Panax notoginseng alleviates oxidative stress through miRNA regulations based on systems biology approach.

BACKGROUND: Herbal medicine Sanqi (SQ), the dried root or stem of Panax notoginseng (PNS), has been reported to have anti-diabetic and anti-obesity effects and is usually administered as a decoction for Chinese medicine. Alternative to utilizing PNS pure compound for treatment, we are motivated to propose an unconventional scheme to investigate the functions of PNS mixture. However, studies providing a detailed overview of the transcriptomics-based signaling network in response to PNS are seldom available. METHODS: To explore the reasoning of PNS in treating metabolic disorders such as insulin resistance, we implemented a systems biology-based approach with RNA sequencing (RNA-seq) and miRNA sequencing data to elucidate key pathways, genes and miRNAs involved. RESULTS: Functional enrichment analysis revealed PNS up-regulating oxidative stress-related pathways and down-regulating insulin and fatty acid metabolism. Superoxide dismutase 1 (SOD1), peroxiredoxin 1 (PRDX1), heme oxygenase-1 (Hmox1) and glutamate cysteine ligase (GCLc) mRNA and protein levels, as well as related miRNA levels, were measured in PNS treated rat pancreatic ß cells (INS-1). PNS treatment up-regulated Hmox1, SOD1 and GCLc expression while down-regulating miR-24-3p and miR-139-5p to suppress oxidative stress. Furthermore, we verified the novel interactions between miR-139-5p and miR-24-3p with GCLc and SOD1. CONCLUSION: This work has demonstrated the mechanism of how PNS regulates cellular molecules in metabolic disorders. Therefore, combining omics data with a systems biology strategy could be a practical means to explore the potential function and molecular mechanisms of Chinese herbal medicine in the treatment of metabolic disorders.

The Changing Global Landscape in the Development of Artemisinin-Based Treatments: A Clinical Trial Perspective.

Artemisinin and its derivatives (ARTs), due to their potent antimalarial activities, are widely used as frontline antimalarials across the world. Although the large-scale deployment of ARTs has significantly contributed to a substantial decline in malaria deaths, the global malaria burden is still high. New antimalarial treatments need to be developed to manage the growing artemisinin resistance. Understanding the status of ART development is crucial for developing strategies for new alternatives and identifying opportunities to develop ART-based treatments. This study sampled ART clinical trials from the past two decades to gain an overview of the global ART-development landscape. A total of 768 trials were collected to analyze the disease focuses, activity trends, development status, geographic distribution, and combination treatment profiles of ART trials. The findings highlighted the constant focus of ARTs on malaria, the evolving combination research focus, the distinctions between ART development preferences across global regions, the urgent demands for treatments for artemisinin-resistant malaria, and the unavoidable need to consider ART combinations in the development of new antimalarials.

A network pharmacology-based study on the quality control markers of antithrombotic herbs: Using Salvia miltiorrhiza - Ligusticum chuanxiong as an example.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza (Danshen, DS), the dried root and rhizome of Salvia miltiorrhiza Bunge and Ligusticum chuanxiong (Chuanxiong, CX), the dried rhizomes of Ligusticum striatum DC are effective in invigorating blood circulation and eliminating stasis which is highly related with cardiovascular disease (CVD). AIM OF STUDY: The identification of activity-based chemical markers is very important, but the complex mechanism of "multi-component, multi-target, and multi-effect" within traditional Chinese medicine (TCM) poses a great challenge to this work. In this study, we combined network pharmacological prediction with experimental validation of the DS and CX to explore an effective method for discovering quality control (QC) of antithrombotic herbs by clarifying the intermediate layer "module/cluster" between the whole complex system and a single component. MATERIALS AND METHODS: Based on structural similarity analysis of compound and the thrombosis network published before, we firstly modularized two layers called chemical cluster (CC) network and functional module (FM) network respectively and linked them into one bilayer modularized compound target (BMCT) network. "Two-step" calculation was applied on identifying the significant compounds as the potential QC markers from CC. The in vitro inhibitory activity of selected QC marker compounds on thrombin was evaluated to partially verify their pharmacological activities. HPLC was used to determine contents. RESULTS: According to the network-based analysis, nine compounds with great importance in the BMCT network were identified as QC markers of DS-CX, including tanshinone I, tanshinone IIA, cryptotanshinone, salvianolic acid B, ferulic acid, salvianolic acid A, rosmarinic acid, chlorogenic acid, and coniferyl ferulate. Enzyme inhibitory test partially verified the activity of tanshinone I and tanshinone IIA. Chemical profiling indicated that the nine marker compounds are the main components in the herbal pair. CONCLUSIONS: This study identified activity-based QC markers of DS-CX herbal pair and provided a new methodology that can be used in the QC of other herbs, herbal pairs, or formulas.

Enzyme Activity of Natural Products on Cytochrome P450.

Drug-metabolizing enzymes, particularly the cytochrome P450 (CYP450) monooxygenases, play a pivotal role in pharmacokinetics. CYP450 enzymes can be affected by various xenobiotic substrates, which will eventually be responsible for most metabolism-based herb-herb or herb-drug interactions, usually involving competition with another drug for the same enzyme binding site. Compounds from herbal or natural products are involved in many scenarios in the context of such interactions. These interactions are decisive both in drug discovery regarding the synergistic effects, and drug application regarding unwanted side effects. Herein, this review was conducted as a comprehensive compilation of the effects of herbal ingredients on CYP450 enzymes. Nearly 500 publications reporting botanicals' effects on CYP450s were collected and analyzed. The countries focusing on this topic were summarized, the identified herbal ingredients affecting enzyme activity of CYP450s, as well as methods identifying the inhibitory/inducing effects were reviewed. Inhibitory effects of botanicals on CYP450 enzymes may contribute to synergistic effects, such as herbal formulae/prescriptions, or lead to therapeutic failure, or even increase concentrations of conventional medicines causing serious adverse events. Conducting this review may help in metabolism-based drug combination discovery, and in the evaluation of the safety profile of natural products used therapeutically.

Molecular evidence of herbal formula: a network-based analysis of Si-Wu decoction.

INTRODUCTION: Emerging network pharmacology (NP) combines phytochemical information with bioinformatics tools allowing herbal formulae to be illustrated holistically in the context of phytochemical basis and therapeutic mechanisms. OBJECTIVE: This study attempted to explore the holistic molecular evidence of herbal formula Si-Wu decoction (SWD) by using the method of NP. MATERIAL AND METHOD: Databases of traditional medicines combined with PubChem, SciFinder, SEA, STRING, and KEGG were employed to gather information for establishing the "compound similarity" (CS) network and the "target-(pathway)-target" (TPT) network. Gephi software was applied to visualise the networks, with further module-based and node-based network topological analysis. Moreover, the approved drugs and shortest path analysis were used to validate the TPT network. RESULTS: The CS network presented the phytochemical profile of SWD, including the major compound groups of iridoid glycosides, glycosides, phthalide lactones, phenylpropanoids, and monoterpenoids. Furthermore, the topological analysis of TPT network depicted the holistic property of SWD in interpretable neuroendocrine immunomodulation (NIM) perspective, and the node degree analysis indicated a closer connection of SWD with endocrine or metabolism system. Moreover, by combing the analysis of the CS network and TPT network, potential active ingredients could be primarily identified. CONCLUSION: The phytochemical profile and molecular target profile, which might pave the way for an understanding of SWD in modern science and provide a reference for relevant quality research and evaluation, were demonstrated by network analysis. Moreover, the methods could be further applied to discover the phytochemical or biomolecular evidence with distinct advantages in dealing with the tremendous separated information.

Interactions of antithrombotic herbal medicines with Western cardiovascular drugs.

Thrombotic events act as a critical factor that interferes with Cardiovascular Diseases (CVDs), and antithrombotic herbal medicine is a long-standing controversial issue. Although a dispute is involved in their clinical application, all parties unanimously agree that herbal products have been widely used in folk medicine, and their interactions with conventional drugs are of high concern. This study aims to investigate how antithrombotic herbal medicines interact with Western cardiovascular drugs on the molecular level by taking an example of the most frequently used herbal pair, Danshen-Chuanxiong (DS-CX), and to discover more scientific evidence on their potential herb-drug interactions. Network pharmacology (NP), as an analytical approach of a complex system, is used to visualize and compare target profiles of DS-CX and Western cardiovascular drugs, which can be applied to predict common herb-drug targets and to construct a solid context for discussing herb-drug interactions. These interactions are further validated by in vitro assays, while in vivo zebrafish model employed for evaluating an overall pharmacological efficacy of herbal pairs in specific combination ratios. The study finds that DS could react directly to the Western cardiovascular drug targets relevant to antithrombotic pathways (i.e., thrombin, coagulation factor Xa and cyclooxygenase-1), whereas CX could not react directly and can synergistically affect antithrombotic effects with DS in specific combination ratios. Moreover, it is indicated that DS-CX may generate wide biological functions by a complicated mechanism of "neuro-immune-metabolism/endocrine" (NIM), which can further cause multiple direct and indirect interactions with Western cardiovascular drugs. From the clinical perspective, herb-drug interactions should be given high attention, especially when multiple herbs are used simultaneously.

Preparative gas chromatography and its applications.

Although hundreds of papers related to preparative gas chromatography (pGC) have been published since the late 1950s, the success of the GC technique has largely been associated with analytical instead of preparative purposes. Actually, pGC is an ideal alternative technique for the preparation of pure substances, especially volatile compounds. This paper reviews the papers (written in English) associated with pGC published over the period from the 1950s to the 2010s. For large scale preparation, large sample injection and vaporization, a high loading capacity column, a gas splitter at the end of the column and a special collecting device are fundamentally important for a pGC system. The primary components of pGC system, including injector, column, splitter, detector and collection traps, are briefly introduced. Furthermore, the applications of pGC in the separation and purification of volatile compounds from natural essential oils, in addition to the purification of isotopes, isomers and enantiomers are summarized.

Applications of biochromatography in the screening of bioactive natural products.

Searching for bioactive compounds from natural resources such as plant materials has become a focus for study. Several models, such as animal (biofluid, organ and tissue) and cellular (several kinds of cell lines), have traditionally been used for this purpose. As a fast, economic and effective way to identify or predict bioactive compounds in complex matrices, biochromatography has developed rapidly during the past years. Combing the properties of traditional chromatography and biomaterials, biochromatographic analysis possesses features of simultaneous screening, separation and structural identification for active compounds in a complex matrix. According to the process, biochromatography can be divided into offline and online approaches. For offline bioextraction, the biomaterials are used as the extraction phase and followed by routine chromatographic analysis. For online biochromatography, the biomaterials are directly used as the stationary phase for chromatographic analysis. This paper reviews the applications of offline bioextraction followed by chromatographic analysis and online biochromatography, including molecular, cell membrane and cell, and artificial biomembrane chromatography in the screening or predicting active compounds from natural sources.

Simultaneous determination of α-, ß- and γ-asarone in Acorus tatarinowii by microemulsion electrokinetic chromatography with [BMIM]PF6 as oil phase.

In the present study, a rapid and repeatable microemulsion electrokinetic chromatography (MEEKC) method was developed for the simultaneous determination of three isomers (α-, ß- and γ-asarone) in Acorus tatarinowii by using ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM]PF(6)) as oil phase. Experimental parameters including the microemulsion compositions (concentrations of surfactant, co-surfactant and oil phase), pH, concentration of borate buffer, capillary temperature and voltage were intensively investigated. Finally, the main compounds in the methanol extract of A. tatarinowii were well separated within 11 min using a running buffer composed of 40 mmol/L sodium dodecyl sulfonate (SDS), 2.0 mol/L n-propanol, 8 mmol/L [BMIM]PF(6) in 10 mmol/L borate buffer of pH 9.5. The developed method was applied to determine the contents of α-, ß- and γ-asarone in A. tatarinowii from five different producing areas in China (Anhui, Hebei, Sichuan, Zhejiang and Chongqing). The results indicated that the contents of three asarones are quite different in the investigated A. tatarinowii samples. On the other hand, the MEEKC with ionic liquid as oil phase should be a promising method for the analysis of volatile components especially isomers in medicinal herbs.