Search

[Display omitted] • PVC-diphenylamine modified cellulose was proposed as sorptive phase. • The synthesis, using the dip-coating technique, is simple and cost-effective. • Opioids interact with the membrane by a mixed-mode interaction. • Direct infusion mass spectrometry allows to reduce the time of analysis. • The approach was successfully applied to real saliva samples containing codeine and tramadol. This article evaluates the potential of cellulose paper as a substrate for preparing a polyvinylchloride (PVC)-diphenylamine sorptive phase that can be used under the thin film microextraction (TFME) format. This phase was easily synthesized using the dip-coating technique to coat the filter paper with PVC, followed by the covalent bonding of diphenylamine. As a result, aromatics rings are available on paper surface to isolate the target analytes by a mixed-mode interaction at physiological pH. The resulting material was characterized by infrared spectroscopy, UV–Vis diffuse reflection spectroscopy, and scanning electron microscopy. As analytical problem, three opioids (methadone, codeine, and tramadol) were determined in saliva samples by direct infusion mass spectrometry. Different variables involved in the extraction procedure have been optimized (e.g. sample pH, extraction time, and sample dilution). The proposed method provides good linearity (R2 > 0.9817) and sensitivity (detection limits in the range from 1.5 µg L−1 to 15 µg L−1). The intra-day and inter-day precision, expressed as relative standard deviation, were better than 16.4 % and 18.5 % respectively. The accuracy, expressed as relative recovery, provides values in the interval from 82 % to 105 %. Finally, the proposed approach has been successfully applied to real saliva samples of patients under codeine and tramadol medical prescription. [ABSTRACT FROM AUTHOR]

Highlights • Quantitative determination of methylxanthines alkaloids in cocoa products. • Paper Spray mass spectrometry for analytical assay. • Comparison of obtained data with HPLC/UV method. Abstract A fast method for the determination of methylxanthines in cocoa products and drugs based on PS-MS/MS under MRM condition has been developed. Analyte ions were generated by applying a high voltage on a paper substrate drenched of sample extract using a small volume (∼15 μL) of spray solvent. The gas phase chemistry of the molecules under investigation has been elucidated. The accuracy values of the methodology ranged from 95 to 110%, while the analytical parameters LOQ, LOD, recovery and reproducibility, calculated analyzing spiked samples, confirmed the consistency of the proposed method. Furthermore, real samples have been analyzed both by the developed methodology and by using a classical HPLC-UV approach obtaining comparable values. [ABSTRACT FROM AUTHOR]

Representation of mass spectrometry analysis with paper spray ionization using different solvents in araticum samples. [Display omitted] • Different araticum fruit parts were evaluated for their chemical profile. • Three solvents were tested; • The fruit, in general, is composed of acetogenins and alkaloids; • The ethanol solvent extracted a more significant number of compounds; • The global evaluation showed that the samples are grouped by the part of the fruit studied regardless of the solvent. The Brazilian cerrado is considered one of the most critical biomes in the world. Araticum (Annona crassiflora Mart.) is a native plant from the Brazilian cerrado, abundant in nutrients and highly energetic. This study aimed to obtain chemical fingerprints of different parts of the araticum fruit, i.e. pulp, peel, and seed. Extracts from these three parts were prepared using different solvents (ethanol, water, and mixtures of ethanol and water) and later analyzed by paper spray ionization mass spectrometry. In general, ethanol extracted more metabolites than the other solvents. The chemical profiles varied according to the fruit part, geographic location, and extractor solvent. Among the metabolites, acetogenins (62.3%) and alkaloids (20.7%) predominated. Principal component analyses revealed that the samples were grouped according to the fruit part, regardless of the extractor solvent used. Araticum shows remarkable potential due to the beneficial properties of the metabolites for human health. The insertion of araticum in the human diet is still underexplored but is a promising alternative. [ABSTRACT FROM AUTHOR]

Abstract: We have corrected (Tetrahedron 2013, 69, 5859–5866) the structures of diterpenoid alkaloids reported in the Journal of Natural Products 2012, 75, 1145–1159. Our follow-up experiments compel us to present further revisions and clarifications on the diterpenoid alkaloids: (1) The naturally occurring forms of carmichaelines B, C, and D in Shi's paper (Journal of Natural Products 2012, 75, 1145–1159) are neither quaternary ammonium hydroxides 2–4 nor the initially revised trifluoroacetates. They are indeed the vakognavine-type C20-diterpenoid alkaloids 11–13. (2) The samples' concentration is the critical factor to the signals' intensity for F3CCOO− in the alkaloid trifluoroacetates. Incorporation of TFA into the corresponding salts resulted in signals' enhancement due to the closeness of δ values (∼116 ppm, ∼159 ppm) of free TFA and those of F3CCOO−. After removal of free TFA, the carbon signals of CF3COO− could become weaker, but their chemical shifts remained almost unchanged. The possible reason might be the ionization of TFA in acetone. (3) The NMR data cannot distinguish TFA from trifluoroacetates (e.g., F3CCOONa and C19-diterpenoid alkaloid trifluoroacetates), indicating that the signal at around δ −76 cannot be used to exclude the existence of trifluoroacetates. In addition to the NMR and CSI-MS data, 1H–15N HMBC technique was also used to distinguish the free alkaloids from their trifluoroacetates. (4) The X-ray crystallographic analysis of compound 20 confirmed that the ‘new alkaloid’ (-b) in the Shi's paper is indeed the known compound aconifine trifluoroacetate. (5) Collectively, Shi's paper mixed-up the free alkaloids with their salts and the concepts of structure and conformation. Naming different structures with A-b and A-c is also confusing. [Copyright &y& Elsevier]

Abstract: Eleven C19-diterpenoid alkaloids reported in Shi's paper were isolated or synthesized. Their 13C NMR and DEPT spectra were recorded using (CD3)2CO+TFA as solvents. Comparison of the acquired NMR data with those reported in Shi's paper, in combination with the fact that all alkaloids, expect for 8, 27, and 28, reported in Shi's paper were isolated using TFA as part of solvent system, led to the following revisions of Shi's paper: (1) compounds 1–4, 6, 7a, 9–26 should be their respective trifluoroacetates. Their structures were revised as 1a–4a, 6a, 7a′, 9a–26a; (2) compounds 7, 27a, and 28a are trifluoroacetates of free bases 8, 27, and 28, respectively; compound 7 should be corrected as 7b; (3) ring A of free bases (such as 8, 27, and 28) exists as chair conformation; while ring A of the protonated versions (such as 7, 27a, 28a, 6a, 9a–26a) exists as boat conformation. Consequently, compounds 7 and 8 are apparently not a pair of conformational isomers, instead, they are indeed a free base and its protonated version existing as a trifluoroacetate, respectively; (4) ‘new’ compounds 6, 13, and 15 are the protonated versions 6a, 13a, and 15a, respectively, of the corresponding known alkaloids, aconifine, deoxyaconitine, 14-benzoylaconine. In addition, all 1H (13C) NMR data for the free bases of new compounds 8, 9, 10, 17, and 24 (Tables 3 and 4) were also assigned based on their 2D NMR spectra. [Copyright &y& Elsevier]

Natural and synthetic alkaloids are widely used for several applications, ranging from clinical purposes to criminal activities. Presumptive color tests are considered a leading tool to reveal on-scene substance identification via rapid chemical reactions that result in visual color changes. Colorimetric tests are popular due to their inherent simplicity, low cost, promptitude and portability; however, in many cases the results of such tests may not be predictable, partly because of the interference from similar species. In this proof-of-concept study, we present a paper-based microfluidic optoelectronic tongue – the so-called μOPTO – comprised of 6 indicators in lieu of one specific test and capable of discriminating 8 different alkaloid drugs (i.e. scopolamine, atropine, cocaine, morphine, ephedrine, caffeine, dipyrone and alprazolam) used for recreational, criminal and medical purposes. The wax printing method was employed to fabricate the microfluidic analytical device with six circular spots for reagent accommodation connected to a centered spot to enable simultaneous reactions with one sample injection. Digital images were obtained using an ordinary flatbed scanner, and the RGB information from before and after sample exposure was extracted using appropriate software. The color changes related to each spot were used to build differential maps with a unique fingerprint for each drug. The chemometric tools (i.e. PCA and HCA) showed suitable discrimination of all studied alkaloids in different quantities. To demonstrate a practical application, different alcoholic beverages spiked with scopolamine – a famous substance that causes drug abuse – were analyzed using the optoelectronic tongue. The results showed that small quantities of the drug were identified in different beverages, demonstrating that our device has the potential to be used in situ to prevent ingestion of contaminated samples. [Display omitted] • A microfluidic paper-based optoelectronic tongue for the discrimination of eight alkaloids is presented. • The array was comprised of 6 chemoresponsive reagents. • The color change after reaction enabled the creation of a unique fingerprint for each alkaloid. • Chemometric tools allowed useful discrimination of the drugs. • The μOPTO was applied to identify contaminated alcoholic beverages. [ABSTRACT FROM AUTHOR]

This paper explores the potential of flavonoid alkaloids, a unique class of compounds that contain both flavonoid and alkaloid structures, as emerging targets for drug discovery. These compounds exhibit diverse biological activities, such as anti-inflammatory, anti-cancer, and anti-diabetic effects, which are attributed to the combination of different flavonoid scaffolds and alkaloid groups. Flavonoid alkaloids have attracted researchers' attention due to their diverse structures and important bio-activities. Therefore, this review summarizes recent advances in the extraction, purification, structural characterization, synthesis pathways and biological activities of flavonoid alkaloids from natural sources. Finally, the potential prospects and challenges associated with this class of compounds in pharmacological research are discussed along with details of a mechanistic investigation and future clinical applications in this research field. This paper explores the potential of flavonoid alkaloids, a unique class of compounds that contain both flavonoid and alkaloid structures, as emerging targets for drug discovery. [Display omitted] [ABSTRACT FROM AUTHOR]

• At least 109 families and 481 tropical species alkaloids-containing were studied. • More than 3000 patents for tropical plant alkaloids have been filed over 20 years. • Pathway elucidation is the principal bottleneck in biosynthesis engineering. • Alkaloid content has been modified by genetic engineering. • Use of elicitors promote higher concentration of different classes of alkaloids. Alkaloids are compounds with wide occurrence in plant species and have been used for thousands of years for medicinal purposes. Industries demand high amounts of these metabolites and their improved production has been achieved due to recent advances in biotechnological techniques. In order to verify the scenario of studies and innovation in alkaloids occurring in tropical species, we surveyed in the Scopus and Espacenet databases, all research papers and patents on this theme. Our survey highlighted that at least 109 families and 481 tropical species were examined for the presence of alkaloids in the last 24 years. In addition, we found that approximately 3,400 patents have been filed in the last 20 years. However, contributions from tropical countries are lower than those from countries outside the region. Finally, we highlight the effort within the most varied biotechnological approaches that have been used to produce and increase the concentration of alkaloids in tropical plants. Although many advances have been made in recent years, challenges such as elucidating pathways in different species, adapting new techniques, discovering new expression vectors with greater compatibility, and elicitation studies for the production of alkaloids in tropical plants still need to be resolved and discussed by the scientific community. [ABSTRACT FROM AUTHOR]

Pandan (Pandanus amaryllifolius Roxb.), a member of the Pandanaceae family, has been consumed as food and medicine since ancient times. The current paper provides an overview of the botanical profile, phytochemistry, pharmacology, and applications of P. amaryllifolius. Information regarding P. amaryllifolius was collected from online sources (using PubMed, Science Direct, Google Scholar, Web of Science, ACS, and CNKI) as well as traditional textbooks. Over 100 compounds have been identified, including its characteristic components 2-Acetyl-1-pyrroline and Pandanus alkaloids. Several therapeutic uses of P. amaryllifolius , such as antioxidant, hypoglycemic, antimicrobial, and antitumor activities, have been demonstrated in modern pharmacological studies. Additionally, it could be applied in various fields, including food, energy, material, and the environment. Continued research on P. amaryllifolius can contribute to the development of new drugs and therapies for various diseases. And further studies are needed to improve its utilization. [Display omitted] [ABSTRACT FROM AUTHOR]

Pepper sprays of the OC type constitute the majority of self-defense sprays available on the market. The active ingredient in these preparations is pepper extract: Oleoresin Capsicum, which contains capsaicinoids - natural compounds with irritant properties. Preparations from OC pepper sprays can be distinguished based on differences in the quantitative ratios of four main capsaicinoids: capsaicin, dihydrocapsaicin, nordihydrocapsaicin, and nonivamide. This raises the question whether information on the quantitative ratios of capsaicinoids can also provide answers to questions regarding comparisons of traces of OC preparations, such as whether traces revealed on the clothing of the victim could originate from an OC spray secured from the suspect, or whether traces on the clothing of the suspect and the victim could come from the same pepper spray. Such comparisons would be viable only if the capsaicinoid profile remained unchanged during evidence storage and as a result of solvent extraction from the tested material. The aim of the presented research was to determine if this is indeed the case. Model aging experiments were conducted to examine whether the capsaicinoid profile in traces of OC preparations changed over time and whether solvent extraction affected this profile. Samples of five different OC preparations were applied to cotton swabs, which, after the evaporation of volatile solvents, were placed in three types of packaging with varying levels of tightness and transparency (tight amber vials, polyethylene bags, paper envelopes). These prepared samples underwent solvent extraction with methanol and analysis using gas chromatography – mass spectrometry, after 28, 84, 147, 196, 252, and 301 days from preparation. The likelihood ratio (LR) was applied as a statistical tool to investigate the data obtained. The LR model was computed using the three variables based on the relative content of nordihydrocapsaicin, nonivamide, and dihydrocapsaicin. The cotton swabs used in the experiments served as a model for both the swabs used by the police for securing liquid evidence and the cotton clothing of individuals sprayed with OC pepper sprays. The findings of the conducted studies suggest that the quantitative relationships of capsaicinoids indeed change over time, both in preparations stored in original containers and in traces of these preparations present on clothing. For traces of OC preparations secured on swabs or present on clothing, these changes are more significant the longer the sample is stored and the less airtight the packaging used. [Display omitted] • Pepper sprays differ in the quantitative ratios of capsaicinoids. • The capsaicinoid profile in traces, e.g., on clothing, changes over time. • Changes depend on the storage duration and packaging method of the samples. • Changes are more significant with longer storage time and less airtight packaging. • Comparing capsaicinoid profiles in traces and preparations is not advisable. [ABSTRACT FROM AUTHOR]

In this paper, the interaction of three berberine mid-chain fatty acid salts ([BBR][FAs]), viz. berberine caproate ([BBR][CAP]), berberine heptylate ([BBR][HEP]) and berberine octoate ([BBR][OCT]), with bovine serum albumin (BSA) was studied by means of UV–visible absorption spectroscopy, fluorescence spectroscopy, fourier transform infrared spectroscopy (FT-IR) and molecular docking techniques. Fluorescence experiments revealed that three berberine salts quench the fluorescence of BSA by static quenching mechanism resulted from a stable [BBR][FAs]-BSA complex formation. The stoichiometric numbers of [BBR][FAs]-BSA complexes were found to be 1:1. Synchronous and three-dimensional fluorescence spectra as well as FT-IR demonstrated that the binding of [BBR][FAs] altered the microenvironment and conformation of BSA. The binding average distance from [BBR][FAs] to BSA (3.2–3.5 nm) was determined according to Förster energy transfer theory. Site probe investigation showed that [BBR][FAs] bound to BSA active site I (sub-domain IIA). The binding promotes the esterase-like activity of BSA. The molecular docking results confirmed the fluorescence competition findings and provided the type of binding forces. Furthermore, the relationship between the anionic chain length of [BBR][FAs] and the interaction was explored, and the positive correlation was found. • Interaction of three berberine mid-chain fatty acid salts with BSA results in a 1:1 complex. • [BBR][FAs] quenches the fluorescence of BSA through static quenching mechanism. • [BBR][FAs] binds to BSA at Sudlow site I mainly through hydrogen bonding and van der Waals force. • [BBR][FAs] exerted a mixed inhibition against the esterase-like activity of BSA. • The anionic chain length is positively correlated with the intensity of interaction of [BBR][FAs] with BSA. [ABSTRACT FROM AUTHOR]

In this paper, the interaction of three berberine mid-chain fatty acid salts ([BBR][FAs]), viz. berberine caproate ([BBR][CAP]), berberine heptylate ([BBR][HEP]) and berberine octoate ([BBR][OCT]), with bovine serum albumin (BSA) was studied by means of UV–visible absorption spectroscopy, fluorescence spectroscopy, fourier transform infrared spectroscopy (FT-IR) and molecular docking techniques. Fluorescence experiments revealed that three berberine salts quench the fluorescence of BSA by static quenching mechanism resulted from a stable [BBR][FAs]-BSA complex formation. The stoichiometric numbers of [BBR][FAs]-BSA complexes were found to be 1:1. Synchronous and three-dimensional fluorescence spectra as well as FT-IR demonstrated that the binding of [BBR][FAs] altered the microenvironment and conformation of BSA. The binding average distance from [BBR][FAs] to BSA (3.2–3.5 nm) was determined according to Förster energy transfer theory. Site probe investigation showed that [BBR][FAs] bound to BSA active site I (sub-domain IIA). The binding promotes the esterase-like activity of BSA. The molecular docking results confirmed the fluorescence competition findings and provided the type of binding forces. Furthermore, the relationship between the anionic chain length of [BBR][FAs] and the interaction was explored, and the positive correlation was found. • Interaction of three berberine mid-chain fatty acid salts with BSA results in a 1:1 complex. • [BBR][FAs] quenches the fluorescence of BSA through static quenching mechanism. • [BBR][FAs] binds to BSA at Sudlow site I mainly through hydrogen bonding and van der Waals force. • [BBR][FAs] exerted a mixed inhibition against the esterase-like activity of BSA. • The anionic chain length is positively correlated with the intensity of interaction of [BBR][FAs] with BSA. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cutting-edge mass spectrometry as the cornerstone for pyrrolizidine alkaloid analysis in complex samples. • Innovative analytical strategies reshaping PAs analysis are presented. • Different applications of PAs containing related samples has been summarized. Pyrrolizidine alkaloids (PAs) in food and natural preparations have received widespread attention due to their hepatotoxicity, genotoxicity, and embryotoxicity. Mass spectrometry (MS), as a high resolution, high sensitive, and high throughput detection tool, has been the most commonly used technique for the determination of PAs. The continuous advancement of new technologies, methods, and strategies in the field of MS has contributed to the improvement of the analytical efficiency and methodological enhancement of PAs. This paper provides an overview of the structure, toxicity properties and commonly employed analytical methods, focusing on the concepts, advances, and novel techniques and applications of MS-based methods for the analysis of PAs. Additionally, the remaining challenges, future perspectives, and trends for PA detection are discussed. This review provides a reference for toxicological studies of PAs, content monitoring, and the establishment of quality control and safety standards for herbal and food products. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance :The genus L. has high medicinal value and has traditional been used to treat a variety of gastrointestinal disorders, as well as diabetes, edema, colds, arthritis, asthma, and traumatic injuries. Aim of the review : This work addresses the missing information by conducting a comprehensive analysis of the traditional uses, chemical components, and pharmacological applications of the more reported species of the genus L. The origin of the genus, its toxicology, and the use of classical therapies in modern medicine were also discussed. It provides references for historical evidence, resource development, and medical research on the genus. ology : Data about the genus L. were gathered via Web of Science, PubMed, Science Direct, Google Scholar, Connected Papers, China National Knowledge Infrastructure (CNKI), electronic ancient books and local chronicles. The WFO Plant List (wfoplantlist.org) and Flora of China (www.iplant.cn) confirmed L.'s Latin name, and the species information. The program ChemBioDraw Ultra 14.0 was used to create the molecular structures of the compounds that were displayed in the text. Currently, at least 740 constituents have been isolated and identified from L. These include 9 groups of chemicals, such as flavonoids, alkaloids, and terpenoids. They have been shown to have over 20 biological properties in vivo and in vitro , such as antibacterial, anti-inflammatory, and anti-oxidant effects. Based on pharmacological investigations, chemical components, and traditional folk applications, L. is considered a medicinal plant having a variety of pharmacological actions. However, although the pharmacological activity of the L. genus has been preliminary demonstrated, most have only been assessed using simple in vitro cell lines or animal disease models. In order to fully elucidate the pharmacological activity and mechanisms of L., future studies should be conducted in a more comprehensive clinical manner. [Display omitted] • A textual study of the origin of Litsea and the main species (L. cubeba) was carried out. • Summarizes the traditional uses of Litsea in different countries. • 740 chemical constituents of the genus Litsea were summarised. • Over 20 pharmacological applications of the genus Litsea are summarised. • The genus Litsea's classical prescriptions play an important role in modern pharmacology. [ABSTRACT FROM AUTHOR]

Bacterial infection is a key challenge for implant and blood-contacting biomaterials due to the biofouling and thrombus formation at their interface. Therefore, design and fabrication of high-efficiency antifouling and bactericidal coatings on substrates are extremely important for biomedical devices. In this paper, we successfully developed a coating with high-efficiency antifouling and bactericidal properties on a polyurethane (PU) substrate through polydopamine (PDA), polyethyleneimine (PEI) assisted codeposition and amidation reaction using our synthesized copolymers of mono-2-(methylpropoxy) ethyl succinate (MSA), sulfobetaine methacrylate (SBMA) and/or ethyl methacrylate trimethyl ammonium chloride (MAC). All the coatings showed improved hydrophilicity. And due to the unique surface hydration of sulfobetaine (SB) zwitterionic groups and high ability to kill attached bacteria of quaternary ammonium cationic groups, the coatings constructed by tripolymers of MSA/MAC/SBMA (defined as PCAS) showed greatly reduced protein adsorption (BSA and Fg), platelet and cell adhesion, and excellent antifouling activity. This bioinspired and efficient surface modification strategy with dual-function coatings has potential application prospects in implantable biomedical devices. • A series of copolymers containing MSA, SBMA and/or MAC were fabricated. • The antifouling and/or bactericidal coatings were constructed on the PU surface by amidation reaction. • The copolymer modified coatings had > 94.0% antifouling and bacteria-killing properties. [ABSTRACT FROM AUTHOR]

Sambucus williamsii Hance, belonging to the Sambucus L. family (Viburnaceae), possesses medicinal properties in its roots, stems, leaves, flowers, and fruits. It is recognized for its ability to facilitate bone reunion, enhance blood circulation, remove stasis, and dispel wind and dampness. This traditional Chinese medicine holds significant potential for development and practical use. Hence, this paper offers an in-depth review of S. williamsii , covering traditional uses, processing guidelines, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics, aiming to serve as a reference for its further development and utilization. Information for this study was gathered from various books, bibliographic databases, and literature sources such as Google Scholar, Web of Science, PubMed, Chinese National Knowledge Infrastructure, Baidu Scholar, VIP Database for Chinese Technical Periodicals, and Wanfang Data. Phytochemical investigations have identified approximately 238 compounds within the root bark, stem branches, leaves, and fruits of S. williamsii. These compounds encompass flavonoids, sugars, glycosides, terpenoids, phenylpropanoids, alkaloids, phenols, phenolic glycosides, and other chemical constituents, with phenylpropanoids being the most prevalent. S. williamsii exhibits a wide range of pharmacological effects, particularly in promoting osteogenesis and fracture healing. This comprehensive review delves into the traditional uses, processing guidelines, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics of S. williamsii. It provides valuable insights into this plant, which will prove beneficial for future research involving S. williamsii. [Display omitted] [ABSTRACT FROM AUTHOR]

Microplastic (MP), as a new pollutant, not only affects the growth and development of plants but also may affect the secondary metabolites of plants. The anti-tumor role of Pinellia ternata is related to secondary metabolites. The role of brassinolide (BR) in regulating plant resistance is currently one of the research hotspots. The paper mainly explores the regulation of BR on growth and physiology of Pinellia ternata under MP stress. The experimental design includes two levels of MP (0, 1%) and two levels of BR (0, 0.1 mg/L). MP led to a marked reduction in plant height (15.0%), Fv/Fm (3.2%), SOD and APX activity (15.0%, 5.1%), whereas induced an evident raise in the rate of O 2 ·- production (29.6%) and GSH content (4.4%), as well as flavonoids (6.8%), alkaloids (75%), and β-sitosterol (26.5%) contents. Under MP addition, BR supply significantly increased plant height (15.7%), aboveground and underground biomass (16.1%, 10.3%), carotenoid and GSH content (11.8%, 4.2%), Fv/Fm (2.9%), and activities of SOD, GR, and MDHAR (32.2%, 21.08%, 20.9%). These results indicate that MP suppresses the growth of P. ternata , although it promotes secondary metabolism. BR can alleviate the inhibitory effect of MP on growth by improving photosynthesis, redox homeostasis, and the AsA-GSH cycle. [Display omitted] • MP reduces growth and antioxidant capacity of P. ternata. • MP promotes the generation of secondary metabolic substances in P. ternata. • BR enhances growth and antioxidant capacity of P. ternata under MP stress. • BR have a potential role in mitigating adverse effects of MP on P. ternata. [ABSTRACT FROM AUTHOR]

Ionic Liquid based micellar structures were probed using spectroscopy and microscopy analysis. [Display omitted] • Switching between neutral and cation forms of SANG is used to probe IL based premicellar and micellar structures. • [Bmim][Os] IL micelles converted SANG from iminium form to alkanolamine. • Concentration dependent morphologies of IL self-assemblies were characterized by AFM and other spectroscopic tools. • Time-resolved properties of alkanolamine showed accurate transition points for premicellar and micellar structures. In this paper, we report the structural and dynamics aspect of self-assembled nano structures formed by an ionic liquid (IL) based surfactant, 1-butyl-3-methylimidazolium [Bmim] octyl sulfate [Os] using photophysical properties of a well-known anti-cancer alkaloid, sanguinarine (SANG). SANG exists in two forms, iminium and alkanolamine, in aqueous solutions at equilibrium which gets disturbed upon addition of [Bmim][Os] IL. The anionic part of this IL is micellar in nature and induces the iminium form to convert into alkanolamine form after reaching critical micelle concentration (CMC) at 31–34 mM. The gradual conversion from iminium to alkanolamine with [Bmim][Os] exhibits interesting transition points at various concentrations of IL. Importantly, on adding IL, the increment in alkanolamine emission at 415 nm exhibited a different trend when compared with iminium emission at 565 nm. Only one transition point at CMC was seen by alkanolamine emission intensity whereas iminium fluorescence undergoes three different slopes of quenching. Atomic force microscopy (AFM) detected different morphologies at 10, 20 and 35 mM concentrations of [Bmim][Os]. Interestingly, time-resolved properties of alkanolamine showed an efficient way for detecting these premicellar transitions. Along with the alkanolamine lifetime component inside the micelle (2.9 ns), the appearance of a short component of fluorescence lifetime ∼ 1.6 ns was characterized as SANG-sulfate interactions using the [Bmim][HSO 4 ]. Overall, three regions of premicellar and micellar states were observed based on spectroscopic analysis of iminium and alkanolamine forms. This kind of switching between prototropic forms of the drug by a surface-active IL (SAIL) is an important aspect for alkaloids and can find potential applications in drug loading and delivery methods. [ABSTRACT FROM AUTHOR]

Ecteinascidin 743 (Et-743), also known by the trade name Yondelis®, is the pioneering marine natural product to be successfully developed as an antitumor drug. Moreover, it is the first tetrahydroisoquinoline natural product used clinically for antitumor therapy since Kluepfel, a Canadian scientist, discovered the tetrahydroisoquinoline alkaloid (THIQ) naphthyridinomycin in 1974. Currently, almost a hundred natural products of bistetrahydroisoquinoline type have been reported. Majority of these bistetrahydroisoquinoline alkaloids exhibit diverse pharmacological activities, with some family members portraying potent antitumor activities such as Ecteinascidins, Renieramycins, Saframycins, Jorumycins, among others. Due to the unique chemical structure and exceptional biological activity of these natural alkaloids, coupled with their scarcity in nature, research seeking to provide material basis for further bioactivity research through total synthesis and obtaining compound leads with medicinal value through structural modification, remains a hot topic in the field of antitumor drug R&D. Despite the numerous reviews on the total synthesis of bistetrahydroisoquinoline natural products, comprehensive reviews on their structural modification are apparently scarce. Moreover, structural modification of bioactive natural products to acquire lead compounds with improved pharmaceutical characteristics, is a crucial approach for innovative drug discovery. This paper presents an up-to-date review of both structural modification and activity of bistetrahydroisoquinoline natural products. It highlights how such alkaloids can be used as antitumor lead compounds through careful chemical modifications. This review offers valuable scientific references for pharmaceutical chemists engaged in developing novel antitumor agents based on such alkaloid modifications, as well as those with such a goal in future. [Display omitted] • Bistetrahydroisoquinoline alkaloids represent a huge reservoir of new pharmaceuticals. • Ecteinascidin 743 (Et-743) is the first marine natural product to be successfully developed as an antitumor drug. • The structural modification of such bistetrahydroisoquinoline natural products has always been challenging. • Structural modification ofnatural products to acquire lead compoundsis a crucial approach fordrug discovery. • This paper presents an up-to-date review of structural modification of bistetrahydroisoquinoline alkaloids. [ABSTRACT FROM AUTHOR]

Corydalis yanhusuo W. T. Wang, also known as yanhusuo , yuanhu , yanhu and xuanhu , is one of the herb components of many Chinese Traditional Medicine prescriptions such as Jin Ling Zi San and Yuanhu-Zhitong priscription. C. yanhusuo was traditionally used to relieve pain and motivate blood and Qi circulation. Now there has been growing interest in pharmacological effects of alkaloids, the main bioactive components of C. yanhusuo. Eighty-four alkaloids isolated from C. yanhusuo are its important bioactive components and can be characterized into protoberberine alkaloids, aporphine alkaloids, opiate alkaloids and others and proper extraction or co-administration methods modulate their contents and efficacy. Alkaloids from C. yanhusuo have various pharmacological effects on the nervous system, cardiovascular system, cancer and others through multiple molecular mechanisms such as modulating neurotransmitters, ion channels, gut microbiota, HPA axis and signaling pathways and are potential treatments for many diseases. Plenty of novel drug delivery methods such as autologous red blood cells, self-microemulsifying drug delivery systems, nanoparticles and others have also been investigated to better exert the effects of alkaloids from C. yanhusuo. This review summarized the alkaloid components of C. yanhusuo , their pharmacological effects and mechanisms, and methods of drug delivery to lay a foundation for future investigations. [Display omitted] • This paper summarized 84 alkaloids from C. yanhusuo. • This paper reviewed pharmacological effects of alkaloids from C. yanhusuo. • This paper summed up mechanisms of alkaloids from C. yanhusuo against diseases. • This paper reviewed drug delivery methods of alkaloids from C. yanhusuo. [ABSTRACT FROM AUTHOR]

Malaria continues to be a serious global public health problem in subtropical and tropical countries of the world. The main drugs used in the treatment of human malaria, quinine and artemisinin, are isolates of medicinal plants, making the use of plants a widespread practice in countries where malaria is endemic. Over the years, due to the increased resistance of the parasite to chloroquine and artemisinin in certain regions, new strategies for combating malaria have been employed, including research with medicinal plants. This review focuses on the scientific production regarding medicinal plants from Brazil whose antimalarial activity was evaluated during the period from 2011 to 2022. For this review, four electronic databases were selected for research: Pubmed, ScienceDirect, Scielo and Periódicos CAPES. Searches were made for full texts published in the form of scientific articles written in Portuguese or English and in a digital format. In addition, prospects for new treatments as well as future research that encourages the search for natural products and antimalarial derivatives are also presented. A total of 61 publications were encountered, which cited 36 botanical families and 92 species using different Plasmodium strains in in vitro and in vivo assays. The botanical families with the most expressive number of species found were Rubiaceae, Apocynaceae, Fabaceae and Asteraceae (14, 14, 9 and 6 species, respectively), and the most frequently cited species were of the genera Psychotria L. (8) and Aspidosperma Mart. (12), which belong to the families Rubiaceae and Apocynaceae. Altogether, 75 compounds were identified or isolated from 28 different species, 31 of which are alkaloids. In addition, the extracts of the analyzed species, including the isolated compounds, showed a significant reduction of parasitemia in P. falciparum and P. berghei , especially in the clones W2 CQ-R (in vitro) and ANKA (in vivo), respectively. The Brazilian regions with the highest number of species analyzed were those of the north, especially the states of Pará and Amazonas, and the southeast, especially the state of Minas Gerais. Although many plant species with antimalarial potential have been identified in Brazil, studies of new antimalarial molecules are slow and have not evolved to the production of a phytotherapeutic medicine. Given this, investigations of plants of traditional use and biotechnological approaches are necessary for the discovery of natural antimalarial products that contribute to the treatment of the disease in the country and in other endemic regions. [Display omitted] • Malaria continues to be a serious global public health problem. • Malaria is endemic in the Amazon and, in Brazil, 99.9% of notifications of cases and deaths from malaria occur in this region. • A total of 61 papers on Brazilian plants with antimalarial activity were published from 2011 to 2022. • 75 compounds were identified or isolated from 23 different species, 31 of which are alkaloids. [ABSTRACT FROM AUTHOR]

• Emetine and dehydroemetine inhibit both coronavirus growth and host-cell protein synthesis at nanomolar concentrations. • The stereochemical requirements of emetine and its analogs for inhibition of both viral growth and host-cell protein synthesis inhibition are the same. • Cardiotoxic effects of emetine and dehydroemetine at I CaL are not stereo-specific and require micromolar concentrations. The emergence of highly infectious pathogens with their potential for triggering global pandemics necessitate the development of effective treatment strategies, including broad-spectrum antiviral therapies to safeguard human health. This study investigates the antiviral activity of emetine, dehydroemetine (DHE), and congeneric compounds against SARS-CoV-2 and HCoV-OC43, and evaluates their impact on the host cell. Concurrently, we assess the potential cardiotoxicity of these ipecac alkaloids. Significantly, our data reveal that emetine and the (-)-R,S isomer of 2,3-dehydroemetine (designated in this paper as DHE4) reduce viral growth at nanomolar concentrations (i.e., IC 50 ∼ 50–100 nM), paralleling those required for inhibition of protein synthesis, while calcium channel blocking activity occurs at elevated concentrations (i.e., IC 50 ∼ 40–60 µM). Our findings suggest that the antiviral mechanisms primarily involve disruption of host cell protein synthesis and is demonstrably stereoisomer specific. The prospect of a therapeutic window in which emetine or DHE4 inhibit viral propagation without cardiotoxicity renders these alkaloids viable candidates in strategies worthy of clinical investigation. [ABSTRACT FROM AUTHOR]

• Synthesis and evaluation of four aromatic stationary phases with LSER model in SFC. • The phases provided π-π and hydrogen bonding interactions to ensure retention capacity. • Electrostatic interactions that were regulated by additives were the key to peak shape. • 9 flavonoids and 4 alkaloids were separated using the aromatic stationary phases in SFC. In the last decade, the separation application based on aromatic stationary phases has been demonstrated in supercritical fluid chromatography (SFC). In this paper, four aromatic stationary phases involving aniline (S-aniline), 1-aminonaphthalene (S-1-ami-naph), 1-aminoanthracene (S-1-ami-anth) and 1-aminopyrene (S-1-ami-py) were synthesized based on full porous particles (FPP) silica, which were not end-capped for providing extra electrostatic interaction. Retention mechanism of these phases in SFC was investigated using a linear solvation energy relationship (LSER) model. The aromatic stationary phases with five positive parameters (a, b, s, e and d+) can provide hydrogen bonding, π-π, dipole-dipole and cation exchange interactions, which belong to the moderate polar phases. The LSER results obtained using routine test solutes demonstrated that the aforementioned interactions of four aromatic stationary phases were influenced by the type and bonding density of the ligand, but to a certain extent. Furthermore, the LSER data verified that the S-1-ami-anth column based on full porous particles silica had higher cation exchange capacity (d+ value), compared to the commercialized 1-AA column (based on the ethylene-bridged hybrid particles). The relationship between the d+ value and SFC additive was quantitatively proved so as to regulate electrostatic interaction reasonably. This value was greatly increased by phosphoric acid, slightly increased by trifluoroacetic acid and formic acid, but significantly reduced by ammonium formate and diethylamine. Taking the S-1-ami-naph column as an example, better peek shape of the flavonoids was obtained after the addition of 0.1 % phosphoric acid in MeOH while isoquinoline alkaloids were eluted successfully within 11 min after adding 0.1 % diethylamine in MeOH. Combined with the unique π-π interaction and controllable electrostatic interaction, the aromatic stationary phases in this study have been proven to have expandable application potential in SFC separation. [ABSTRACT FROM AUTHOR]

Coix lacryma-jobi var. ma-yuen (Romanet du Caillaud) Stapf is a plant of the genus Coix in the Gramineae family. Coix seed is cultivated in various regions throughout China. In recent years, with the research on the medicinal value of Coix seed, it has received more and more widespread attention from people. Numerous pharmacological effects of Coix seed have been demonstrated through modern pharmacological studies, such as hypoglycemia, improving liver function, anti-tumor, regulating intestinal microbiota, improving spleen function, and anti-inflammatory effects. This article is a literature review. In recent years, despite the extensive research on Coix seed, there has yet to be a comprehensive review of its traditional usage, medicinal resources, chemical components, and pharmacological effects is still lacking. To fill this gap, the paper provides an overview of the latest research progress on Coix seed, aiming to offer guidance and references for its further development and comprehensive utilization. To gather information on the traditional usage, phytochemical ingredients, and pharmacological properties of Coix seed, we conducted a literature search using both Chinese and English languages in five databases: PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Springer. This article is a literature review. The chemical constituents of Coix seed include various fatty acids, esters, polysaccharides, sterols, alkaloids, triterpenes, tocopherols, lactams, lignans, phenols, flavonoids and other constituents. Modern pharmacological research has indeed shown that Coix seed has many pharmacological effects and is a natural anti-tumor drug. In addition to its anti-tumor effect, it also has pharmacological effects such as hypoglycemia, improving liver function, regulating intestinal microbiota, improving spleen function, and anti-inflammatory effects. This article provides a brief overview of the traditional uses, biotechnological applications, chemical components, and pharmacological effects of Coix seed. It highlights the importance of establishing quality standards, discovering new active ingredients, and exploring pharmacological mechanisms in Coix seed research. The article also emphasizes the significance of clinical trials, toxicology studies, pharmacokinetics data, and multidisciplinary collaboration for further advancements in this field. Overall, it aims to enhance understanding of Coix seed and its potential in pharmaceutical development and wellness products. Research progress on traditional and medicinal use, the chemical components and pharmacological effect of Coix seed. [Display omitted] • This article introduces the research progress in the traditional usage and medicinal resources of Coix seed. • The chemical components of Coix seed include fatty acids and other compounds. • Coix seed has pharmacological effects such as lowering blood sugar. [ABSTRACT FROM AUTHOR]

Epimedium koreanum Nakai (E. koreanum), a member of the genus Epimedium in the family Berberidaceae, is a well-known and well-liked traditional herb used as a "kidney tonic". For thousands of years, it has been utilized for renal yang deficiency, impotence, spermatorrhea, impotence, weakness of tendons and bones, rheumatic paralysis and discomfort, numbness, and constriction. The paper aims to comprehensively in-depth, and methodically review the most recent research on the traditional uses, phytochemistry, pharmacology, and toxicity of E. koreanum. Scientific databases including Web of Science, PubMed, Google Scholar, Elsevier, Springer, ScienceDirect, Baidu Scholar, and CNKI and medicine books in China were searched for relevant information on E. koreanum. In traditional uses, E. koreanum is frequently used to treat various diseases like erectile dysfunction, infertility, rheumatoid arthritis, osteoporosis, asthma, kidney-yang deficiency syndrome, etc. To date, more than 379 compounds have been discovered from various parts of E. koreanum , including flavonoids, lignans, organic acids, terpenoids, hydrocarbons, dihydrophenanthrene derivatives, alkaloids, and others. Research has revealed that the compounds and crude extracts have a wide range of pharmacological effects on the reproductive, cardiovascular, and nervous systems, as well as anti-osteoporosis, anti-tumor, antioxidant, anti-inflammatory, immunomodulatory, hepatoprotective, and antiviral properties. Besides, the crude extracts show potential hepatotoxicity. Based on recent domestic and international research investigations, E. koreanum contains a wealth of chemical components with pronounced pharmacological activities. Its traditional uses are numerous, and the majority of these traditional uses have been supported by contemporary pharmacological investigations. Crude extracts, on the other hand, can result in hepatotoxicity. Therefore, additional in vivo and in vitro experimental research on the pharmacology and toxicology of E. koreanum are required in the future to assess its safety and efficacy. This will give a firmer scientific foundation for its safe application and the development of new drugs in the future. [Display omitted] • More than 379 chemical constituents of E. koreanum are first reviewed. • Flavonoids are the predominant bioactive constituents of E. koreanum. • Traditional uses, pharmacology, and toxicity of E. koreanum are comprehensively discussed. [ABSTRACT FROM AUTHOR]

The chemical structure of sinoacutine is formed by a phenanthrene nucleus and an ethylamine bridge. Because it has a similar parent structure to morphine, it is subdivided into morphinane. At present, all reports have pointed out that the basic skeleton of morphine alkaloids is salutaridine (the isomer of sinoacutine), which is generated by the phenol coupling reaction of (R)-reticuline. This study shows that the biosynthetic precursors of sinoacutine and salutaridine are different. In this paper, the sinoacutine synthetase (SinSyn) gene was cloned from Sinomenium acutum and expressed SinSyn protein. Sinoacutine was produced by SinSyn catalyzed (S)-reticuline, according to the results of enzyme-catalyzed experiments. The optical activity, nuclear magnetic resonance, and mass spectrum of sinoacutine and salutaridine were analyzed. The classification and pharmacological action of isoquinoline alkaloids were discussed. It was suggested that sinoacutine should be separated from morphinane and classified as sinomenine alkaloids. [Display omitted] [ABSTRACT FROM AUTHOR]

• Effect of age and location on various narcissus alkaloids is quantified in this paper. • Results clearly indicate that age have a significant effect on different alkaloid contents specifically galanthamine. • It is also evident that effect of location on galanthamine contents is not significant but contents of other alkaloids vary significantly due to location. Narcissus is mostly grown for horticultural/decorative purposes in the fields and home gardens. Previously, galanthamine isolation (from the bulbs to produce medicine for the treatment of Alzheimer's disease) has been established as a novel use. Moreover, recent studies have also shown that Narcissus bulbs are also a source of several other interesting biologically active compounds and particularly some alkaloids. Various metabolites are produced at different time points during the growth cycle of plants. Also, for Narcissus bulbs it is important to find from an economical point of view the optimum time point for harvesting in its growth cycle, as the levels of galanthamine might be correlated with the age of the Narcissus bulbs. The aim of this study was to investigate the differences in the metabolites and specifically in the alkaloid contents based on a 1, 2- or 3-years harvesting cycle of Narcissus bulbs. Moreover, the effect of the cultivation site was studied for Narcissus pseudonarcissus cv Carlton which is well known for galanthamine production. Different methods were used for the analysis of these alkaloids. Untargeted NMR based metabolomics was used for overall metabolic changes and galanthamine quantitation. Whereas targeted GC-FID and GC–MS were used respectively for quantitative and qualitative analysis of major and minor alkaloids. An alkaloid specific acid-base extraction method was used in the GC–MS and GC–FID analysis. The results show that the contents of the metabolites vary significantly with the age of the bulbs. The contents of galanthamine were highest in two years old bulbs. It was also found that the alkaloid contents from the same variety grown at different locations differ from each other. Results presented here clearly indicate that] age of the bulb are important factors to consider for the industrial production of certain alkaloids from the plants as yields of alkaloids may vary, certain conditions may lead to an increase of the yield with 10–15%. [ABSTRACT FROM AUTHOR]

Polygonati Rhizoma (PR), which contains rich national cultural connotations, is a traditional Chinese medicine with homology of medicine and food. It has been used for a long time as a tonic in China's multi-ethnic medical system, and is also used to treat diseases such as premature graying hair, deficiency of blood and essence, diabetes, hypertension, etc. Meanwhile, PR is often used as food in China, India, South Korea and other Asian countries, which can satisfy hunger and provide many health benefits. This paper systematically reviewed the ethnopharmacology, botany, phytochemistry, pharmacology and related applications research of PR, and provided a reference for the comprehensive applications of PR, including basic research, product development and clinical applications. This paper also refined the national application characteristics of PR, such as rich plant resources, special chemical components and anti-hidden hungry, which laid a foundation for its high value and high connotation development in the future. The literature information was collected systematically from the electronic scientific databases, including PubMed, Science Direct, Google Scholar, Web of Science, Geen Medical, China National Knowledge Infrastructure, as well as other literature sources, such as classic books of herbal medicine. A comprehensive analysis of the above literature confirmed that PR has been used in the ethnic medicine system of Asian countries such as China for thousands of years. In this paper, 12 species including official species that can be used as PR are summarized, which provide rich plant resources for PR. The chemical components in PR are divided into nutritional components and active components. The former not only contains non-starch polysaccharides and fructo-oligosaccharides, which account for about 50% in PR and are recognized as high-quality diet in the world, but also contains inorganic elements and mineral elements. And a total of 199 kinds active ingredients, including saponins, flavonoids, alkaloids, etc., were sorted out by us. The above ingredients make PR have a special property of anti-hidden hunger. Studies have shown that PR has a wide range of pharmacological activities, such as immune regulation, blood glucose regulation, lipid-lowering, antioxidant, anti-tumor, antibacterial, etc. It has been widely used in medicine, food, cosmetics, gardens and other fields. PR, as a classic medicinal material of the same origin, is widely used in the traditional ethnic medicine system. It contains abundant potential plant resources, chemical components and pharmacological activities. This paper also suggests that PR with high application value in food industry, has the potential to become a high-quality coarse grain. Exploring the way of grain and industrialization of PR is beneficial to fully develop the economic value of PR. [Display omitted] • PR is a potential high-quality crop and food that can fight hidden hunger. • The material base and pharmacological mechanism of PR need to be further studied. • Challenges for PR industry are mainly uncontrolled quality and declining wild resources. • Promoting the development of PR for industrialization is conducive to play its value fully. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine and ethnic medicine together play an important value in the modern medicine system that is different from that of chemical drugs. Chinese medicine and ethnic medicine with hemostatic effect have unique advantages and development potential in the prevention and treatment of clinical hemorrhagic diseases, reflecting multi-component, multi-target and multi-pathway effects. In this paper, the active ingredients related to the hemostatic effect of traditional Chinese medicine and ethnic medicine are taken as the starting point, and the traditional Chinese medicine and ethnic medicine with traditional hemostatic purposes are reviewed, and the existing research progress on the active ingredients and their mechanism of action of these drugs is systematically expounded, aiming to provide theoretical reference for the development of traditional hemostatic drugs, the discovery of hemostatic active ingredients and the research of new hemostatic methods. Hemostatic chinese medicine and ethnic medicine were collected and summarized from the classic books of Materia Medica, public literature database and doctoral or master's thesis repositories. At the same time, we discussed the classification of various types of hemostatic active ingredients of traditional Chinese medicine and ethnic medicine according to the different mechanisms of hemostasis. A total of 436 traditional Chinese medicine and ethnic medicine with hemostatic effects have been collected, and their hemostatic active ingredients include alkaloids, quinones, flavonoids, phenylpropanoids, organic acids, amino acids, terpenoids, steroids, phenols, tannins, esters, polysaccharides and herbal extracts, etc. These active ingredients accelerate the formation of hemostasis by improving endogenous and exogenous hemostatic pathways mainly through enhancing vascular wall contraction, increasing platelet aggregation, promoting coagulation system activation and inhibiting fibrinolysis. This article reviews the previous data on various aspects of the hemostatic effect of traditional Chinese medicine and ethnomedicine. Many traditional hemostatic drugs have been discovered and many active ingredients and mechanisms have been reported. However, although there are a large number of drugs with traditional hemostatic effects, there are still few developed and applied. At the same time, the hemostatic components of many drugs still remain in the study of the activity of their total extracts, and the potential link between some drug components achieving hemostatic effects through different mechanisms remains to be elucidated. [Display omitted] • A total of 436 traditional Chinese medicine and ethnic medicine with hemostatic effects have been collected. • The hemostatic active ingredients include alkaloids, quinones, flavonoids, phenylpropanol and other chemical components. • These active ingredients accelerate the formation of hemostasis mainly through four different pathways. • In this paper, many data of traditional drugs for hemostasis and provides a reference for the development of new drugs and methods for hemostasis. [ABSTRACT FROM AUTHOR]

Since the first natural carbazole alkaloid, murrayanine, was isolated from Mwraya Spreng , carbazole alkaloid derivatives have been widely concerned for their anti-tumor, anti-viral and anti-bacterial activities. In recent decades, a growing body of data suggest that carbazole alkaloids and their derivatives have different biological activities. This is the first comprehensive description of the antifungal and antibacterial activities of carbazole alkaloids in the past decade (2012–2022), including natural and partially synthesized carbazole alkaloids in the past decade. Finally, the challenges and problems faced by this kind of alkaloids are summarized. This paper will be helpful for further exploration of this kind of alkaloids. [Display omitted] • This review enclosed antimicrobial activity of natural and semi-synthetic carbazole alkaloids. • Classification of carbazole alkaloids according to structure. • It laid a foundation for antibacterial evaluation of carbazole alkaloids. [ABSTRACT FROM AUTHOR]

Fritillaria unibracteata is an endangered medicinal plant whose bulb has been used as a Chinese herb to suppress cough, asthma and excessive phlegm for centuries. Steroidal alkaloids, which are synthesized via the steroid synthesis pathways, are their significant bioactive constituents. However, few studies on genes involved in steroidal alkaloid biosynthesis in F. unibracteata have been reported, mainly due to the lack of the F. unibracteata genome. In this paper, comparative transcriptomic and metabolomic analyses of four different tissues of F. unibracteata (leaves, flowers, stems, and bulbs) were performed. Imperialine, peiminine, and peimisine were among the significant bioactive compounds that were considerably abundant in bulb tissue, according to the metabolomic findings. Then, 83.60 Gb transcriptome sequencing of four different tissues was performed, of which one gene encoding phosphomevalonate kinase was directly functionally characterized to verify the accuracy of sequences obtained from the transcriptome. A total of 9217 differentially expressed unigenes (DEGs) were identified in four different tissues of F. unibracteata. GO and KEGG enrichments revealed that phenylpropanoid biosynthesis, MVA-mediated terpenoid backbone biosynthesis, and steroid biosynthesis were enriched in bulb tissue, whereas enrichment of MEP-mediated terpenoid backbone biosynthesis, photosynthesis, photosynthesis-antenna protein and carotenoid biosynthesis was observed in aerial tissues. Moreover, clustering analysis indicated that the downstream steroid biosynthesis pathway was more important in steroidal alkaloid biosynthesis compared to the upstream terpenoid backbone biosynthesis pathway. Hence, MVA-mediated biosynthesis of steroidal alkaloids was proposed, in which 15 bulb-clustered DEGs were positively correlated with a high accumulation of bioactive steroid alkaloids, further validating our proposal. In addition, 36 CYP450s showing a positive correlation with bioactive steroidal alkaloids provided candidate enzymes to catalyze the subsequent steps of steroidal alkaloid biosynthesis. In addition, the transcription factors and ABC transporters clustered in bulb tissue might be responsible for the regulation and transportation of steroidal alkaloid biosynthesis. Protein-protein interaction analysis implied a highly complex steroid alkaloid biosynthesis network in which delta (24)-sterol reductase might be one of the central catalysts. Based on the integrated transcriptome and metabolome, this current study is a first step in understanding the tissue-specific biosynthesis of steroidal alkaloids in F. unibracteata. Furthermore, key genes and regulators identified herein could facilitate metabolic engineering to improve steroidal alkaloids in F. unibracteata. The proposed biosynthesis of steroidal alkaloids in Fritillaria unibracteata. [Display omitted] • Three bioactive steroidal alkaloids were highly enriched in bulb of Fritillaria unibracteata. • The steroidal alkaloid biosynthesis is involved in MVA-mediated pathway. • The downstream delta (24)-sterol reductase might be one of the central catalysts. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Aconitum has been used as local and traditional medicines in many asian regions for the treatment of various diseases such as collapse, syncope, painful joints, oedema, bronchial asthma et al. Higenamine, a plant-based alkaloid, was initially isolated from Aconitum and identified as the active cardiotonic component of Aconitum . It has been tested as a candidate of pharmacologic stress agent in the detection of coronary artery diseases (CADs) and now researchers have just accomplished the phase III clinical studies successfully in China. Besides, a large number of studies have revealed the various pharmacological properties and potentially multi-spectral medical applications of higenamine. However, to date, no comprehensive review on higenamine has been published. Aim of the review This present paper aims to compile a comprehensive update regarding the biochemistry, pharmacokinetic features, pharmacological activities, clinical and potential clinical uses and toxicities on higenamine with the ultimate objective of providing a guide for future research on this drug. Materials and methods The selection of relevant data was made through a search using the keyword “higenamine” in “Web of science”, “Pubmed”, and “China Knowledge Resource Integrated (CNKI)”. Information was also acquired from local classic herbal literature, government reports and conference papers. Results In addition to Aconitum , higenamine also exists in many other plants including Tinospora crispa , Nandina domestica T HUNBERG , Gnetum Parvifolium C.Y. Cheng, sarum Heterotropoides , Nelumbo nucifera , N.nucifera . The pharmacokinetic studies conducted in animals and humans showed that higenamine conformed to a two-compartment pharmacokinetic model. Studies over the last four decades on higenamine have revealed its various pharmacological properties such as positive inotropic and chronotropic effect, activating slow channel effect, vascular and tracheal relaxation effect, anti-thrombotic, anti-apoptotic and anti-oxidative effect, anti-inflammatory and immunomodulatory effect. This phytochemical constituent has shown its potential therapeutic effects for diseases like heart failure, disseminated intravascular coagulation (DIC), shock, arthritis, asthma, ischemia/reperfusion (I/R) injuries and erectile dysfunction. Conclusions Extensive basic and clinical studies on higenamine showed valuable therapeutic effects on different disorders. However, the underlying mechanisms of higenamine have not been established. Therefore, the safety, tolerability and efficacy of higenamine are as yet, not fully understood. Additionally, some of the studies were small sample-sized and unreliable. To sum up, there is a need for deeper investigation in the mechanisms of higenamine action, as well as well-designed preclinical and clinical trials studies to test the safety and clinical value of the drug. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Crinum macowanii is a deciduous bulbous plant which grows in east, central and southern Africa. Crinum macowanii has been used as herbal medicine by the indigenous people of east and southern Africa has for several centuries. The bulb, leaves and roots of C. macowanii are reported to possess diverse medicinal properties and used to treat or manage various human and animal diseases and ailments throughout its distributional range. Crinum macowanii is used traditionally as a remedy for boils, diarrhoea, fever, inflammation, respiratory system problems, skin rashes, tuberculosis, wounds and urinary tract problems. Aim of the review The present review aims to summarize comprehensively the research that has been done on the ethnomedicinal uses, botany, phytochemistry and pharmacology of C. macowanii in different locations throughout its geographical range in east, central and southern African region so as to highlight research gaps and provide a foundation for further investigations on the plant species. Materials and methods A review of the literature was undertaken and an in-depth analysis of previous research on ethnobotany, therapeutic value, phytochemistry and pharmacology of C. macowanii throughout its distributional range in east, central and southern Africa. Literature sources included papers published in international journals, reports from international, regional and national organizations, conference papers, books, theses, websites and other grey literature. Electronic search engines such as Google, Google scholar, publishing sites such as Elsevier, scienceDirect, BMC, PubMed and other scientific database sites such as ChemSpider, PubChem were used as well as searching the library collections of the National Herbarium and Botanic Gardens (SRGH), Harare, Zimbabwe and the University of Fort Hare, South Africa. Results A total of 32 ethnomedicinal uses of C. macowanii are documented in literature, which can be grouped into seven major ethnomedicinal general purpose usages, namely “fever”, “wounds, sores and skin rashes”, “boils and inflammation”, “respiratory system problems”, “blood cleansing”, “urinary tract problem” and “veterinary uses”. The chemical composition of C. macowanii is dominated by various isoquinoline alkaloids, which have been isolated from the bulbs, flowering stalks, leaves and roots. Major biological activities demonstrated by C. macowanii include antifungal, antiviral and antiplasmodial activities, cardiovascular effects as well as effects on the central nervous system. The population of C. macowanii is declining in the wild as the bulbs are over-collected for sale in medicinal ( muthi ) markets in southern Africa. Conclusion A literature search revealed that C. macowanii has a lot of potential as a possible source of pharmaceutical products for the treatment of a wide range of human and animal diseases and ailments. Some of the alkaloids isolated from C. macowanii have demonstrated various biological activities when investigated in in vitro assays. However, some of the ethnomedicinal uses of C. macowanii still require pharmacological investigations. Therefore, further studies are required to improve our knowledge about the mechanisms of action, efficacy, toxicity and clinical relevance of the plant species as well as its bioactive compounds. [ABSTRACT FROM AUTHOR]

A new simple, rapid and sensitive method using microemulsion electrokinetic chromatography (MEEKC) coupled with large volume sample stacking (LVSS) for the detection of five Tripterygium wilfordii sesquiterpene alkaloids (peritassine A, wilforgine, wilfordine, triptonine B and wilforine) was developed in this paper. For the separation of five Tripterygium wilfordii sesquiterpene alkaloids, a running buffer composed of 0.5% (w/v, 17 mmol/L) sodium dodecyl sulfate, 3.0% (v/v) n-butanol, 0.5% (v/v) n-hexane, 3.0% (v/v) ethanol, 7.0% (v/v) acetonitrile and 86.5% (v/v) 5 mmol/L Na 2 B 4 O 7 –10 mmol/L NaH 2 PO 4 buffer (pH 8.5) was used. In order to improve the sensitivity, MEEKC combined with on-line preconcentration of large volume sample stacking was applied. The detection limits (defined as S/N = 3) in the range of 0.003–0.009 μg/mL were feasible. The proposed LVSS-MEKC was successfully applied to the detection of four analytes in Tripterygium wilfordii root bark with the average recoveries ranged from 103.2% to 107.2%. Unlabelled Image • A LVSS-MEEKC method for the detection of five Tripterygium wilfordii sesquiterpene alkaloids was developed. • The developed method was simple, fast, sensitive and environmental friendly. • The proposed method was applied in pharmaceutical analysis. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Magnoliae Officinalis Cortex (the dried bark of Magnolia officinalis), a widely used traditional Chinese medicine, is also known as ' Houpo ' (Chinese: 厚朴). Magnoliae Officinalis Cortex has a wide range of pharmacological effects and has been used to treat conditions such as abdominal distention, vomiting, diarrhea, food accumulation, Qi stagnation, constipation, phlegm and fluid retention and cough resulting from asthma. Aims of the review The present paper reviews advances in research relating to the botany, ethnopharmacology, phytochemistry, pharmacology and toxicology of Magnoliae Officinalis Cortex. Prospects for future investigation and application of this herb are also discussed. Materials and methods Information on Magnoliae Officinalis Cortex was obtained from published materials, including ancient and modern books; PhD and MSc dissertations; monographs on medicinal plants; the pharmacopoeia of different countries and electronic databases, such as SCI finder, PubMed, Web of Science, ACS, Science Direct, Wiley, Springer, Taylor, AGRIS, Europe PMC, EBSCO host, CNKI, WanFang DATA, J-STAGE and Google Scholar. Results More than 200 chemical compounds have been isolated from Magnoliae Officinalis Cortex, including lignans, phenylethanoid glycosides, phenolic glycosides, alkaloids, steroids and essential oils. The plant has been reported to have pharmacological effects on the digestive system, nervous system and cardiovascular and cerebrovascular systems, as well as antibacterial, anti-tumour, analgesic, anti-inflammatory and anti-oxidative effects. Conclusions Magnoliae Officinalis Cortex is an essential traditional Chinese medicine with pharmacological activities that mainly affect the digestive system, nervous system and cardiovascular and cerebrovascular systems. This review summarises its botany, ethnopharmacology, phytochemistry, pharmacology and toxicology. These information suggest that we should focus on the development of new drugs related to Magnoliae Officinalis Cortex, including specific constituents, so that Magnoliae Officinalis Cortex can exert greater therapeutic potential. Meanwhile, it is important to pay attention to the rational use of Magnolia resources, avoiding over-harvesting which could lead to lack of resources. We should also pursue research on Magnolia substitutes and develop resources such as Magnoliae Officinalis Flos and Magnolia Leaf. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Abstract This paper developed a novel, sensitive, and selective ultra-performance liquid chromatography–triple quad mass spectrometry method to simultaneously determine seven effective constituents (triptolide, triptophenolide, celastrol, wilforgine, wilforine, wilfordine and wilfortrine) of Tripterygium glycosides (GTW) in human serum and urine. The chromatographic separation was performed on the C18 column using an ammonium acetate buffer solution–acetonitrile (both containing 0.1% formic acid) in a gradient program with a flow rate of 0.3 mL/min. Monitoring reaction mode was applied to target compounds quantitative analysis in the positive electrospray ionization (ESI) mode. The analysis process took 11 min in total. This method was fully validated with a linear range of 1–200 ng/mL for triptolide, 0.4–80 ng/mL for celastrol, 0.1–20 ng/mL for triptophenolide, wilforgine, wilforine, wilfordine, and wilfortrine. The intra-day and inter-day accuracy and precision of the target compounds all met the 15% criterion in both serum and urine. Extraction recovery, matrix effect, and dilution integrity were also validated. The short-term and long-term stability results indicated that all the constituents were stable in human serum and urine under the investigated storage conditions. 10 patients' specimens were collected and analyzed. Most of the compounds exhibited the tendency of higher concentration in urine than that in serum. The concentration that was detected in the serum and in the urine of alkaloids showed a positive-correlation property. This is the first time that triptophenolide was quantified in human bio-matrices. The method is feasible for multi-components therapeutic monitoring or pharmacokinetics study in clinical pharmaceutical research of Tripterygium glycosides. Highlights • Tripterygium glycosides tablet is widely applied to treat autoimmune diseases. • This preparation has excellent pharmacological activity compared with side effects. • Lack of analytical method for its active constituents limits clinical monitoring. • Method of 7 constituents simultaneous determination in human matrices was developed. • This method could contribute to providing a clinical reference for the regimen. [ABSTRACT FROM AUTHOR]

Abstract In this full paper, a stereocontrolled strategy for the total synthesis of (−)-vindoline is described. This synthetic route features: 1) rapid construction of the stereochemical center at C19 through a highly diastereoselective vinylogous Mannich addition; 2) tandem Heathcock/aza-Prins cyclization to install rings C and E in vindoline; 3) oxidative transformation of β-ketoester to enone; 4) stereoselective inversion of C4 stereochemistry with triphenylphosphine and carbon tetrabromide followed by Brønsted acid. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Abstract This study focuses on the elucidation of the stress-induced reverse changes of major indole alkaloids in Vinca minor , primarily on the postulated conversion of vincamine and vincadifformine to yield 9-methoxyvincamine, minovincine, and minovincinine, respectively. By applying the P450 enzyme inhibitors, naproxen and resveratrol, it was shown that the oxidative reaction involved in the postulated conversion of vincamine and vincadifformine is catalyzed by cytochrome P450 enzymes. In combination with the identification of 9-hydroxyvincamine as a postulated intermediate, this result confirms that the observed stress-induced reverse changes in the alkaloid pattern are caused by modifications of the alkaloids which regularly accumulate in the healthy Vinca minor plants. Up to now, just two main types of defense compounds are distinguished: phytoalexins, which are synthesized de novo from primary metabolites and phytoanticipins, which are constitutively present in plants - either intrinsically active or are activated after cell death by hydrolysis or oxidation of the precursors. In contrast, the results presented in this paper demonstrate that indole alkaloids, representing typical phytoanticipins, are just slightly modified in response to a stress-related elicitation. Accordingly, these modified alkaloids neither represent classical phytoalexins (being synthesized de novo), nor can they be classified as phytoanticipins, since modification does not occur postmortem. Consequently, we propose a new category for these modified alkaloids that we call phytomodificines. Graphical abstract Image 1 Highlights • In response to MeJA vincamine and vincadifformine are modified. • The oxidative modification is putatively performed by cytochrome P450 enzymes. • The altered alkaloids represent a new category of specialized metabolites. • Such phytomodificines represent phytoanticipins which had been modified in vital cells. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Zanthoxylum armatum DC. possesses several medicinal properties and has been commonly used in different indigenous medicinal practices to cure several diseases because of its stomachic, carminative and anthelmintic properties. Aim This review paper aims to provide an update on and analysis of information about the ecology, uses, phytochemistry, pharmacology, trade opportunities, policy gaps for the commercialization of this species forming a basis for further scientific innovations Materials and methods Information was gathered through a search of different books, journals, articles, annual reports, proceedings and web-based materials. Result Alkaloids, sterols, phenolics, lignins coumarins, terpenoids and flavonoids have been identified from leaves, fruits, stem, bark and seeds. Its trade value is also very high with its manifold applications in Ayurveda, allopathy, general pharmacy, and other industries. Antimicrobial, antiviral, antioxidant, anti-inflammatory, cytotoxic, hepato-protective, insecticidal/larvicidal effects are of particular relevance. Conclusion It is one of the prioritized medicinal plants for economic development in Nepal. Owing to its diverse applications, the species can be developed as an important commodity for alleviation of poverty in rural areas. The various ethno-pharmacological applications of Zanthoxylum armatum have been verified by several related researches. More extensive study on the individual specific phyto-component can lead to novel innovations for the well-being of mankind. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Abstract Since the content of alkaloids is usually low in plants and they are easily co-eluted with other constituents, enrichment of alkaloids is essential in the discovery of bioactive lead compounds from natural products. In this paper, an easy SPE enrichment method was developed in a buffer-free solvent system based on electrostatic repulsion mechanism. The feasibility of the new method was verified by successful enrichment of alkaloids from Scopolia tangutica (S. tangutica) with an optimized eluting condition. Then this developed method was applied to other representative plants in different families, including Przewalskia tangutica and Peganum harmala L , Lycoris radiata and Menispermum dauricum DC , which enlarged the scope of applicability. Additionally, the new SPE procedure avoided possible structural change destruction caused by pH change. Simple solvent system, including formic acid (FA) and methanol, would benefit subsequent mass analysis, quantity determination and bioactivity screening, and so on. Highlights • We successfully developed a buffer-free alkaloids enrichment method using AC18 as a RP/SAX material. • AC18 with high charge density could elute alkaloid constituent efficiently and selectively. • This method could enrich alkaloids easily and benefit subsequent procedure such as activity screening and LC–MS analysis. • Mild acidic solvent system helped avoid possible structural damage caused by pH change for pH-sensitive alkaloids. • This method was applied successful in alkaloids enrichment from S. tangutica and four other TCMs. [ABSTRACT FROM AUTHOR]

Abstract In the North Eastern region of Morocco, many people are interested in medicinal plants and their uses. However, the rationale for the utilization of medicinal plants has remained largely underestimated with little or no scientific data on plant safety. In this paper we attempt to describe and establish a detailed list of current knowledge in relation to the toxicity of these plants and to evaluate the scientific data concerning the harmful effects of the selected natural products. Our approach consists of collecting published data from literature in specialized journals, books and website related to the toxic plants. This research revealed that 89 plant species, retrieved from 287 plants used as medicine in the North-Eastern region of Morocco, are considered toxic or present some kind of toxicity. Our data determines 55 compounds isolated from the plants which are dominated by five groups of toxic compounds: alkaloids followed by glucosides, terpenoids, protides and phenolics. The present work discusses toxicity-related issues arising from the use of medicinal plants by local people. We conclude that the database considered in this study could serve as an important source of information on the toxicity of medicinal plants used by this society. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Abstract Piperine (E,E-) is a naturally occurring pungent and spicy constituent of black pepperand is also used as an added flavoring ingredient to foods and beverages. Piperine has been determined safe under conditions of intended use as a flavoring substance by regulatory and scientific expert bodies. While concurring with the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and Flavor and Extract Manufacturers Association (FEMA) Expert Panel on the safety of piperine, the European Food Safety Authority (EFSA) requested additional toxicological data. The results of a 90-day GLPcompliant dietary study, conducted in Sprague-Dawley rats at target doses of 0, 5, 15, or 50 mg/kg bw/day, to respond to this request are presented herein. No adverse effects were found attributable to ingestion of piperine. Statistically significant changes in food consumption, body weight gain, and plasma cholesterol levels were not considered adverse as discussed in this paper. Therefore, the oral no-observed-adverse-effect level (NOAEL) was determined to be the highest dose tested of 50 mg/kg bw/day. EFSA derived a lower NOAEL of 5 mg/kg bw/day based on increased plasma cholesterol levels which still affords an adequate margin of safety of over 48,000 and concluded that piperine is not of safety concern. Highlights • GLP-compliant 90-day study of piperine following OECD guideline. • Piperine produces no adverse effects in rats fed diets containing up to 3600 ppm of added flavor for 90 days. • A threshold of toxicity (NOAEL) of 50 mg/kg bw/day is proposed for piperine. [ABSTRACT FROM AUTHOR]

[Display omitted] In this paper, for the first time, the method of determination of the alkaloid of quinoline derivation, quinine (QN), was developed. A miniatured planar electrochemical cell with a working electrode, a boron-doped diamond electrode (BDDE), was used. QN is easily oxidized in a strongly acidic environment – 2 M HClO 4 at a potential of E pa = +1.42 V, and in an alkaline environment. E pa = +0.94 – +1.18 V, depending on the pH of the medium at the surface of BDDE. Also, QN is reduced within wide pH ranges at the background of the Britton–Robinson buffer (E pc = −1.11 – −1.51 V). This enables the simultaneous determination of QN by anodic and cathodic currents. The conditions for the determination of QN were optimized. Calibration curves under optimal conditions were obtained using differential pulse voltammetry (DPV) and square-wave voltammetry (SWV). The limit of detection of QN according to the cathodic peak is at the level of 10−7 M. According to the peak of QN oxidation, the sensitivity is worse, and the limit of detection of QN is at the level of 10−6 M. The developed method was tested in the analysis of soft drinks. The results were compared with those of high performance liquid chromatography. The obtained results were statistically processed using the relative errors and Student t -test. Uric acid, nicotine, and caffeine, which can often be present in biological fluids, do not affect the oxidation and reduction of QN on BDDE. Various methods of urine sample preparation for voltammetric analysis were investigated. The proposed method can determine QN in urine at the level of 1.0 μg/ml of urine. [ABSTRACT FROM AUTHOR]

• This paper is the first to include cultural practices in G. elwesii. • The best cytotoxic activity against the MCF-7 cell line was in Zn treatment. • Galanthamine and lycorine synthesis were increased by 755% and 815%, respectively. Galanthus elwesii Hook belongs to the Amaryllidaceae family and is an ornamental plant that naturally spreads in the region between Turkey and Europe. It also contains bioactive compounds in the nutraceutical and pharmaceutical field. The objective of this study was to evaluate the effects of zinc (Zn) and phosphorus (P) in the synthesis of alkaloid compounds and bioactive properties in G. elwesii. The plants were subjected to three different concentrations of zinc (2.5, 5, and 10 mg kg−1), and phosphorus (3, 6, and 12 mg kg−1), and compared with the control. Two harvests were evaluated, between 2020 and 2021. The total phenolic content (TPC), total flavonoid content (TFC), and total alkaloid content (TAC) were identified by Folin-Ciocalteu, aluminum chloride, and bromocresol green-complex assays, respectively. TPC (85.09 ± 0.4 mg QE/g), TFC (267.7 ± 1.6 mg GAE/g), and TAC (320.58 ± 2.4 mg CoE/g) were the highest in the treatments of Zn 10, Zn 10 and Zn 2.5 + P 3 mg kg−1, respectively. RP-HPLC analysis revealed that, compared with the control group, galanthamine, and lycorine synthesis were increased by 755% (Zn 5 + P 3 mg kg−1) and 815% (Zn 2.5 mg kg−1) respectively. The highest antioxidant activities of were found to be 80.21% (10 mg kg−1 Zn) and 78.05% (2.5 mg kg−1Zn + 3mg kg−1 P), respectively. The extracts exhibit strong anti-microbial activity, particularly against Bacillus subtilis, Candida albicans, Pseudomonas aeruginosa, Saccharomyces cerevisiae , and Staphylococcus aureus. The MCF-7 cell line was used to investigate its anti-cancer activity properties. The MTT assay result was obtained from extracts treated with Zn 10 mg kg−1 for the best cytotoxic activity against the MCF-7 cell line (IC 50 value: 31.57 ± 0.70 μg/mL). [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Physostigmine is a major alkaloid found in the seeds of the fabaceous plant Physostigma venenosum. It is a powerful and reversible acetylcholine esterase inhibitor which effectively increases the concentration of acetylcholine at the sites of cholinergic transmission. It exerts its cholinesterase inhibitor effect in both the periphery and central nervous system. Many studies on physostigmine have involved the reliance on techniques that extract and quantify physostigmine in biological samples. This paper presents an overview of the currently applied methodologies for the determination of physostigmine and its metabolites in various biological samples. Papers published from January 1980 to December 2003 were taken into consideration for the discussion of the metabolism and analytical method of physostigmine. HPLC methods have been discussed and used in most of the references cited in this review. A few CE and RIA methods that have been recently reported are also mentioned in this paper. Basic information about the sample assayed, sample preparation, chromatographic column, mobile phase, detection mode and validation data are summarized in a table. [Copyright &y& Elsevier]

Ethnopharmacological relevance Areca catechu L. (Arecaceae), widely distributed in South and Southeast Asia, is a popular traditional herbal medicine that can be chewed for the purpose of dispersing accumulated fluid in the abdominal cavity and killing worms. The present paper aims to provide an up-to-date review on the traditional uses and advances in the botany, phytochemistry, pharmacology and toxicology of this plant. Furthermore, the possible trends and a perspective for future research of this plant are also discussed. Materials and methods A literature search was performed on A. catechu based on classic books of herbal medicine, PhD. and MSc. dissertations, government reports, the state and local drug standards, scientific databases including Pubmed, SciFinder, Scopus, the Web of Science, Google Scholar, and others. Various types of information regarding this plant are discussed in corresponding parts of this paper. In addition, perspectives for possible future studies of A. catechu are discussed. Results The seeds of A. catechu (areca nut) have been widely used in clinical practice in China, India and other South and Southeast Asian Countries. Currently, over 59 compounds have been isolated and identified from A. catechu , including alkaloids, tannins, flavones, triterpenes, steroids, and fatty acids. The extracts and compounds isolated from A. catechu have many pharmacological activities. These include antiparasitic effects, anti-depressive effects, anti-fatigue effects, antioxidant effects, antibacterial and antifungal effects, antihypertensive effects, anti-inflammatory and analgesic effects, anti-allergic effects, the promotion of digestive functions, suppression of platelet aggregation, regulatory effects on blood glucose and lipids, etc . Although arecoline is the primary active constituent of A. catechu , it is also the primary toxic compound. The main toxicities of arecoline are the promotion of oral submucosal fibrosis (OSF) and cytotoxic effects on normal human cells, which involve inducing apoptosis. Conclusion As an important herbal medicine, A. catechu has potential for the treatment of many diseases, especially parasitic diseases, digestive function disorders, and depression. Many traditional uses of A. catechu have now been validated by current investigations. However, further research should be undertaken to investigate the clinical effects, toxic constituents, target organs, and pharmacokinetics and to establish criteria for quality control for A. catechu- derived medications. In addition, it will be interesting to investigate the active macromolecular compounds and active constituents other than alkaloids in both raw and processed products of A. catechu . [ABSTRACT FROM AUTHOR]

Background: Naloxone is a prescription medication that can quickly and effectively reverse opioid overdose. Medicaid is a major payer of substance use disorder services, and Medicaid beneficiaries experience especially high rates of opioid overdose. As opioid overdose rates have risen sharply, every state has modified its laws to make naloxone easier to access. The aim of this paper is to determine whether implementation of different provisions of naloxone access laws led to increased naloxone dispensing financed by Medicaid.Methods: We reviewed naloxone legislation passed by every state between 2007 and 2016. We used the Medicaid State Drug Utilization dataset to examine the effect of different types of state naloxone access law provisions, separately and as a whole, on the number of outpatient naloxone prescriptions reimbursed by Medicaid from 2007 to 2016. We included state-level covariates in our models that may be correlated with naloxone utilization in Medicaid and passage of naloxone access laws.Results: We found that the presence of any naloxone law was significantly associated with increases in outpatient naloxone reimbursed through Medicaid. Laws containing standing order provisions were most consistently associated with increases in naloxone dispensing across models. Standing order provisions led on average to an increase of approximately 33 naloxone prescriptions per state-quarter, which is equivalent to 74% of the average number of naloxone prescriptions per state-quarter.Conclusions: Naloxone access laws, particularly those with standing order provisions, appear to be an effective policy approach to increasing naloxone access among Medicaid beneficiaries. [ABSTRACT FROM AUTHOR]

Corydalis Rhizoma (Yanhuso), is a crucial antianalgesic Traditional Chinese Medicine in clinic. Its adulterants (Northeast Yanhusuo), which are also from Corydalis and distributed in Northeast area of China, are used instead of Corydalis Rhizoma in the local places with a long history. In this paper, we compared the chemical differences of Corydalis Rhizoma and its seven adulterants by HPLC-DAD-Q-TOF-MS associated with chemometric analysis. 48 alkaloids are identified from them, and 14 alkaloids are reported for the first time based on the Mass data. The classification of different species is verified through PLS-DA and Hierarchical Clustering Heatmap analysis based on 26 samples. We find that large discrimination existing in the categories and content of the alkaloids between different species. C.y. is similar with C.t., which mainly contains protoberberine, tetrahydroprotoberberine and protopine types of alkaloids. Six other Northeast Yanhusuo, including C.r., C.w., C.a. as well as its three formas, can be classified into one category, because they mainly contained benzophenanthridines and aprophines. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Species of the genus Codonopsis are perennial herbs mainly distributed throughout East, Southeast and Central Asia. As recorded, they have been used as traditional Chinese medicines since the Qing Dynasty, where they were claimed for strengthening the spleen and tonifying the lung, as well as nourishing blood and engendering liquid. Some species are also used as food materials in southern China and Southeast Asia, such as tea, wine, soup, plaster, and porridge. Aim of the review The review aims to assess the ethnopharmacological uses, explicit the material basis and pharmacological action, promote the safety of medical use, and suggest the future research potentials of Codonopsis . Materials and methods Information on the studies of Codonopsis was collected from scientific journals, books, and reports via library and electronic data search (PubMed, Elsevier, Scopus, Google Scholar, Springer, Science Direct, Wiley, Researchgate, ACS, EMBASE, Web of Science and CNKI). Meanwhile, it was also obtained from published works of material medica, folk records, ethnopharmacological literatures, Ph.D. and Masters Dissertation. Plant taxonomy was confirmed to the database “The Plant List” ( www.theplantlist.org ). Results Codonopsis has been used for medicinal purposes all around the world. Some species are also used as food materials in southern China and Southeast Asia. The chemical constituents of Codonopsis mainly are polyacetylenes, polyenes, flavonoids, lignans, alkaloids, coumarins, terpenoids, steroids, organic acids, saccharides, and so on. Extract of Codonopsis exhibit extensive pharmacological activities, including immune function regulation, hematopoiesis improvement, cardiovascular protection, neuroprotection, gastrointestinal function regulation, endocrine function regulation, cytotoxic and antibacterial effects, anti-aging and anti-oxidation, etc. Almost no obvious toxicity or side effect are observed and recorded for Codonopsis . Conclusions The traditional uses, phytochemistry, pharmacology and toxicology of Codonopsis are reviewed in this paper. Species of the genus have long been used as traditional medicines and food materials, they are reported with a large number of chemical constituents with different structures, extensive pharmacological activities in immune system, blood system, digestive system, etc. and almost no toxicity. More profound studies on less popular species, pharmacodynamic material basis and pharmacological mechanism, and quality assurance are suggested to be carried out to fulfil the research on the long-term clinical use and new drug research of Codonopsis . [ABSTRACT FROM AUTHOR]

Mitragyna speciosa (Kratom) is a psychoactive plant that has recently emerged as a recreational drug. Mitragyna alkaloids are not within the scope of traditional forensic toxicology screening methods, which may contribute to under-reporting. Solid phase extraction (SPE) and liquid chromatography-quadrupole/time of flight mass spectrometry (LC-Q/TOF-MS) were used to identify five alkaloids in urine. Target analytes included the two known psychoactive compounds, mitragynine and 7-hydroxymitragynine, in addition to speciociliatine, speciogynine, and paynantheine. Two deuterated internal standards (mitragynine-D 3 and 7-hydroxymitragynine-D 3 ) were employed. Using traditional reversed phase chromatography all compounds and isomers were separated in 10 min. The procedure was validated in accordance with the Scientific Working Group for Forensic Toxicology (SWGTOX) Standard Practices for Method Validation. Extraction efficiencies were 63–96% and limits of quantitation were 0.5–1 ng/mL. Precision, bias and matrix effects were all within acceptable thresholds, with the exception of 7-hydroxymitragynine, which is notably unstable and unsuitable for quantitative analysis. In this paper we present a simultaneous quantitative analytical method for mitragynine, speciociliatine, speciogynine and paynantheine, and a qualitative assay for 7-hydroxymitragynine in urine using high resolution mass spectrometry (HRMS). [ABSTRACT FROM AUTHOR]