Correction: Dong et al. Identification of the Trace Components in BopuzongJian and Macleaya cordata Extract Using LC-MS Combined with a Screening Method. Molecules 2021, 26, 3851.

The article in question [...].

Plants of the Genus Zingiber: A Review of Their Ethnomedicine, Phytochemistry and Pharmacology.

Plant of the genus Zingiber (Zingiberaceae) have primarily distributed in subtropical and tropical Asia, South America and Africa. The species of this genus have been widely used as food and in folk with a long history for treating various diseases. Reports related to the phytochemistry and phytochemistry of Zingiber species are numerous, but articles on the summary of the genus Zingiber remain scarce. This review aims at presenting comprehensive information about the genus Zingiber and providing a reference for the future application by systematically reviewing the literature from 1981 to 2020. Currently, a total of 447 phytochemical constituents have been isolated and identified from this genus, in which volatile oils, diarylheptanoids, gingerols, flavonoids and terpenoids are the major components. Gingerols, which are the main functional components, are the spicy and aromatic ingredients in the Zingiber species. Extracts and single compounds from Zingiber plants have been discovered to possess numerous biological functions, such as anti-inflammatory, anticancer, antimicrobial, larvicidal, antioxidant and hypoglycemic activities. This review provides new insights into the ethnomedicine, phytochemistry and pharmacology of the genus Zingiber and brings to the forefront key findings on the functional components of this genus in food and pharmaceutical industries.

Effect of Natural Antioxidants from Marigolds (Tagetes erecta L.) on the Oxidative Stability of Soybean Oil.

In recent years, synthetic antioxidants that are widely used in foods have been shown to cause detrimental health effects, and there has been growing interest in antioxidants realised from natural plant extracts. In this study, we investigate the potential effects of natural antioxidant components extracted from the forage plant marigold on the oxidative stability of soybean oil. First, HPLC-Q-TOF-MS/MS was used with 1,1-diphenyl-2-picrylhydrazyl (DPPH) to screen and identify potential antioxidant components in marigold. Four main antioxidant components were identified, including quercetagetin-7-O-glucoside (1), quercetagetin (2), quercetin (3) and patuletin (4). Among them, quercetagetin (QG) exhibited the highest content and the strongest DPPH radical scavenging activity and effectively inhibited the production of oxidation products in soybean oil during accelerated oxidation, as indicated by reductions in the peroxide value (PV) and acid value (AV). Then, the fatty acids and volatile compounds of soybean oil were determined with gas chromatography-mass spectrometry (GC-MS) and headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS). A total of 108 volatile components, including 16 alcohols, 23 aldehydes, 25 ketones, 4 acids, 15 esters, 18 hydrocarbons, and 7 other compounds, were identified. QG significantly reduced the content and number of aldehydes and ketones, whereas the formation of acids and hydrocarbons was completely prevented. In addition, the fatty acid analysis demonstrated that QG significantly inhibited oxidation of unsaturated fatty acids. Consequently, QG was identified as a potential, new natural antioxidant that is believed to be safe, effective and economical, and it may have potential for use in plant extracts feed additives.

Identification of the Impurities in Bopu Powder® and Sangrovit® by LC-MS Combined with a Screening Method.

Bopu powder® and Sangrovit® were developed from Macleayacordata and are widely used in agriculture and animal husbandry, but their impurities have been rarely reported in the literature. Impurity analysis is of great importance to the quality and safety of veterinary drugs. In this study, high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS) combined with a screening method was used to screen and characterize the impurities in Bopu powder® and Sangrovit®. A total of 58 impurities were screened from Bopu powder® and Sangrovit® using the screening strategies, of which 39 were identified by their accurate m/z value, characteristic MS/MS data, and fragmentation pathways of references. This established method was used for impurity analysis for the first time and proved to be a useful and rapid tool to screen and identify the impurities of Bopu powder® and Sangrovit®, especially for those at trace levels in a complex sample. In addition, this study marks the first comprehensive research into impurities in these two products and has great significance for the systematic detection of impurities in other plant-derived drugs.

Systematic identification of compounds in Macleaya microcarpa by high-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry combined with mass spectral fragmentation behavior of Macleaya alkaloids.

RATIONALE: Macleaya microcarpa (Maxim.) Fedde belongs to the genus Macleaya of the Papaveraceae family. Benzylisoquinoline alkaloids (BIAs) are considered the main bioactive constituents of M. microcarpa. METHODS: Using high-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (HPLC/QTOFMS/MS) we identified BIAs in the aerial parts of M. microcarpa in the early flowering stage. Target profiling and identification of BIAs in the extracted samples from the fresh aerial parts of M. microcarpa were exclusively based on a personal, accurate, mass database of known compounds and the mass spectral fragmentation behavior of Macleaya alkaloids. RESULTS: A total of 97 alkaloids, comprising 7 benzyltetrahydroisoquinolines, 1aporphine, 9 tetraprotoberberines, 3 protoberberines, 2 N-methyltetrahydroprotoberberines, 4 protopines, 47 dihydrobenzophenanthridines, and 24 benzophenanthridines, were identified from the fresh aerial parts of M. microcarpa, and 77 of these were detected for the first time in M. microcarpa. In addition, some of the screened alkaloids were related to the biosynthetic pathways of sanguinarine and chelerythrine. CONCLUSIONS: The integrated method is sensitive and reliable for screening and identifying trace or ultra-trace isoquinoline alkaloids and has contributed to a better understanding of BIAs in the fresh aerial parts of M. microcarpa.

Chemical Composition and Bioactivity of Essential Oil of Ten Labiatae Species.

Using antibiotics as feed additives have been successively banned worldwide from 1986; therefore, it is an urgent task to finding safe and effective alternatives. As natural products of plant origin, essential oils (EOs) are an outstanding option due to their reported bioactivity. In this research, ten EOs of Labiatae species were extracted by steam distillation and its chemical constituents were identified by gas chromatography-mass spectrometry (GC-MS). A total of 123 chemical compounds, including alkenes, phenols, aldehydes and ketones, were identified. The results of antioxidant activity carried out through DPPH free radical scavenging (DPPH) and ferric reducing antioxidant power (FRAP), showing that EOs of Ocimum basilicum Linn. (ObEO), Thymus mongolicus Ronn. (TmEO), Origanum vulgare Linn. (OvEO) and Mosla chinensis Maxim. (McEO) have strong antioxidant activities. Their 50%-inhibitory concentration (IC50) value was <1.00, 1.42, 1.47 and 1.92 µg/mL, respectively; and their FRAP value was 1536.67 ± 24.22, 271.84 ± 4.93, 633.71 ± 13.14 and 480.66 ± 29.90, respectively. The results of filter paper diffusion showing that McEO, OvEO and TmEO inhibition zone diameter (IZD) are all over 30 mm. The results of two-fold dilution method showed that McEO, OvEO and TmEO have strong antibacterial activities against Staphylococcus aureus (S. aureus) and their minimal inhibitory concentrations (MIC) value was 1 µL/mL, 2 µL/mL, and 2 µL/mL, respectively. In conclusion, the results in this work demonstrate the possibility for development and application of EOs as potential feed additives.

Systematic Detection and Identification of Bioactive Ingredients from Citrus aurantium L. var. amara Using HPLC-Q-TOF-MS Combined with a Screening Method.

Bitter orange, Citrus aurantium L. var. amara (CAVA), is an important crop and its flowers and fruits are widely used in China as a food spice, as well as in traditional Chinese medicine, due to its health-promoting properties. The secondary metabolites that are present in plant-derived foods or medicines are, in part, responsible for the health benefits and desirable flavor profiles. Nevertheless, detailed information about the bioactive ingredients in CAVA is scarce. Therefore, this study was aimed at exploring the phytochemicals of CAVA by high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). Here, a systematic screening method combined with HPLC-Q-TOF-MS was presented. This technique was used to systematically screen metabolites, primarily from the complex matrix of CAVA, and to identify these compounds by their exact masses, characteristic fragment ions, and fragmentation behaviors. A total of 295 metabolites were screened by the screening method and 89 phytochemicals were identified in the flowers, fruits, roots, leaves, and branches of CAVA. For the first time, 69 phytochemicals (flavonoids, alkaloids, terpenoids, etc.) were reported from CAVA. The results highlight the importance of CAVA as a source of secondary metabolites in the food, medicine, and nutraceutical industries.

Medicinal plants of the genus Macleaya (Macleaya cordata, Macleaya microcarpa): A review of their phytochemistry, pharmacology, and toxicology.

In the genus Macleaya, Macleaya cordata and Macleaya microcarpa have been recognized as traditional herbs that are primarily distributed in China, North America, and Europe and have a long history of medicinal usage. These herbs have been long valued and studied for detumescence, detoxification, and insecticidal effect. This review aims to provide comprehensive information on botanical, phytochemical, pharmacological, and toxicological studies on plants in the genus Macleaya. Plants from the genus of Macleaya provide a source of bioactive compounds, primarily alkaloids, with remarkable diversity and complex architectures, thereby having attracted attention from researchers. To date, 291 constituents have been identified and/or isolated from this group. These purified compounds and/or crude extract possess antitumor, anti-inflammatory, insecticidal, and antibacterial activities in addition to certain potential toxicities. Macleaya species hold potential for medicinal applications. However, despite the pharmacological studies on these plants, the mechanisms underlying the biological activities of active ingredients derived from Macleaya have not been thoroughly elucidated to date. Additionally, there is a need for research focusing on in vivo medical effects of Macleaya compounds and, eventually, for clinical trials.

Metal-Free Photoredox Catalyzed Cyclization of O-(2,4-Dinitrophenyl)oximes to Phenanthridines.

A metal-free visible-light photoredox-catalyzed intermolecular cyclization reaction of O-2,4-dinitrophenyl oximes to phenanthridines was developed. In this study, the organic dye eosin Y and i-Pr2NEt were used as photocatalyst and terminal reductant, respectively. The oxime substrates were transformed into iminyl radical intermediates by single-electron reduction, which then underwent intermolecular homolytic aromatic substitution (HAS) reactions to give phenanthridine derivatives.

[Study on Alkaloids of Fruit from Macleaya cordata].

Objective: To study the alkaloids from the fruit of Macleaya cordata. Methods: The alkaloids were isolated and purified by silica gel column chromatography and preparative high performance liquid chromatography,and the structures were elucidated based on the spectral data. Results: Eight alkaloids were obtained from the fraction of ethanol extract and identified as 6-cyanodihydrosanguinarine( 1),6-acetonyldihydrosanguinarine( 2),6-acetonyldihydrochelerythrine( 3),chelerythrine( 4),dihydrochelerythrine( 5),13,14-dehydrogen-N-methyl-coptisine( 6),N-methyl-canadine( 7) and berberine( 8). Conclusion: Compounds 1 and 6 are new nature products,and compound 7 is isolated from this plant for the first time.

[Chemical Constituents from the Roots of Macleaya cordata].

Objective: To investigate the chemical constituents from the roots of Macleaya cordata. Methods: The compounds were isolated and purified by silica gel,recrystallization and semi-preparative HPLC, their structures were eclucidated by physicochemistry properties, MS and NMR. Results: Seven compounds were isolated and identified as 6-cyanodihydrochelerythrine (1),6-cyanodihydrochelilutine (2),dihydrochelirubine (3),6-methoxynorchelerythrine (4),dihydrosanguinarine (5),6-actonyldihydrosanguinarine (6) and stigmasterol (7). Conclusion: Compounds 1,2 are new natural compounds and compound 4 is obtained from Macleaya cordata for the first time.

Structural speculation and identification of alkaloids in Macleaya cordata fruits by high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry combined with a screening procedure.

RATIONALE: Alkaloids with significant therapeutic effects are the main active constituents of Macleaya cordata, which is a perennial herb plant in the Papaveraceae family. A systematic and novel method for speculating and identifying the structures of alkaloids in M. cordata fruits by high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (HPLC/Q-TOF-MS) with a screening procedure was reported. METHODS: Investigation of mass spectral fragmentation of alkaloids was carried out based on the tandem mass spectrometry (MS/MS) data analyses of eight reference substances. The skeletons of alkaloids were determined by their ultraviolet spectra (UV) and MS/MS data. The substituent groups of the alkaloids were acquired through a screening procedure developed in our laboratory and MS/MS data. The substituent linkage sites were deduced by MS/MS fragmentation behavior, as well as biosynthetic pathways of related alkaloids. RESULTS: The structures of 21 alkaloids were speculated in this study, 10 of which were reported for the first time in M. cordata. Furthermore, benzyltetrahydroisoquinoline and N-methyltetrahydroprotoberberine-type alkaloids were discovered, which indirectly proved that the biosynthetic pathways of benzophenanthridine alkaloids reported in Eschscholtzia california existed in M. cordata as well. CONCLUSIONS: HPLC/Q-TOF-MS combined with a screening procedure was a systematic and reliable method for speculating and elucidating the structures of alkaloids. This study might be useful for the identification of other compounds in herbal medicines.

Synthesis of 5-methyl phenanthridium derivatives: a new class of human DOPA decarboxylase inhibitors.

DOPA decarboxylase (DDC) is responsible for the decarboxylation of l-DOPA and related aromatic amino acids and correlates closely with a number of clinical disorders. Sanguinarine, a natural quaternary benzophenanthridine alkaloid (QBA), was reported to be inhibitor of rat DDC and possessed a different inhibitory mechanism. In this study, several natural QBAs were assayed as human DDC inhibitors for the first time. A series of 5-methyl phenanthridium derivatives that contain the basic core structure of QBAs were also synthesized and evaluated as human DDC inhibitors. The title compounds still possessed DDC inhibitory potential. Among the synthesized compounds, 2-hydroxyl-8-methoxy-5-methylphenanthridinium chloride (11k) showed good inhibitory activity with an IC50 value of 0.12mM. Preliminary structure-activity relationship indicated that DDC inhibitory potential of 5-methyl phenanthridium derivatives correlated with the π-electro densities on CN double bond of iminium cation. The hydroxyl group on compound 11k possibly contributed to the formation of hydrogen bond between DDC and the inhibitor.

Non-targeted Metabolomics Analysis Reveals Distinct Metabolic Profiles Between Positive and Negative Emotional Tears of Humans: A Preliminary Study.

Background Basal, reflex, and emotional tears differ in chemical components. It is not yet known whether chemical differences exist in tears of different emotions. We investigated the biochemical basis of emotional tears by performing non-targeted metabolomics analyses of positive and negative emotional tears of humans. Methods Samples of reflex, negative, and positive emotional tears were obtained from 12 healthy college participants (11 females and one male). Untargeted metabolomics was performed to identify metabolites in different types of tears. The differentially altered metabolites were screened and assessed using univariate and multivariate analyses. Results The orthogonal partial least squares discriminant analysis model showed that reflex, negative, and positive emotional tears were clearly separated. A total of 133 significantly differentially expressed metabolites of electrospray ionization source (ESI-) mode were identified between negative and positive emotional tears. The top 50 differentially expressed metabolites between negative and positive emotional tears were highly correlated. Pathway analysis revealed that secretion of negative emotional tears was associated with some synapses in the brain, regulation of a series of endocrine hormones, including the estrogen signaling pathway, and inflammation activities, while secretion of positive emotional tears was correlated with biotin and caffeine metabolism. Conclusions It is indicated that metabolic profiles of reflex, positive, and negative emotional tears of humans are distinct, and secretion of the tears involves distinct biological activities. Therefore, we present a chemical method for detecting human emotions, which may become a powerful tool for the diagnosis of mental diseases and the identification of fake tears.

Antidepressant-like activity, active components and related mechanism of Hemerocallis citrina Baroni extracts.

Hemerocallis citrina Baroni [Asphodelaceae], which is traditional herbal medicine, has been widely used for treating depressive disorders in Eastern-Asia countries. However, the active compounds and corresponding mechanism of anti-depression are not yet completely clarified. In this study, the anti-depressive activities of six H. citrina extracts were primarily evaluated. The results showed that the water extract of H. citrina flowers (HCW) displays significant anti-depressive activity. A total of 32 metabolites were identified from HCW by high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS) and nuclear magnetic resonance (NMR). And then, the anti-depressive activity of the high-level compound (rutin) in HCW was also estimated. The results indicated that rutin displayed significant anti-depressive activity and was one of the main active ingredients. Finally, the anti-depressive mechanisms of HCW and rutin were investigated based on the intestinal microorganisms. The results showed that HCW and rutin increase the diversity and richness of the intestinal flora and regulate the specific intestinal microorganisms such as Bacteroides and Desulfovibrio genera in depressed mice. This work marks the first comprehensive study of the active components, anti-depressive activities and corresponding mechanisms of different H. citrina extracts, which provide a potential possibility for developing new antidepressants.

Identification of seven undescribed cucurbitacins in Cucumis sativus (cucumber) and their cytotoxic activity.

Cucurbitacin C-type cucurbitacins that are only identified in Cucumis sativus (cucumber) are, in part, responsible for the health benefits and bitter flavor. Nevertheless, detailed information about those functional ingredients in cucumber is scarce. In this study, ten cucurbitacin C analogues including seven undescribed ones have been isolated from the bitter leaves of cucumber, in which six compounds showed growth inhibition capabilities against tumor cell lines HepG2, A549, DU145 and HCT116. Intriguingly, cucurbitacin C6 and C7 exhibited a significant inhibition effect compared to the positive control taxol (IC50 = 1.86 ± 0.17 µM) on HepG2 cell line with IC50 values of 10.06 ± 0.34 µM and 4.16 ± 0.42 µM, respectively. The mechanism of cucurbitacin-induced apoptosis is likely down-regulating the expression of caspase-related proteins. This work enlarges the knowledge of the cucurbitacins in cucumber and highlights the importance of cucumber as a source of specialized metabolites in the food and medicinal industries.

Establishing the metabolic network of isoquinoline alkaloids from the Macleaya genus.

Metabolic networks can provide insight into the biosynthesis pathways of natural products present in plant-derived medicines. Here, we primarily established a highly efficient and targeted method for the systematic screening of isoquinoline alkaloids from the Macleaya genus. A total of 392 potential alkaloids were detected, 204 of which were further identified according to their tandem mass spectrometry (MS/MS) spectra and the characteristic fragmentation patterns of references. A metabolic network of isoquinoline alkaloids from the Macleaya genus was then constructed based on the structural relationships, metabolic level differences, and the isotopically labeled [ring-13C6]-tyrosine feeding experiments. New biosynthesis pathways for well-known alkaloids (berberine, sanguinarine, and chelerythrine) in the Macleaya genus were proposed on the basis of the established metabolic network. This work marks the first comprehensive study of the metabolic network of isoquinoline alkaloids in the Macleaya genus and provides a template for constructing the metabolic networks of other plant-derived medicines.

Influence of different elicitors on BIA production in Macleaya cordata.

Sanguinarine (SAN) and chelerythrine (CHE) have been widely used as substitutes for antibiotics for decades. For a long time, SAN and CHE have been extracted from mainly Macleaya cordata, a plant species that is a traditional herb in China and belongs to the Papaveraceae family. However, with the sharp increase in demand for SAN and CHE, it is necessary to develop a new method to enhance the supply of raw materials. Here, we used methyl jasmonate (MJ), salicylic acid (SA) and wounding alone and in combination to stimulate aseptic seedlings of M. cordata at 0 h, 24 h, 72 h and 120 h and then compared the differences in metabolic profiles and gene expression. Ultimately, we found that the effect of using MJ alone was the best treatment, with the contents of SAN and CHE increasing by 10- and 14-fold, respectively. However, the increased SAN and CHE contents in response to combined wounding and MJ were less than those for induced by the treatment with MJ alone. Additionally, after MJ treatment, SAN and CHE biosynthetic pathway genes, such as those encoding the protopine 6-hydroxylase and dihydrobenzophenanthridine oxidase enzymes, were highly expressed, which is consistent with the accumulation of SAN and CHE. At the same time, we have also studied the changes in the content of synthetic intermediates of SAN and CHE after elicitor induction. This study is the first systematic research report about using elicitors to increase the SAN and CHE in Macleaya cordata.

Fermented traditional Chinese medicine alters the intestinal microbiota composition of broiler chickens.

For a long time, phytogenic resources have been widely used as substitutes for antibiotics in livestock production. However, few studies have examined the relationship between the intestinal microbiota and fermented herbal medicines. Here, 252 Arbor Acres broiler plus broiler chickens were randomly assigned to a control group, which was fed a basal diet; an unfermented healthy chicken powder group (JJS) fed a basal diet containing 20 g/kg JJS; or one of 5 fermented JJS groups, which were fed a basal diet containing 20 g/kg JJS, fermented with by 5 different bacterial strains for 42 days. The growth performances of the different groups were measured and the changes in the intestinal microbiota were analyzed. The body weight gain in the Bacillus subtilis group (Bs) was the highest among the 6 groups, while the feed conversion ratio (FCR) was best with Z. rouxii fermentation. The result indicated that products of JJS fermentation products of JJS by B. subtilis and Z. rouxii had important effects on chicken growth performance. The foregut and hindgut microbial communities of Bs, Zr, the control group and the JJS group, were collected for 16S rDNA sequencing. The results showed that JJS and its fermentation products mainly acted on the foregut and had little effect on the hindgut, and Z. rouxii fermentation products can increased the diversity in the foregut microbial community. In addition, the relative abundance of Bifidobacterium in the foregut of the Z. rouxii group was significantly increased, which may be an important factor in promoting growth.

The chromosome-level Hemerocallis citrina Borani genome provides new insights into the rutin biosynthesis and the lack of colchicine.

Hemerocallis citrina Borani (huang hua cai in Chinese) is an important horticultural crop whose flower buds are widely consumed as a delicious vegetable in Asia. Here we assembled a high-quality reference genome of H. citrina using single-molecule sequencing and Hi-C technologies. The genome assembly was 3.77 Gb and consisted of 3183 contigs with a contig N50 of 2.09 Mb, which were further clustered into 11 pseudochromosomes. A larger portion (3.25 Gb or 86.20%) was annotated as a repetitive content and 54,295 protein-coding genes were annotated in the genome. Genome evolution analysis showed that H. citrina experienced a recent whole-genome duplication (WGD) event at ~15.73 million years ago (Mya), which was the main factor leading to many multiple copies of orthologous genes. We used this reference genome to predict 20 genes involved in the rutin biosynthesis pathway. Moreover, our metabolomics data revealed neither colchicine nor its precursors in H. citrina, challenging the long-standing belief that this alkaloid causes poisoning by the plant. The results of our disruptive research are further substantiated by our genomic finding that H. citrina does not contain any genes involved in colchicine biosynthesis. The high-quality genome lays a solid foundation for genetic research and molecular breeding of H. citrina.