Multiple Bioactive Components Research Articles

Seeking Optimal Extraction Method for Augmenting Hibiscus sabdariffa Bioactive Compounds and Antioxidant Activity

The dried flowers of Hibiscus sabdariffa (HS), available worldwide, have various applications in both non-medicinal and medicinal fields. The growing global interest in the health benefits of HS is linked to its potential prevention or management of non-communicable diseases. The aim of this research was to find the optimal extraction method that ensures the maximum yield of multiple beneficial bioactive components, such as polyphenols, anthocyanins, vitamin C, β-carotene, antioxidant activity, free radical scavenging activity DPPH and ferric reducing antioxidant power (FRAP). To this end, stirring, pulsed electric field, and ultrasound-assisted extraction were evaluated, either alone or in combination. Under optimized extraction conditions, the obtained extract exhibited an elevated total polyphenol content (37.82 mg of gallic acid equivalents/g dry weight (dw)), total anthocyanin content (610.42 μg of cyanidin equivalents/g dw), total carotenoids content (921.84 μg of β-carotene equivalents/g dw), and ascorbic acid content (507.44 mg/100 g dw). Remarkably, the extracts exhibited strong antioxidant properties (487.51 μmol of ascorbic acid equivalents (AAE)/g dw and 243.42 μmol AAE/g dw as evidenced by FRAP and DPPH assays, respectively). This research advances the parameters that should be employed to produce the optimal and nutritionally enhanced HS flower extracts, that can be used in the commercial sector.

Chemical Profiling of Shen-Wu-Yi-Shen Tablets Using UPLC-Q-TOF-MS/MS and Its Quality Evaluation Based on UPLC-DAD Combined with Multivariate Statistical Analysis.

Shen-Wu-Yi-Shen tablets (SWYST) is a traditional Chinese medicine prescription used for treating chronic kidney disease (CKD). This study aims to characterize the constituents in SWYST and evaluate the quality based on the quantification of multiple bioactive components. SWYST samples were analyzed with ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and a data-processing strategy. As a result, 215 compounds in SWYST were unambiguously identified or tentatively characterized, including 14 potential new compounds. Meanwhile, strategies based on characteristic fragments for rapid identification were summarized, indicating that the qualitative method is accurate and feasible. Notably, the glucose esters of laccaic acid D-type anthraquinone were first found and their fragmentation patterns were described by comparing that of O-glycoside isomers. Besides, based on comparisons of the cleavage ways of mono-acyl glucose with different acyl groups or acylation sites, differences in fragmentation pathways between 1,2-di-O-acyl glucose and 1,6-di-O-acyl glucose were proposed for the first time and verified by reference substances. In addition, a validated UPLC-DAD was established for the determination of 11 major bioactive components related to treatment of CKD (albiflorin, paeoniflorin, 2,3,5,4'-tetrahydroxy-stilbene-2-O-β-d-glucoside (TSG), 1-O-galloyl-2-O-cinnamoyl-β-d-glucose, emodin-8-O-β-d-glucoside, chrysophanol-O-β-d-glucoside, aloe-emodin, rhein, emodin, chrysophanol and physcion). Moreover, TSG and 1-O-galloyl-2-O-cinnamoyl-β-d-glucose were found as the quality markers related to the origins of SWYST based on multivariate statistical analysis. Conclusively, the findings in this work provide a feasible reference for further studies on quality research and mechanisms of action in treating CKD.

Network pharmacology and molecular docking analyses of the potential target proteins and molecular mechanisms underlying the anti-arrhythmic effects of Sophora Flavescens.

The objective was to investigate the potential cardiac arrhythmia-related target proteins and molecular mechanisms underlying the anti-arrhythmic effects of Sophora flavescens using network pharmacology and molecular docking. The bioactive ingredients and related target proteins of S flavescens obtained from the Traditional Chinese medicine systems pharmacology data platform, and gene names for target proteins were obtained from the UniProt database. Arrhythmia-related genes were identified by screening GeneCards and Online Mendelian inheritance in man databases. A Venn diagram was used to identify the key arrhythmia-related genes that are potentially targeted by the bioactive ingredients of S flavescens. Furthermore, CytoScape 3.7.2 software was used to construct an "ingredient-target" network diagram and the "drug-ingredient-target-disease" network diagram. We performed gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis in the Metascape database and performed the docking analysis using CB-Dock software. We identified 45 main bioactive ingredients, from S flavescens and 66 arrhythmia-related target proteins. Gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that these targets were related to the chemical carcinogenesis-receptor activation signaling pathway, lipid and atherosclerosis signaling pathway, and fluid shear stress and atherosclerosis signaling pathway. Molecular docking showed that the target protein had good binding power with the main active components of the compound of S flavescens. Our study demonstrated the synergistic effects of multiple bioactive components of S flavescens on multiple arrhythmia-related target proteins and identified potential therapeutic mechanisms underlying the anti-arrhythmic effects of S flavescens, providing new clinical ideas for arrhythmia treatment.

Inhibiting virus replication and excessive inflammatory response: Mechanism of combined prescription of Ma-Xing-Shi-Gan decoction and Xiao-Chai-Hu decoction against influenza virus

Ethnopharmacological relevanceThe combined prescription of two classical decoctions (Ma-Xing-Shi-Gan decoction with Xiao-Chai-Hu decoction), named as San-Yang-He-Zhi (SYHZ) decoction, has been widely used for the treatment of influenza virus (IFV) infections for decades. Aim of the studyThis study aimed to evaluate the anti-influenza effect of SYHZ decoction and explore the underlying mechanism. Materials and methodsThe ingredients of SYHZ decoction were analyzed by mass spectrometry. An animal model of IFV infection was established by challenging C57BL/6J mice with PR8 virus. Three groups of mice were infected with lethal or non-lethal doses of IFV, then followed by oral administration of phosphate-buffered saline (PBS), or SYHZ, or oseltamir; blank control mice (without IFV infection) were treated with PBS. Survival rate, Lung index, colon length, body weight loss and IFV viral load were measured 7 days post infection; histology and electron-microscopy examinations of lung tissue were performed; cytokine and chemokine levels in lung and serum were measured; and the intestinal metagenome, the cecum metabolome, and the lung transcriptome were analyzed. ResultsSYHZ treatment significantly improved survival rate compared with PBS (40% vs 0%); improved lung index, colon length, and body weight loss; and alleviated lung histological damage and viral load. SYHZ-treated mice had significantly lower levels of IL-1β, TNF-α, IL-6, CCL2, CXCL10 in lung and serum, and increased levels of multiple bioactive components in cecum. Pro-inflammatory cytokines, Toll- and NOD-like receptors, pro-apoptosis molecules, and lung-injury-related proteins were downregulated in SYHZ mice, whereas surfactant protein and mucin were upregulated. The NOD-like receptor pathway, Toll-like receptor pathway, and NF-κB pathway were downregulated by SYHZ treatment. ConclusionsSYHZ decoction alleviated IFV infection in a mouse model. Multiple bioactive ingredients of SYHZ may inhibit replication of IFV and suppress excessive immune response.

Red blood cell membrane-functionalized Nanofibrous tubes for small-diameter vascular grafts

The off-the-shelf small-diameter vascular grafts (SDVGs) have inferior clinical efficacy. Red blood cell membrane (Rm) has easy availability and multiple bioactive components (such as phospholipids, proteins, and glycoproteins), which can improve the clinic's availability and patency of SDVGs. Here we developed a facile approach to preparing an Rm-functionalized poly-ε-caprolactone/poly-d-lysine (Rm@PCL/PDL) tube by co-incubation and single-step rolling. The integrity, stability, and bioactivity of Rm on Rm@PCL/PDL were evaluated. The revascularization of Rm@PCL/PDL tubes was studied by implantation in the carotid artery of rabbits. Rm@PCL/PDL can be quickly prepared and showed excellent bioactivity with good hemocompatibility and great anti-inflammatory. Rm@PCL/PDL tubes as the substitute for the carotid artery of rabbits had good patency and quick remodeling within 21 days. Rm, as a “self” biomaterial with high biosafety, provides a new and facile approach to developing personalized or universal SDVGs for the clinic, which is of great significance in cardiovascular regenerative medicine and organ chip.

Chemical, Nutritional and Biological Evaluation of a Sustainable and Scalable Complex of Phytochemicals from Bergamot By-Products

The present paper reports a sustainable raw material obtained from the by-products derived from the industrial production of bergamot (Citrus × Bergamia Risso & Poiteau) essential oils. The procedure to obtain the raw material is designed to maintain as much of the bioactive components as possible and to avoid expensive chemical purification. It consists of spray-drying the fruit juice obtained by squeezing the fruits, which is mixed with the aqueous extract of the pulp, i.e., the solid residue remained after fruit pressing. The resulting powder bergamot juice (PBJ) contains multiple bioactive components, in particular, among others, soluble fibers, polyphenols and amino-acid betaines, such as stachydrine and betonicine. LC-MS analysis identified 86 compounds, with hesperetin, naringenin, apigenin and eridictyol glucosides being the main components. In the second part of the paper, dose-dependent anti-inflammatory activity of PBJ and of stachydrine was found, but neither of the compounds were effective in activating Nrf2. PBJ was then found to be effective in an in vivo model of a metabolic syndrome induced by a high-sugar, high-fat (HSF) diet and evidenced by a significant increase of the values related to a set of parameters: blood glucose, triglycerides, insulin resistance, systolic blood pressure, visceral adipose tissue and adiposity index. PBJ, when given to control rats, did not significantly change these values; in contrast, they were found to be greatly affected in rats receiving an HSF diet. The in vivo effect of PBJ can be ascribed not only to bergamot polyphenols with well-known anti-inflammatory, antioxidant and lipid-regulating effects, but also to the dietary fibers and to the non-phenolic constituents, such as stachydrine. Moreover, since PBJ was found to affect energy homeostasis and to regulate food intake, a mechanism on the regulation of energy homeostasis through leptin networking should also be considered and deserves further investigation.

Exosomes for angiogenesis induction in ischemic disorders.

Ischaemic disorders are leading causes of morbidity and mortality worldwide. While the current therapeutic approaches have improved life expectancy and quality of life, they are unable to "cure" ischemic diseases and instate regeneration of damaged tissues. Exosomes are a class of extracellular vesicles with an average size of 100-150 nm, secreted by many cell types and considered a potent factor of cells for paracrine effects. Since exosomes contain multiple bioactive components such as growth factors, molecular intermediates of different intracellular pathways, microRNAs and nucleic acids, they are considered as cell-free therapeutics. Besides, exosomes do not rise cell therapy concerns such as teratoma formation, alloreactivity and thrombotic events. In addition, exosomes are stored and utilized more convenient. Interestingly, exosomes could be an ideal complementary therapeutic tool for ischemic disorders. In this review, we discussed therapeutic functions of exosomes in ischemic disorders including angiogenesis induction through various mechanisms with specific attention to vascular endothelial growth factor pathway. Furthermore, different delivery routes of exosomes and different modification strategies including cell preconditioning, gene modification and bioconjugation, were highlighted. Finally, pre-clinical and clinical investigations in which exosomes were used were discussed.

Gut microbiota profiling in aged dogs after feeding pet food contained Hericium erinaceus.

Health concern of dogs is the most important issue for pet owners. People who have companied the dogs long-term provide the utmost cares for their well-being and healthy life. Recently, it was revealed that the population and types of gut microbiota affect the metabolism and immunity of the host. However, there is little information on the gut microbiome of dogs. Hericium erinaceus (H. erinaceus; HE) is one of the well-known medicinal mushrooms and has multiple bioactive components including polyphenol, β-glucan, polysaccharides, ergothioneine, hericerin, erinacines, etc. Here we tested a pet food that contained H. erinaceus for improvement in the gut microbiota environment of aged dogs. A total of 18 dogs, each 11 years old, were utilized. For sixteen weeks, the dogs were fed with 0.4 g of H. erinaceus (HE-L), or 0.8 g (HE-H), or without H. erinaceus (CON) per body weight (kg) with daily diets (n = 6 per group). Taxonomic analysis was performed using metagenomics to investigate the difference in the gut microbiome. Resulting from principal coordinates analysis (PCoA) to confirm the distance difference between the groups, there was a significant difference between HE-H and CON due to weighted Unique fraction metric (Unifrac) distance (p = 0.047), but HE-L did not have a statistical difference compared to that of CON. Additionally, the result of Linear discriminate analysis of effect size (LEfSe) showed that phylum Bacteroidetes in HE-H and its order Bacteroidales increased, compared to that of CON, Additionally, phylum Firmicutes in HE-H, and its genera (Streptococcus, Tyzzerella) were reduced. Furthermore, at the family level, Campylobacteraceae and its genus Campylobacter in HE-H was decreased compared to that of CON. Summarily, our data demonstrated that the intake of H. erinaceus can regulate the gut microbial community in aged dogs, and an adequate supply of HE on pet diets would possibly improve immunity and anti-obesity on gut-microbiota in dogs.

A Tunable Tumor Microenvironment through Recombinant Bacterial Collagen-Hyaluronic Acid Hydrogels.

Laboratory models of the tumor microenvironment require control of mechanical and biochemical properties to ensure accurate mimicry of patient disease. In contrast to pure natural or synthetic materials, hybrid approaches that pair recombinant protein fragments with synthetic scaffolding show many advantages. Here we demonstrate production of a recombinant bacterial collagen-like protein (CLP) for thiol-ene pairing to norbornene functionalized hyaluronic acid (NorHA). The resultant hydrogel material shows an adjustable modulus with evidence for strain-stiffening behavior that resembles natural tumor matrices. Cysteine terminated peptide binding motifs are incorporated to adjust the cell-adhesion points. The modular hybrid gel shows good biocompatibility and was demonstrated to control cell adhesion, proliferation, and the invasive properties of MCF7 and MD-MBA-231 breast adenocarcinoma cells. The ease in which multiple structural and bioactive components can be integrated provides a robust framework to form models of the tumor microenvironment for fundamental studies and drug development.

Natural medicine HLXL targets multiple pathways of amyloid-mediated neuroinflammation and immune response in treating alzheimer's disease

BackgroundBased on the complex pathology of AD, a single chemical approach may not be sufficient to deal simultaneously with multiple pathways of amyloid-tau neuroinflammation. A polydrug approach which contains multiple bioactive components targeting multiple pathways in AD would be more appropriate. Here we focused on a Chinese medicine (HLXL), which contains 56 bioactive natural products identified in 11 medicinal plants and displays potent anti-inflammatory and immuno-modulatory activity. Hypothesis/PurposeWe investigated the neuroimmune and neuroinflammation mechanisms by which HLXL may attenuate AD neuropathology. Specifically, we investigated the effects of HLXL on the neuropathology of AD using both transgenic mouse models as well as microglial cell-based models. Study designThe 5XFAD transgenic animals and microglial cell models were respectively treated with HLXL and Aβ42, and/or lipopolysaccharide (LPS), and then analyzed focusing on microglia mediated Aβ uptake and clearance, as well as pathway changes. MethodsWe showed that HLXL significantly reduced amyloid neuropathology by upregulation of microglia-mediated phagocytosis of Aβ both in vivo and in vitro. HLXL displayed multi-modal mechanisms regulating pathways of phagocytosis and energy metabolism. ResultsOur results may not only open a new avenue to support pharmacologic modulation of neuroinflammation and the neuroimmune system for AD intervention, but also identify HLXL as a promising natural medicine for AD. ConclusionIt is conceivable that the traditional wisdom of natural medicine in combination with modern science and technology would be the best strategy in developing effective therapeutics for AD.

Mitoprotective Effects of a Synergistic Nutraceutical Combination: Basis for a Prevention Strategy Against Alzheimer's Disease.

Evidence to date suggests the consumption of food rich in bioactive compounds, such as polyphenols, flavonoids, omega-3 fatty acids may potentially minimize age-related cognitive decline. For neurodegenerative diseases, such as Alzheimer’s disease (AD), which do not yet have definitive treatments, the focus has shifted toward using alternative approaches, including prevention strategies rather than disease reversal. In this aspect, certain nutraceuticals have become promising compounds due to their neuroprotective properties. Moreover, the multifaceted AD pathophysiology encourages the use of multiple bioactive components that may be synergistic in their protective roles when combined. The objective of the present study was to determine mechanisms of action underlying the inhibition of Aβ1–42-induced toxicity by a previously determined, three-compound nutraceutical combination D5L5U5 for AD. In vitro experiments were carried out in human neuroblastoma BE(2)-M17 cells for levels of ROS, ATP mitophagy, and mitobiogenesis. The component compounds luteolin (LUT), DHA, and urolithin A (UA) were independently protective of mitochondria; however, the D5L5U5 preceded its single constituents in all assays used. Overall, it indicated that D5L5U5 had potent inhibitory effects against Aβ1–42-induced toxicity through protecting mitochondria. These mitoprotective activities included minimizing oxidative stress, increasing ATP and inducing mitophagy and mitobiogenesis. However, this synergistic nutraceutical combination warrants further investigations in other in vitro and in vivo AD models to confirm its potential to be used as a preventative therapy for AD.

Potential multiple bioactive components from Sinopodophyllum hexandrum explored by affinity ultrafiltration with four drug targets

Background: Sinopodophyllum hexandrum (S. hexandrum) is a typical Chinese herbal medicine with multiple components and pharmacological activities. However, the specific phytochemicals responsible for its anti-proliferative, anti-inflammatory and anti-viral effects remain unexplored. Purpose: This study aimed to explore the specific bioactive phytochemicals from S. hexandrum responsible for its multiple remarkable pharmacological in an effort to construct and decipher its empirical therapeutic roles. Study design: Bio-affinity ultrafiltration (AUF) with multiple drug targets corresponding to its empirical anti-proliferative, anti-inflammatory and anti-viral activities was developed to screen for potential bioactive ligands from S. hexandrum, and then in vitro bioactivity assays or molecular docking methods were used to verify those bioactive ligands. Methods: The integrative analytical strategy was developed to rapidly screen and identify bioactive ligands from S. hexandrum. The in vitro anti-proliferative, COX-2 and ACE2 inhibitory assays of ligands were further verified by SRB cell proliferation and cytotoxicity detection, COX-2 and ACE2 inhibitor screening kits, respectively. Molecular docking analysis was also implemented by the AutoDockTools 1.5.6 software. Results: Ten, seven, nine and nine phytochemicals were screened out and identified as the potential Topo I, Topo II, COX-2 and ACE2 ligands, respectively. Hereinto, podophyllotoxin and quercetin with higher EF values displayed strong inhibitory effects on A549 and HT-29 cells comparable with etoposide and 5-FU as the positive controls. Furthermore, compared with indomethacin at 0.73 ± 0.07 μM, kaempferol and podophyllotoxin with higher EF values exerted stronger inhibitory effects with IC50 values at 0.36 ± 0.02 μM and 10.49 ± 0.61 μM, respectively. Isorhamnetin with a higher EF value exerted stronger inhibitory effect against ACE2 with IC50 value at 118.46 ± 14.78 μM in contrast to podophyllotoxin with relatively lower EF value at > 970.00 μM. In addition, the optimal binding sites and mode of action between multiple drug targets and bioactive ligands were determined by molecular docking. Conclusion: This study showcased a quick and reliable experimental strategy for unveiling the underlying mechanism of S. hexandrum, which could also provide valuable information for better understanding the therapeutic targets and ligands of other herbal medicines.

A Critical Review on Phytochemical Profile and Biological Effects of Turnip (Brassica rapa L.).

A growing number of medicinal and edible plants have attracted increasing attention due to their abundant constituents and biological activities including turnip. Turnip (Brassica rapa L.) is an herbaceous biennial plant belonging to Cruciferae Brassica. As one of the oldest cultivated vegetables widely consumed in Asia, the turnip has received significant attention in the studies of its bioactive components and biological function. Multiple bioactive components in turnip, such as glucosinolates, isothiocyanate, phenolic compounds, flavonoids, and organic acids, were identified. The bioactivity studies on turnip revealed its anticancer, antimicrobe, anti-hypoxia, anti-diabetes, anti-oxidation, and nephroprotective activity. The present review mainly summarized the previous studies on the chemical compositions of turnip and the bioactivities associated with turnip. Further studies on the extraction and purification of compounds from a turnip as well as its potential molecular mechanisms are highly needed to utilize turnip as a functional food plant in a better way.

Research advance in multi-component pharmacokinetics of Chinese herbal extracts in recent five years

The multi-component pharmacokinetic study of Chinese herbal extracts elaborates the in vivo processes,including absorption,distribution,metabolism,and excretion,of multiple bioactive components,which is of significance in revealing pharmacodynamic material basis of Chinese herbal medicine. In recent years,with the innovation in ideas,and development of techniques and methods on traditional Chinese medicine( TCM) research,the pharmacokinetic studies of Chinese herbal extracts were extensively performed,and notable progress has been made. This paper reviewed the advancement of multi-component pharmacokinetics of Chinese herbal extracts in recent five years from analysis technology of biological sample,the pharmacokinetic characteristics of Chinese herbal medicine with complex system,and the impacts of processing and pathological state on pharmacokinetics of Chinese herbal extracts,aiming to provide a reference for quality control,product development and rational medication of Chinese herbal extracts.

Oat proteins as emerging ingredients for food formulation: where we stand?

Over the last decades, interest in oats (Avena sativa L.) as healthy foods increased due to their multiple functional and bioactive components such as dietary fibers, polyphenols, and proteins. Protein extracted from oats received considerable attention being more abundant (12–20%) and having a distinct composition compared to other cereal grains. Oat proteins also present pleasant sensorial attributes compared to proteins deriving from legumes and oil seeds. Protein isolates or concentrates can be dry- or wet- extracted, and subsequent enzymatic hydrolysis can release peptides with bioactive properties. Several strategies have been successfully applied to improve the techno-functionality of oat proteins. In terms of food application, there are few oat protein-based food products available in the market, which urge food developers to build tailored strategies and food portfolios of these ingredients. This review will address oat proteins extraction technologies and pre/post-treatment strategies, main characteristics, and applications. Future research is still required to take advantage of breeding progress to select high grain-protein oat varieties and to boost the incorporation of oat proteins in foods while keeping in mind the cost and the environmental impact.

Fabrication of Folic Acid-Decorated Hollow ZIF-8/Au/CuS Nanocomposites for Enhanced and Selective Anticancer Therapy.

Hollow nanomaterials have been used as an attractive platform for the integration of multiple bioactive components for effective anticancer therapy. Herein, we report a novel and facile strategy for the fabrication of hollow and monodispersed zeolitic imidazolate framework-8 (ZIF-8) by the self-template method with folic acid (FA) as a bioetcher. Gold nanocluster and folic acid were critical for the formation of the hollow ZIF-8 (thickness of 38 nm) during solvothermal synthesis. By integrating CuS nanoparticles (size of 4.9 nm), the resultant quadruple ZIF-8/Au/CuS/FA nanocomposites (denoted as FACZ) exhibited effective anticancer activities on FA receptor-positive MCF-7 and HepG-2 tumor cells but a weak killing effect on HCMEC/D3 cells. Folic acid molecules were conjugated to the external surface of FACZ, which simultaneously offered an excellent tumor-targeting ability and fluorescence imaging property. Although the photothermal therapy caused by CuS was not so obvious due to partial reduction, the nanosized FACZ after cellular uptake was able to release Cu(I) to enable chemodynamic therapy. This catalytically decomposed H2O2 to produce highly reactive oxygen species via the Fenton-like reaction as determined by the extracellular and intracellular hydroxyl radical. Our work offers a simple route for the fabrication of hollow ZIF-8 nanocomposite with active and selective anticancer activity. This is envisaged to have great potentials in biomedical applications.

Quantitative analysis and pharmacokinetic comparison of multiple bioactive components in rat plasma after oral administration of Qi-Shen-Ke-Li formula and its single-herb extracts using ultra-high-performance liquid chromatography-tandem mass spectrometry.

Qi-Shen-Ke-Li (QSKL), a traditional Chinese formula prepared from six herbs, has long been used for the treatment of coronary heart disease and chronic heart failure. However, the herbal combination mechanism and underlying material basis of this multi-herbal formula are not clear. In this study, an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to simultaneously determine multiple bioactive compounds in QSKL was established and validated. Using the developed method, 18 bioactive components in rat plasma after oral administration of QSKL formula and its single herb extracts were quantified. Based on these results, pharmacokinetic (PK) parameters (T1/2 , Tmax , Cmax , AUC0-48h , and AUC0-∞ ) of the 18 bioactive components were analyzed and compared using PKSlover 2.0 PK software. The experimental data suggested that significant changes in PK profiles were observed between the QSKL formula and its single-herb extracts. The herbal combination in QSKL significantly influences the system exposure and the PK behaviors of the 18 bioactive components, indicating multicomponent interactions among the herbs. This study provides insight into the herbal combination mechanism and underlying material basis of the QSKL formula.

Milk for Skeletal Muscle Health and Sarcopenia in Older Adults: A Narrative Review.

Skeletal muscle aging manifests as a decline in muscle quantity and quality that accelerates with aging, increasing the risk of sarcopenia. Sarcopenia is characterized by a loss of muscle strength and mass, and contributes to adverse health outcomes in older adults. Intervention studies have shown that sarcopenia may be treated by higher protein intake in combination with resistance exercise (RE). In comparison, less is known about the role of whole protein-containing foods in preventing or treating sarcopenia. Liquid milk contains multiple nutrients and bioactive components that may be beneficial for muscle, including proteins for muscle anabolism that, alone or with RE, may have myoprotective properties. However, there is a lack of evidence about the role of milk and its effects on muscle aging. This narrative review considers evidence from three observational and eight intervention studies that used milk or fortified milk, with or without exercise, as an intervention to promote muscle health and function in older adults (aged 50–99 years). The observational studies showed no association between higher habitual milk consumption and muscle-related outcomes. The results of intervention studies using fortified milk in relation to elements of sarcopenia were also negative, with further inconclusive results from the studies using a combination of (fortified) milk and exercise. Although milk contains nutrients that may be myoprotective, current evidence does not show beneficial effects of milk on muscle health in older adults. This could be due to high habitual protein intakes (>1.0 g/kg BW/d) in study participants, differences in the type of milk (low-fat vs whole) and timing of milk consumption, length of interventions, as well as differences in the sarcopenia status of participants in trials. Adequately powered intervention studies of individuals likely to benefit are needed to test the effectiveness of a whole food approach, including milk, for healthy muscle aging.

Enhancing enrichment ability of ZIF-8 mixed matrix membrane microextraction by reverse micelle strategy for analysis of multiple ionizable bioactive components in biological samples

Recent research aimed at the design of mixed-matrix membrane (MMM) to be used for microextraction emphasized on membrane extraction phase with high surface area and porosity. This study explored the influence that surfactants have on MMM extraction efficiency for the first time. The zeolitic imidazolate framework 8-based MMM (ZIF-8-MMM) was synthesized by in situ self-assembly of ZIF-8 on the inner wall of a hollow fiber membrane with the aim of fabricating a microextraction device. By prompting the encapsulation of ionizable analytes in the polar core of reverse micelles, the presence of surfactants in extraction solvent assisted the dissolution of analytes in the fiber membrane lumen and enhanced their adsorption onto ZIF-8. Notably, hereby a microextraction method based on the novel ZIF-8-MMM–reverse micelle (ZIF-8-MMM-RM) system was developed and employed for the extraction and quantitation of two alkaloids (berberine and jatrorrhizine) and two flavonoids (wogonin and wogonoside) in biological samples. The main factors affecting microextraction performance, identity of the extraction solvent, surfactant concentration, sample solution pH and extraction time, were investigated in detail. The method showed good linearity (r2 > 0.99) and repeatability (RSD < 10%), low limits of detection (0.10–0.31 ng mL−1) and high relative recoveries (90.03–98.84%). The enrichment factor values ranged between 48.47 and 54.96. Reverse micelle formation prompted by surfactant addition was demonstrated to effectively assist the extraction of multiple ionizable analytes from biological samples, resulting in a marked improvement of ZIF-8-MMM extraction performance.

Synergistic anticancer effects of curcumin and 3',4'-didemethylnobiletin in combination on colon cancer cells.

Chemoprevention strategies employing the use of multiple dietary bioactive components and their metabolites in combination offer advantages due to their low toxicity and potential synergistic interactions. Herein, for the first time, we studied the combination of curcumin and 3',4'-didemethylnobiletin (DDMN), a primary metabolite of nobiletin, to determine their combinatory effects in inhibiting growth of human colon cancer cells. Isobologram analysis revealed a synergistic interaction between curcumin and DDMN in the inhibition of cell growth of HCT116 colon cancer cells. The combination treatment induced significant G2 -M cell-cycle arrest and extensive apoptosis, which greatly exceeded the effects of individual treatments with curcumin or DDMN. Proteins associated with these heightened anticarcinogenic effects were p53, p21, HO-1, c-poly(ADP-ribose) polymerase, Cdc2, and Cdc25c; each of the proteins was confirmed to be substantially impacted by the combination treatment, more than by individual treatments alone. Interestingly, an increase in the stability of curcumin was also observed with the presence of DDMN in cell culture medium, which could offer an explanation in part for the synergistic interaction between curcumin and DDMN. This newly identified synergy between curcumin and DDMN should be explored further to determine its chemopreventive potential against colon cancer in vivo. PRACTICAL APPLICATION: This study identifies for the first time the synergistic inhibition of colon cancer cell growth by the dietary component curcumin present in turmeric, in combination with a metabolite of nobiletin, a unique citrus flavonoid. The synergism of the combination may be due to cell-cycle arrest and apoptosis induced by the combination as well as an improvement in the stability of curcumin as a result of the antioxidant property of the nobiletin metabolite. These significant findings of synergism between curcumin and the nobiletin metabolite could offer potential chemopreventive value against colon cancer.