Targeted Liposomes Sensitize Plastic Melanoma to Ferroptosis via Senescence Induction and Coenzyme Depletion.

Ferroptotic cancer therapy has been extensively investigated since the genesis of the ferroptosis concept. However, the therapeutic efficacy of ferroptosis induction in heterogeneous and plastic melanoma has been compromised, because the melanocytic and transitory cell subpopulation is resistant to iron-dependent oxidative stress. Here, we report a phenotype-altering liposomal nanomedicine to enable the ferroptosis-resistant subtypes of melanoma cells vulnerable to lipid peroxidation via senescence induction. The strategy involves the ratiometric coencapsulation of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor (palbociclib) and a ferroptosis inducer (auranofin) within cRGD peptide-modified targeted liposomes. The two drugs showed a synergistic anticancer effect in the model B16F10 melanoma cells, as evidenced by the combination index analysis (<1). The liposomes could efficiently deliver both drugs into B16F10 cells in a targeted manner. Afterward, the liposomes potently induced the intracellular redox imbalance and lipid peroxidation. Palbociclib significantly provoked cell cycle arrest at the G0/G1 phase, which sensitized auranofin-caused ferroptosis through senescence induction. Meanwhile, palbociclib depleted intracellular glutathione (GSH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH), further boosting ferroptosis. The proof-of-concept was also demonstrated in the B16F10 tumor-bearing mice model. The current work offers a promising ferroptosis-targeting strategy for effectively treating heterogeneous melanoma by manipulating the cellular plasticity.

Ceria nanoclusters coupled with Ce-Nx sites for efficient oxygen reduction in Zn-air batteries.

Rational construction of efficient carbon-supported rare earth cerium nanoclusters as oxygen reduction reaction (ORR) is of great significance to promote the practical application of zinc-air batteries (ZABs). Herein, N doped conductive carbon black anchored CeO2 nanoclusters (CeO2 Clusters/NC) for the ORR is reported. The volatile cerium species vaporized by CeO2 nanoclusters at high temperatures are captured by nitrogen-rich carbon carriers to form highly dispersed Ce-Nx active sites. Benefiting from the coupling effect between oxygen vacancies-enriched CeO2 nanoclusters and highly dispersed Ce-Nx sites, the prepared 2CeO2 Clusters/NC catalyst possesses an ORR half-wave potential of 0.88 V, superior electrochemical stability, and better methanol tolerance compared to commercial Pt/C catalysts. Moreover, the 2CeO2 Clusters/NC involved liquid ZABs show excellent energy efficiency, superior stability, and a high energy density of 982 Wh kg-1 at 10 mA cm-2.

Aerosol Jet Printing of Hybrid Ti3C2T x /C Nanospheres for Planar Micro-supercapacitors.

When utilized in energy devices, the restacking tendency of MXene Ti3C2T x inhibits its electrochemical performance. Using aerosol jet printing (AJP) technology, hybrid Ti3C2T x /C nanospheres are synthesized with C nanoparticle-bonded MXene nanosheets, and the restacking of MXene nanosheets is blocked efficiently. The formation mechanism for hybrid Ti3C2T x /C nanospheres has been hypothesized, and the Ti3C2T x /C is anticipated to assemble and shape along the droplet surface in tandem with the Marangoni flow within the droplet. The planar microsupercapacitor devices generated from these hybrid spherical nanostructures with increased interlayer spacing exhibit exceptional areal capacitance performance. This concept offers a straightforward and effective method for constructing 3D-structured MXene with suppressed self-stacking for diverse high-performance micro energy storage devices.

Screening of different chemical components of sedative and hypnotic effects of Ziziphi Spinosae Semen before and after frying and determination of the Q-Marker.

Ziziphi Spinosae Semen (ZSS) is a traditional Chinese medicine used for sedation and hypnosis. Preliminary studies have shown that frying it could increase its sedative and hypnotic effects due to an increase in its chemical contents. However, the correlation between increased ZSS contents and therapeutic effects remains unclear. This study aimed to identify chemical components that change between ZSS and Fried Ziziphi Spinosae Semen (FZSS) and Q-markers related to these changed components' sedative and hypnotic effects. Differences between ZSS and FZSS were investigated using the UPLC fingerprint analysis. Components significantly different between ZSS and FZSS were screened using the UPLC-Q-TOF-MS analysis combined with a multivariate statistical method. In addition, ZSS and FZSS extracts were treated with diazepam in vitro to observe their differences in saturation competition between ZSS extract and diazepam, before and after processing, and diazepam on the GABA receptor in SD rats' brain tissue. Then, the chemical components of ZSS and FZSS that competed with diazepam to bind to the GABA receptor were identified by LC-MS/MS analysis. Finally, the binding efficiency of the different medicinal components was assessed using molecular docking technology. The results indicated significant differences in the content of various chemical components between ZSS and FZSS. Among them, the contents of adenosine, spinosin, 6'″-feruloylspinosin, jujuboside A and betulinic acid were found to be significantly increased after frying. LC-MS/MS and molecular docking analysis screened spinosin, 6'″-feruloylspinosin and betulinic acid as Q markers for the sedative and hypnotic effects of ZSS and FZSS. In summary, this study identified the changed sedative-hypnotic chemical components and Q-markers of ZSS before and after frying.

Study on a terahertz biosensor based on graphene-metamaterial.

The interaction between the terahertz wave propagating in free space and the sample is weak, which leads to the weak signal of the sample, which cannot meet the detection needs of trace samples. In order to meet the detection of trace samples, a kind of metamaterial absorber (the basic unit of the absorber is composed of gold-high resistance silicon-aluminum three-layer structure) is designed, and the monolayer graphene is transferred on the surface of the metamaterial absorber to construct the graphene-metamaterial absorber heterostructure. The transmission spectrum of the resonant cavity is simulated and measured by terahertz time domain spectroscopy system, and the obvious resonance frequency shift is observed. The results show that the graphene-metamaterial absorber heterostructure can detect josamycin antibiotic solution with concentration of 0.02 mg/L (the mass of josamycin is 0.2 ng). Compared with using the same structure metamaterial absorber to detect josamycin antibiotics, the sensitivity is increased by an order of magnitude. Using graphene-metamaterial heterostructure to detect the relative change of heterostructure reflectivity caused by josamycin antibiotics can reach 40%. The research in this paper provides a new technical means for accurate and rapid detection in terahertz band.

Co/Co-N/Co-O Rooted on rGO Hybrid BCN Nanotube Arrays as Efficient Oxygen Electrocatalyst for Zn-Air Batteries.

Developing high-performance non-noble metal bifunctional oxygen reduction and evolution reaction electrocatalysts is a critical factor for the commercialization of rechargeable Zn-air batteries. Herein, Co/Co-N/Co-O rooted on reduced graphene oxide (rGO) hybrid boron and nitrogen codoped carbon (BCN) nanotube arrays (BCN/rGO-Co) is prepared by facile low-temperature precross-linking and high-temperature pyrolysis treatment. Benefit from the synergistic effect of its B/N codoping, Co/Co-N/Co-O bifunctional active sites, 3D hybrid porous structure of BCN nanotubes, and highly conductive rGO sheets. The obtained BCN/rGO-Co exhibits superior bifunctional oxygen catalytic activity with a positive ORR half-wave potential (0.85 V) and a low OER potential (1.61 V) at 10 mA cm-2. Additionally, the BCN/rGO-Co-based liquid Zn-air batteries displays a large peak power density of 157 mW cm-2, and a long charge/discharge cycle stability of 200 h, outdoing the commercial Pt/C+Ru/C catalyst.

Droplets Patterning of Structurally Integrated 3D Conductive Networks-Based Flexible Strain Sensors for Healthcare Monitoring.

Flexible strain sensors with significant extensibility, stability, and durability are essential for public healthcare due to their ability to monitor vital health signals noninvasively. However, thus far, the conductive networks have been plagued by the inconsistent interface states of the conductive components, which hampered the ultimate sensitivity performance. Here, we demonstrate structurally integrated 3D conductive networks-based flexible strain sensors of hybrid Ag nanorods/nanoparticles(AgNRs/NPs) by combining a droplet-based aerosol jet printing(AJP) process and a feasible transfer process. Structurally integrated 3D conductive networks have been intentionally developed by tweaking droplets deposition behaviors at multi-scale for efficient hybridization and ordered assembly of AgNRs/NPs. The hybrid AgNRs/NPs enhance interfacial conduction and mechanical properties during stretching. In a strain range of 25%, the developed sensor demonstrates an ideal gauge factor of 23.18. When real-time monitoring of finger bending, arm bending, squatting, and vocalization, the fabricated sensors revealed effective responses to human movements. Our findings demonstrate the efficient droplet-based AJP process is particularly capable of developing advanced flexible devices for optoelectronics and wearable electronics applications.

Integrating Constituents Absorbed into Blood, Network Pharmacology, and Quantitative Analysis to Reveal the Active Components in Rubus chingii var. suavissimus that Regulate Lipid Metabolism Disorder.

Rubus chingii var. suavissimus (S. K. Lee) L. T. Lu (RS)-a sweet plant also known as Tiancha distributed in the south of China where it is used as a beverage-recently gained extensive attention as adjuvant therapy of diabetes and hypertension. Although pharmacological studies indicate that RS has beneficial effects in regulating lipid metabolism disorder characteristics, the active chemicals responsible for this effect remains unclear. The present study aims to predict the effective substances of RS on regulating lipid metabolism disorder through the analysis of the chemical profile of RS, the absorbed prototype components in rat plasma, and network pharmacology. Also, a UPLC method able to quantify the screened potential effective chemicals of RS products was established. First, a total of 69 components-including diterpene, triterpenoids, flavonoids, polyphenols, and lignans-were systematically characterized in RS. Of those, 50 compounds were detected in the plasma of rats administered with RS extract. Through network pharmacology, 9 potential effective components, 71 target genes, and 20 pathways were predicted to be involved in RS-mediated regulation of lipid metabolism disorder. The quantitative analysis suggested that the contents of potential effective components varied among samples from different marketplaces. In conclusion, the presented results provide a chemical basis for further research of Rubus chingii var. suavissimus.

Rubus chingii var. suavissimus alleviates high-fat diet-induced lipid metabolism disorder via modulation of the PPARs/SREBP pathway in Syrian golden hamsters.

While the underlying mechanism remains unknown, Rubus chingii var. suavissimus (S. K. Lee) L. T. Lu or Rubus suavissimus S. Lee (RS), a sweet plant distributed in southwest of China, has been used as beverage and folk medicine. Pharmacological studies indicated the potential of RS improving the obesity phenotype and hyperlipidemia. The mechanism is still not yet to be put forward. To verify the substantial effects of RS on lipid metabolism, a Syrian golden hamster model was adopted. The physiological and pathological evaluation of experimental animals demonstrated that RS can relieve the lipid metabolism disorder induced by high-fat diet and alleviated liver injury. RS upregulation the expressions of peroxisome proliferator-activated receptor α (PPARα), PPARγ and CCAAT/enhancer binding protein α (C/EBPα), as well as adipocyte-specific genes, glucose transporter 4 (Glut4), lipoprotein lipase (LPL) and fatty acid binding protein 4 (aP2). On the other side, RS suppressed the sterol regulatory element binding protein 1 (SREBP1) and downstream acetyl-CoA carboxylase 1 (ACC1), stearoyl-CoA desaturase-1 (SCD1) and fatty acid synthase (FAS). In conclusion, RS alleviated lipid metabolism disorder symptoms caused by high-fat diet accompanied with 8 weeks of treatment, involving enhanced ß-oxidation, increased adipogenesis and decreased the metabolism of fatty acids, via modulation of the PPARs/SREBP pathway in Syrian golden hamsters.

[Changes in chemical compositions of Chrysanthemi Flos after frying and protective effects on CCl_4-induced acute liver injury in mice].

To reveal the processing mechanism of Chrysanthemi Flos from the changes of chemical compositions after frying and its effect on the efficacy of liver protection. Ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS) and ultra high performance liquid chromatography(HPLC) were used for the qualitative and quantitative researches of chemical compositions before and after Chrysanthemi Flos frying. Progenesis QI and SPSS software were used for principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), variable importance projection(VIP) analysis and t-test to identify the compositions with significant changes. Pharmacodynamics experiment was used to investigate the protective effect of crude and fried Chrysanthemi Flos on CCl_4-induced acute liver injury in mice. According to mass spectrometry data, there were 28 chemical compositions in crude and fried Chrysanthemi Flos, mainly including flavonoids and organic acids. 13 compositions such as luteolin, apigenin and luteolin glycoside were increased significantly after frying, while 7 compositions such as chlorogenic acid, luteolin-7-O-glucuronide and apigenin-7-O-glucuronide were decreased significantly after frying. Through principal component analysis, crude and fried Chrysanthemi Flos products were divided into two categories, indicating that there were internal differences in quality. The results of liver injury protection experiment in mice showed that the AST, ALT and MDA contents were significantly decreased and SOD level was increased in mice with liver injury in both the high and medium dose groups. Histopathological examination showed that crude and fried Chrysanthemi Flos can protect the liver by reducing inflammatory cell infiltration, reducing steatosis, and repairing damaged liver cells. The results of this study showed that the chemical compositions had obvious changes after frying, and both crude and fried Chrysanthemis Flos had protective effects on CCl_4-induced acute liver injury in mice. In addition, in the range of high, medium and low doses, the liver protection effect of crude and fried Chrysanthemi Flos increased with the increase of dose. The experiment results provided reference for the mechanism of fried Chrysanthemi Flos and clinical selection of processed products.

1H-NMR Metabolomics Analysis of the Effect of Rubusoside on Serum Metabolites of Golden Hamsters on a High-Fat Diet.

Rubusoside is a natural sweetener and the active component of Rubus suavissimus. The preventive and therapeutic effect of rubusoside on high-fat diet-induced (HFD) serum metabolite changes in golden hamsters was analyzed by 1H-NMR metabolomics to explore the underlying mechanism of lipid metabolism regulation. 1H-NMR serum metabolomics analyses revealed a disturbed amino acid-, sugar-, fat-, and energy metabolism in HFD animals. Animals supplemented with rubusoside can partly reverse the metabolism disorders induced by high-fat diet and exerted good anti-hypertriglyceridemia effect by intervening in some major metabolic pathways, involving amino acid metabolism, synthesis of ketone bodies, as well as choline and 4-hydroxyphenylacetate metabolism. This study indicates that rubusoside can interfere with and normalize high-fat diet-induced metabolic changes in serum and could provide a theoretical basis to establish rubusoside as a potentially therapeutic tool able to revert or prevent lipid metabolism disorders.

Metabolomics of the Protective Effect of Ampelopsis grossedentata and Its Major Active Compound Dihydromyricetin on the Liver of High-Fat Diet Hamster.

The flavonoid dihydromyricetin (DMY) is the main component of Ampelopsis grossedentata (Hand-Mazz) W. T. Wang (AG), a daily beverage and folk medicine used in Southern China to treat jaundice hepatitis, cold fever, and sore throat. Recently, DMY and AG were shown to have a beneficial effect on lipid metabolism disorder. However, the mechanisms of how DMY and AG protect the liver during lipid metabolism disorder remain unclear. In this study, we first analyzed the chemical compounds of AG by HPLC-DAD-ESI-IT-TOF-MS n . Of the 31 compounds detected, 29 were identified based on previous results. Then, the effects of DMY and AG on high-fat diet hamster livers were studied and the metabolite levels and metabolic pathway activity of the liver were explored by 1H NMR metabolomics. Compared to the high-fat diet group, supplementation of AG and DMY attenuated the high-fat-induced increase in body weight, liver lipid deposition, serum triglycerides and total cholesterol levels, and normalized endogenous metabolite concentrations. PCA and PLS-DA score plots demonstrated that while the metabolic profiles of hamsters fed a high-fat diet supplemented with DMY or AG were both far from those of hamsters fed a normal diet or a high-fat diet alone, they were similar to each other. Our data suggest that the underlying mechanism of the protective effect of DMY and AG might be related to an attenuation of the deleterious effect of high-fat diet-induced hyperlipidemia on multiple metabolic pathways including amino acid metabolism, ketone body metabolism, energy metabolism, tricarboxylic acid cycle, and enhanced fatty acid oxidation.

Advances in the Detection, Mechanism and Therapy of Chronic Kidney Disease.

Chronic Kidney Disease (CKD) is characterized by the gradual loss of renal mass and functions. It has become a global health problem, with hundreds of millions of people being affected. Both its incidence and prevalence are increasing over time. More than $20,000 are spent on each patient per year. The economic burden on the patients, as well as the society, is heavy and their life quality worsen over time. However, there are still limited effective therapeutic strategies for CKD. Patients mainly rely on dialysis and renal transplantation, which cannot prevent all the complications of CKD. Great efforts are needed in understanding the nature of CKD progression as well as developing effective therapeutic methods, including pharmacological agents. This paper reviews three aspects in the research of CKD that may show great interests to those who devote to bioanalysis, biomedicine and drug development, including important endogenous biomarkers quantification, mechanisms underlying CKD progression and current status of CKD therapy.

Effect of Cyclocarya Paliurus on Hypoglycemic Effect in Type 2 Diabetic Mice.

BACKGROUND The aim of this study was to assess the hypoglycemic effect of Cyclocarya paliurus extract (CPE) on diabetes mellitus (DM) mice. MATERIAL AND METHODS A DM mouse model was established to test FBG, TC, and TG. The DM mice were divided into 3 groups: a DM group, a DM+CPE (0.5 g/Kg) group, and a DM+CPE (1.0 g/Kg) group. The FBG and body weight were measured. The glucose tolerance ability was determined by OGTT test. FINS was measured to calculate ISI and IRI. Serum MDA, SOD, and GSH-Px levels were detected. NIT-1 cells were cultured in vitro and divided into 4 groups: a control group, a STZ group, a STZ+CPE (80 µg/mL) group, and a STZ+CPE (160 µg/mL) group. Cell apoptosis and ROS content were assessed by flow cytometry. Cell proliferation was detected by EdU staining. RESULTS Compared with the control group, FBG, TC, and TG were significantly increased in the DM group. CPE gavage obviously reduced FBG level, increased body weight, enhanced glucose tolerance, elevated FINS level and ISI, and reduced IRI, all in a dose-dependent manner. CPE gavage reduced serum MDA content and increased SOD and GSH-Px enzyme activities in DM mice. STZ markedly enhanced ROS production, induced apoptosis, and inhibited proliferation in NIT-1 cells. CPE treatment clearly reduced ROS production and apoptosis, enhanced cell proliferation, and alleviated STZ damage to NIT-1 cells. CONCLUSIONS CPE has the effects of decreasing blood glucose and insulin resistance, and enhancing glucose tolerance in DM mice, which may be related to its effects of reducing oxidation and reduced apoptosis, and relieving STZ in pancreatic beta cell injury.

Application of terahertz spectroscopy and chemometrics for discrimination of transgenic camellia oil.

Discrimination of transgenic edible oil has become the focus of attention in the field of food safety. In this paper, we propose a method for discrimination of transgenic edible oils by using terahertz spectroscopy combine with weighted linear discriminant analysis (WLDA). To evaluate the lustiness of the model, we employ successive projection arithmetic (SPA) and partial least squares (PLS) to verify the discrimination performance through variable selection. The results demonstrate that the SPA-WLDA model has higher classification accuracy than PLS-WLDA. In conclusion, terahertz spectroscopy is coupled with chemometrics is an effective method for discriminating various types of transgenic edible oils.

Activation of Na+/H+ exchanger other than formation of transmembrane pore underlies the cytotoxicity of nematocyst venom from Chrysaora helvola Brandt jellyfish.

We previously reported unexpected apoptosis-like cell death induced by nematocyst venom (NV) from Chrysaora helvola Brandt (C. helvola) jellyfish. To assess whether the pore formation mechanism underlay the action of NV, the change in cell membrane permeability was studied in both chicken erythrocytes and human CNE-2 cells. Initially, paradoxical results were derived from osmoprotectant protection assays. Polyethylene glycol (PEG)2000, which completely inhibited the NV induced hemolysis, failed to protect CNE-2 cells. Detailed experiments showed that PEG protection from hemolysis is concentration dependent and indicated caution when estimating the pore size formed by NV with the osmotic protection method. NV-treated CNE-2 cells remained impermeable to dyes with various molecular weights (MWs) (622.6-40,000 Da). Furthermore, membrane depolarization and selective permeability to Na+ other than K+ were induced in CNE-2 cells. No oxidative damage to the cell membrane was detected. Amiloride, an inhibitor of Na+/H+ exchanger (NHE), substantially protected both CNE-2 cells and erythrocytes from NV. Combined with the previously reported increase in intracellular pH, we supposed that NV activated plasma membrane NHE without forming transmembrane pores. Interestingly, glutathione (GSH) showed significant protection to CNE-2 cells while potentiating the hemolytic power of NV. This finding may suggest a key role of reactive oxygen species (ROS) in the cytotoxicity of NV. To the best of our knowledge, this is the first report that a hemolytic jellyfish venom acts through NHE in a manner other than compromising membrane integrity. The current work provides new insight into the arsenal of toxic jellyfishes.

The nematocysts venom of Chrysaora helvola Brandt leads to apoptosis-like cell death accompanied by uncoupling of oxidative phosphorylation.

The present work investigated the effects of the nematocysts venom (NV) from the Chrysaora helvola Brandt (C. helvola) jellyfish on the human nasopharyngeal carcinoma cell line, CNE-2. The medium lethal concentration (LC50), quantified by MTT assays, was 1.7 ± 0.53 µg/mL (n = 5). An atypical apoptosis-like cell death was confirmed by LDH release assay and Annexin V-FITC/PI staining-based flow cytometry. Interestingly, activation of caspase-4 other than caspase-3, -8, -9 and -1 was observed. Moreover, the NV stimuli caused a time-dependent loss of mitochondrial membrane potential (ΔΨm) as was an intracellular ROS burst. These results indicated that there was uncoupling of oxidative phosphorylation (UOP). An examination of the intracellular pH value by a pH-sensitive fluorescent probe, BCECF, suggested that the UOP was due to the time-dependent increase in the intracellular pH. This is the first report that jellyfish venom can induce UOP.

Apoptosis-like cell death induced by nematocyst venom from Chrysaora helvola Brandt jellyfish and an in vitro evaluation of commonly used antidotes.

The present work investigated the in vitro cytotoxicity of nematocyst venom (NV) from Chrysaora helvola Brandt (C. helvola) jellyfish against human MCF-7 and CNE-2 tumor cell lines. Potent cytotoxicity was quantified using the MTT assay (LC50=12.07±3.13 and 1.6±0.22µg/mL (n=4), respectively). Apoptosis-like cell death was further confirmed using the LDH release assay and Annexin V/PI double staining-based flow cytometry analysis. However, only activation of caspase-4 was observed. It is possible that some caspase-independent pathways were activated by the NV treatment. Since no reference or antivenom is available, the effects of several commonly used antidotes on the cytotoxicity of NV were examined on more sensitive CNE-2 cells to determine the appropriate emergency measures for envenomation by C. helvola. The phospholipase A2 (PLA2) inhibitor para-bromophenacyl bromide (pBPB) showed no protective effect, while Mg(2+) potentiated cytotoxicity. Voltage-gated L-type Ca(2+) channel blockers (verapamil, nifedipine and felodipine) and Na-Ca(2+) exchanger inhibitor KB-R7943 also showed no effect. Assays using Ca(2+)-free culture media or the intracellular Ca(2+) chelator BAPTA also could not inhibit the cytotoxicity. Taken together, these results suggest that PLA2 and Ca(2+) are not directly involved in the cytotoxicity of NV from C. helvola. Our work also suggests caution regarding the choice for first aid for envenomation by C. helvola jellyfish.

Saussurea involucrata: A review of the botany, phytochemistry and ethnopharmacology of a rare traditional herbal medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea involucrata Matsum. & Koidz. is an endangered species of the Asteraceae family, growing in the high mountains of central Asia. It has been, and is, widely used in traditional Uyghur, Mongolian and Kazakhstan medicine as well as in Traditional Chinese Medicine as Tianshan Snow Lotus (Chinese: ). In traditional medical theory, S. involucrata can promote blood circulation, thereby alleviating all symptoms associated with poor circulation. It also reputedly eliminates cold and dampness from the body, diminishes inflammation, invigorates, and strengthens Yin and Yang. It has long been used to treat rheumatoid arthritis, cough with cold, stomach ache, dysmenorrhea, and altitude sickness in Uyghur and Chinese medicine. AIM OF THE REVIEW: To comprehensively summarize the miscellaneous research that has been done regarding the botany, ethnopharmacology, phytochemistry, biological activity, and toxicology of S. involucrata. METHOD: An extensive review of the literature was carried out. Apart from different electronic databases including SciFinder, Chinese National Knowledge Infrastructure (CNKI), ScienceDirect that were sourced for information, abstracts, full-text articles and books written in English and Chinese, including those traditional records tracing back to the Qing Dynasty. Pharmacopoeia of China and other local herbal records in Uighur, Mongolian and Kazakhstan ethnomedicines were investigated and compared for pertinent information. RESULTS: The phytochemistry of S. involucrata has been comprehensively investigated. More than 70 compounds have been isolated and identified; they include phenylpropanoids, flavonoids, coumarins, lignans, sesquiterpenes, steroids, ceramides, polysaccharides. Scientific studies on the biological activity of S. involucrata are equally numerous. The herb has been shown to have anti-neoplastic, anti-inflammatory, analgesic, anti-oxidative, anti-fatigue, anti-aging, anti-hypoxic, neuroprotective and immunomodulating effects. Many have shown correlations to the traditional clinical applications in Traditional Chinese Medicine and medicines. The possible mechanisms of S. involucrata in treating various cancers are revealed in the article, these include inhibition of cancer cells by affecting their growth, adhesion, migration, aggregation and invasion, inhibition of epidermal growth factor receptor signaling in cancer cells, hindrance of cancer cell proliferation, causing cytotoxicity to cancer cells and promoting expression of tumor suppressor genes. Dosage efficacy is found to be generally concentration- and time-dependent. However, studies on the correlation between particular chemical constituents and specific bioactivities are limited. CONCLUSION: In this review, we have documented the existing traditional uses of S. involucrata and summarized recent research into the phytochemistry and pharmacology of S. involucrata. Many of the traditional uses have been validated by phytochemical and modern pharmacological studies but there are still some areas where the current knowledge could be improved. Although studies have confirmed that S. involucrata has a broad range of bioactivities, further in-depth studies on the exact bioactive molecules and the mechanism of action are expected. Whether we should use this herb independently or in combination deserves to be clarified. The exact quality control as well as the toxicology studies is necessary to guarantee the stability and safety of the clinic use. The sustainable use of this endangered resource was also addressed. In conclusion, this review was anticipated to highlight the importance of S. involucrata and provides some directions for the future development of this plant.

Binary chromatographic fingerprint analysis of stemonae radix from three Stemona plants and its applications.

The dried root tubers of Stemona tuberosa, S. japonica and S. sessilifolia are the original sources of Stemonae Radix (SR) for antitussive and insecticidal activities. The products of SR which are available on the market are variable, and imitations exist. In order to characterize the overall chemical constituents of SR and evaluate its quality, a novel, binary high-performance liquid chromatographic fingerprinting method, describing the pattern of alkaloids (fingerprint I) and non-alkaloids (fingerprint II) of SR was developed. It was also applied to determine whether the medicinal parts and the processing methods affect the quality of SR. Similarity and high-performance liquid chromatography-mass spectrometry (HPLC-MS(n)) were utilized to compare or identify the chemical constituents of SR. The results indicate that the chemical constituents from different parts of the underground material of Stemona plants are diverse and that the processing methods affect certain constituents in the root tuber samples. The similarity and the resulting chemical consitituents obtained show that the binary chromatographic fingerprint method can be used to differentiate the three official Stemona species or the adulterants of SR, which is helpful for the identification and quality evaluation of SR.