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Twelve new Cephalotaxus alkaloids with cytotoxic activities from the twigs and leaves of Cephalotaxus sinensis.

Twelve new

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.

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.

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.

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.

Fusion with host cell membrane is the main mechanism of infection of SARS-CoV-2. Here, we propose a new strategy to double block SARS-CoV-2 membrane fusion by using Harringtonine (HT), a small-molecule antagonist. By using cell membrane chromatography (CMC), we found that HT specifically targeted the SARS-CoV-2 S protein and host cell TMPRSS2, and then confirmed that HT can inhibit pseudotyped virus membrane fusion. Furthermore, HT successfully blocked SARS-CoV-2 infection, especially in the delta and Omicron mutant. Since HT is a small-molecule antagonist, it is minimally affected by the continuous variation of SARS-CoV-2. Our findings show that HT is a potential small-molecule antagonist with a new mechanism of action against SARS-CoV-2 infection, and thus HT mainly targets the S protein, and thus, greatly reduces the damage of the S protein’s autotoxicity to the organ system, has promising advantages in the clinical treatment of COVID-19.

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.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.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.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-1β, 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.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.

Nine steroidal components, including a new pregnane glycoside (1), were obtained from the roots and rhizomes of Smilacina henryi. Their structures were determined via extensive spectroscopic data including, IR, HRESIMS and 1D, 2D NMR data analysis. Furthermore, their cytotoxic activities against human HepG2 and SW620 tumor cells were evaluated by the MTT method and compounds 2, 3, 5, 8 and 9 showed moderate activity with IC50 values raging from 18.4 to 86.3 μM.

Two new cholestanol glycosides (1 and 2) were obtained from the roots and rhizomes of Smilacina henryi. Their structures were determined as 5α-cholest-9(11)-ene-3β, 26-dihydroxy-16, 22-dione 3-O-β-D-glucopyranosyl-(1→2)-β-D-galactopyranoside (1), 5α-cholest-9(11)-ene-3β, 26-dihydroxy-16, 22-dione 3-O-β-D-glucopyranosyl-(1→2)- [β-D-glucopyranosyl-(1→3)]-β-D-galactopyranoside (2), by physicochemical properties and spectroscopic methods. In addition, the isolated glycosides were tested for their cytotoxic activity against human HepG2 tumor cells and compound 2 showed moderate activity with IC50 value of 59.32 μM.

Hylomecon japonica is considered a natural medicinal plant with anti-inflammatory, anticancer and antibacterial activity. The assessment of climate change impact on its habitat suitability is important for the wild cultivation and standardized planting of H. japonica. In this study, the maximum entropy model (Maxent) and geographic information system (ArcGIS) were applied to predict the current and future distribution of H. japonica species, and the contributions of variables were evaluated by using the jackknife test. The area under the receiver operating characteristic curve (AUC) value confirmed the accuracy of the model prediction based on 102 occurrence records. The predicted potential distributions of H. japonica were mainly concentrated in Jilin, Liaoning, Shaanxi, Chongqing, Henan, Heilongjiang and other provinces (adaptability index &gt, 0.6). The jackknife experiment showed that the precipitation of driest month (40.5%), mean annual temperature (12.4%), the precipitation of wettest quarter (11.6%) and the subclass of soil (9.7%) were the most important factors affecting the potential distribution of H. japonica. In the future, only under the shared socioeconomic Pathway 245 (SSP 245) scenario model in 2061–2080, the suitable habitat area for H. japonica is expected to show a significant upward trend. The area under other scenarios may not increase or decrease significantly.

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 IC

Steroid saponins are the medicinal compounds and nutrition ingredients of medicine food homology (MFH)

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 IC

Two new yohimbine-type monoterpene indole alkaloids, rauvines A and B, and six known derivatives were obtained from the leaves of R. vomitoria. The structures of rauvines A and B were determined by extensive spectroscopic analyses, 13 C-NMR, and ECD calculations. This is the first time to determine the absolute configurations of yohimbine-type N-oxides by quantum chemistry calculations (13 C-NMR and ECD calculations). All the isolates were tested for their cytotoxicity against five human cancer cell lines. Rauvine B showed moderate cytotoxicity on human MCF-7 breast, SWS80 colon, and A549 lung cancer cell lines with IC50 values of 25.5, 22.6, and 26.0 μM, respectively.

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.

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.

Five new peraksine derivatives rauvomine C–G (1–5) along with four known analogues (6–9) were isolated from the stems of Rauvolfia vomitoria Afzel. (Apocynaceae). Structural determinations of the new monoterpene indole alkaloids were elucidated via comprehensive spectroscopic analyses and ECD calculations. Rauvomine C (1) with an unprecedented framework type represents the first example of C18 peraksine-type nor-monoterpene indole alkaloid featuring a chlorine atom at C-16 and its plausible biosynthetic pathway was also proposed. All the isolates were evaluated for their anti-inflammatory, cytotoxic, and acetylcholinesterase inhibitory activities. Among them, the new framework alkaloid rauvomine C (1) showed significant anti-inflammatory activities on NO production in LPS-induced RAW264.7 mouse macrophages with IC50 value of 10.76 μM. Additionally, peraksine-type alkaloids featuring pyran ring (5, 8, and 9) exhibited potential anti-inflammatory activities with IC50 values ranging from 17.52 to 20.99 μM.

Seventeen monoterpene indole alkaloids, including seven new alkaloids (1−7) and ten known analogues (8−17), were isolated and identified from the leaves of R. vomitoria. The structures of new alkaloids were elucidated by extensive spectroscopic analysis and single-crystal X-ray diffraction analysis. Rauvomitorine I (1) represents the first example of an unprecedented C22 yohimbine-type monoterpene indole alkaloid featuring a carboxymethyl at C-14. The exceedingly rare vobasenal (2−3) and affinisine oxindole (5−6) framework type alkaloids are first reported from the Rauvolfia genus. Most notably, the structure of vobasenal-type alkaloids (2−3) were first determined by single-crystal X-ray diffraction analyses. Alkaloids 1−17 were tested their cytotoxicity against five cancer cell lines, however, none of them showed significant cytotoxicity at a concentration of 40 μM. All the isolated alkaloids were evaluated their acetylcholinesterase (AChE) inhibitory activities. Alkaloid 3 exhibited significant anti-AChE activity with an IC50 value of 16.39 ± 1.41 μM and alkaloids 8 and 10 showed moderate anti-AChE activities whereas the others (2, 9, 13, and 17) were week inhibitors. This is the first report of vobasenal-type alkaloids as AChE inhibitors, indicating this type of alkaloids may be important sources for the discovery of new AChE inhibitors. A preliminary structure-activity relationship for AChE inhibitory activities showed the presence of the N-methyl group in vobasenal-type alkaloids may be essential for anti-AChE activity. Further molecular docking studies of vobasenal-type alkaloids revealed that interaction with Trp133 and Trp86 residues at hydrophobic subsite are necessary for the AChE inhibitory activities. This study not only enriches the chemical diversity of alkaloids in Apocynaceae plants but also provides new potential leading compounds and versatile scaffolds for the design and development of new AChE inhibitors to treat AD.

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.

Nine undescribed monoterpene indole alkaloids, rauvomitorine A−I, including an unprecedented C-9-methoxymethylene-sarpagine framework alkaloid, two rare suaveoline framework type alkaloids, and six yohimbine framework type alkaloids, as well as eleven known alkaloids, were isolated from the stems of Rauvolfia vomitoria Afzel. (Apocynaceae). The structures of the unreported alkaloids were elucidated by extensive spectroscopic analysis and single-crystal X-ray diffraction analysis with Cu Kα radiation. Rauvomitorine A with an unreported framework type represents the first example of C-9-methoxymethylene-sarpagine alkaloids and its plausible biosynthetic pathway was proposed. All the isolated alkaloids were evaluated their acetylcholinesterase inhibitory (AChE) activities and cytotoxicity against five cancer cell lines and some of them exhibited potential anti-AChE activities with IC50 values ranging from 49.76 to 186.62 μM. Importantly, this is the first report of the AChE inhibitory activities on suaveoline framework type alkaloids, suggesting this type of alkaloids may be valuable sources for the discovery of AChE inhibitory agents. A preliminary structure-activity relationship for AChE inhibitory activities of the isolated alkaloids is also discussed, providing some clues to designing lead compounds for AChE inhibitors.

Diosgenin (DIO), the starting material for the synthesis of steroidal anti-inflammatory drugs in the pharmaceutical industry, has been previously demonstrated to display pharmaceutical effects against cerebral ischemic reperfusion (I/R). However, the alterations of brain proteome profiles underlying this treatment remain elusive. In the present study, the proteomics analysis of the brain tissues from I/R rats after DIO treatment was performed using an integrated TMT-based quantitative proteomic approach coupled with the liquid chromatography with tandem mass spectrometry technology. A total of 5043 proteins (ProteomeXchange identifier: PXD016303) were identified, of which 58 common differentially expressed proteins were significantly dysregulated in comparison between sham versus I/R and I/R versus DIO. The eight validated proteins including EPG5, STAT2, CPT1A, EIF2AK2, GGCT, HIKESHI, TNFAIP8, and EMC6 by quantitative polymerase chain reaction and western blotting consistently supported the TMT-based proteomic results, which were mainly associated with autophagy and inflammation response. Considering the anti-inflammatory characters of DIO, the biological functions of STAT2 and HIKESHI that are the probable direct anti-inflammatory targets were further investigated during the course of I/R treated with DIO. In addition, the combination of verified STAT2 and HIKESHI in peripheral blood samples from stroke patients resulted in the area under the curve value of 0.765 with P < 0.004 to distinguish stroke patients from healthy controls. Taken together, the current findings first mapped comprehensive proteomic changes after I/R was treated with DIO to better decipher the molecular mechanisms mainly based on the anti-inflammatory aspect underlying this therapeutic effect, providing a foundation for developing potentially therapeutic targets of anti-I/R of DIO and clinically prognostic biomarkers of stroke.

Ethnopharmacological relevance Dioscorea zingiberensis C. H. Wright (D. zingiberensis), Dioscoreaceae, is used extensively in traditional Chinese medicines. The aim of the current review paper is to give a comprehensive overview of the traditional usage and phytochemistry of the plant. Clinical studies performed and products prepared from the plant and active principles will be mentioned. In addition a review of the taxonomy of the genus Dioscorea is given. Materials and methods A systematic search on literature has been performed in databases like Google Scholar, Science Direct, Scifinder, Web of Science, and in Chinese databases (China Knowledge Resource Integrated, i.e., CNKI and Wanfang) including Ph.D. and M.Sc. dissertations. These from the period 1983–2016 have been searched. Results D. zingiberensis is an endemic plant in China widely distributed in some provinces, especially Hubei and Shaanxi. The rhizomes are the medicinal part in Dun-Ye-Guan-Xin-Ning tablets and are used for isolation of diosgenin. Steroidal saponins are believed to be the active principles. More than 70 compounds have been identified. Several of these have been tested in preclinical assays and clinical trials. A wide spectrum of biological effects including cardiovascular, anti-thrombosis, hyperlipidemia, neuroprotection, anti-inflammatory, and anthelmintic effect has been verified. Conclusions Because of the promising results from the investigations on the plant material of D. zingiberensis, further in depth analyses ought to be performed to evaluate its potential as either a traditional drug or a source of bioactive principle. The presently performed studies do not explain mechanism of action, pharmacokinetics (ADME properties), or toxicity. All of these topics need more elaborate investigations.

Diosgenin wastewater produced from Dioscorea zingiberensis C. H. Wright in diosgenin enterprise is the by-product of numerous operations chiefly including washing raw materials, acid hydrolysis, and cleaning the apparatus with water. It requires the removal of high concentrations of various organic and inorganic contaminants from this wastewater in order to avoid pollution to the environment and fresh water system. Currently, several different methods such as chemical, physicochemical, biological recovery resource, constructed wetland, and integrated methods of these processes are being applied for treating diosgenin wastewater. Aiming to get a comprehensive overview, available reports from experimental scale to industry scale about the treatment of this wastewater were collected and summarized. Therefore, this review paper will provide appropriate choice for the efficient treatment of diosgenin wastewater and supportive information for the other scientists who want to continue this valuable research in the future.

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

The present study was designed to assess the antiarthritic potential of ECF in collagen-induced arthritis (CIA) and explore its underlying mechanism. Methods. In vitro, lymphocyte proliferation assay was measured by CCK-8 kit. In vivo, the therapeutic potential of ECF on CIA was investigated; surface marker, Treg cell, and intracellular cytokines (IL-17A and IFN-γ) were detected by flow cytometry. Th1 cell differentiation assay was performed, and mRNA expression in interferon-γ-related signaling was examined by q-PCR analysis. Results. In vitro, ECF markedly inhibited the proliferation of splenocytes in response to ConA and anti-CD3. In vivo, ECF treatment reduced the severity of CIA, inhibited IFN-γ and IL-6 secretion, and decreased the proportion of CD11b+Gr-1+ splenic neutrophil. Meanwhile, ECF treatment significantly inhibited the IFN-γ expression in CD4+T cell without obviously influencing the development of Th17 cells and T regulatory cells. In vitro, ECF suppressed the differentiation of naive CD4+ T cells into Th1. Furthermore, ECF intensely blocked the transcriptional expression in interferon-γ-related signaling, including IFN-γ, T-bet, STAT1, and STAT4. Conclusion. Our results indicated that ECF exerted antiarthritic potential in collagen-induced arthritis by suppressing Th1 immune response and interferon-γ-related signaling.

The aim of the present study is to explore the potential cerebroprotection of diosgenin against the transient focal cerebral ischemia-reperfusion (I/R) injury and its possible underlying mechanisms. The diosgenin at two dose levels, namely 100 and 200mgkg(-1), was intragastrically administrated once daily for 7-day period prior to the surgery. Then, the rats were subjected to middle cerebral artery occlusion (MCAO) using the intraluminal thread for 90min. After 24h reperfusion, several diagnostic indicators were evaluated and all animals were sacrificed to harvest their brains and blood for subsequent biochemical analyses. The results indicated that diosgenin treatment significantly inhibited the death rate and improved the impaired neurological functions along with neurological deficit scores and cerebral infarct size as compared with the rats exposed to I/R insult without agents administration. The increase in the number of apoptotic cells determined by TUNEL in the hippocampus CA1 and cortex was also apparently attenuated in the diosgenin treatment group, which was closely correlated with suppression of Caspase-3 activity and Bax/Bcl-2 ratio. In addition the elevated concentrations of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in blood serum of the I/R treated rats were reduced almost to their normal level. Further results obtained from the Western blotting analysis revealed that the protein expression of IκBα in the injured brain was up-regulated, while the p65 subunit of NF-κB was down-regulated in nucleus after the treatment. Collectively, this neuroprotection of diosgenin against I/R injury may be attained through its anti-apoptosis, anti-inflammation and intervening the NF-κB signal pathway properties. Due to the satisfactory findings, diosgenin might be a powerful therapeutic agent to combat the similar disease in future clinic.

Henryiosides F and G (

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.

A new sesquiterpene, 7α-H-11-hydroxyeremophil-1(10)-en-2-one (1), together with 14 known sesquiterpenoids (2–15), were isolated from the extract of the whole plant of Ligularia fischeri. Among them, compounds 2–6 and 15 were isolated from Ligularia fischeri for the first time. The new compound was characterized by means of spectroscopic methods including 1D and 2D NMR and HR-ESI-MS, and the known ones were established by comparing their NMR data with those of the corresponding compounds in the literature.

In this paper, the novel hydrophilic magnetic molecularly imprinted nanoparticles were developed for selective separation and determination of chlorogenic acid in aqueous fruit juices. The polymers were prepared by using amino-functionalized magnetic nanoparticles as carriers, branched polyethyleneimine as functional monomer, and chlorogenic acid as template molecule. Branched polyethyleneimine with abundant active amino groups could react with template sufficiently, and its unique dendritic structure may amplify the number of the imprinted cavities. Meanwhile, it would improve the hydrophilicity of imprinted materials for attaining high extraction efficiency. The resulted polymers exhibit fast kinetics, high adsorption capacity, and favorable selectivity. In addition, the obtained nanoparticles were used as solid-phase extraction sorbents for selective isolation and determination of chlorogenic acid in peach, apple, and grape juices (0.92, 4.21, and 0.75 μg mL(-1), respectively).

In light of the significance of glycoprotein biomarkers for early clinical diagnostics and treatments of diseases, it is essential to develop efficient and selective enrichment platforms for glycoproteins. In this study, we present a facile and general strategy to prepare the boronate affinity-based magnetic imprinted nanoparticles. Boronic acid ligands were first grafted on the directly aldehyde-functionalized magnetic nanoparticles through amidation reaction. Then, template glycoproteins were immobilized on the boronic acid-modified magnetic nanoparticles via boronate affinity binding. Subsequently, a thin layer of dopamine was formed to coat the surface of magnetic nanoparticles through self-polymerization. After the template glycoproteins were removed, the cavities that can specific bind the template glycoproteins were fabricated. Adopting horseradish peroxidase as model template, the effects of imprinting conditions as well as the properties and performance of the obtained products were investigated. The resultant imprinted materials exhibit highly favorable features, including uniform surface morphology with thin imprinted shell of about 8 nm, super-paramagnetic property, fast kinetics of 40 min, high adsorption capacity of 60.3 mg g−1, and satisfactory reusability for at least five cycles of adsorption-desorption without obvious deterioration. Meanwhile, the obtained magnetic imprinted nanoparticles could capture target glycoprotein from nonglycoproteins, but also from other glycoproteins because the synergistic selectivity of boronate affinity and imprinting effect. In addition, the facile preparation method shows feasibility in the imprinting of different glycoproteins.

Bovine hemoglobin (BHb), as one of the high-abundance proteins, could seriously mask and hamper the analysis of low-abundance proteins in serum. To selectively deplete BHb, we design a simple and effective strategy for preparation of biocompatible molecularly imprinted shell on superparamagnetic iron oxide nanoparticles through surface imprinting technique combined with template immobilization strategy. Firstly, template proteins are immobilized on the directly aldehyde-functionalized magnetic nanoparticles through imine bonds. Then, with gelatin as functional monomer, a polymeric network molded around the immobilized template proteins is obtained. Finally, the specific cavities for BHb are fabricated after removing the template proteins. The effects of imprinting conditions were investigated and the optimal imprinting conditions are found to be 40mg of BHb, 150mg of gelatin, and 8h of polymerization time. The resultant materials exhibit good dispersion, high crystallinity, and satisfactory superparamagnetic property with a high saturation magnetization (33.43emug(-1)). The adsorption experiments show that the imprinted nanomaterials have high adsorption capacity of 93.1mgg(-1), fast equilibrium time of 35min, and satisfactory selectivity for target protein. Meanwhile, the obtained polymers could be used without obvious deterioration after six adsorption-desorption cycles. In addition, the resultant polymers are successfully applied in the selective isolation BHb from bovine blood sample, which could provide an alternative solution for the preparatory work of proteomics.

Background Radix Gentianae Macrophyllae, commonly known as Qinjiao (秦艽in Chinese), is dried roots of medicinal plants that belong to Gentianaceae family and Gentiana genus. It has medically been used for the treatment of various diseases such as arthritis, stroke, facial paralysis, and scapulohumeral periarthritis in China since ancient times. Purpose The aim of this paper is to provide a comprehensive and constructive overview of Qinjiao mainly containing Gentiana macrophylla Pall., Gentiana straminea Maxim., Gentiana crasicaulis Duthie ex Burk., and Gentiana daurica Fisch. in botany, traditional use, phytochemicals, pharmacology (biological activities and pharmacokinetics), quality control, and authentication according to the up-to-date data of available scientific literatures. Materials and methods All information regarding these four plants was collected from various academic search engines for example Google, Google Scholar, Web of Science, SciFinder, Pubmed, CNKI, and Wanfang. Additional information was obtained from botanical books, Chinese classic texts, and medical monographs. Results So far 166 compounds have been isolated and identified from Qinjiao plants together with Gentiana tibetica King ex Hook. f., Gentiana siphonantha Maxim., Gentiana officinalis H. Smith, and Gentiana waltonii Burk. Their constituents are mainly classified into iridoid glycosides, triterpenes, flavones, sterols, benzene derivatives, etc. The pharmacological studies demonstrate that Qinjiao plants display a wide range of bioactivities e.g. anti-inflammatory, anti-oxidant, hepato-protective, cardio- and neuro-protective, insecticidal, and anti-influenza effects. The conventional quality control is performed by determination of the concentration of some compounds, e.g., gentiopicroside, or establishment of the fingerprint. In addition to seed propagation, tissue culture technology has been used to address the limited supplies and guarantee the sustainable development of Qinjiao in the experimental scale. Conclusions Although the identification of compounds from Qinjiao and demonstration of medicinal uses in vitro and in vivo have been carried out, various other studies on these plants should deserve our more attention. More efforts should be concentrated on the underlying mechanisms of their beneficial bioactivities. The proper toxic evaluation is indispensable to guarantee the safety, efficacy, and eligibility for medical use. To sum up, the summarized achievements could highlight the importance of Qinjiao and provide a solid foundation for scientists not only to further exploit the therapeutic potentials, but also possibly develop novel drugs in the subsequent research.

A series of 2,3-substituted-2-iminothiazoline-4-ones derivatives have been synthesized via an improved method including an auto-catalyzed reaction. This method avoided using any extra catalyst except for the reaction material. This method has been successful in both the aromatic substituted 2-iminothiazolines and the alkyl substituted 2-iminothiazolines. The special product with a hydroxyl group on the 2-iminogroup of 1,3-thiazoline-4-ones has also been obtained unexpectedly. The possible mechanism has been proposed for the special process of dealkylation and hydroxylation. This method offered a special way to afford the 2-hydroxyimino-substituted thiazoline-4-one derivatives in an efficient and eco-friendly way. The mechanism of the transformation under acid condition has also been proposed.