Synergistic Effects of Icariin and Extracellular Vesicles Derived from Rabbit Synovial Membrane-Derived Mesenchymal Stem Cells on Osteochondral Repair via the Wnt/ß-Catenin Pathway.

Objectives: Osteochondral defects (OCDs) are localized areas of damaged cartilage and underlying subchondral bone that can produce pain and seriously impair joint function. Literature reports indicated that icariin (ICA) has the effect of promoting cartilage repair. However, its mechanism remains unclear. Here, we explored the effects of icariin and extracellular vesicles (EVs) from rabbit synovial-derived mesenchymal stem cells (rSMSCs) on repairing of OCDs. Materials and Methods: Rabbit primary genicular chondrocytes (rPGCs), knee skeletal muscle cells (rSMCKs), and rSMSCs, and extracellular vesicles derived from the latter two cells (rSMCK-EVs and rSMSC-EVs) were isolated and identified. The rPGCs were stimulated with ICA, rSMSC-EVs either separately or in combination. The rSMCK-EVs were used as a control. After stimulation, chondrogenic-related markers were analyzed by quantitative RT-PCR and western blotting. Cell proliferation was determined by the CCK-8 assay. The preventative effects of ICA and SMSC-EVs in vivo were determined by H&E and toluidine blue staining. Immunohistochemical analyses were performed to evaluate the levels of COL2A1 and ß-catenin in vivo. Results. In vitro, the proliferation of rPGCs was markedly increased by ICA treatment in a dose-dependent manner. When compared with ICA or rSMSC-EVs treatment alone, combined treatment with ICA and SMSC-EVs produced stronger stimulative effects on cell proliferation. Moreover, combined treatment with ICA and rSMSC-EVs promoted the expression of chondrogenic-related gene, including COL2A1, SOX-9, and RUNX2, which may be via the activation of the Wnt/ß-catenin pathway. In vivo, combined treatment with rSMSC-EVs and ICA promoted cartilage repair in joint bone defects. Results also showed that ICA or rSMSC-EVs both promoted the COL2A1 and ß-catenin protein accumulation in articular cartilage, and that was further enhanced by combined treatment with rSMSC-EVs and ICA. Conclusion: Our findings highlight the promising potential of using combined treatment with ICA and rSMSC-EVs for promoting osteochondral repair.

Myricetin mitigates motor disturbance and decreases neuronal ferroptosis in a rat model of Parkinson's disease.

Ferroptosis is an iron-dependent cell death form characterized by reactive oxygen species (ROS) overgeneration and lipid peroxidation. Myricetin, a flavonoid that exists in numerous plants, exhibits potent antioxidant capacity. Given that iron accumulation and ROS-provoked dopaminergic neuron death are the two main pathological hallmarks of Parkinson's disease (PD), we aimed to investigate whether myricetin decreases neuronal death through suppressing ferroptosis. The PD models were established by intraperitoneally injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into rats and by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP+), respectively. Ferroptosis was identified by assessing the levels of Fe2+, ROS, malondialdehyde (MDA), and glutathione (GSH). The results demonstrated that myricetin treatment effectively mitigated MPTP-triggered motor impairment, dopamine neuronal death, and α-synuclein (α-Syn) accumulation in PD models. Myricetin also alleviated MPTP-induced ferroptosis, as evidenced by decreased levels of Fe2+, ROS, and MDA and increased levels of GSH in the substantia nigra (SN) and serum in PD models. All these changes were reversed by erastin, a ferroptosis activator. In vitro, myricetin treatment restored SH-SY5Y cell viability and alleviated MPP+-induced SH-SY5Y cell ferroptosis. Mechanistically, myricetin accelerated nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and subsequent glutathione peroxidase 4 (Gpx4) expression in MPP+-treated SH-SY5Y cells, two critical inhibitors of ferroptosis. Collectively, these data demonstrate that myricetin may be a potential agent for decreasing dopaminergic neuron death by inhibiting ferroptosis in PD.

Phytochemical profiling, antiviral activities, molecular docking, and dynamic simulations of selected Ruellia species extracts.

The antiviral properties of the flowering aerial extracts of Ruellia tuberosa and Ruellia patula were investigated through phytochemical profiling via LC-MS/MS and HPLC techniques. Qualitative LC-MS/MS analyses identified seventy-seven metabolites from both Ruellia species. R. tuberosa had the highest phenolic content (49.3%), whereas R. patula had the highest flavonoid content (57.8%). Additionally, quantitative HPLC investigations of the compounds identified by LC-MS/MS were performed using the available standard compounds. The main constituents in the R. tuberosa extract was found to be catechin (5321.63 µg/g), gallic acid (2878.71 µg/g), and ellagic acid (2530.79 µg/g), whereas the major compounds in the R. patula extract was found to be rutin (11,074.19 µg/g) and chlorogenic acid (3157.35 µg/g). Furthermore, the antiviral activities of both Ruellia species against HAdV-40, herpes simplex type 2 and H1N1 were evaluated. These findings demonstrated that R. tuberosa was more active than R. patula against all tested viruses, except for the HSV-2 virus, against which R. patula showed greater activity than R. tuberosa, with IC50 values of 20, 65, 22.59, and 13.13 µg/ml for R. tuberosa flowering aerial parts and 32.26, 11.66, and 23.03 µg/ml for R. patula flowering aerial parts, respectively for HAdV-40, herpes simplex type 2, and H1N1. Additionally, computational docking and molecular dynamics simulations were used to assess the molecular interactions between the bioactive compounds and specific viral targets. The combined findings from the in-vitro and in-silico experiments comprehensively evaluated the antiviral activities of both Ruellia species extracts.

Icariside II in NSCLC and COVID-19: Network pharmacology and molecular docking study.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) are susceptible to coronavirus disease-2019 (COVID-19), but current treatments are limited. Icariside II (IS), a flavonoid compound derived from the plant epimedin, showed anti-cancer,anti-inflammation and immunoregulation effects. The present study aimed to evaluate the possible effect and underlying mechanisms of IS on NSCLC patients with COVID-19 (NSCLC/COVID-19). METHODS: NSCLC/COVID-19 targets were defined as the common targets of NSCLC (collected from The Cancer Genome Atlas database) and COVID-19 targets (collected from disease database of Genecards, OMIM, and NCBI). The correlations of NSCLC/COVID-19 targets and survival rates in patients with NSCLC were analyzed using the survival R package. Prognostic analyses were performed using univariate and multivariate Cox proportional hazards regression models. Furthermore, the targets in IS treatment of NSCLC/COVID-19 were defined as the overlapping targets of IS (predicted from drug database of TMSCP, HERBs, SwissTarget Prediction) and NSCLC/COVID-19 targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of these treatment targets were performed aiming to understand the biological process, cellular component, molecular function and signaling pathway. The hub targets were analyzed by a protein-protein interaction network and the binding capacity with IS was characterized by molecular docking. RESULTS: The hub targets for IS in the treatment of NSCLC/COVID-19 includes F2, SELE, MMP1, MMP2, AGTR1 and AGTR2, and the molecular docking results showed that the above target proteins had a good binding degree to IS. Network pharmacology showed that IS might affect the leucocytes migration, inflammation response and active oxygen species metabolic process, as well as regulate the interleukin-17, tumor necrosus factor and hypoxia-inducible factor-1 signaling pathway in NSCLC/COVID-19. CONCLUSIONS: IS may enhance the therapeutic efficacy of current clinical anti-inflammatory and anti-cancer therapy to benefit patients with NSCLC combined with COVID-19.

Methyl jasmonate-induced bHLH42 mediates tissue-specific accumulation of anthocyanins via regulating flavonoid metabolism-related pathways in Caitai.

Anthocyanin is a type of plant secondary metabolite beneficial to human health. The anthocyanin content of vegetable and fruit crops signifies their nutritional quality. However, the molecular mechanism of anthocyanin accumulation, especially tissue-specific accumulation, in Caitai, as well as in other Brassica rapa varieties, remains elusive. In the present study, taking advantage of three kinds of Caitai cultivars with diverse colour traits between leaves and stems, we conducted a comparative transcriptome analysis and identified the molecular pathway of anthocyanin biosynthesis in Caitai leaves and stems, respectively. Our further investigations demonstrate that bHLH42, which is robustly induced by MeJA, closely correlates with tissue-specific accumulation of anthocyanins in Caitai; bHLH42 upregulates the expression of flavonoid/anthocyanin biosynthetic pathway genes to activate anthocyanin biosynthesis pathway, importantly, overexpression of bHLH42 significantly improves the anthocyanin content of Caitai. Our analysis convincingly suggests that bHLH42 induced by jasmonic acid signalling plays a crucial role in tissue-specific accumulation of anthocyanins in Caitai.

Suppressing the virulence factors of Candida auris with baicalein through multifaceted mechanisms.

Candida auris, a rapidly spreading multi-drug-resistant fungus, is causing lethal infections under certain conditions globally. Baicalin (BE), an active ingredient extracted from the dried root of Scutellaria baicalensis Georgi, exhibits antifungal activity. However, studies have shown the distinctive advantages of Traditional Chinese medicine in combating fungal infections, while the effect of BE, an active ingredient extracted from the dried roots of Scutellaria baicalensis Georgi, on C. auris, remains unknown. Therefore, this study aims to evaluate the potential of BE as an antifungal agent against the emerging multidrug-resistant C. auris. Various assays and models, including microbroth dilution, time growth curve analysis, spot assays, adhesion tests, flocculation test, cell surface hydrophobicity assay, hydrolase activity assays, XTT assay, violet crystal assay, scanning electron microscope (SEM), confocal laser scanning microscope (CLSM), flow cytometry, Live/dead fluorescent staining, reactive oxygen species (ROS), cell wall assay, aggregation assay, porcine skin model, Galleria mellonella larvae (G. mellonella larvae) infection model, and reverse transcription-quantitative polymerase chain reaction (RT-PCR) were utilized to investigate how baicalein suppresses C. auris through possible multifaceted mechanisms. The findings indicate that BE strongly inhibited C. auris growth, adhesion, and biofilm formation. It also effectively reduced drug resistance and aggregation by disrupting the cell membrane and cell wall while reducing colonization and invasion of the host. Transcriptome analysis showed significant modulation in gene expression related to different virulence factors post-BE treatment. In conclusion, BE exhibits significant effectiveness against C. auris, suggesting its potential as a viable treatment option due to its multifaceted suppression mechanisms.

Identification of tomato F-box proteins functioning in phenylpropanoid metabolism.

Phenylpropanoids, a class of specialized metabolites, play crucial roles in plant growth and stress adaptation and include diverse phenolic compounds such as flavonoids. Phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS) are essential enzymes functioning at the entry points of general phenylpropanoid biosynthesis and flavonoid biosynthesis, respectively. In Arabidopsis, PAL and CHS are turned over through ubiquitination-dependent proteasomal degradation. Specific kelch domain-containing F-Box (KFB) proteins as components of ubiquitin E3 ligase directly interact with PAL or CHS, leading to polyubiquitinated PAL and CHS, which in turn influences phenylpropanoid and flavonoid production. Although phenylpropanoids are vital for tomato nutritional value and stress responses, the post-translational regulation of PAL and CHS in tomato remains unknown. We identified 31 putative KFB-encoding genes in the tomato genome. Our homology analysis and phylogenetic study predicted four PAL-interacting SlKFBs, while SlKFB18 was identified as the sole candidate for the CHS-interacting KFB. Consistent with their homolog function, the predicted four PAL-interacting SlKFBs function in PAL degradation. Surprisingly, SlKFB18 did not interact with tomato CHS and the overexpression or knocking out of SlKFB18 did not affect phenylpropanoid contents in tomato transgenic lines, suggesting its irreverence with flavonoid metabolism. Our study successfully discovered the post-translational regulatory machinery of PALs in tomato while highlighting the limitation of relying solely on a homology-based approach to predict interacting partners of F-box proteins.

In vitro and in silico evaluation of bioactivities and chemical composition of the aerial parts of Anchusa officinalis L. methanol extract.

The main objective of the study is to evaluate the antioxidant, anticancer, and antimicrobial activities of Anchusa officinalis L. in vitro and in silico. The dried aerial parts of A. officinalis L. were extracted with methanol. Total phenolic and flavonoid content was analyzed. Antioxidant and antimicrobial effects were tested against both gram-positive and gram-negative bacteria. Gas chromatography-mass spectrometry analysis revealed the presence of 10 phytochemical compounds, and cyclobutane (26.07%) was identified as the major photochemical compound. The methanol extract exhibited the maximum amount of total phenolic content (118.24 ± 4.42 mg QE/g dry weight of the dry extract) (R2 = 0.994) and the total flavonoid content was 94 ± 2.34 mg QE/g dry weight of the dry extract (R2 = 0.999). The IC50 value for 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid was 107.12 ± 3.42 µg/mL, and it was high for 1,1-diphenyl-2-picryl hydrazyl (123.94 ± 2.31 µg/mL). The IC50 value was 72.49 ± 3.14 against HepG2 cell lines, and a decreased value was obtained (102.54 ± 4.17 g/mL) against MCF-7 cell lines. The methanol extract increased the expression of caspase mRNA and Bax mRNA levels when compared to the control experiment (p < .05). The conclusions, A. officinalis L. aerial parts extract exhibited antibacterial, antifungal, and antioxidant activities.

GC-MS based metabolomic profiling of Aporosa cardiosperma (Gaertn.) Merr. leaf extracts and evaluating its therapeutic potential.

Aporosa cardiosperma is a plant species majorly found in the Indian Western Ghats that belongs to the phyllanthaceae family with ethnobotanical importance. Using a Fourier Transform-Infrared Spectrometer (FT-IR) and Gas Chromatography-Mass Spectrometry (GC-MS) for evaluating leaf extracts of A. cardiosperma, significant functional groups and metabolite constituents were determined, and its total flavonoid, phenol, and tannin content were quantified. Further, its antibacterial efficacy was investigated against microorganisms that cause fish and human disease and are resistant to common antibiotics, including Staphylococcus aureus, Bacillus subtilis, Mycobacterium tuberculosis, Klebsiella pneumoniae, Aeromonas hydrophila, and Pseudomonas aeruginosa. Regarding the outcomes of GC-MS analysis, the primary metabolites in the A. cardiosperma leaf extracts were heneicosane (57.06%), silane (13.60%), 1-heptadecene (10.09%), 3-hexadecene (9.99%), and pentadecane (9.54%). In comparison to other solvents, methanolic extract of A. cardiosperma leaves had increased phenolic, flavonoid, and tannin content; these findings are consistent with in vitro antioxidant potential and obtained that the methanolic extract (100 µg/mL) exhibited the higher percentage of inhibition in DPPH (82.35%), FRAP (86.20%), metal chelating (72.32%), and ABTS (86.06%) antioxidant assays respectively. Similar findings were found regarding the antibacterial efficacy against pathogenic bacteria. Comparatively, to other extracts, methanolic extracts showed more significant antibacterial activity at a lower minimum inhibitory concentration (MIC) value (250 µg/mL), whilst ethyl acetate and hexane solvent extracts of A. cardiosperma leaves had higher MIC values 500 µg/mL and 1000 µg/mL respectively. The antimicrobial potential was validated by investigating bacterial growth through the extracts acquired MICs and sub-MICs range. Bacterial growth was completely inhibited at the determined MIC range. In conclusion, A. cardiosperma leaf extract's phytochemical fingerprint has been determined, and its potent antibacterial and antioxidant activities were discovered. These findings of the current study will pave the way for developing herbal treatments from A. cardiosperma for various fish and human diseases.

Icariin suppresses nephrotic syndrome by inhibiting pyroptosis and epithelial-to-mesenchymal transition.

CONTEXT: Nephrotic syndrome(NS) has emerged as a worldwide public health problem. Renal fibrosis is the most common pathological change from NS to end-stage renal failure, seriously affecting the prognosis of renal disease. Although tremendous efforts have been made to treat NS, specific drug therapies to delay the progression of NS toward end-stage renal failure are limited. Epimedium is generally used to treat kidney disease in traditional Chinese medicine. Icariin is a principal active component of Epimedium. METHODS: We used Sprague Dawley rats to establish NS models by injecting doxorubicin through the tail vein. Then icariin and prednisone were intragastric administration. Renal function was examined by an automatic biochemical analyzer. Pathology of the kidney was detected by Hematoxylin-Eosin and Masson staining respectively. Furthermore, RT-PCR, Enzyme-Linked Immunosorbent Assay, Immunohistochemistry, Western Blot and Terminal-deoxynucleotidyl Transferase Mediated Nick End Labeling staining were employed to detect the proteins related to pyroptosis and EMT. HK-2 cells exposed to doxorubicin were treated with icariin, and cell viability was assessed using the MTT. EMT was assessed using Enzyme-Linked Immunosorbent Assay and Western Blot. RESULTS: The study showed that icariin significantly improved renal function and renal fibrosis in rats. In addition, icariin effectively decreased NOD-like receptor thermal protein domain associated protein 3,Caspase-1, Gasdermin D, Ly6C, and interleukin (IL)-1ß. Notably, treatment with icariin also inhibited the levels of TGF-ß, α-SMA and E-cadherin. DISCUSSION AND CONCLUSIONS: It is confirmed that icariin can improve renal function and alleviate renal fibrosis by inhibiting pyroptosis and the mechanism may be related to epithelial-to-mesenchymal transition. Icariin treatment might be recommended as a new approach for NS.

Rapid identification of various chemical components in Cinnamomi ramulus by UPLC-Q-Orbitrap-MS.

Cinnamomi ramulus (CR) is a common Chinese herbal medicine with a long history. It is often used to treat exogenous wind-cold diseases in clinic, but its chemical compositions remain to be studied. In this study, CR was extracted with 75% ethanol, and UPLC-Q-Orbitrap-MS combined with data post-processing method was used to identify the chemical components in the extract. Through this technology, the components in CR can be separated and accurately identified. A total of 61 compounds were identified, including 14 simple phenylpropanoids, 3 coumarins, 5 lignans, 14 flavonoids, 10 benzoic acids, 8 organic acids, and 7 others. This study confirmed the existence of these compounds in CR and speculated the cleavage pathways of each compound, which enriched the mass spectrometry data and cleavage rules. This study can provide a reference for CR and other research.

Untargeted metabolomic profiling of Prinsepia utilis Royle leaves by Ultra-Performance Liquid Chromatography-Quadrupole-Time of Flight-Mass Spectrometry.

Prinsepia utilis Royle, native to the Himalayas, is esteemed in Chinese and Indian folk medicine for its diverse medicinal benefits, targeting arthritis, pain relief, bone disorders, and joint discomfort. This study examined the 25% aqueous methanol extract of P. utilis leaves using UPLC-Q-TOF-MS/MS, identifying 78 metabolites, 76 of which were reported for the first time in P. utilis. These included 64 phenolics represented by 56 flavonoids, 5 phenolic acids, 3 phenolic glycosides, 4 terpenoids, 2 lignan glycosides, and 8 other compounds, expanding the knowledge of its chemical composition. These findings lay a foundation for further research, providing insights into potential bioactive compounds and opening avenues for applications in natural product drug discovery, traditional medicine, and nutraceutical development, leveraging the plant's established traditional uses.

Metabolic and Transcriptional Analysis Reveals Flavonoid Involvement in the Drought Stress Response of Mulberry Leaves.

Abiotic stress, especially drought stress, poses a significant threat to terrestrial plant growth, development, and productivity. Although mulberry has great genetic diversity and extensive stress-tolerant traits in agroforestry systems, only a few reports offer preliminary insight into the biochemical responses of mulberry leaves under drought conditions. In this study, we performed a comparative metabolomic and transcriptomic analysis on the "drooping mulberry" (Morus alba var. pendula Dippel) under PEG-6000-simulated drought stress. Our research revealed that drought stress significantly enhanced flavonoid accumulation and upregulated the expression of phenylpropanoid biosynthetic genes. Furthermore, the activities of superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) content were elevated. In vitro enzyme assays and fermentation tests indicated the involvement of flavonol synthase/flavanone 3-hydroxylase (XM_010098126.2) and anthocyanidin 3-O-glucosyltransferase 5 (XM_010101521.2) in the biosynthesis of flavonol aglycones and glycosides, respectively. The recombinant MaF3GT5 protein was found to recognize kaempferol, quercetin, and UDP-glucose as substrates but not 3-/7-O-glucosylated flavonols and UDP-rhamnose. MaF3GT5 is capable of forming 3-O- and 7-O-monoglucoside, but not di-O-glucosides, from kaempferol. This implies its role as a flavonol 3, 7-O-glucosyltransferase. The findings from this study provided insights into the biosynthesis of flavonoids and could have substantial implications for the future diversified utilization of mulberry.

Effects of Foliar Dressing with Chemical Nano-Selenum and Na2SeO3 on the Antioxidant System and Accumulation of Se and Bioactive Components in Cyclocarya paliurus (Sweet Tea Tree).

Selenium (Se)-rich Cyclocarya paliurus is popular for its bioactive components, and exogenous Se fortification is the most effective means of enrichment. However, the effects of exogenous Se fortification on the nutritional quality of C. paliurus are not well known. To investigate the nutrient contents and antioxidant properties of C. paliurus following Se treatment, we used a foliar spray to apply Se in two forms-chemical nano-Se (Che-SeNPs) and sodium selenite (Na2SeO3). Sampling began 10 days after spraying and was conducted every 5 days until day 30. The Se, secondary metabolite, malondialdehyde contents, antioxidant enzyme activity, Se speciation, and Se-metabolism-related gene expression patterns were analyzed in the collected samples. Exogenous Se enhancement effectively increased the Se content of leaves, reaching a maximum on days 10 and 15 of sampling, while the contents of flavonoids, triterpenes, and polyphenols increased significantly during the same period. In addition, the application of Se significantly enhanced total antioxidant activity, especially the activity of the antioxidant enzyme peroxidase. Furthermore, a positive correlation between the alleviation of lipid peroxidation and Se content was observed, while methylselenocysteine formation was an effective means of alleviating Se stress. Finally, Na2SeO3 exhibited better absorption and conversion efficiency than Che-SeNPs in C. paliurus.

Baicalin protects against hepatocyte injury caused by aflatoxin B1 via the TP53-related ferroptosis Pathway.

OBJECTIVE: Baicalin has antioxidative, antiviral, and anti-inflammatory properties. However, its ability to alleviate oxidative stress (OS) and DNA damage in liver cells exposed to aflatoxin B1 (AFB1), a highly hepatotoxic compound, remains uncertain. In this study, the protective effects of baicalin on AFB1-induced hepatocyte injury and the mechanisms underlying those effects were investigated. METHODS: Stable cell lines expressing CYP3A4 were established using lentiviral vectors to assess oxidative stress levels by conducting assays to determine the content of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Additionally, DNA damage was evaluated by 8-hydroxy-2-deoxyguanosine (8-OHdG) and comet assays. Transcriptome sequencing, molecular docking, and in vitro experiments were conducted to determine the mechanisms underlying the effects of baicalin on AFB1-induced hepatocyte injury. In vivo, a rat model of hepatocyte injury induced by AFB1 was used to evaluate the effects of baicalin. RESULTS: In vitro, baicalin significantly attenuated AFB1-induced injury caused due to OS, as determined by a decrease in ROS, MDA, and SOD levels. Baicalin also considerably decreased AFB1-induced DNA damage in hepatocytes. This protective effect of baicalin was found to be closely associated with the TP53-mediated ferroptosis pathway. To elaborate, baicalin physically interacts with P53, leading to the suppression of the expression of GPX4 and SLC7A11, which in turn inhibits ferroptosis. In vivo findings showed that baicalin decreased DNA damage and ferroptosis in AFB1-treated rat liver tissues, as determined by a decrease in the expression of γ-H2AX and an increase in GPX4 and SLC7A11 levels. Overexpression of TP53 weakened the protective effects of baicalin. CONCLUSIONS: Baicalin can alleviate AFB1-induced OS and DNA damage in liver cells via the TP53-mediated ferroptosis pathway. In this study, a theoretical foundation was established for the use of baicalin in protecting the liver from the toxic effects of AFB1.

Investigation of the effect of Myricetin on Cisplatin-induced liver hepatotoxicity.

OBJECTIVE: Cisplatin, a widely used anticancer agent, induces hepatotoxicity alongside organ damage. Understanding Cisplatin's toxicity mechanism and developing preventive measures are crucial. Our study explores Myricetin, a flavonoid, for its protective effects against Cisplatin-induced hepatotoxicity. METHODS: In our study, a total of 32 Wistar albino male rats were utilized, which were categorized into four distinct groups: Control, Myricetin, Cisplatin, and Myricetin+Cisplatin. For the histological assessment of hepatic tissues, hematoxylin-eosin and periodic acid Schiff staining were employed, alongside immunohistochemical measurements of TNF-α, interleukin-17, and interleukin-6 immunoreactivity. Additionally, aspartate transaminase and alanine transaminase values were examined by biochemical analysis. RESULTS: In the histological evaluation of the tissues, a normal healthy cell structure and a strong periodic acid Schiff (+) reaction were observed in the hepatocyte cells in the tissues of the Control and Myricetin groups, while intense eosinophilia, minimal vacuolization, congestion, and sinusoidal expansions were observed in the hematoxylin-eosin stainings, and a decrease in the positive reaction in the periodic acid Schiff staining was observed in the Cisplatin group. Consistent with these histological findings, an increase in TNF-α, interleukin-17, and interleukin-6 expressions (p<0.0001) and a concomitant increase in aspartate transaminase and alanine transaminase values were observed in the Cisplatin group. In the group protected by Myricetin, a significant improvement was observed in all these histological and biochemical values. CONCLUSION: Cisplatin induces notable histopathological alterations in the liver. In this context, Myricetin exhibits the potential to alleviate Cisplatin-induced damage by modulating histological parameters and biochemical processes.

The flavonoids from the fruits of Psoralea corylifolia and their potential in inhibiting metastasis of human non-small cell lung cancers.

Nineteen flavonoids were isolated from the fruits of Psoralea corylifolia L., including a novel flavanol (3) and three novel isoflavones (12-14). Their chemical structures were unequivocally determined through comprehensive spectral data analysis. The anti-proliferative effect of the isolated flavonoids was assessed in vitro using the MTT assay. Molecular docking and ELISA were employed to determine the inhibitory effects of the active compounds on ALK5. Isobavachalcone was found to inhibit TGF-ß1 induced EMT in A549 cells by Wound healing assay and Transwell chamber assay. Immunofluorescence assay and Western blot assay showed that IBC could inhibit cytoskeleton rearrangement, reduce the phosphorylation of ALK5, ERK, and Smad, down-regulate Snail expression, and up-regulate E-cadherin expression in TGF-ß1 induced A549 cells, thereby exerting the potential inhibitory effects on epithelial-mesenchymal transition (EMT) process in A549 cells. The findings presented herein establish a fundamental basis for investigating the anti-proliferative and anti-metastatic properties of psoralen flavonoids in human non-small cell lung cancer.

The Flavonoid Glycoside from Abrus cantoniensis Hance Alleviates Alcoholic Liver Injury by Inhibiting Ferroptosis in an AMPK-Dependent Manner.

Abrus cantoniensis Hance is a vegetative food and can be used as a folk beverage or soup to clear liver toxins and prevent liver damage. However, the components and effects of A. cantoniensis Hance in alcohol-induced liver injury were unknown. This study aimed to obtain abundant phytochemicals from A. cantoniensis Hance and identify the potency of the isolates in preventing alcohol-induced liver injury. Alcohol-stimulated AML12 cells and Lieber-DeCarli diet-fed mice were used to establish in vitro and in vivo models, respectively. Our findings indicated that flavonoid glycosides, especially AH-15, could significantly alleviate alcohol-induced liver injury by inhibiting oxidative stress. Furthermore, we demonstrated that AH-15 inhibited ferroptosis induced by lipid peroxidation. Mechanically, we found that AH-15 regulated nuclear factor erythroid 2-related factor 2 (NRF2) expression via activation of AMP-activated protein kinase (AMPK) signaling. These results indicate that A. cantoniensis Hance is a great potential functional food for alleviating alcohol-induced liver injury.

Integrative analyses of metabolome and transcriptome reveal the dynamic accumulation and regulatory network in rhizomes and fruits of Polygonatum cyrtonema Hua.

BACKGROUND: According to Chinese ancient books, both fruits and rhizomes of Polygonatum cyrtonema Hua have medicinal and edible values. Up to now, there is no report about the metabolite profiles and regulatory network in fruits and different year-old rhizomes of P. cyrtonema. RESULTS: In this study, we performed integrative analyses of metabolome and transcriptome to reveal the dynamic accumulation and regulatory network of fruits and different year-old rhizomes in P. cyrtonema. The relative content of phenolic acids, lignans and coumarins, flavonoids and alkaloids increased with growth years, while steroids and lipids decreased with it. In addition, the relative content of nucleotides and derivatives, flavonoids, organic acids, steroids and lipids in fruits were higher than rhizomes. Genes that might relate to the biosynthesis of polysaccharides, flavonoids, triterpene saponins and alkaloids biosynthesis were further analyzed by transcriptome analysis, including sacA, GMPP, PMM, CCoAOMT, CHI, ANR, CHS, DXS, GGPS, ZEP, CYP72A219 and so on, for their expressions were positively correlated with the relative content of the metabolites. Additionally, the correlation network in sugar and aromatic amino acids metabolites were constructed to further illustrate the biosynthesis of polysaccharides, flavonoids and alkaloids in P. cyrtonema, and some transcription factors (TFs) were screened, such as C2C2, MYB, bZIP, GRAS and NAC. CONCLUSIONS: This study can deepen our understanding of the accumulation patterns and molecular mechanism of the main compounds in P. cyrtonema, and provide reference for the standardize production of P. cyrtonema.

[Correlation between ecological factors and effective component content, flower, and leaf traits of Epimedium pubescens].

No systematic research has been reported on the correlation between different ecological factors and the effective component content, flower, and leaf traits of Epimedium pubescens. In this study, 21 kinds of E. pubescens in different regions were investigated, and the content of two effective components of icariin(I) and Epimedin C(C), as well as six leaf traits and 12 flower traits were determined. The correlation between 11 ecological factors and the above traits in different regions for five consecutive years was explored. The results showed that no significant correlation was observed between the ecological factors and the total content of two effective components(I+C) of E. pubescens. Latitude and temperature(including annual average temperature, annual average minimum temperature, and soil temperature of each soil layer) were significantly positively and negatively correlated with the ratio of the content of the two effective components(C/I)(P<0.01), respectively. There was a significant correlation between ecological factors and flower traits, and the annual average soil temperature of each soil layer, annual average temperature, and annual average minimum temperature were significantly correlated with most flower traits in multiple years(P<0.01). However, a weak correlation between ecological factors and leaf traits was detected. A significant positive correlation of the annual average soil temperature of each soil layer and annual average humidity(P<0.01) with the width of nutrient leaf in only a few years was detected. Therefore, it was concluded that the total content of effective components of E. pubescens was determined by genetics, with a slight influence of ecological factors. The annual average temperature, annual average minimum temperature, and soil temperature of each soil layer were the ecological factors that had the most significant impact on flower traits, which showed significant differences in different regions, and similar results were not found in leaf traits. Overall, this study systematically conducted a correlation analysis between ecological factors and the effective components, as well as flower and leaf traits, providing guidance for the quality improvement, introduction, and domestication of E. pubescens.