A comprehensive review on traditional and modern research of the genus Bupleurum (Bupleurum L., Apiaceae) in recent 10 years.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Bupleurum (family Apiaceae), comprising approximately 248 accepted species, is widely distributed and used in China, Japan, India, Central Asia, North Africa and some European countries as traditional herbal medicines. Certain species have been reported to have significant therapeutic effects in fever, inflammatory disorders, cancer, gastric ulcer, virus infection and other diseases. AIM OF THE REVIEW: we performed a comprehensive review of the ten-year research progress in phytochemistry, pharmacology, toxicity, along with bibliometrics research of the genus Bupleurum, aiming to identify knowledge gaps for future research. MATERIALS AND METHODS: All the literatures are retrieved from library and electronic sources including Web of Science, PubMed, Elsevier, Google Scholar, CNKI and Baidu Scholar. These papers cover studies of the traditional use, phytochemistry, pharmacology, and toxicology of the genus Bupleurum. RESULTS: There is a long history of using the genus Bupleurum in traditional herbal medicine that dated back to over 2000 years ago. Twenty-five species and 8 varieties with 3 variants within this genus have been reported to be effective to treat fever, pain, liver disease, inflammation, thoracolumbar pain, irregular menstruation and rectal prolapse. The main phytochemicals found in these plants are triterpene saponins, volatile oil, flavonoid, lignans, and polysaccharides. Many of these compounds have also been shown to have anti-inflammatory, anti-tumor, antimicrobial, immunoregulation, neuroregulation, hepatoprotective and antidiabetic activities. Meanwhile, improper usage of Bupleurum may induce cytotoxic effects, and polyacetylenes may be the main poisonous compounds. CONCLUSIONS: This article summarized recent findings about Bupleurum research from many different aspects. While a small number of Bupleurum species have been investigated through modern pharmacology methods, there are still major knowledge gaps due to inadequate studies and ambiguous findings. Future research could focus on more specific phytochemistry studies combined with mechanistic analysis to provide better guidance to utilize Bupleurum as medicinal resources.

Lidocaine alleviates inflammation and pruritus in atopic dermatitis by blocking different population of sensory neurons.

BACKGROUND AND PURPOSE: Atopic dermatitis is a common chronic pruritic inflammatory disease of the skin involving neuro-immune communication. Neuronal mechanism-based therapeutic treatments remain lacking. We investigated the efficacy of intravenous lidocaine therapy on atopic dermatitis and the underlying neuro-immune mechanism. EXPERIMENTAL APPROACH: Pharmacological intervention, immunofluorescence, RNA-sequencing, genetic modification and immunoassay were performed to dissect the neuro-immune basis of itch and inflammation in atopic dermatitis-like mouse model and in patients. KEY RESULTS: Lidocaine alleviated skin lesions and itch in both atopic dermatitis patients and calcipotriol (MC903)-induced atopic dermatitis model by blocking subpopulation of sensory neurons. QX-314, a charged NaV blocker that enters through pathologically activated large-pore ion channels and selectivity inhibits a subpopulation of sensory neurons, has the same effects as lidocaine in atopic dermatitis model. Genetic silencing NaV 1.8-expressing sensory neurons was sufficient to restrict cutaneous inflammation and itch in the atopic dermatitis model. However, pharmacological blockade of TRPV1-positive nociceptors only abolished persistent itch but did not affect skin inflammation in the atopic dermatitis model, indicating a difference between sensory neuronal modulation of skin inflammation and itch. Inhibition of activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons by lidocaine largely accounts for the therapeutic effect of lidocaine in the atopic dermatitis model. CONCLUSION AND IMPLICATIONS: NaV 1.8+ sensory neurons play a critical role in pathogenesis of atopic dermatitis and lidocaine is a potential anti-inflammatory and anti-pruritic agent for atopic dermatitis. A dissociable difference for sensory neuronal modulation of skin inflammation and itch contributes to further understanding of pathogenesis in atopic dermatitis.

Quantitative analysis of multi-components by single marker method combined with UPLC-PAD fingerprint analysis based on saikosaponin for discrimination of Bupleuri Radix according to geographical origin.

Background: Saikosaponins are regarded as one of the most likely antipyretic constituents of Bupleuri Radix, establishing a comprehensive method that can reflect both the proportion of all constituents and the content of each saikosaponin is critical for its quality evaluation. Methods: In this study, the combination method of quantitative analysis of multiple components with a single marker (QAMS) and fingerprint was firstly established for simultaneous determination of 7 kinds of saikosaponins in Bupleuri Radix by ultra-high performance liquid chromatography (UPLC). Results: The results showed that saikosaponin d was identified as the optimum IR by evaluating the fluctuations and stability of the relative calibration factors (RCFs) under four different conditions. The new QAMS method has been confirmed to accurately quantify the 7 kinds of saikosaponins by comparing the obtained results with those obtained from external standard method and successfully classify the 20 batches of Bupleuri Radix from 8 provinces of China. The experimental time of fingerprint was significantly reduced to approximate 0.5 h through UPLC-PAD method, a total of 17 common peaks were identified. Conclusion: The QAMS-fingerprint method is feasible and reliable for the quality evaluation of Bupleuri Radix. This method could be considered to be spread in the production enterprises of Bupleuri Radix.

Free-electrodeposited anodic stripping voltammetry sensing of Cu(II) based on Ti3C2Tx MXene/carbon black.

A proof-of-principle concept for free-electrodeposited anodic stripping voltammetry (ASV) sensing of Cu2+ is proposed by using Ti3C2Tx MXene/carbon black (Ti3C2Tx@CB) nanohybrids as electrode materials. Owing to the high adsorption and reduction capability of Ti3C2Tx towards Cu2+, Ti3C2Tx MXene enables Cu2+ to be immobilized and self-reduced directly to form Cu0 on the Ti3C2Tx@CB electrode surface. As a result an oxidation peak current appears from the re-oxidation of Cu0 via differential pulse voltammetry. Carbon black (CB) was introduced to prevent Ti3C2Tx Mxene aggregation and improve the related electron transfer as well as enhance their surface area. After optimizing various conditions, a considerable low limit of detection (4.6 nM) and a wide linear range (0.01-15.0 µM) for Cu2+ were achieved at the working potential from - 0.3 V to 0.0 V (vs SCE). Relative standard deviation (RSD) of eight individual Ti3C2Tx@CB electrodes is 3.72%, and the recoveries from tap water sample and lake water sample were in the ranges of 97.0-108% and 104-107%, respectively.

Novel methodology for anodic stripping voltammetric sensing of heavy-metal ions using Ti3C2Tx nanoribbons.

Conventional anodic stripping voltammetry (ASV) sensing of heavy-metal ions (HMIs) generally includes a two-step approach: (a) preconcentration via electrodeposition and (b) re-oxidation, while the requirement of the electrodeposition step makes the detection processes more complex. Herein, a novel methodology using self-reduction instead of electrodeposition was developed for the ASV sensing of HMIs (selecting Cd2+ as a representative analyte) by introducing Ti3C2Tx MXene nanoribbons (Ti3C2Tx NR) as a sensing element that can exhibit direct adsorption and reduction capabilities towards HMIs. Compared with conventional ASV technology, the proposed methodology is simpler and power-saving, and has a significant low detection limit (0.94 nM) and wide linear range (0.005-3.0 µM).

Dual-Signal Electrochemical Enantiospecific Recognition System via Competitive Supramolecular Host-Guest Interactions: The Case of Phenylalanine.

For developing highly selective and sensitive electrochemical sensors for chiral recognition, taking advantage of the synthetical properties of ß-cyclodextrin (ß-CD, strong host-guest recognition) and carbon nanotubes wrapped with reduced graphene oxide (CNTs@rGO, excellent electrochemical property and large surface area), as well as the differences in binding affinity between ß-CD and guest molecules, a dual signal electrochemical sensing strategy was proposed herein for the first time in chiral recognition based on the competitive host-guest interaction between probe and chiral isomers with ß-CD/CNTs@rGO. As a model system, rhodamine B (RhB) and phenylalanine enantiomers (d- and l-Phe) were introduced as probe and target enantiomers, respectively. Due to the host-guest interactions, RhB can enter into the ß-CD cavity, showing remarkable oxidation peak current of RhB. In the presence of l-Phe, competitive interaction with the ß-CD cavity occurs and RhB are replaced by l-Phe owing to the stronger binding affinity between l-Phe and ß-CD, which results in the peak current of RhB decreasing and the peak current of l-Phe appears, and interestingly, the changes of both signals linearly correlate with the concentration of l-Phe. As for d-Phe, it cannot replace RhB owing to the weaker binding affinity between d-Phe and ß-CD. Based on this, a dual-signal electrochemical sensor was developed successfully for recognizing Phe. This dual-signal sensing strategy can provide highly selective and sensitive recognition compared to single-signal sensor and has important potential applications in chiral recognition.

Reactivity of (1-methoxycarbonylpentadienyl)iron(1+) cations with hydride, methyl, and nitrogen nucleophiles.

The reaction of tricarbonyl and (dicarbonyl)triphenylphosphine (1-methoxycarbonyl-pentadientyl)iron(1+) cations 7 and 8 with methyl lithium, NaBH3CN, or potassium phthalimide affords (pentenediyl)iron complexes 9a-c and 11a-b, while reaction with dimethylcuprate, gave (E,Z-diene)iron complexes 10 and 12. Oxidatively induced-reductive elimination of 9a-c gave vinylcyclopropanecarboxylates 17a-c. The optically active vinylcyclopropane (+)-17a, prepared from (1S)-7, undergoes olefin cross-metathesis with excess (+)-18 to yield (+)-19, a C9-C16 synthon for the antifungal agent ambruticin. Alternatively reaction of 7 with methanesulfonamide or trimethylsilylazide gave (E,E-diene)iron complexes 14d and e. Huisgen [3+2] cyclization of the (azidodienyl)iron complex 14e with alkynes afforded triazoles 25a-e.

De Novo Asymmetric Synthesis of (+)-Monanchorin.

A de novo asymmetric total synthesis of the guanidine alkaloid natural product (+)-monanchorin has been achieved in nine steps from the commodity chemicals furan and caproic acid. The asymmetry of the route was introduced by a Noyori reduction of an acylfuran. In addition, this route relies upon an Achmatowicz rearrangement, a diastereoselective palladium catalyzed glycosylation, reductive amination, and an acid catalyzed bicyclic guanidine mixed acetal formation.

Identification and characterization of the first Escherichia coli strain carrying NDM-1 gene in China.

New Delhi metallo-ß-lactamase-1 (NDM-1), an acquired class B carbapenemase, is a significant clinical threat due to its extended hydrolysis of ß-lactams including carbapenems. In this study, we identified the first confirmed clinical isolate of Escherichia coli BJ01 harboring bla(NDM-1) in China. The isolate is highly resistant to all tested antimicrobials except polymyxin. bla(NDM-1), bla(CTX-M-57), and bla TEM-1 were identified in the isolate. bla(NDM-1) was transferable to E. coli EC600 and DH5α in both plasmid conjugation experiments and plasmid transformation tests. BJ01 was identified as a new sequence type, ST224, by multilocus sequence typing. Analysis of genetic environment shows complex transposon-like structures surrounding the bla NDM-1 gene. Genetic analysis revealed that the region flanking bla(NDM-1) was very similar to previously identified NDM-positive Acinetobacter spp. isolated in China. The findings of this study raise attention to the emergence and spread of NDM-1-carrying Enterobacteriaceae in China.

Cationic metal-corrole complexes: design, synthesis, and properties of guanine-quadruplex stabilizers.

A series of pyridinium and quaternary ammonium copper corroles has been designed and synthesized. All new compounds have been fully characterized by NMR spectroscopy, high-resolution mass spectrometry, UV/Vis spectrscopy, and elemental analysis. Biochemical studies have indicated that all of these corrole derivatives can stabilize G-quadruplex structures, with corrole 4 being the most effective according to the results of circular dichroism (CD) melting experiments, polymerase chain reaction (PCR) stop assays, and surface plasmon resonance (SPR) experiments. Moreover, both corroles 3 and 4 tend to induce the human telomeric sequence to form hybrid G-quadruplex structures, whereas corroles 8 and 9 are more inclined to induce the human telomeric sequence to form antiparallel G-quadruplex structures.