Roles of gender and smoking in the associations between urinary phytoestrogens and asthma/wheeze and lung function: evidence from a cross-sectional study.

BACKGROUND: The role of phytoestrogens in asthma/wheeze and lung function remains controversial. Thus, we aimed to examine whether phytoestrogens have beneficial effects on asthma/wheeze, lung function for subgroups and mortality. METHODS: Participants in this study were individuals aged 20 years or older from the National Health and Nutrition Examination Survey. Multivariate logistic regression models were fitted to examine the associations of urinary phytoestrogens with the risk of asthma/wheeze and lung function in individuals with and without asthma/wheeze. Cox proportional hazards regression was used to examine the relationship between urinary phytoestrogens and all-cause mortality. Stratified analyses were conducted based on gender and smoking status. RESULTS: We included 2465 individuals in this study. Enterolactone levels in the highest quartile were associated with a lower risk of asthma than those in the lowest quartile. As compared with the lowest quartile, the highest quartile of enterodiol and enterolactone was associated with a lower risk of wheeze. Significant associations were observed between subtypes of phytoestrogens (equol and enterolactone) and lung function (forced vital capacity (FVC) and forced expiratory volume in 1 s). Besides, FVC was higher in individuals with higher levels of enterodiol. The results were consistent in subpopulations without asthma/wheeze, while the significant difference was not observed in individuals with asthma/wheeze. The stratified analyses revealed that the associations between phytoestrogens and lung function differed by gender and smoking status among subgroups. No significant association was found between urinary phytoestrogens and all-cause mortality. CONCLUSION: In summary, subtypes of phytoestrogens were associated with lower risk of asthma/wheeze and beneficial for lung function improvement in individuals without asthma/wheeze. Furthermore, gender and smoking may interact in the relationship between phytoestrogens and asthma/wheeze, and lung function. Further researches are needed to confirm these associations and explain the results of stratified analyses.

Schisandrin B from Schisandra chinensis alleviated pain via glycine receptors, Nav1.7 channels and Cav2.2 channels.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis, the dried and ripe fruit of the magnolia family plant Schisandra chinensis (Turcz.) Baill, was commonly used in traditional analgesic prescription. Studies have shown that the extract of Schisandra chinensis (SC) displayed analgesic activity. However, the analgesic active component and the exact mechanisms have yet to be revealed. AIM OF THE STUDY: The present study was to investigate the anti-nociceptive constituent of Schisandra chinensis, assess its analgesic effect, and explore the potential molecular mechanisms. MATERIALS AND METHODS: The effects of a series of well-recognized compounds from SC on glycine receptors were investigated. The analgesic effect of the identified compound was evaluated in three pain models. Mechanistic studies were performed using patch clamp technique on various targets expressed in recombinant cells. These targets included glycine receptors, Nav1.7 sodium channels, Cav2.2 calcium channels et al. Meanwhile, primary cultured spinal dorsal horn (SDH) neurons and dorsal root ganglion (DRG) neurons were also utilized. RESULTS: Schisandrin B (SchB) was a positive allosteric modulator of glycine receptors in spinal dorsal horn neurons. The EC50 of SchB on glycine receptors in spinal dorsal horn neurons was 2.94 ± 0.28 µM. In three pain models, the analgesic effect of SchB was comparable to that of indomethacin at the same dose. Besides, SchB rescued PGE2-induced suppression of α3 GlyR activity and alleviated persistent pain. Notably, SchB could also potently decrease the frequency of action potentials and inhibit sodium and calcium channels in DRG neurons. Consistent with the data from DRG neurons, SchB was also found to significantly block Nav1.7 sodium channels and Cav2.2 channels in recombinant cells. CONCLUSION: Our results demonstrated that, Schisandrin B, the primary lignan component of Schisandra chinensis, may exert its analgesic effect by acting on multiple ion channels, including glycine receptors, Nav1.7 channels, and Cav2.2 channels.

Insecticidal Activity and Molecular Target by Morphological Analysis, RNAseq, and Molecular Docking of the Aryltetralin Lignan Lactone Helioxanthin, Isolated from Taiwania flousiana Gaussen.

Botanical insecticides are considered an environmentally friendly approach to insect control because they are easily biodegraded and cause less environmental pollution compared to traditional chemical pesticides. In this study, we reported the insecticidal activities of the ingredients from Taiwania flousiana Gaussen (T. flousiana). Five compounds, namely helioxanthin (C1), taiwanin E (C2), taiwanin H (C3), 7,4'-dimethylamentoflavone (C4), and 7,7″-di-O-methylamentoflavone (C5), were isolated and tested against the second, third, and fourth instar larvae of Aedes aegypti. Our results indicated that all five compounds showed insecticidal activities, and helioxanthin, which is an aryltetralin lignan lactone, was the most effective with LC50 values of 0.60, 2.82, and 3.12 mg/L, respectively, 48 h after application, with its activity against the second instar larvae similar to that of pyrethrin and better than that of rotenone. Further studies found that helioxanthin accumulated in the gastric cecum and the midgut and caused swelling of mitochondria with shallow matrices and fewer or disappeared crista. Additionally, our molecular mechanisms studies indicated that the significantly differentially expressed genes (DEGs) were mainly associated with mitochondria and the cuticle, among which the voltage-dependent anion-selective channel (VDAC) gene was the most down-regulated by helioxanthin, and VDAC is the potential target of helioxanthin by binding to specific amino acid residues (His 122 and Glu 147) via hydrogen bonds. We conclude that aryltetralin lignan lactone is a potential class of novel insecticides by targeting VDAC.

Computational analysis followed by in vitro studies to explore cytokines (TNF-α, IL-6 and IL-1ß) inhibition potential of the new natural molecule polonilignan.

Targeting pro-inflammatory cytokines and their production is found to be of therapeutic benefit for the regulation of inflammation in various chronic autoimmune diseases. Our continued efforts to discover small molecular-weight pro-inflammatory cytokine inhibitors resulted in identifying a novel natural lignan molecule named polonilignan, isolated from the culture broth extract of an endophytic fungus Penicillium polonicum. An in silico study (molecular docking, ADME predictions, binding free energy calculation and molecular dynamics simulation) of the polonilignan over the pro-inflammatory cytokines proteins TNF-α, IL-6 and IL-1ß was performed using Schrodinger LLC software to understand the binding interactions, drug-like properties, and stability of the ligand-protein complex. Further, in-vitro testing of inhibition of TNF-α, IL-6 and IL-1ß by polonilignan was carried out using ELISA and RT-PCR on LPS-induced RAW 264.7 cell lines along with the testing of nitrite production effect (Griess assay) and cytotoxicity (MTT) analysis. Under the computational study, polonilignan revealed good docking scores, binding interactions, and stability under MDS and desirable in silico ADME results over the proteins TNF-α, IL-1ß and IL-6. Poloniligan showed significant inhibition of IL-1ß, IL-6 and TNF-α with IC50 values of 2.01 µM, 6.59 µM and 42.10 µM, respectively. Also, it reduced the translocation of the NF-κB subunit p65 to the nucleus (confocal microscopy). The mRNA expression levels of pro-inflammatory markers IL-1ß, TNF-α and IL-6 levels were lowered significantly (p < .001) by the compound, and the diminution was higher with IL-1ß. Further, the lignan was non-cytotoxic and effective in attenuating nitrite release (IC50 48.56 µM). Thus, polonilignan has been identified as a new pan-cytokine and NO inhibitor, it is recommended to optimise a method for the synthesis of this small molecular weight lignan and explore its pharmacokinetic characteristics, toxicity and therapeutic effect under various chronic inflammatory disease models.

Pinoresinol diglucoside mitigates dexamethasone-induced osteoporosis and chondrodysplasia in zebrafish.

BACKGROUND: The global increase in the aging population has led to a higher incidence of osteoporosis among the elderly. OBJECTIVE: This study aimed to evaluate the protective properties of pinoresinol diglucoside (PDG), an active constituent of Eucommia ulmoides, against dexamethasone-induced osteoporosis and chondrodysplasia. METHODS: A zebrafish model of osteoporosis was established by exposing larval zebrafish to dexamethasone. The impact of PDG on bone mineralization was assessed through alizarin red and calcein staining. Alkaline phosphatase activity was quantified to evaluate osteoblast function. The influence of PDG on chondrogenesis was estimated using alcian blue staining. Fluorescence imaging and motor behavior analysis were employed to assess the protective effect of PDG on the structure and function of dexamethasone-induced skeletal teratogenesis. qPCR determined the expression of osteogenesis and Wnt signaling-related genes. Molecular docking was used to assess the potential interactions between PDG and Wnt receptors. RESULTS: PDG significantly increased bone mineralization and corrected spinal curvature and cartilage malformations in the zebrafish model. Furthermore, PDG enhanced swimming abilities compared to the model group. PDG mitigated dexamethasone-induced skeletal abnormalities in zebrafish by upregulating Wnt signaling, showing potential interaction with Wnt receptors FZD2 and FZD5. CONCLUSION: PDG mitigates dexamethasone-induced osteoporosis and chondrodysplasia by promoting bone formation and activating Wnt signaling.

An acute herb-drug interaction of Magnoliae Officinalis Cortex with methotrexate via inhibiting multidrug resistance-associated protein 2.

Magnoliae Officinalis Cortex (MOC), an herbal drug, contains polyphenolic lignans mainly magnolol (MN) and honokiol (HK). Methotrexate (MTX), a critical drug for cancers and autoimmune deseases, is a substrate of multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). This study investigated the effect of coadministration of MOC on the pharmacokinetics of MTX and relevant mechanisms. Sprague-Dawley rats were orally administered MTX alone and with single dose (2.0 and 4.0 g/kg) and repeated seven doses of MOC (2.0 g/kg thrice daily for 2 days, the 7th dose given at 0.5 h before MTX). The serum concentrations of MTX were determined by a fluorescence polarization immunoassay. The results showed that a single dose of MOC at 2.0 g/kg significantly increased the AUC0-t and MRT of MTX by 352% and 308%, and a single dose at 4.0 g/kg significantly enhanced the AUC0-t and MRT by 362% and 291%, respectively. Likewise, repeated seven doses of MOC at 2.0 g/kg significantly increased the AUC0-t and MRT of MTX by 461% and 334%, respectively. Mechanism studies indicated that the function of MRP2 was significantly inhibited by MN, HK and the serum metabolites of MOC (MOCM), whereas BCRP was not inhibited by MOCM. In conclusion, coadministration of MOC markedly enhanced the systemic exposure and mean residence time of MTX through inhibiting the MRP2-mediated excretion of MTX.

Dibenzocyclooctadiene Lignans from Schisandra chinensis with Anti-Inflammatory Effects.

Schisandra chinensis (Schisandraceae) is a medicinal plant widely used in traditional Chinese medicine. Under the name Wu Wei Zi, it is used to treat many diseases, especially as a stimulant, adaptogen, and hepatoprotective. Dibenzocyclooctadiene lignans are the main compounds responsible for the effect of S. chinensis. As a part of ongoing studies to identify and evaluate anti-inflammatory natural compounds, we isolated a series of dibenzocyclooctadiene lignans and evaluated their biological activity. Furthermore, we isolated new sesquiterpene 7,7-dimethyl-11-methylidenespiro[5.5]undec-2-ene-3-carboxylic acid. Selected dibenzocyclooctadiene lignans were tested to assess their anti-inflammatory potential in LPS-stimulated monocytes by monitoring their anti-NF-κB activity, antioxidant activity in CAA assay, and their effect on gap junction intercellular communication in WB-ras cells. Some S. chinensis lignans showed antioxidant activity in CAA mode and affected the gap junction intercellular communication. The anti-inflammatory activity was proven for (-)-gomisin N, (+)-γ-schisandrin, rubrisandrin A, and (-)-gomisin J.

Schisandrin B enhances embryo competence and potentially mitigates endoplasmic reticulum stress during porcine preimplantation development.

Endoplasmic reticulum (ER) stress induced by agents such as tunicamycin (TM) substantially impedes the developmental progression of porcine embryos. Lignan compounds such as Schisandrin B (Sch-B), may have the potential to mitigate this stress. However, there are few studies on the effects of Sch-B on embryo development. To address this research gap, this study evaluates the protective efficacy of Sch-B against TM-induced ER stress during pivotal stages of porcine embryogenesis. Notably, embryos treated with Sch-B exhibited pronounced resistance to TM-induced developmental arrest, particularly at the 4-cell stage, facilitating progression to the 8-cell stage and subsequent blastocyst formation. It was also observed that Sch-B effectively reduced reactive oxygen species (ROS) levels and improved mitochondrial membrane potential (MMP). Furthermore, Sch-B positively influenced the expression of several stress-related genes. These findings highlight the promising role of Sch-B in improving porcine embryo development and mitigating ER stress.

Identification of Dihydrobenzofuran Neolignans as Novel PDE4 Inhibitors and Evaluation of Antiatopic Dermatitis Efficacy in DNCB-Induced Mice Model.

Atopic dermatitis is a chronic relapsing skin disease characterized by recurrent, pruritic, localized eczema, while PDE4 inhibitors have been reported to be effective as antiatopic dermatitis agents. 3',4-O-dimethylcedrusin (DCN) is a natural dihydrobenzofuran neolignan isolated from Magnolia biondii with moderate potency against PDE4 (IC50 = 3.26 ± 0.28 µM) and a binding mode similar to that of apremilast, an approved PDE4 inhibitor for the treatment of psoriasis. The structure-based optimization of DCN led to the identification of 7b-1 that showed high inhibitory potency on PDE4 (IC50 = 0.17 ± 0.02 µM), good anti-TNF-α activity (EC50 = 0.19 ± 0.10 µM), remarkable selectivity profile, and good skin permeability. The topical treatment of 7b-1 resulted in the significant benefits of pharmacological intervention in a DNCB-induced atopic dermatitis-like mice model, demonstrating its potential for the development of novel antiatopic dermatitis agents.

Effects of schisandrin B on hypoxia-related cognitive function and protein expression in vascular dementia rats.

Vascular dementia (VD) a heterogenous group of brain disorders in which cognitive impairment is attributable to vascular risk factors and cerebrovascular disease. A common phenomenon in VD is a dysfunctional cerebral regulatory mechanism associated with insufficient cerebral blood flow, ischemia and hypoxia. Under hypoxic conditions oxygen supply to the brain results in neuronal death leading to neurodegenerative diseases including Alzheimer's (AD) and VD. In conditions of hypoxia and low oxygen perfusion, expression of hypoxia-inducible factor 1 alpha (HIF-1α) increases under conditions of low oxygen and low perfusion associated with upregulation of expression of hypoxia-upregulated mitochondrial movement regulator (HUMMR), which promotes anterograde mitochondrial transport by binding with trafficking protein kinesin 2 (TRAK2). Schisandrin B (Sch B) an active component derived from Chinese herb Wuweizi prevented ß-amyloid protein induced morphological alterations and cell death using a SH-SY5Y neuronal cells considered an AD model. It was thus of interest to determine whether Sch B might also alleviate VD using a rat bilateral common carotid artery occlusion (BCAO) dementia model. The aim of this study was to examine the effects of Sch B in BCAO on cognitive functions such as Morris water maze test and underlying mechanisms involving expression of HIF-1α, TRAK2, and HUMMR levels. The results showed that Sch B improved learning and memory function of rats with VD and exerted a protective effect on the hippocampus by inhibition of protein expression of HIF-1α, TRAK2, and HUMMR factors. Evidence indicates that Sch B may be considered as an alternative in VD treatment.

Guided isolation of enantiomeric lignans from Cimicifuga heracleifolia Kom. by antioxidant activity and molecular networking.

Under the guidance of antioxidant evaluation combined with molecular networking, six pairs of enantiomeric lignans including seven undescribed ones (1a, 2a/2b-4a/4b), along with five known analogs (1b, 5a/5b-6a/6b) were isolated from Cimicifuga heracleifolia Kom. Their structures were determined by extensive spectroscopic data analysis, including HRESIMS, 1D and 2D NMR, experimental and calculated ECD. All the enantiomeric isolates were evaluated for antioxidation by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2'-azino-bis (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging tests. Compounds 1a and 3a/3b exhibited great DPPH and ABTS scavenging activities. The results are of great value for understanding structurally interesting enantiomeric lignans with antioxidant activity from C. heracleifolia in depth and providing its further development in functional evaluation and drug development.

Effect of pinoresinol-lariciresinol reductases on biosynthesis of lignans with substrate selectivity in Schisandra chinensis.

Schisandra lignans are the main bioactive compounds found in Schisandra chinensis fruits, such as schisandrol lignans and schisandrin lignans, which play important roles in organ protection or other clinical roles. Pinoresinol-lariciresinol reductase (PLR) plays a pivotal role in plant lignan biosynthesis, however, limited research has been conducted on S. chinensis PLR to date. This study identified five genes as ScPLR, successfully cloned their coding sequences, and elucidated their catalytic capabilities. ScPLR3-5 could recognize both pinoresinol and lariciresinol as substrates, and convert them into lariciresinol and secoisolariciresinol, respectively, while ScPLR2 exclusively catalyzed the conversion of (+)-pinoresinol into (+)-lariciresinol. Transcript-metabolite correlation analysis indicated that ScPLR2 exhibited unique properties that differed from the other members. Molecular docking and site-directed mutagenesis revealed that Phe271 and Leu40 in the substrate binding motif were crucial for the catalytic activity of ScPLR2. This study serves as a foundation for understanding the essential enzymes involved in schisandra lignan biosynthesis.

Sesamin alleviates lipid accumulation induced by oleic acid via PINK1/Parkin-mediated mitophagy in HepG2 cells.

Sesamin, a special compound present in sesame and sesame oil, has been reported a role in regulating lipid metabolism, while the underlying mechanisms remain unclear. Autophagy has been reported associated with lipid metabolism and regarded as a key modulator in liver steatosis. The present work aimed to investigate whether sesamin could exert its protective effects against lipid accumulation via modulating autophagy in HepG2 cells stimulated with oleic acid (OA). Cell viability was evaluated using the CCK-8 method, and triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein, cholesterol (LDL-C), alanine aminotransferase (ALT), along with aspartate aminotransferase (AST) were assessed by oil red O staining, transmission electron microscopy (TEM), and biochemical kits to investigate the lipid-lowering effects of sesamin. Differentially expressed genes were screened by RNA sequencing and validated using real-time quantitative PCR and Western blot. Autophagy and mitophagy related molecules were analyzed employing TEM, Western blot, and immunofluorescence. The data shows that in HepG2 cells stimulated by OA, sesamin reduces levels of TG, TC, LDL-C, ALT, and AST while elevating HDL-C, alleviates the lipid accumulation and improves fatty acid metabolism through modulating the levels of fat metabolism related genes including PCSK9, FABP1, CD36, and SOX4. Sesamin restores the suppressed autophagy in HepG2 cells caused by OA, which could be blocked by autophagy inhibitors. This indicates that sesamin improves fatty acid metabolism by enhancing autophagy levels, thereby mitigating the intracellular lipid accumulation. Furthermore, sesamin significantly enhances the mitophagy and improves mitochondrial homeostasis via activating the PINK/Parkin pathway. These data suggest that sesamin alleviates the excessive lipid accumulation in HepG2 caused by OA by restoring the impaired mitophagy via the PINK1/Parkin pathway, probably playing a preventive or therapeutic role in hepatic steatosis.

Revealing receptor-ligand interactions of atypical antipsychotic drugs and screening anti-schizophrenia ingredients in Magnolia officinalis based on 5-HTR2A-SNAP-Tag/CMC and DRD2-SNAP-Tag/CMC models.

Schizophrenia is a serious mental illness with unknown etiology, and shows increasing incidence and high lifetime prevalence rate. The main receptors related to the disease are DRD2 and 5-HTR2A. Thus, a comprehensive understanding of the interaction mode between antipsychotic drugs with relevant receptors is very important for developing more effective drugs. 5-HTR2A-SNAP-Tag/CMC and DRD2-SNAP-Tag/CMC models constructed in this work provided a new method for studying the interaction between atypical antipsychotics and the two receptors. The results of comparative experiments showed that the new models not only met the high selectivity and specificity of the screening requirements but were also more stable and long-lasting than the traditional CMC model. Binding assays showed that the effects of three atypical antipsychotics (including clozapine, olanzapine, and quetiapine) on 5-HTR2A were stronger than their effects on DRD2. Additionally, two potentially active components, magnolol and honokiol, were screened in Magnolia officinalis methanol extract using the 5-HTR2A-SNAP-Tag/CMCHPLC-MS system. Nonlinear chromatographic analysis and molecular docking were conducted to study the interactions between screened compounds and the two receptors. The binding constants (KA) of magnolol and honokiol with 5-HTR2A were 17,854 ± 1,117 M-1 and 38,858 ± 4,964 M-1, respectively, and KA values with DRD2 were 4,872 ± 1,618 M-1 and 20,692 ± 10,267 M-1, respectively. We concluded that the established models are reliable for studying receptor-ligand interactions and screening antagonists of schizophrenia.

A newly-discovered tea population variety processed Bai Mu Dan white tea: Flavor characteristics and chemical basis.

The quality of white tea (WT) is impacted by selected tea cultivars. To explore the organoleptic quality of a recently-discovered WT ("Caicha", CC), HS-SPME/GC-MS and UPLC were employed to identify volatile and non-volatile compounds in tea samples. Multiple statistical methods demonstrated the distinctions between CC and four mainstream WT varieties from main producing areas. CC exhibited abundant volatile alcohol, terpenoids, ketone, aldehyde and ester, as well as non-volatile lignans and coumarins, phenolic acids and low-molecular carbohydrates. These substances combinedly contributed to the flavor attributes of CC, characterized by an intense herbal/citrus-like cleanness and flower/fruit-like sweetness, scarce in existing commercial WT varieties. Sensory evaluation corroborated these findings. In conclusion, we have processed a new tea variety (CC) with WT manufacturing technology, and discovered the unique cleanness and sweetness of it. This study enriches the raw material database for WT production and blending, and boosts the development of more premium WT varieties.

Lactic acid responsive sequential production of hydrogen peroxide and consumption of glutathione for enhanced ferroptosis tumor therapy.

Ferroptosis is characterized by the lethal accumulation of lipid reactive oxygen species (ROS), which has great potential for tumor therapy. However, developing new ferroptosis-inducing strategies by combining nanomaterials with small molecule inducers is important. In this study, an enzyme-gated biodegradable natural-product delivery system based on lactate oxidase (LOD)-gated biodegradable iridium (Ir)-doped hollow mesoporous organosilica nanoparticles (HMONs) loaded with honokiol (HNK) (HNK@Ir-HMONs-LOD, HIHL) is designed to enhance ferroptosis in colon tumor therapy. After reaching the tumor microenvironment, the outer LOD dissociates and releases the HNK to induce ferroptosis. Moreover, the released dopant Ir4+ and disulfide-bridged organosilica frameworks deplete intracellular glutathione (GSH), which is followed by GSH-mediated Ir(IV)/Ir(III) conversion. This leads to the repression of glutathione peroxidase 4 (GPX4) activity and decomposition of intratumoral hydrogen peroxide (H2O2) into hydroxyl radicals (•OH) by Ir3+-mediated Fenton-like reactions. Moreover, LOD efficiently depletes lactic acid to facilitate the generation of H2O2 and boost the Fenton reaction, which in turn enhances ROS generation. With the synergistic effects of these cascade reactions and the release of HNK, notable ferroptosis efficacy was observed both in vitro and in vivo. This combination of natural product-induced and lactic acid-responsive sequential production of H2O2 as well as the consumption of glutathione may provide a new paradigm for achieving effective ferroptosis-based cancer therapy.

Construction of Magnolol Nanoparticles for Alleviation of Ethanol-Induced Acute Gastric Injury.

Ethanol (EtOH) has been identified as a potential pathogenic factor in gastric ulcer development primarily due to its association with gastric injury and excessive production of reactive oxygen species. Magnolol (Mag), the principal active compound in Magnolia officinalis extract, is well studied for its notable anti-inflammatory and antioxidant properties. However, its limited solubility, propensity for agglomeration, and low absorption and utilization rates significantly restrict its therapeutic use. This study aims to overcome these challenges by developing a Mag nanoparticle system targeting the treatment and prevention of EtOH-induced gastric ulcers in mice. Utilizing a click chemistry approach, we successfully synthesized this system by reacting thiolated bovine serum albumin (BSA·SH) with Mag. The in vitro analysis revealed effective uptake of the BSA·SH-Mag nanoparticle system by human gastric epithelial cells (GES-1), showcasing its antioxidant and anti-inflammatory capabilities. Additionally, BSA·SH-Mag exhibited gradual disintegration and release in simulated gastric fluid, resulting in a notable reduction of oxidative stress in gastric tissues and mucosal tissue repair and effectively reducing inflammatory expression. Furthermore, BSA·SH-Mag attenuated EtOH-induced gastric inflammation by decreasing the level of NOX4 protein expression and augmenting the level of Nrf2 protein expression. In conclusion, our findings indicate that BSA·SH-Mag represents a promising candidate as an oral therapeutic for gastric ulcer treatment.

Magnolol attenuates macrophage pyroptosis triggered by Streptococcus equi subsp. zooepidemicus.

Streptococcus equi subsp. zooepidemicus (SEZ) is a zoonotic bacterial pathogen that causes life-threatening infections and various diseases such as meningitis, endocarditis and pneumonia. With the use of antibiotics being severely restricted in the international community, an alternative to antibiotics is urgently needed against bacterial. In the present study, the herbal extract magnolol protected mice against SEZ infection, reflected by increased survival rate and reduced bacterial burden. A pro-inflammatory form of cell death occurred in SEZ-infected macrophage. Magnolol downregulated the expression of pyroptosis-related proteins and reduced the formation of cell membrane pores in infected macrophages to suppress the development of subsequent inflammation. We further demonstrated that magnolol directly suppressed SEZ-induced macrophage pyroptosis, which partially protected macrophages from SEZ infection. Our study revealed that magnolol suppressed inflammation and protected mice against SEZ infection, providing a possible treatment for SEZ infection.

Transcriptomic Insights and Cytochrome P450 Gene Analysis in Kadsura coccinea for Lignan Biosynthesis.

Kadsura coccinea is a medicinal plant from the Schisandraceae family that is native to China and has great pharmacological potential due to its lignans. However, there are significant knowledge gaps regarding the genetic and molecular mechanisms of lignans. We used transcriptome sequencing technology to analyze root, stem, and leaf samples, focusing on the identification and phylogenetic analysis of Cytochrome P450 (CYP) genes. High-quality data containing 158,385 transcripts and 68,978 unigenes were obtained. In addition, 36,293 unigenes in at least one database, and 23,335 across five databases (Nr, KEGG, KOG, TrEMBL, and SwissProt) were successfully annotated. The KEGG pathway classification and annotation of these unigenes identified 10,825 categorized into major metabolic pathways, notably phenylpropanoid biosynthesis, which is essential for lignan synthesis. A key focus was the identification and phylogenetic analysis of 233 Cytochrome P450 (CYP) genes, revealing their distribution across 38 families in eight clans, with roots showing specific CYP gene expression patterns indicative of their role in lignan biosynthesis. Sequence alignment identified 22 homologous single genes of these CYPs, with 6 homologous genes of CYP719As and 1 of CYP81Qs highly expressed in roots. Our study significantly advances the understanding of the biosynthesis of dibenzocyclooctadiene lignans, offering valuable insights for future pharmacological research and development.

Anti-inflammatory effect of lignans from flaxseed after fermentation by lactiplantibacillus plantarum SCB0151 in vitro.

Lignan, a beneficial constituent of Flaxseed (Linum usitatissimum L.) showed great interest in researchers because of its multiple functional properties. Nonetheless, a challenge arises due to the glycosidic structure of lignans, which the gut epithelium cannot readily absorb. Therefore, we screened 18 strains of Lactiplantibacillus plantarum, Lacticaseibacillus casei, Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, Pediococcus pentosaceus, Pediococcus acidilactici, and Enterococcus durans to remove glycosides from flaxseed lignan extract enzymatically. Among our findings, Lactiplantibacillus plantarum SCB0151 showed the highest activity of ß-glucosidase (8.91 ± 0.04 U/mL) and higher transformed efficiency of Secoisolariciresinol (SECO) (8.21 ± 0.13%). The conversion rate of Secoisolariciresinol diglucoside (SDG) and the generation rate of SECO was 58.30 ± 3.78% and 32.13 ± 2.78%, respectively, under the optimized conditions. According to the LC-HRMSMS analysis, SECO (68.55 ± 6.57 µM), Ferulic acid (FA) (32.12 ± 2.50 µM), and Coumaric acid (CA) (79.60 ± 6.21 µM) were identified in the biotransformation products (TP) of flaxseed lignan extract. Results revealed that the TP exhibited a more pronounced anti-inflammatory effect than the flaxseed lignan extract. SECO, FA, and CA demonstrated a more inhibitory effect on NO than that of SDG. The expression of iNOS and COX-2 was significantly suppressed by TP treatment in LPS-induced Raw264.7 cells. The secretion of IL-6, IL-2, and IL-1ß decreased by 87.09 ± 0.99%, 45.40 ± 0.87%, and 53.18 ± 0.83%, respectively, at 60 µg/mL of TP treatment. Given these data, the bioavailability of flaxseed lignan extract and its anti-inflammatory effect were significantly enhanced by Lactiplantibacillus plantarum SCB0151, which provided a novel approach to commercializing flaxseed lignan extract for functional food.