, all compounds are found to interact with BSA through a static approach, as further attested by FRET detection. The DFT and molecular docking calculations were also performed to realize the electronic structure, reactivity, and binding capability of all test samples with CT-DNA, BSA, and the SARS-CoV-2 3CL^Pro, which revealed the binding energies were in a range of −8.1 to −8.9, −7.5 to −10.5 and −6.7–−8.8 kcal/mol, respectively. The higher reactivity of the complexes than the free ligand is supported by the FMO theory. Among all the observed data for antioxidant properties against DPPH^᛫, ^᛫OH, O₂^−• and NO^᛫ free radicals, complex (1a) had the best biological efficacy. The antimicrobial and cytotoxic characteristics of all test compounds have been studied by screening against certain selected microorganisms as well as against A549, HepG2, MCF-7, and NHDF cell lines, respectively. The observed findings revealed that the activity enhances coordination as compared to free ligand via Overtone’s and Tweedy’s chelation mechanisms. This is especially encouraging given that in every case, the experimental findings and theoretical detections were in perfect accord. Full article

In recent years, there has been a great deal of interest in the ectopic roles of olfactory receptors (ORs) throughout the human body. Especially, the ectopic function of OR in the skin is one of the most actively researched areas. Suberic acid, a scent compound, was hypothesized to increase collagen synthesis in the ultraviolet B (UVB)-irradiated human dermal fibroblasts (Hs68) through a specific olfactory receptor. Suberic acid ameliorated UVB-induced decreases in collagen production in Hs68 cells. Using in silico docking to predict the binding conformation and affinity of suberic acid to 15 ectopic ORs detectable in Hs68, several ORs were identified as promising candidates. The effect of suberic acid on collagen synthesis in UVB-exposed dermal fibroblasts was nullified only by a reduction in OR10A3 expression via specific siRNA. In addition, using the cells transiently expressing OR10A3, we demonstrated that suberic acid can activate OR10A3 by assessing the downstream effector cAMP response element (CRE) luciferase activity. We examined that the activation of OR10A3 by suberic acid subsequently stimulates collagen synthesis via the downstream cAMP-Akt pathway. The findings support OR10A3 as a promising target for anti-aging treatments of the skin. Full article

Skin ageing is strictly related to chronic inflammation of the derma and the decay of structural proteins of the extracellular matrix. Indeed, it has become common practice to refer to this phenomenon as inflammageing. Biotech innovation is always in search of new active principles that induce a youthful appearance. In this paper, apple-derived nanovesicles (ADNVs) were investigated as novel anti-inflammatory compounds, which are able to alter the extracellular matrix production of dermal fibroblasts. Total RNA sequencing analysis revealed that ADNVs negatively influence the activity of Toll-like Receptor 4 (TLR4), and, thus, downregulate the NF-κB pro-inflammatory pathway. ADNVs also reduce extracellular matrix degradation by increasing collagen synthesis (COL3A1, COL1A2, COL8A1 and COL6A1) and downregulating metalloproteinase production (MMP1, MMP8 and MMP9). Topical applications for skin regeneration were evaluated by the association of ADNVs with hyaluronic-acid-based hydrogel and patches. Full article

The inflammasome is a platform for inflammatory signaling, and the NLRP3 inflammasome recognizes stimuli in vitro and in vivo, and releases inflammatory cytokines that trigger inflammation and pyroptosis. In the gut, the NLRP3 inflammasome is a key sensor for protecting the body from damage and exogenous pathogens. It plays a fundamental role in maintaining the stability of the gut’s immune system. We focus on the role of NLRP3 as a key node in maintaining the homeostasis of gut microbiota which has not been fully highlighted in the past; gut microbiota and innate immunity, as well as the NLRP3 inflammasome, are discussed in this article. Full article

Retinoids, one of the most robust bioactive materials, have been widely used to improve various dermatological and pathological conditions. The body has an endogenous mechanism that modulates the exogenous retinoid above physiological concentrations, which limits the bioavailability or pharmacological efficacy of retinoids. Considering that most retinoids trigger extensive irritation in users, it is necessary to enhance the pharmacological efficacy of retinoids, thereby achieving a higher efficacy at a lower dosage. Here, we present approaches for enhancing the efficacy of retinol by enhancing retinoid-induced RAR gamma (RAR-γ) activity and inhibiting the hydroxylation of retinoic acid. Using both in vitro and ex vivo experiments, retinoid boosters were demonstrated to enhance pharmacological efficacy. A small pilot study was conducted to investigate the efficacy for improvement of facial wrinkles, whose results revealed that these boosters could enhance the pharmacological efficacy of topical applications of both retinol and retinoic acid for cosmetic use. These results promote not only a higher compliance among retinoids users, but also provide significant insights into the mechanisms underlying the action of retinoids. Full article