Non-cytotoxic nanomolar concentration of arctigenin protects neuronal cells from chemotherapy-induced ferroptosis by regulating SLC7A11-cystine-cysteine axis.

Neurotoxicity is a common side effect of certain types of therapeutic drugs, posing a major hurdle for their clinical application. Accumulating evidence suggests that ferroptosis is involved in the neurotoxicity induced by these drugs. Therefore, targeting ferroptosis is considered to be a reasonable approach to prevent such side effect. Arctigenin (ATG) is a major bioactive ingredient of Arctium lappa L., a popular medicinal plant in Asia, and has been reported to have multiple bioactivities including neuroprotection. However, the mechanisms underlying the neuroprotection of ATG has not been well elucidated. The purpose of this study was to investigate whether the neuroprotection of ATG was associated with its ability to protect neuronal cells from ferroptosis. Using neuronal cell ferroptosis model induced by either classic ferroptosis induces or therapeutic drugs, we demonstrated for the first time that ATG in the nanomolar concentration range effectively prevented neuronal cell ferroptosis induced by classic ferroptosis inducer sulfasalazine (SAS) and erastin (Era), or therapeutic drug oxaliplatin (OXA) and 5-fluorouracil (5-FU). Mechanistically, we uncovered that the anti-ferroptotic effect of ATG was attributed to its ability to activate SLC7A11-cystine-cysteine axis. The findings of the present study implicate that ATG holds great potential to be developed as a novel agent for preventing SLC7A11 inhibition-mediated neurotoxicity.

Comparison of Metabolic Profiles of Fruits of Arctium lappa, Arctium minus, and Arctium tomentosum.

Metabolites of the edible and medicinal plant Arctium have been shown to possess beneficial activities. The phytochemical profile of Arctium lappa is well-explored and its fruits are known to contain mainly lignans, fatty acids, and sterols. But the fruits of other Arctium species have not been thoroughly investigated. Therefore, this study compares the metabolic profiles of the fruits of A. lappa, Arctium tomentosum, and Arctium minus. Targeted metabolomics led to the putative identification of 53 metabolites in the fruit extracts, the majority of these being lignans and fatty acids. Quantification of the major lignans showed that the year of collection had a significant effect on the lignan content. Furthermore, A. lappa fruits contained lesser amounts of arctigenin but greater amounts of arctigenin glycoside than A. minus fruits. Regarding the profile of fatty acids, A. minus fruits differed from the others in the presence of linolelaidic acid.

Amide alkaloids and neolignans from Piper hongkongense and their inhibitory activities of PCSK9 expression.

Four undescribed amide alkaloids hongkongensines A-C and 1-(1-oxo-6-hydroxy-2E,4E-dodecadienyl)-piperidine, five known amide alkaloids, and three known neolignans were isolated from the aerial part of Piper hongkongense. The planar structures of these compounds were determined by detailed analyses of HR-ESI-MS and NMR data. The absolute configurations of hongkongensines A-C were elucidated by single-crystal X-ray diffraction analysis and ECD calculations. Moreover, the inhibitory activities of PCSK9 expression in vitro for all compounds were assessed by PCSK9 AlphaLISA screening. Kadsurenone (10) displayed a significant inhibitory activity at 5 µM with an inhibition rate of 51.98%, compared with 55.55% of berberine (BBR 5 µM).

[A new nor-neolignan compound identified from Itea yunnanensis].

Various separation methods in combination with spectral data analysis, X-ray single crystal diffraction analysis, and litera-ture data comparison were employed to clarify the chemical constituents of Itea yunnanensis. Seven compounds were obtained from I. yunnanensis, which were identified as(S)-3-[1-(4-hydroxyphenyl)propane-2-yl]-4-methoxybenzoate methyl ester(1), iteafuranal B(2), syringaresinol(3), dihydrokaempferol(4), trimethoxybenzene(5), eicosane(6), and nonacosane(7), respectively. Among them, compound 1 was a new nor-neolignan compound named iteanorneoligan A, and the rest of the compounds were identified from I. yunnanensis for the first time. The anti-hepatocellular carcinoma effect of the compound was evaluated based on Sk-hep-1 cells model via MTT assay, and compound 2 showed a significant inhibitory effect on the proliferation of Sk-hep-1 cells with an IC_(50) of 9.4 µmol·L~(-1). The antioxidant capacity was determined via DPPH, ABTS~(·+), and O■ radical scavenging ability, and compound 1 exhibited a significant ABTS~(·+) radical scavenging effect with an IC_(50) of 0.178 mg·mL~(-1).

Extensive targeted metabolomics analysis reveals the identification of major metabolites, antioxidants, and disease-resistant active pharmaceutical components in Camellia tuberculata (Camellia L.) seeds.

Sect. tuberculata plant belongs to the Camellia genus and is named for the "tuberculiform protuberance on the surface of the ovary and fruit". It is a species of great ornamental value and potential medicinal value. However, little has been reported on the metabolites of C. tuberculata seeds. Therefore, this study was conducted to investigate the metabolites of C. tuberculata seeds based on UPLC/ESI-Q TRAP-MS/MS with extensively targeted metabolomics. A total of 1611 metabolites were identified, including 107 alkaloids, 276 amino acids and derivatives, 283 flavonoids, 86 lignans and coumarins, 181 lipids, 68 nucleotides and derivatives, 101 organic acids, 190 phenolic acids, 10 quinones, 4 steroids, 17 tannins, 111 terpenoids, and 177 other metabolites. We compared the different metabolites in seeds between HKH, ZM, ZY, and LY. The 1311 identified different metabolites were classified into three categories. Sixty-three overlapping significant different metabolites were found, of which lignans and coumarins accounted for the largest proportion. The differentially accumulated metabolites were enriched in different metabolic pathways between HKH vs. LY, HKH vs. ZM, HKH vs. ZY, LY vs. ZY, ZM vs. LY and ZM vs. ZY, with the most abundant metabolic pathways being 4, 2, 4, 7, 7 and 5, respectively (p < 0.05). Moreover, among the top 20 metabolites in each subgroup comparison in terms of difference multiplicity 7, 8 and 13. ZM and ZY had the highest phenolic acid content. Ninety-six disease-resistant metabolites and 48 major traditional Chinese medicine agents were identified based on seven diseases. The results of this study will not only lead to a more comprehensive and in-depth understanding of the metabolic properties of C. tuberculata seeds, but also provide a scientific basis for the excavation and further development of its medicinal value.

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.

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.

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.

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.

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.

Waterlogging in soil restricts the growth of Gleditsia sinensis seedlings and inhibits the accumulation of lignans and phenolic acids in thorns.

Gleditsia sinensis, commonly known as Chinese Zaojiao, has important economic value and medicinal compounds in its fruits and thorns, making it widely cultivated artificially in China. However, the available literature on the impact of waterlogging on the growth of G. sinensis seedlings and the accumulation of metabolite compounds in its thorns is limited. To address this knowledge gap, G. sinensis seedlings were planted in soil supplemented with pindstrup substrate, which enhances the water-holding capacity of the soil. The analyses of morphological traits and nutrient elements in one-year-old G. sinensis seedlings grown naturally under ambient conditions and metabolite accumulation in its thorns were conducted. The results showed that the waterlogged soil significantly diminished the height, fresh weight, and dry weight of seedling roots and stems (P < 0.05). Furthermore, waterlogging hindered the uptake of iron (Fe) and manganese (Mn), as well as the transport of potassium (K). The identified metabolites within the thorns were categorized into 16 distinct groups. Relative to the control soil, fatty acids and derivatives were the most down-regulated metabolites in the waterlogged soil, accounting for 40.58% of the total metabolites, followed by lignans (38.71%), phenolic acids (34.48%), saccharides and alcohols (34.15%), steroids (16.67%), alkaloids (12.24%), flavonoids (9.28%), and glycerophospholipids (7.41%). Conversely, nucleotides and derivatives experienced the greatest up-regulation in the waterlogged soil, accounting for 50.00% of the total metabolites. In conclusion, waterlogging negatively impacted the growth of G. sinensis seedlings and inhibited the accumulation of metabolites. Hence, when considering the accumulation of secondary metabolites such as lignans and phenolic acids, appropriate management of soil moisture levels should be taken into account.

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.

Undescribed (2-7')-neolignans and polyoxygenated cyclohexene glycosides from the aerial parts of Piper mutabile C. DC. and their inhibitory effects on nitric oxide production.

A phytochemical study of the aerial parts of Piper mutabile C. DC. revealed seven undescribed compounds [two (2-7')-neolignans and five polyoxygenated cyclohexene glycosides] and six known propenylcatechol derivatives. The chemical structures of the isolated compounds were elucidated by extensive HR-ESI-MS and NMR analyses, as well as comparison with the literature. The absolute configurations of the (2-7')-neolignans were confirmed by GIAO 13C NMR calculations with a sorted training set strategy and TD-DFT calculation ECD spectra. The (2-7')-neolignans and polyoxygenated cyclohexene glycosides are unusual in natural sources. Undescribed neolignans 1 and 2 inhibited NO production in RAW 264.7 cells, with respective IC50 values of 14.4 and 9.5 µM.

Arctigenin from Arctium lappa L. inhibits chikungunya virus by affecting its entry and replication.

BACKGROUND: Dengue and chikungunya, caused by dengue virus (DENV) and chikungunya virus (CHIKV) respectively, are the most common arthropod-borne viral diseases worldwide, for which there are no FDA-approved antivirals or effective vaccines. Arctigenin, a phenylpropanoid lignan from the seeds of Arctium lappa L. is known for its anti-inflammatory, anti-cancer, antibacterial, and immunomodulatory properties. Arctigenin's antimicrobial and immunomodulatory capabilities make it a promising candidate for investigating its potential as an anti-DENV and anti-CHIKV agent. PURPOSE: The aim of the study was to explore the anti-DENV and anti-CHIKV effects of arctigenin and identify the possible mechanisms of action. METHODS: The anti-DENV or anti-CHIKV effects of arctigenin was assessed using various in vitro and in silico approaches. Vero CCL-81 cells were infected with DENV or CHIKV and treated with arctigenin at different concentrations, temperature, and time points to ascertain the effect of the compound on virus entry or replication. In silico molecular docking was performed to identify the interactions of the compound with viral proteins. RESULTS: Arctigenin had no effects on DENV. Various time- and temperature-dependent assays revealed that arctigenin significantly reduced CHIKV RNA copy number and infectious virus particles and affected viral entry. Entry bypass assay revealed that arctigenin inhibited the initial steps of viral replication. In silico docking results revealed the high binding affinity of the compound with the E1 protein and the nsp3 macrodomain of CHIKV. CONCLUSION: This study demonstrates the in-vitro anti-CHIKV potential of arctigenin and suggests that the compound might affect CHIKV entry and replication. Further preclinical and clinical studies are needed to identify its safety and efficacy as an anti-CHIKV drug.

Curculigoside, a traditional Chinese medicine monomer, ameliorates oxidative stress in Alzheimer's disease mouse model via suppressing ferroptosis.

Alzheimer's disease (AD) is a neurodegenerative disorder where oxidative stress, induced by ferroptosis, has been linked to neuronal damage and cognitive deficits. The objective of this study is to investigate if the potential therapeutic agent, Curculigoside (CUR), could ameliorate AD by inhibiting ferroptosis. The potential therapeutic targets, such as GPX4 and SLC7A11, were identified using weighted gene co-expression network analysis (WGCNA). Concurrently, CUR was also screened against these potential targets using various analytical methods. For the in vivo studies, intragastric administration of CUR significantly ameliorated cognitive impairment in AD model mice induced by scopolamine and okadaic acid (OA). In vitro, CUR protected neuronal cells by altering the levels of ferroptosis-related specific markers in OA and scopolamine-induced neurotoxicity. The administration of CUR through intragastric route significantly reduced the levels of AD-promoting factors (such as Aß1-42, p-tau) and ferroptosis-promoting factors in the hippocampus and cortex of AD mice. Furthermore, CUR up-regulated the expression of GPX4 and decreased the expression of SLC7A11 in the ferroptosis signaling pathway, thereby increasing the ratio of glutathione (GSH)/oxidized glutathione (GSSG) in vivo and vitro. In conclusion, the cumulative results suggest that the natural compound CUR may serve as a promising therapeutic agent to ameliorate AD by inhibiting ferroptosis.

Establishment of cluster of differentiation 20 immobilized cell membrane chromatography for the screening of active antitumor components in traditional Chinese medicine.

Non-Hodgkin lymphoma (NHL) is a heterogeneous group of malignant tumors occurring in B or T lymphocytes, and no small molecule-positive drugs to treat NHL have been marketed. Cluster of differentiation 20 (CD20) is an important molecule regulating signaling for the life and differentiation of B lymphocytes and possesses the characteristics of a drug target for treating NHL. 2-Methoxyestradiol induces apoptosis in lymphoma Raji cells and CD20 protein is highly expressed by Raji lymphoma cells. Therefore, in this study, a CD20-SNAP-tag/CMC model was developed to validate the interaction of 2-methoxyestradiol with CD20. 2-Methoxyestradiol was used as a small molecule control compound, and the system was validated for good applicability. The cell membrane chromatography model was combined with high-performance liquid chromatography ion trap time-of-flight mass spectroscopy (HPLC-IT-TOF-MS) in a two-dimensional system to successfully identify, analyze, and characterize the potential active compounds of Schisandra chinensis (Turcz.) Baill. extract and Lysionotus pauciflorus Maxim. extract, including Schisandrin A, Schizandrol A, Schizandrol B, Schisantherin B, and Nevadensin, which can act on CD20 receptors. The five potential active compounds were analyzed by non-linear chromatography. The thermodynamic and kinetic parameters of their interaction with CD20 were also analyzed, and the mode of interaction was simulated by molecular docking. Their inhibitory effects on lymphoma cell growth were assessed using a Cell Counting Kit-8 (CCK-8). Nevadensin and Schizandrin A were able to induce apoptosis in Raji cells within a certain concentration range. In conclusion, the present experiments provide some bases for improving NHL treatment and developing small molecule lead compounds targeting CD20 with low toxicity and high specificity.

Lignan contents of Schisandra chinensis (Turcz.) Baill. from different origins-A new model for evaluating the content of prominent components of Chinese herbs.

BACKGROUND: As a traditional Chinese herbal medicine, Schisandra chinensis exhibits various effects such as liver protection, blood sugar regulation, blood lipid regulation, immune function regulation, antidepressant activity, etc. However, because of its intricate composition, diverse origins, and medicinal effects depending on complex compound groups, there are differences in the lignan composition of S. chinensis from different origins. Therefore, it is currently difficult to evaluate the quality of medicinal materials from plants of different origins using a single qualitative quality control index. PURPOSE: This paper aims to investigate the potential relationship between the lignan components of S. chinensis from different origins and to establish stable assessment indices for determining the lignan content of S. chinensis from multiple perspectives. METHODS: In this study, we collected S. chinensis samples of seven major origins in China, and randomly sampled 6-9 batches of each origin for a total of 60 batches. The lignan content was determined by HPLC, and its distribution law of the ratio of each lignan component of S. chinensis to Schisandrol A content was analyzed. Combining network pharmacology and differential analysis between samples, the stable and effective substances used as quality markers were determined. RESULTS: There were some correlations among the lignan contents of S. chinensis, some correlations between schisandrin A and other lignans of S. chinensis could be determined. The ratio of each component to the indicator component schisandrol A was evenly distributed and reflected the lignan content of S. chinensis to some extent. Four substances (schisandrol A, schisandrol B, schisantherin A, and schisandrin C) were determined by network pharmacology combined with the analysis results of HCA, PCA and PLS-DA to further optimize the model. They displayed a strong connection with the core target, a large contribution rate to the principal components, and a stable content in each batch of samples, suggesting that these components may be the main active substances of S. chinensis lignans. Therefore, they could be used as main indicators evaluating the advantages and disadvantages of S. chinensis by examining the consistency of component proportions. CONCLUSION: This method can intuitively evaluate the content of main lignans in S. chinensis. This quality assessment model is an exploration of the multi-component comprehensive evaluation system of S. chinensis, providing a new concept for the quality evaluation system of Chinese herbal medicines.

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.

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.

Phillygenin Inhibits TGF-ß1-induced Hepatic Stellate Cell Activation and Inflammation: Regulation of the Bax/Bcl-2 and Wnt/ß-catenin Pathways.

Hepatic fibrosis (HF), a precursor to cirrhosis and hepatocellular carcinoma, is caused by abnormal proliferation of connective tissue and excessive accumulation of extracellular matrix in the liver. Notably, activation of hepatic stellate cells (HSCs) is a key link in the development of HF. Phillygenin (PHI, C21H24O6) is a lignan component extracted from the traditional Chinese medicine Forsythiae Fructus, which has various pharmacological activities such as anti-inflammatory, antioxidant and anti-tumour effects. However, whether PHI can directly inhibit HSC activation and ameliorate the mechanism of action of HF has not been fully elucidated. Therefore, the aim of the present study was to investigate the in vitro anti-HF effects of PHI and the underlying molecular mechanisms. Transforming growth factor-ß1 (TGF-ß1)-activated mouse HSCs (mHSCs) and human HSCs (LX-2 cells) were used as an in vitro model of HF and treated with different concentrations of PHI for 24 h. Subsequently, cell morphological changes were observed under the microscope, cell viability was analyzed by MTT assay, cell cycle and apoptosis were detected by flow cytometry, and the mechanism of anti-fibrotic effect of PHI was explored by immunofluorescence, ELISA, RT-qPCR and western blot. The results showed that PHI suppressed the proliferation of TGF-ß1-activated mHSCs and LX-2 cells, arrested the cell cycle at the G0/G1 phase, decreased the levels of α-SMA, Collagen I, TIMP1 and MMP2 genes and proteins, and promoted apoptosis in activated mHSCs and LX-2 cells. Besides, PHI reduced the expression of inflammatory factors in activated mHSCs and LX-2 cells, suggesting a potential anti-inflammatory effect. Mechanically, PHI inhibited TGF-ß1-induced HSC activation and inflammation, at least in part through modulation of the Bax/Bcl-2 and Wnt/ß-catenin pathways. Overall, PHI has significant anti-HF effects and may be a promising agent for the treatment of HF.