Anti-inflammatory effect and pharmacokinetics of dehydroandrographolide, an active component of Andrographis paniculata, on Poly(I:C)-induced acute lung injury.

Acute lung injury (ALI) is a common and critical respiratory disorder caused by various factors, with viral infection being the leading contributor. Dehydroandrographolide (DAP), a constituent of the Chinese herbal plant Andrographis paniculata, exhibits a range of activities including anti-inflammatory, in vitro antiviral and immune-enhancing effects. This study evaluated the anti-inflammatory effects and pharmacokinetics (PK) profile of DAP in ALI mice induced by intratracheal instillation of Poly(I:C) (PIC). The results showed that oral administration of DAP (10-40 mg/kg) effectively suppressed the increase in lung wet-dry weight ratio, total cells, total protein content, accumulation of immune cells, inflammatory cytokines and neutrophil elastase levels in bronchoalveolar lavage fluid of PIC-treated mice. DAP concentrations, determined by an LC-MS/MS method, in plasma after receiving DAP (20 mg/kg) were unchanged compared to those in normal mice. However, DAP concentrations and relative PK parameters in the lungs were significantly altered in PIC-treated mice, exhibiting a relatively higher maximum concentration, larger AUC, and longer elimination half-life than those in the lungs of normal mice. These results demonstrated that DAP could improve lung edema and inflammation in ALI mice, and suggested that lung injury might influence the PK properties of DAP, leading to increased lung distribution and residence. Our study provides evidence that DAP displays significant anti-inflammatory activity against viral lung injury and is more likely to distribute to damaged lung tissue.

Shen Yuan extract exerts a hypnotic effect via the tryptophan/5-hydroxytryptamine/melatonin pathway in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Sleep plays a critical role in several physiologic processes, and sleep disorders increase the risk of depression, dementia, stroke, cancer, and other diseases. Stress is one of the main causes of sleep disorders. Ginseng Radix et Rhizoma and Polygalae Radix have been reported to have effects of calming the mind and intensifying intelligence in Chinese Pharmacopoeia. Traditional Chinese medicine prescriptions composed of Ginseng Radix et Rhizoma and Polygalae Radix (Shen Yuan, SY) are commonly used to treat insomnia, depression, and other psychiatric disorders in clinical practice. Unfortunately, the underlying mechanisms of the SY extract's effect on sleep are still unknown. AIM OF THE STUDY: This study aimed to investigate the hypnotic effect of the SY extract in normal mice and mice with chronic restraint stress (CRS)-induced sleep disorders and elucidate the underlying mechanisms. MATERIALS AND METHODS: The SY extract (0.5 and 1.0 g/kg) was intragastrically administered to normal mice for 1, 14, and 28 days and to CRS-treated mice for 28 days. The open field test (OFT) and pentobarbital sodium-induced sleep test (PST) were used to evaluate the hypnotic effect of the SY extract. Liquid chromatography-tandem mass spectrometry and enzyme-linked immunosorbent assay were utilized to detect the levels of neurotransmitters and hormones. Molecular changes at the mRNA and protein levels were determined using real-time quantitative polymerase chain reaction and Western blot analysis to identify the mechanisms by which SY improves sleep disorders. RESULTS: The SY extract decreased sleep latency and increased sleep duration in normal mice. Similarly, the sleep duration of mice subjected to CRS was increased by administering SY. The SY extract increased the levels of tryptophan (Trp) and 5-hydroxytryptamine (5-HT) and the expression of tryptophan hydroxylase 2 (TPH2) in the cortex of normal mice. The SY extract increased the Trp level, transcription and expression of estrogen receptor beta and TPH2 in the cortex in mice with sleep disorders by decreasing the serum corticosterone level, which promoted the synthesis of 5-HT. Additionally, the SY extract enhanced the expression of arylalkylamine N-acetyltransferase, which increased the melatonin level and upregulated the expressions of melatonin receptor-2 (MT2) and Cryptochrome 1 (Cry1) in the hypothalamus of mice with sleep disorders. CONCLUSIONS: The SY extract exerted a hypnotic effect via the Trp/5-HT/melatonin pathway, which augmented the synthesis of 5-HT and melatonin and further increased the expressions of MT2 and Cry1.

Overview of T-2 Toxin Enterotoxicity: From Toxic Mechanisms and Detoxification to Future Perspectives.

Fusarium species produce a secondary metabolite known as T-2 toxin, which is the primary and most harmful toxin found in type A trichothecenes. T-2 toxin is widely found in food and grain-based animal feed and endangers the health of both humans and animals. T-2 toxin exposure in humans and animals occurs primarily through food administration; therefore, the first organ that T-2 toxin targets is the gut. In this overview, the research progress, toxicity mechanism, and detoxification of the toxin T-2 were reviewed, and future research directions were proposed. T-2 toxin damages the intestinal mucosa and destroys intestinal structure and intestinal barrier function; furthermore, T-2 toxin disrupts the intestinal microbiota, causes intestinal flora disorders, affects normal intestinal metabolic function, and kills intestinal epidermal cells by inducing oxidative stress, inflammatory responses, and apoptosis. The primary harmful mechanism of T-2 toxin in the intestine is oxidative stress. Currently, selenium and plant extracts are mainly used to exert antioxidant effects to alleviate the enterotoxicity of T-2 toxin. In future studies, the use of genomic techniques to find upstream signaling molecules associated with T-2 enterotoxin toxicity will provide new ideas for the prevention of this toxicity. The purpose of this paper is to review the progress of research on the intestinal toxicity of T-2 toxin and propose new research directions for the prevention and treatment of T-2 toxin toxicity.

Abietane diterpenoids and iridoids from Caryopteris mongolica.

Six new abietane diterpenoids (1-6) and five undescribed iridoids (7-11) have been isolated from the aerial parts of Caryopteris mongolica. The intricate structural characterization of these compounds was meticulously undertaken using an array of advanced spectroscopic techniques. This process was further enhanced by the application of DP4+ probability analyses and electronic circular dichroism (ECD) calculations. Following isolation and structural elucidation, the cytotoxicity of these compounds was evaluated. Among them, compound 3 stood out, displaying significant cytotoxic activity against HeLa cells with an IC50 value of 7.83 ± 1.28 µmol·L-1. Additionally, compounds 1, 2, 4, 9, and 10 manifested moderate cytotoxic effects on specific cell lines, with IC50 values ranging from 11.7 to 20.9 µmol·L-1.

Gut Microbiota Combined with Serum Metabolomics to Investigate the Hypoglycemic Effect of Actinidia arguta Leaves.

Actinidia arguta leaves (AAL) are an excellent source of bioactive components for the food industry and possess many functional properties. However, the hypoglycemic effect and mechanism of AAL remain unclear. The aim of this work was to investigate the potential hypoglycemic effect of AAL and explore its possible mechanism using 16S rRNA sequencing and serum metabolomics in diabetic mice induced by high-fat feeding in combination with streptozotocin injection. A total of 25 flavonoids from AAL were isolated and characterized, and the contents of the extract from the AAL ranged from 0.14 mg/g DW to 8.97 mg/g DW. The compound quercetin (2) had the highest content of 8.97 ± 0.09 mg/g DW, and the compound kaempferol-3-O-(2'-O-D-glucopyl)-ß-D-rutinoside (12) had the lowest content of 0.14 ± 0.01 mg/g DW. In vivo experimental studies showed that AAL reduced blood glucose and cholesterol levels, improved insulin sensitivity, and ameliorated oxidative stress and liver and kidney pathological damage. In addition, gut microbiota analysis found that AAL significantly reduced the F/B ratio, enriched the beneficial bacteria Bacteroides and Bifidobacterium, and inhibited the harmful bacteria Lactobacillus and Desulfovibrio, thereby playing an active role in intestinal imbalance. In addition, metabolomics analysis showed that AAL could improve amino acid metabolism and arachidonic acid metabolism, thereby exerting a hypoglycemic effect. This study confirmed that AAL can alleviate type 2 diabetes mellitus (T2DM) by regulating intestinal flora and interfering with related metabolic pathways, providing a scientific basis for its use as a dietary supplement and for further exploration of the mechanism of AAL against T2DM.

Interaction between potato starch and barley ß-glucan and its influence on starch pasting and gelling properties.

The interactions between potato starch (PtS) and barley ß-glucan (BBG) were investigated by preparing PtS-BBG mixtures, and the pasting, rheological, gelling and structural properties were evaluated. Rapid viscosity analysis suggested that BBG reduced the peak and breakdown viscosity, while increasing the setback viscosity of PtS. PtS-12%BBG showed the lowest leached amylose content (12.02 ± 0.36 %). The particle size distribution pattern of PtS was not changed with the addition of BBG, and the median diameter of PtS-12%BBG (88.21 ± 0.41 µm) was smaller than that of PtS (108.10 ± 6.26 µm). Rheological results showed that PtS and PtS-BBG gels exhibited weak gel behaviors, and BBG could remarkably affect the elastic and viscous modulus of PtS gels. Textural analysis suggested that the strength and hardness of PtS gels were increased when few BBG (<6 %, w/w) was present in the system. BBG improved the freeze-thaw stability of PtS gels. Structural analysis indicated that hydrogen bonds were the main force in the PtS-BBG systems. These results indicated that BBG interacted with starch via hydrogen bonds, which delayed starch gelatinization and improved gelling properties of PtS gels. Overall, this study gained insights into starch-polysaccharide interactions and revealed the possible applications of BBG in food processing.

Isolation and identification of 3,4-seco-labdane diterpenoids from Callicarpa nudiflora and investigation of their cytotoxicity against HepG2 cells.

Twenty-one previously undescribed compounds, including nineteen 3,4-seco-labdanes (nudiflopenes P-W, Y, AI-JI), one 3,4-seco-pimarane (nudiflopene X), and one labdane (nudiflopene Z), along with nine known compounds (one 3,4-seco-pimarane and eight 3,4-seco-labdanes) were isolated from the leaves of Callicarpa nudiflora Hook. Et Arn. The structures of these compounds were elucidated by high-resolution electrospray ionization mass spectrometry and one- and two-dimensional nuclear magnetic resonance spectroscopy. In addition, configurations of the isolated compounds were determined by electronic circular dichroism, DP4+ probability analysis, and single-crystal X-ray diffraction experiments. All undescribed compounds were evaluated for their cytotoxicity against HepG2 cells in vitro, among which compound 12 exhibited a moderate activity with an IC50 value of 27.8 µM.

Transcription factors GmERF1 and GmWRKY6 synergistically regulate low phosphorus tolerance in soybean.

Soybean (Glycine max) is a major grain and oil crop worldwide, but low phosphorus (LP) in soil severely limits the development of soybean production. Dissecting the regulatory mechanism of the phosphorus (P) response is crucial for improving the P use efficiency of soybean. Here, we identified a transcription factor, GmERF1 (ethylene response factor 1), that is mainly expressed in soybean root and localized in the nucleus. Its expression is induced by LP stress and differs substantially in extreme genotypes. The genomic sequences of 559 soybean accessions suggested that the allelic variation of GmERF1 has undergone artificial selection, and its haplotype is significantly related to LP tolerance. GmERF1 knockout or RNA interference resulted in significant increases in root and P uptake efficiency traits, while the overexpression of GmERF1 produced an LP-sensitive phenotype and affected the expression of 6 LP stress-related genes. In addition, GmERF1 directly interacted with GmWRKY6 to inhibit transcription of GmPT5 (phosphate transporter 5), GmPT7, and GmPT8, which affects plant P uptake and use efficiency under LP stress. Taken together, our results show that GmERF1 can affect root development by regulating hormone levels, thus promoting P absorption in soybean, and provide a better understanding of the role of GmERF1 in soybean P signal transduction. The favorable haplotypes from wild soybean will be conducive to the molecular breeding of high P use efficiency in soybean.

Peri-Conceptional Folic Acid Supplementation and Children's Physical Development: A Birth Cohort Study.

BACKGROUND: Maternal lack of folic acid supplementation during pregnancy may increase the risk of low birth weight and preterm delivery. However, little is known about the relationship between folic acid supplementation during pregnancy and the physical development of offspring in the later stage. OBJECTIVE: This study aimed to explore the association between maternal folic acid supplementation status during pregnancy and the physical development of preschool children. METHODS: A total of 3064 mother-child pairs with data on maternal folic acid supplementation status during pregnancy and children's anthropometric measurements were recruited from the Ma'anshan-Anhui Birth Cohort (MABC) in China. Maternal folic acid supplementation status during pregnancy was the main exposure, and the primary outcomes were children's growth development trajectories. Children's growth development trajectories were fitted using group-based trajectory models. The association between maternal folic acid supplementation status during pregnancy and children's growth trajectories was performed using multiple logistic regression models. RESULTS: After adjusting for potential confounders, we found that the absence of maternal folic acid supplementation before pregnancy and in the first trimester was significantly associated with a "high level" trajectory (trajectory 3) and a "high rising level" trajectory (trajectory 4) of BMI-Z scores in children 0 to 6 years of age (OR = 1.423, 95%CI:1.022-1.982; OR = 1.654, 95%CI: 1.024-2.671). In children aged 4 to 6 years old, a "high level" trajectory (trajectory 3) of body fat ratio was substantially related to maternal no folic acid supplementation before pregnancy and in the first trimester (OR = 1.833, 95%CI:1.037-3.240). No significant additional benefits associated with physical developmental indicators in preschool children have been observed with continued folic acid supplementation after the first trimester of gestation. CONCLUSIONS: Maternal non-supplementation with folic acid during pregnancy is associated with a "high level" BMI trajectory and a "high level" body fat ratio trajectory in preschool-aged children.

Covalent Organic Framework Nanobowls as Activatable Nanosensitizers for Tumor-Specific and Ferroptosis-Augmented Sonodynamic Therapy.

Covalent organic frameworks (COFs) have attracted increasing attention for biomedical applications. COFs-based nanosensitizers with uniform nanoscale morphology and tumor-specific curative effects are in high demand; however, their synthesis is yet challenging. In this study, distinct COF nanobowls are synthesized in a controlled manner and engineered as activatable nanosensitizers with tumor-specific sonodynamic activity. High crystallinity ensures an ordered porous structure of COF nanobowls for the efficient loading of the small-molecule sonosensitizer rose bengal (RB). To circumvent non-specific damage to normal tissues, the sonosensitization effect is specifically inhibited by the in situ growth of manganese oxide (MnOx ) on RB-loaded COFs. Upon reaction with tumor-overexpressed glutathione (GSH), the "gatekeeper" MnOx is rapidly decomposed to recover the reactive oxygen species (ROS) generation capability of the COF nanosensitizers under ultrasound irradiation. Increased intracellular ROS stress and GSH consumption concomitantly induce ferroptosis to improve sonodynamic efficacy. Additionally, the unconventional bowl-shaped morphology renders the nanosensitizers with enhanced tumor accumulation and retention. The combination of tumor-specific sonodynamic therapy and ferroptosis achieves high efficacy in killing cancer cells and inhibiting tumor growth. This study paves the way for the development of COF nanosensitizers with unconventional morphologies for biomedicine, offering a paradigm to realize activatable and ferroptosis-augmented sonodynamic tumor therapy.

Metabolomic Analysis of Stephania tetrandra-Astragalus membranaceus Herbal Pair-Improving Nephrotic Syndrome Identifies Activation of IL-13/STAT6 Signaling Pathway.

The Stephania tetrandra−Astragalus membranaceus herbal pair (FH) is a classic herbal pair widely used in the treatment of nephrotic syndrome (NS). The effects of Stephania tetrandra (FJ) and Astragalus membranaceus (HQ) on NS have been reported, but the mechanism of their combination on the improvement of NS are still unclear. The NS model was established by injecting adriamycin into the tail vein. FH intervention reduced the levels of serum triglyceride, total cholesterol, interleukin-6 (IL-6), blood urea nitrogen (BUN), urinary protein, and the gene expression levels of aquaporin 2 (AQP2) and arginine vasopressin (AVP) in NS rats. In addition, FH improved kidney injury in NS rats by inhibiting the expression of interleukin 13 (IL-13), phospho-signal transducers, and activators of transcription 6 (p-STAT6), Bax, cleaved-caspase3, while promoting the expression of Bcl-2. By comprehensive comparison of multiple indexes, the effects of FH on lipid metabolism, glomerular filtration rate, and inflammation were superior to that of FJ and HQ. Metabonomic studies showed that, compared with FJ and HQ, FH intervention significantly regulated tricarboxylic acid (TCA) cycle, cysteine and methionine metabolism, and alanine, aspartic acid and glutamic acid metabolism. Pearson correlation analysis showed that succinic acid and L-aspartic acid were negatively correlated with urinary protein, cystatin C (Cys C) and BUN (p < 0.05). In summary, FH could reduce renal injury and improve NS through inhibiting the IL-13/STAT6 signal pathway, regulating endogenous metabolic pathways, such as TCA cycle, and inhibiting the expression of AQP2 and AVP genes. This study provides a comprehensive strategy to reveal the mechanism of FH on the treatment of NS, and also provides a reasonable way to clarify the compatibility of traditional Chinese medicine.

The impact of phyto- and endo-cannabinoids on central nervous system diseases：A review.

Background and aim: Cannabis sativa L. is a medicinal plant with a long history. Phyto-cannabinoids are a class of compounds from C. sativa L. with varieties of structures. Endocannabinoids exist in the human body. This article provides an overview of natural cannabinoids (phyto-cannabinoids and endocannabinoids) with an emphasis on their pharmacology activities. Experimental procedure: The keywords "Cannabis sativa L″, "cannabinoids", and "central nervous system (CNS) diseases" were used for searching and collecting pieces of literature from PubMed, ScienceDirect, Web of Science, and Google Scholar. The data were extracted and analyzed to explore the effects of cannabinoids on CNS diseases. Result and conclusion: In this paper, schematic diagrams are used to intuitively show the phyto-cannabinoids skeletons' mutual conversion and pharmacological activities, with special emphasis on their relevant pharmacological activities on central nervous system (CNS) diseases. It was found that the endocannabinoid system and microglia play a crucial role in the treatment of CNS diseases. In the past few years, pharmacological studies focused on Δ9-THC, CBD, and the endocannabinoids system. It is expected to encourage new studies on a more deep exploration of other types of cannabinoids and the mechanism of their pharmacological activities in the future.

Nontargeted metabolomic analysis of four different parts of Actinidia arguta by UPLC-Q-TOF-MSE.

Actinidia arguta, an edible berry plant with high nutritional values, has been widely used in Asian countries as a food and traditional medicinal herb. The well-recognized health-promoting properties of A. arguta were associated with its bioactive components in its different botanical parts. To rapidly screen and identify chemical components and simultaneously determine the potential metabolites from different parts of A. arguta, UPLC-Q-TOF-MSE coupled with UNIFI platform and multivariate statistical analysis approach was established in this study. As a result, a total of 107 components were identified from the four different parts of A. arguta, in which 31 characteristic chemical markers were discovered among them, including 12, 8, 6, and 5 compounds from the fruits, leaves, roots, and stems, respectively. These results suggested that the combination of UPLC-Q-TOF-MSE and metabolomic analysis is a powerful method to rapidly screen characteristic markers for the quality control of A. arguta.

Kunxian Capsule Extract Inhibits Angiogenesis in Zebrafish Embryos via PI3K/AKT-MAPK-VEGF Pathway.

OBJECTIVE: To investigate the anti-angiogenic activity of Kunxian Capsule (KX) extract and explore the underlying molecular mechanism using zebrafish. METHODS: The KX extract was prepared with 5.0 g in 100 mL of 40% methanol followed by ultrasonication and freeze drying. Freeze dried KX extract of 10.00 mg was used as test stock solution. Triptolide and icariin, the key bioactive compounds of KX were analyzed using ultra-high performance liquid chromatography. The transgenic zebrafish Tg(flk1:GFP) embryos were dechorionated at 20-h post fertilization (hpf) and treated with PTK 787, and 3.5, 7, 14 and 21 µg/mL of KX extract, respectively. After 24-h post exposure (hpe), mortality and malformation (%), intersegmental vessels (ISV) formation, and mRNA expression level of angiogenic pathway genes including phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), extracellular signal-regulated kinases (ERKs), mitogen-activated protein kinase (MAPK), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF-2) were determined. Further, the embryos at 72 hpf were treated with KX extract to observe the development of sub-intestinal vein (SIV) after 24 hpe. RESULTS: The chromatographic analysis of test stock solution of KX extract showed that triptolide and icariin was found as 0.089 mg/g and 48.74 mg/g, respectively, which met the requirements of the national drug standards. In zebrafish larvae experiment, KX extract significantly inhibited the ISV (P<0.01) and SIV formation (P<0.05). Besides, the mRNA expression analysis showed that KX extract could significantly suppress the expressions of PI3K and AKT, thereby inhibiting the mRNA levels of ERKs and MAPK. Moreover, the downstream signaling cascade affected the expression of VEGF and its receptors (VEGFR and VEGFR-2). FGF-2, a strong angiogenic factor, was also down-regulated by KX treatment in zebrafish larvae. CONCLUSION: KX extract exhibited anti-angiogenic effects in zebrafish embryos by regulating PI3K/AKT-MAPK-VEGF pathway and showed promising potential for RA treatment.

Investigation of the chemical profile and anti-inflammatory mechanisms of flavonoids from Artemisia vestita Wall. ex Besser via targeted metabolomics, zebrafish model, and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia vestita Wall. ex Besser is wildly distributed in the western high-altitude area of China and has been used as a Tibetan medicine to treat inflammatory diseases. We previously demonstrated the total flavonoids of Artemisia vestita Wall. ex Besser (TFA) showed obvious anti-inflammatory effects and its content was 276.62 mg/g. However, the chemical profile, active ingredients, and anti-inflammatory mechanisms of TFA are not clear. AIM OF THE STUDY: This study aimed to study the components of TFA, evaluate the anti-inflammatory effects of TFA, and preliminarily predict the anti-inflammatory mechanism of TFA. MATERIALS AND METHODS: TFA was prepared by the semi-biomimetic extraction method and purified by macroporous resin. The components of TFA were analyzed based on LC-MS combined with the targeted metabolomics method. The anti-inflammatory activity of TFA was evaluated using CuSO4-induced and tail cutting-induced zebrafish inflammation models. Based on the network pharmacology method, the anti-inflammatory mechanism of the main components of TFA was preliminarily predicted. RESULTS: A total of 185 components were identified in TFA. TFA showed significant anti-inflammatory effects on CuSO4-induced and tail cutting-induced zebrafish inflammation models. According to network pharmacology prediction and experimental verification, 10 compounds were identified as the main active ingredients, including 3,7-di-O-methylquercetin, Hesperetin 5-O-glucoside, Myricitrin, et al. Twenty key targets were recognized, such as TNF, AKT1, VEGFA, MMP9, EGFR, PTGS2 et al. Moreover, the TNF signaling pathway and NOD-like receptor signaling pathway were identified to play vital roles in the anti-inflammatory effects of TFA. CONCLUSIONS: This study revealed the chemical profile of TFA and identified the main active ingredients, key targets, and pathways of TFA in anti-inflammatory effects, which is helpful to elucidate the pharmacodynamic substances and action mechanisms of Artemisia vestita Wall. ex Besser, to promote its clinical rational application.

Antioxidant Effects of Roasted Licorice in a Zebrafish Model and Its Mechanisms.

Licorice (Gan-Cao, licorice) is a natural antioxidant and roasted licorice is the most common processing specification used in traditional Chinese medicine prescriptions. Traditional Chinese medicine theory deems that the honey-roasting process can promote the efficacy of licorice, including tonifying the spleen and augmenting "Qi" (energy). The antioxidant activity and mechanisms underlying roasted licorice have not yet been reported. In this study, we found that roasted licorice could relieve the oxidative stress injury induced by metronidazole (MTZ) and could restrain the production of excessive reactive oxygen species (ROS) induced by 2,2'-azobis (2-methylpropionamidine) dihydrochloride (AAPH) in a zebrafish model. It was further found that roasted licorice could exert its oxidative activity by upregulating the expression of key genes such as heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), glutamate-cysteine ligase modifier subunit (GCLM), and glutamate-cysteine ligase catalytic subunit (GCLC) in the nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway both in vivo and in vitro. Furthermore, consistent results were obtained showing that rat serum containing roasted licorice was estimated to reduce cell apoptosis induced by H2O2. Then, the UHPLC-Q-Exactive Orbitrap MS analysis results elucidated the chemical composition of rat plasma containing roasted licorice extracts, including ten prototype chemical components and five metabolic components. Among them, six compounds were found to have binding activity with Kelch-like ECH-associated protein 1 (KEAP1), which plays a crucial role in the transcriptional activity of NRF2, using a molecular docking simulation. The results also showed that liquiritigenin had the strongest binding ability with KEAP1. Immunofluorescence further confirmed that liquiritigenin could induce the nuclear translocation of NRF2. In summary, this study provides a better understanding of the antioxidant effect and mechanisms of roasted licorice, and lays a theoretical foundation for the development of a potential antioxidant for use in clinical practice.

Exploring Active Ingredients, Beneficial Effects, and Potential Mechanism of Allium tenuissimum L. Flower for Treating T2DM Mice Based on Network Pharmacology and Gut Microbiota.

Forty compounds were isolated and characterized from A. tenuissimum flower. Among them, twelve flavonoids showed higher α-glucosidase inhibition activities in vitro than acarbose, especially kaempferol. The molecular docking results showed that the binding of kaempferol to α-glucosidase (GAA) could reduce the hydrolysis of substrates by GAA and reduce the glucose produced by hydrolysis, thus exhibiting α-glucosidase inhibition activities. The in vivo experiment results showed that flavonoids-rich A. tenuissimum flower could decrease blood glucose and reduce lipid accumulation. The protein expression levels of RAC-alpha serine/threonine-protein kinase (AKT1), peroxisome proliferator activated receptor gamma (PPARG), and prostaglandin G/H synthase 2 (PTGS2) in liver tissue were increased. In addition, the Firmicutes/Bacteroidetes (F/B) ratio was increased, the level of gut probiotics Bifidobacterium was increased, and the levels of Enterobacteriaceae and Staphylococcus were decreased. The carbohydrate metabolism, lipid metabolism, and other pathways related to type 2 diabetes mellitus were activated. This study indicating flavonoids-rich A. tenuissimum flower could improve glycolipid metabolic disorders and inflammation in diabetic mice by modulating the protein expression and gut microbiota.

Electroacupuncture of the trigeminal nerve causes N-methyl-D-aspartate receptors to mediate blood-brain barrier opening and induces neuronal excitatory changes.

The blood-brain barrier (BBB) is an important structure for maintaining environmental stability in the central nervous system (CNS). Our previous study showed that specific parameters of electroacupuncture (EA) at the head points Shuigou (GV26) and Baihui (GV20) can open the BBB; however, the mechanism by which stimulation of body surface acupuncture points on the head results in peripheral stimulation and affects the status of the central BBB and the neuronal excitatory changes has not been elucidated. We used laser spectroscopy, the In Vivo Imaging System (IVIS), immunofluorescence and immunoblotting to verified the role of the trigeminal nerve in BBB opening during EA, and we applied the central N-methyl-D-aspartate (NMDA) receptors blocker MK-801 to verify the mediating role of NMDA receptors in EA-induced BBB opening. Next, electroencephalogram (EEG) and in vivo calcium imaging techniques were applied to verify the possible electrical patterns of BBB opening promoted by different intensities of EA stimulation. The results showed that the trigeminal nerve plays an important role in the alteration of BBB permeability promoted by EA stimulation of the head acupoints. Brain NMDA receptors play a mediating role in promoting BBB permeability during EA of the trigeminal nerve, which may affect the expression of the TJ protein occludin, and thus alter BBB permeability. The analysis of the electrical mechanism showed that there was no significant change in the rhythm of local field potentials (LFP) in different brain regions across frequency bands immediately after EA of the trigeminal nerve at different intensities. However, the local primary somatosensory (S1BF) area corresponding to the trigeminal nerve showed a transient reduction in the delta rhythm of LFP with no change in the high-frequency band, and the action potential (spike) with short inter spike interval (ISI) varied with EA intensity. Meanwhile, EA of the trigeminal nerve resulted in rhythmic changes in calcium waves in the S1BF region, which were influenced by different EA intensities. This study provides a research perspective and a technical approach to further explore the mechanism of EA-induced BBB opening and its potential clinical applications.

Cookies Fortified with Lonicera japonica Thunb. Extracts: Impact on Phenolic Acid Content, Antioxidant Activity and Physical Properties.

Lonicera japonica Thunb [...].

Erythrocyte Membrane-Enveloped Salvianolic Acid B Nanoparticles Attenuate Cerebral Ischemia-Reperfusion Injury.

Purpose: Ischemic stroke is the second leading cause of death and the third leading cause of disability worldwide. Salvianolic acid B (SAB), a water-soluble phenolic acid derived from the traditional Chinese medicine Salvia miltiorrhiza, exerted protective effects on cerebral ischemia-reperfusion injury. However, the efficacy of SAB is seriously hindered by poor blood brain barrier (BBB) permeability and short biological half-life in plasma. Brain targeted biomimetic nanoparticle delivery systems offer much promise in overcoming these limitations. Methods: A brain targeted biomimetic nanomedicine (RR@SABNPs) was developed, which comprised of SAB loaded bovine serum albumin nanoparticles and functionalized red blood cell membrane (RBCM) with Arg-Gly-Asp (RGD). The characterization parameters, including particle size, zeta potential, morphology, Encapsulation Efficiency (EE), Drug Loading (DL), release behavior, stability, and biocompatibility, were investigated. Moreover, the middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model was used to assess the therapeutic efficacy of RR@SABNPs on ischemic stroke. Finally, the reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were detected by DHE and JC­1 staining in oxygen-glucose deprivation/reperfusion (OGD/R) and H2O2 injured PC12 cells. Results: RR@SABNPs exhibited spheric morphology with core-shell structures and good stability and biocompatibility. Meanwhile, RR@SABNPs can significantly prolong SAB circulation time by overcoming the reticuloendothelial system (RES) and actively targeting ischemic BBB. Moreover, RR@SABNPs had comprehensive protective effects on MCAO/R model mice, manifested as a reduced infarct volume and improved neurological and sensorimotor functions, and significantly scavenged excess ROS and maintained MMP. Conclusion: The designed brain targeted biomimetic nanomedicine RR@SABNPs can significantly prolong the half-time of SAB, deliver SAB into the ischemic brain and exhibit good therapeutic effects on MCAO/R model mice.