Polycyclic pyrroloindoline-containing natural products with a unique 3-heptyl-2a,4a-diazapentaleno[1,6-ab]indene core isolated from Alstonia scholaris.

Alscholarine C (1), featuring an unprecedented pyrroloindoline-containing natural product (PiNP) with a 6/5/5/5 tetracyclic carbon skeleton, and four known PiNPs (2-5), namely demethylalstoscholarinine E (2), Nb-demethylechitamine (3), winphylline A (4), and echitamine (5), were isolated from Alstonia scholaris. Compound 1 was characterized by a hexahydropyrrolo[2,3-b] indole (HPI) core fused to a unique 4-heptylimidazolidine motif, forming an unparalleled 3-heptyl-2a,4a-diazapentaleno[1,6-ab]indene ring system. Their structures were established by spectroscopic analysis, quantum-chemical calculated 13C NMR data with DP4+ probability analyses, and ECD calculations and comparison. A plausible biosynthetic pathway of 1 was proposed. Compound 1 exhibited potential anti-inflammatory activity against LPS-stimulated NO production in RAW264.7 cells.

Alscholarines A and B, two rearranged monoterpene indole alkaloids from Alstonia scholaris.

Alscholarines A and B (1 and 2), two unprecedented rearranged monoterpene indole alkaloids, were isolated from Alstonia scholaris. Alscholarine A (1) features an imidazole ring fused with a rearranged vallesamine-type alkaloid possessing an unparalleled 6/5/6/6 tetracyclic skeleton through an unprecedented C7-C-19 connectivity. Alscholarine B (2), incorporating an unusual 7-oxa-1-azabicyclo[3.2.1]octane moiety, represents a unique rearranged vallesamine-type alkaloid with a 6/5/6/6/5 ring system via an unprecedented C-6-C-20 connectivity. Their structures were established by spectroscopic analysis, X-ray crystallography, and quantum-chemical calculations. Their plausible biosynthetic pathways were proposed. The vasorelaxant and anti-inflammatory activities of them were also evaluated. Compounds 1-3 showed moderate vasorelaxant activities.

Conocarpus lancifolius (Combretaceae): Pharmacological Effects, LC-ESI-MS/MS Profiling and In Silico Attributes.

In folklore medicine, Conocarpus lancifolius is used to treat various illnesses. The main objective of this study was a comprehensive investigation of Conocarpus lancifolius leaf aqueous extract (CLAE) for its antioxidant, cardioprotective, anxiolytic, antidepressant and memory-enhancing capabilities by using different in vitro, in vivo and in silico models. The in vitro experimentation revealed that CLAE consumed an ample amount of total phenolics (67.70 ± 0.15 µg GAE/mg) and flavonoids (47.54 ± 0.45 µg QE/mg) with stronger antiradical effects through DPPH (IC50 = 16.66 ± 0.42 µg/mL), TAC (77.33 ± 0.41 µg AAE/mg) and TRP (79.11 ± 0.67 µg GAE/mg) assays. The extract also displayed suitable acetylcholinesterase (AChE) inhibitory (IC50 = 110.13 ± 1.71 µg/mL) activity through a modified Ellman's method. The toxicology examination presented no mortality or any signs of clinical toxicity in both single-dose and repeated-dose tests. In line with the cardioprotective study, the pretreatment of CLAE was found to be effective in relieving the isoproterenol (ISO)-induced myocardial injury in rats by normalizing the heart weight index, serum cardiac biomarkers, lipid profile and various histopathological variations. In the noise-stress-induced model for behavior attributes, the results demonstrated that CLAE has the tendency to increase the time spent in the central zone and elevated open arms in the open field and elevated plus maze tests (examined for anxiety assessment), reduced periods of immobility in the forced swimming test (for depression) and improved recognition and working memory in the novel object recognition and Morris water maze tests, respectively. Moreover, the LC-ESI-MS/MS profiling predicted 53 phytocompounds in CLAE. The drug-likeness and ADMET analysis exhibited that the majority of the identified compounds have reasonable physicochemical and pharmacokinetic profiles. The co-expression of molecular docking and network analysis indicated that top-ranked CLAE phytoconstituents act efficiently against the key proteins and target multiple signaling pathways to exert its cardiovascular-protectant, anxiolytic, antidepressant and memory-enhancing activity. Hence, this artifact illustrates that the observed biological properties of CLAE elucidate its significance as a sustainable source of bioactive phytochemicals, which appears to be advantageous for pursuing further studies for the development of new therapeutic agents of desired interest.

Harringtonine: A more effective antagonist for Omicron variant.

Fusion with host cell membrane is the main mechanism of infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we propose that a new strategy to screen small-molecule antagonists blocking SARS-CoV-2 membrane fusion. Using cell membrane chromatography (CMC), we found that harringtonine (HT) simultaneously targeted SARS-CoV-2 S protein and host cell surface TMPRSS2 expressed by the host cell, and subsequently confirmed that HT can inhibit membrane fusion. HT effectively blocked SARS-CoV-2 original strain entry with the IC50 of 0.217 µM, while the IC50 in delta variant decreased to 0.101 µM, the IC50 in Omicron BA.1 variant was 0.042 µM. Due to high transmissibility and immune escape, Omicron subvariant BA.5 has become the dominant strain of the SARS-CoV-2 virus and led to escalating COVID-19 cases, however, against BA.5, HT showed a surprising effectiveness. The IC50 in Omicron BA.5 was even lower than 0.0019 µM. The above results revealed the effect of HT on Omicron is very significant. In summary, we characterize HT as a small-molecule antagonist by direct targeting on the Spike protein and TMPRSS2.

Molecular Networking Accelerated Discovery of Biflavonoid Alkaloids from Cephalotaxus sinensis.

Four undescribed biflavonoid alkaloids, sinenbiflavones A-D, were isolated from Cephalotaxus sinensis using a MS/MS-based molecular networking guided strategy. Their structures were elucidated by series of spectroscopic methods (HR-ESI-MS, UV, IR, 1D, and 2D NMR). Sinenbiflavones A-D are the first examples of amentoflavone-type (C-3'-C-8'') biflavonoid alkaloids. Meanwhile, sinenbiflavones B and D are the unique C-6-methylated amentoflavone-type biflavonoid alkaloids. Sinenbiflavone D showed weak SARS-CoV-2 3CLpro inhibitory activity with 43 % inhibition rate at 40 µM.

Structurally diverse monoterpene indole alkaloids with vasorelaxant activities from the branches of Alstonia scholaris.

Seven undescribed monoterpene indole alkaloids alstoscholarinines A‒G, along with nineteen known alkaloids, were isolated from the branches of Alstonia scholaris (L.) R. Br. The isolated alkaloids were classified into ten framework types. The structures of the undescribed alkaloids were elucidated by extensive spectroscopic analysis, ECD calculation, and single-crystal X-ray diffraction analysis. Alstoscholarinine A is an unreported and unusual monoterpene indole alkaloid incorporating three nitrogen atoms, characterized by a compact 6/5/6/6/6/5 hexacyclic system bearing a piperidine ring and a unique oxazolidine ring. Alstoscholarinine B represents the first naturally C-17 nor-isositsirikine-type alkaloid. Plausible biosynthetic pathways of alstoscholarinines A and B were proposed. All isolates were evaluated for their vasorelaxant activities against phenylephrine-induced contraction of rat mesenteric arteries. Among them, seven alkaloids showed significant vasorelaxant activities with EC50 values less than 10 µM. Importantly, the akuammicine-type alkaloids in this study showed much better vasorelaxant activities than other framework type alkaloids, indicating that this type of alkaloid may be a valuable source for the discovery of vasodilators. A preliminary structure-activity relationship for vasorelaxant activities of the isolated akuammicine-type alkaloids is also discussed.

Research progress of diosgenin extraction from Dioscorea zingiberensis C. H. Wright: Inspiration of novel method with environmental protection and efficient characteristics.

Diosgenin was the starting materials to synthesize various hormone drugs and mainly generated from Dioscorea zingiberensis C. H. Wright by acidolysis, enzymolysis, microbiological fermentation, and integrated manner. Only acidic hydrolysis with strong acid such as hydrochloric acid or sulfuric acid was used in practice in diosgenin enterprises due to their feasibility and simplicity, nevertheless finally resulting in a great deal of unmanageable wastewater and severely polluted the surrounding environment. Aiming to provide a comprehensive and up-to date information of researches on diosgenin production from this plant, 151 cases were collected from scientific databases including Web of Science, Pubmed, Science Direct, Wiley, Springer, and China Knowledge Resource Integrated (CNKI). Their advantages and disadvantages with different production methods were analyzed based on these available data in this review paper. Considering the fact that nearly all of diosgenin enterprises were closed for the environmental protection and the life health of the people, this review paper was beneficial for providing useful guidelines to develop novel technologies with environmentally-friendly and cleaner features for diosgenin production or facilitate the transformation of other methods like enzymolysis, microbiological fermentation, or integrated methods from laboratory scale to industry scale.

6-Methoxydihydrosanguinarine induces apoptosis and autophagy in breast cancer MCF-7 cells by accumulating ROS to suppress the PI3K/AKT/mTOR signaling pathway.

6-Methoxydihydrosanguinarine (6-MDS) is a natural benzophenanthridine alkaloid extracted from Hylomecon japonica (Thunb.) Prantl. It is the first time to explore the effect and mechanism of 6-MDS in breast cancer. Network pharmacology, molecular docking, and molecular dynamics simulation technology were adopted to identify the potential targets and pathways of 6-MDS in breast cancer. Besides, cell proliferation, apoptosis, and western blotting assays were conducted to investigate the effect of 6-MDS on MCF-7 cells. Network pharmacology, molecular docking, and molecular dynamics simulation results confirmed the effect of 6-MDS on resisting breast cancer via the PI3K/AKT/mTOR signaling pathway. In addition, the functional experiments results demonstrated that 6-MDS inhibited proliferation and induced apoptosis and autophagy. The autophagy inhibitor chloroquine and the silence of Atg5 augmented the effect of 6-MDS on promoting apoptosis. Furthermore, 6-MDS suppressed the PI3K/AKT/mTOR signaling pathway, and the PI3K inhibitor LY294002 enhanced these changes and promoted the 6-MDS pro-apoptotic and autophagy effects. 6-MDS triggered the generation of reactive oxygen species. The pretreatment with antioxidant N-acetyl-L-cysteine reversed the changes induced by 6-MDS, including increases in apoptosis and autophagy and inhibition of the PI3K/AKT/mTOR pathway. In conclusion, 6-MDS induces the apoptosis and autophagy of MCF-7 cells by ROS accumulation to suppress the PI3K/AKT/mTOR signaling pathway.

Cytotoxic alkaloids from the twigs and leaves of Cephalotaxus sinensis.

Twelve new Cephalotaxus alkaloids (1-12) and nine known analogues (13-21) were isolated and identified from the twigs and leaves of Cephalotaxus sinensis. The structures of the new compounds (1-12) were elucidated by extensive spectroscopic analysis and single-crystal X-ray diffraction analysis. Cephalosine H (8) is the third example of an alkaloid containing the cephalolancine skeleton. Cephalosines J and K (10 and 11) are the rare natural Δ(2)1-alkene-6-hydroxyl homoerythrina-type alkaloids isolated from the Cephalotaxus genus. The racemization of cephalotaxine-type alkaloids is discussed. Alkaloids 6, 7, 11, 16, 18 and 19 exhibited broad and potent cytotoxicities against five human cancer cell lines, with IC50 values ranging from 0.053 to 10.720 µM, highlighting these compounds as promising leads for the development of new antitumor agents.

Metabolites with antioxidant and α-glucosidase inhibitory activities produced by the endophytic fungi Aspergillus niger from Pachysandra terminalis.

One new compound and 13 known compounds were isolated from Aspergillus niger, a plant endophytic fungus of Pachysandra terminalis collected from Qinling Mountains, Xi'an, China. The structure of new compound 1 was classically determined by extensive spectroscopic analysis. Compounds 5, 6, 8, and 14 were first reported from Aspergillus, while compound 2 was isolated from A. niger for the first time. All isolated compounds were further evaluated for their antioxidant and α-glucosidase inhibitory activities. Compounds 2 and 3 exhibited significant antioxidant activities with IC50 values of 31.64 µm and 24.32 µm, respectively, similar to the positive control ascorbic acid. Additionally, compound 1 displayed remarkable inhibitory activity against α-glucosidase with an IC50 value of 96.25 µm, which was 3.4-fold more potent than that of the positive control acarbose. Compound 1 has great potential for development as a new lead compound owing to its simple structure and remarkable biological activity.

Isoquinoline alkaloids from Hylomecon japonica and their potential anti-breast cancer activities.

Four pairs of undescribed enantiomeric isoquinoline alkaloids (6S/R-(N,N-diethylacetamido)yl-dihydrochelerythrine, 6R/S-acetonyl-9-hydroxy-dihydrochelerythrine, 6S/R-acroleinyl-dihydrochelerythrine, 6S/R-acetatemethyl-dihydrochelerythrine), five undescribed isoquinoline alkaloids (6,10-dimethoxydihydrochelerythrine, 6-ethoxy-ethaniminyl-dihydrochelandine, 9-hydroxy-dihydrochelerythrine, 9-methoxy-10-hydroxy-norchelerythrine, chelidoniumine A), together with 13 known isoquinoline alkaloids were isolated from an extract of the roots and rhizomes of Hylomecon japonica. The structures of the undescribed compounds were identified by NMR, HRESIMS, UV, IR, and their absolute configurations were defined via electronic circular dichroism data and optical rotation. All of the isolated compounds were tested for their anti-breast cancer activities in MCF-7 cells. Among them, the undescribed alkaloids 6S/R-acroleinyl-dihydrochelerythrine, 6,10-dimethoxydihydrochelerythrine, 6-ethoxy-ethaniminyl-dihydrochelandine, 9-methoxy-10-hydroxy-norchelerythrine and other known alkaloids 6-methoxydihydrosanguinarine, 6-acetaldehyde-dihyrochelerythrine, dihydrosanguinaline and 10-methoxy boconoline had good inhibitory effects on MCF-7 cells of breast cancer with an IC50 lower than 20 µM.

Diosgenin revealed potential effect against cerebral ischemia reperfusion through HIKESHI/HSP70/NF-κB anti-inflammatory axis.

BACKGROUND: It is a research hotspot to use natural compounds in treatment of cerebral ischemia reperfusion (I/R) for a refractory disease throughout the worldwide without available drugs or treatments at present. Our previous study has demonstrated that diosgenin (DIO), a starting material to synthesize various steroid anti-inflammatory drugs in medical industry, showed medicinal effect against I/R via inhibiting aberrant inflammatory reaction induced by I/R. However, the detailed anti-inflammatory network of DIO in treatment of I/R still remains to be further explored. PURPOSE: HIKESHI was firstly identified as a novel target of DIO used for I/R by rat brain proteomic analysis, and mechanistic efforts were focused based on this gene. Hopefully, extensive detailed molecular mechanisms of DIO against I/R was established and confirmed. METHODS: The effect of DIO against I/R was examined in vitro and in vivo, which cells (SH-SY5Y and PC12) and rats were experienced to ORD/RP and MCAO exposures, respectively, to establish I/R modes. Staining was used to evaluate the pathological procedure of DIO used for I/R. Protein changes including expression, interaction, and activity during DIO's anti-I/R effect were assessed with real time PCR, western blot, Co-IP, luciferase reporter assay. RESULTS: In the current study, HIKESHI and HSP70 were both upregulated, when I/R cells and rats were treated with DIO in vitro and in vivo. Mechanistically, DIO stimulated the binding of HIKESHI to HSP70 and facilitated the translocation of HSP70 into nucleus. Subsequently, HSP70 blunted the transcription activity of NF-κB after physical interaction with this transcription factor, and therefore led to the suppression of its downstream pro-inflammatory cytokine (TNF-α, IL-1ß, and IL-6) release into surrounding I/R lesion area. Conversely, HIKESHI or HSP70 knockdowns attenuated the nuclear translocation and restraint on NF-κB-mediated inflammation, finally resulting in the abolishment of DIO-induced anti-I/R effect. NF-κB activation also relieved the inhibitory inflammation and reversed DIO's effect against I/R, suggesting that NF-κB was the downstream target of HIKESHI and HSP70 in I/R treatment with DIO. CONCLUSIONS: These findings established a novel HIKESHI/HSP70/NF-κB signaling pathway associated with DIO-treated I/R, which might be as therapeutic targets or drugs with potential implications for the therapeutic use of I/R in clinic.

New phenylpropanoids and monoterpene alkaloids with vasorelaxant activities from the branches of Alstonia scholaris.

Two new phenylpropanoids (1-2), one new nor-monoterpenoid alkaloid (3), one new monoterpene alkaloid (4), together with nine known compounds (5-13) were obtained from the branches of Alstonia scholaris. The structures of the undescribed compounds were determined by extensive spectroscopic analysis. Alkaloid 3 represented the first example of C-4 methylated nor-monoterpenoid alkaloids. A possible biosynthetic pathway for this new type of monoterpene alkaloids was proposed. All the isolates were evaluated for vasorelaxant activity against phenylephrine-induced contraction of rat mesenteric arteries. Compounds 1, 4, 9, 12, and 13 showed significant vasorelaxant activity with relaxation rates above 90% at 200 µM and exhibited moderate vasorelaxant activity with IC50 values ranging from 41.87 to 93.30 µM by further studies. It was the first report on the potential vasorelaxant activity of monoterpene alkaloids. Monoterpene alkaloids 3 and 4 may be served as the potential lead compounds for the discovery of vasodilators, due to their simple and optimizable structures.

3-Epipachysamine B suppresses proliferation and induces apoptosis of breast cancer cell via PI3K/AKT/mTOR signaling pathway.

3-Epipachysamine B is a natural steroidal alkaloid isolated from Pachysandra terminalis Sieb. et Zucc. (known locally as Kunxianqi). Kunxianqi contains numerous compounds with demonstrated activity against breast cancer (BRCA). However, it is unknown whether 3-epipachysamine B also has anti-BRCA efficacy. In the present study, we employed network pharmacology technology to search and find potential molecular targets of 3-epipachysamine B. We applied cell proliferation, apoptosis, and western blotting assays to test the predicted key targets and the effects of 3-epipachysamine B against BRCA. Network pharmacology disclosed 80 potential BRCA-related targets of 3-epipachysamine B and assigned them to 75 signaling pathways. Of these, the most highly enriched was the PI3K/AKT signaling pathway. PIK3R1, AKT1, and mTOR had high degrees and betweenness centrality in protein-protein interaction network and are associated with PI3K/AKT signaling. Molecular docking and molecular dynamics simulation indicated strong binding between 3-epipachysamine B and PIK3R1, AKT1, and mTOR. 3-Epipachysamine B repressed the proliferation and induced the apoptosis of BRCA cells, as well as downregulated P-AKT/AKT, P-mTOR/mTOR, and P-PI3K/PI3K in the cells. The PI3K inhibitor LY294002 augmented these changes. Hence, 3-epipachysamine could also prove effective as an anticancer agent in future animal tumor model and human clinical breast cancer trials. Successful validation results could lead to a safe and effective new breast cancer treatment that improves patient prognosis and quality of life.

New steroid saponins from Dioscorea zingiberensis yam and their medicinal use against I/R via anti-inflammatory effect.

Steroid saponins are the medicinal compounds and nutrition ingredients of medicine food  homology (MFH) Dioscorea zingiberensis C. H. Wright (D. zingiberensis) yam. Our phytochemical investigation of the edible rhizomes resulted in 9 new furostanol steroid saponins named dioscins A-I (1-9), together with 11 known steroid saponins. Their chemical structures were elucidated based on spectroscopic and chemical analyses. The new dioscins were evaluated for their anti-inflammatory and beneficial effects against cerebral ischemia reperfusion (I/R) injury on RAW264.7 and PC12 cells in vitro, respectively. Dioscins A, B, and G revealed considerable anti-I/R effect through an anti-inflammatory mechanism based on the decreasing concentration of pro-inflammatory (TNF-α and IL-6) and down-regulating the NF-κB expression. The present research demonstrated that daily consumption of this yam plant probably prevented the I/R occurrence via the anti-inflammatory property of steroid saponins, and it also enriched the steroid saponin library, providing the possibility to develop MFH-containing steroid saponins into functional foods for maintenance of human health or drugs for the treatment of I/R disease.

Exploring the mechanism of Cremastra Appendiculata (SUANPANQI) against breast cancer by network pharmacology and molecular docking.

BACKGROUND: SUANPANQI, the pseudo phosphorous stem of Cremastra appendiculata, is one of the most well-known traditional Chinese medicine, which has been shown to inhibit tumorigenesis in various human cancers. However, the underlying mechanism of SUANPANQI treatment against breast cancer (BRCA) remains unclear. In this study. we aim to investigate the bioactive compounds and mechanisms of SUANPANQI in the treatment of BRCA based on network pharmacology and molecular docking. METHODS: The compounds were collected from previous research. SwissADME was used to screen bioactive compounds. The targets corresponding to SUANPANQI and BRCA were obtained using MalaCards and SwissTargetPrediction. SUANPANQI-related and BRCA-related targets were found and then overlapped to get intersections, which represented potential anti-BRCA targets of SUANPANQI. The Cytoscape software was used to construct bioactive compounds targeting the BRCA network. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the targets was extracted from the metascape database, then conducted using the Cluster Profiler package in R software. Protein-Protein interaction (PPI) network was constructed using the STRING online database and analyzed using Cytoscape software. Pivotal genes were screened using the topological analysis, survival analysis, and pathological stage analysis. Molecular docking analysis was used to verify whether the bioactive compounds had a definite affinity with the pivotal targets. RESULTS: Sixty-five bioactive compounds of SUANPANQI were involved with 225 predicted BRCA targets. Then, a compound-target network and a PPI network were constructed. The GO analysis and KEGG enrichment analysis suggested that SUANPANQI worked against BRCA via PI3K-Akt, Ras, FoxO, Rap1, and ErbB signaling pathways, etc. After topological analysis, survival analysis, and pathological stage analysis of the SUANPANQI potential targets against BRCA, 6 pivotal target genes (AR, HSP90AA1, MMP9, PGR, PTGS2, TNF) that were highly responsible for the therapeutic effects of SUANPANQI against BRCA were obtained. Molecular docking results showed that 6 bioactive compounds of SUANPANQI had strong binding efficiency with the 6 pivotal genes. CONCLUSIONS: The present study clarifies the mechanism of SUANPANQI against BRCA through multiple targets and pathways, and provides evidence to support its clinical use.

The genus Cassia L.: Ethnopharmacological and phytochemical overview.

Nature gifts medicinal plants with the untapped and boundless treasure of active chemical constituents with significant therapeutic potential that makes these plants a beneficial source in the development of phytomedicines. Genus Cassia, with approximately 500 species, is a large group of flowering plants in the family Fabaceae. Cassia species are widely distributed throughout different regions mainly tropical Asia, North America, and East Africa. In the folk medicinal history, these plants are used as laxative and purgative agents. In the Ayurveda system of medicine, they are used to cure headache and fever. Cassia plants exhibit pharmacological activities at large scales such as antimicrobial, anticancer, antiinflammatory, antioxidant, hypoglycemic, hyperglycemic, antimutagenic, and antivirals. The phytochemical investigations of genus Cassia demonstrate the presence of more than 200 chemical compounds, including piperidine alkaloids, anthracene derivatives (anthraquinones), flavonoids, pentacyclic triterpenoids, sterols, phenylpropanoids, and γ-naphthopyrones. The literature illustrated anthraquinones and flavonoids as major secondary metabolites from this genus. However, some Cassia plants, with rich contents of anthraquinones, still show toxicology properties. As Cassia plants are used extensively in the herbal system of medicine, but only senna dosage forms have achieved the status of the pharmaceutical market as standard laxative agents. In conclusion, further investigations on isolating newer biologically active constituents, unknown underlying mechanisms, toxicology profiles, and clinical studies of Cassia species are needed to be explored. This review article specifies the systematic breach existing between the current scientific knowledge and the fundamentals for the marketization of genus Cassia products.

Cytotoxic steroidal saponins from the roots and rhizomes of Maianthemum henryi.

Henryiosides F and G (1 and 2), two new steroidal saponins along with two known analogues (3 and 4) were obtained from the roots and rhizomes of Maianthemum henryi. Their structures were determined by physicochemical properties and spectroscopic methods including 1D, 2D-NMR, IR and HR-ESI-MS data analysis. Cytotoxic activity in human HepG2 and SW620 tumour cells were evaluated by the MTT method and all of the saponins exhibited cytotoxicity with IC50 values ranging from 15.33 µM to 57.85 µM.

Prevention properties on cerebral ischemia reperfusion of medicine food homologous Dioscorea yam-derived diosgenin based on mediation of potential targets.

I/R (cerebral ischemia reperfusion injury) is the secondary complication of ischemic stroke patients that are immediately treated with drug thrombolysis or vascular recanalization in clinic. Diosgenin (DIO) purified from medicine food homologous (MFH) Dioscorea yam source is served as a fatal starting material to synthesize multifarious steroidal anti-inflammatory drugs in medicinal field, and has previously been demonstrated the potential prevention of I/R. However, the detailed mechanisms of neuroprotective effects against I/R remain elusively understood. Here, a global proteomic dynamics of rat right hemisphere brains was executed to investigate the protein expression patterns with a quantitative LC-MSn. In total, 5043 proteins were identified and 418 ones were determined to be significantly dysregulated DEPs (differentially expressed proteins) in comparison of Sham verse I/R and I/R verse DIO after onset stage of I/R, among which 5 DEPs namely BICD2, HNRNPK, CEP41, PPM1K, and ARL2BP, whose biological functions were mainly clustered into the mediation of nervous system, were selected for further validation in vitro and in vivo, and the change tendency expectedly supported the proteomic findings. Additionally, the AUC value of the combined ROC of these 5 DEPs was 0.988 with P < 0.0001, higher than every single one. Collectively, these scientific findings attributed to a typical investigation of dietary Dioscorea-enriched diosgenin in MFH research, suggesting that diosgenin or its derivatives were potential to be developed into food supplements or healthy food products to reveal healthy benefits in natural prevention and reduction risk of I/R. This work also promoted reasonable consumption of Dioscorea yams and contributed to the function of diosgenin-derived products and their applications in food industry.

SRY-related high-mobility-group box 6 suppresses cell proliferation and is downregulated in breast cancer.

Breast cancer is one of the most common cancers endangering women's health. SRY-related high-mobility-group box 6 (SOX6) is associated with many cancers, though its role has not been reported in breast cancer. Here, we aimed to explore the expression and function of SOX6 in breast cancer. On the basis of the analysis of SOX6 in The Cancer Genome Atlas, Cancer Cell Line Encyclopedia and Genotype-Tissue Expression databases, we revealed that SOX6 was downregulated in breast cancer, and we verified the results at the cellular level by means of western blotting and quantitative real-time PCR. When SOX6 was overexpressed, the proliferation of breast cancer cells was inhibited, and apoptosis was promoted. Moreover, the methylation level of the SOX6 promoter in breast cancer was significantly higher than that in normal tissues. 5'-Aza-2'-deoxycytidine reversed the high level of methylation that was caused by decreased expression of SOX6. This evidence suggests that SOX6 is a tumor suppressor gene associated with breast cancer. This study could provide a new target for breast cancer treatment.