Lactation-promoting ingredients of Hemerocallis citrina Borani and the corresponding mechanisms.

Hemerocallis citrina Borani is a traditional folk food used to promote the lactation of postpartum mothers in China; however, the active ingredients and corresponding mechanisms are still unknown. In this study, the lactogenic effect of alcoholic and aqueous extracts of H. citrina was primarily evaluated, and the aqueous extract (1,000 and 2,000 mg/kg) displayed significant lactation-promoting effects. Three eluates of the aqueous extract (0%, 30%, and 50%HCW) were further evaluated for their lactogenic effect, and 30% and 50% HCW showed significant lactation-promoting activity. Nineteen ingredients, including those with a high content of rutin and isoquercetin, were then identified from 30% and 50%HCW using the ultra-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) method. Finally, the lactogenic effect of rutin and isoquercetin was evaluated, and both compounds displayed significant lactation-promoting activity. The mechanisms relative to the lactation-promoting active ingredients for H. citrina extracts and compounds are to stimulate the release of prolactin (PRL) and progesterone (P), as well as to induce the expression of prolactin receptor (PRLR) and improve the morphology of mammary tissue. This study first clarified the lactation-promoting active ingredients of H. citrina and the corresponding mechanisms, which provide a new insight into the new lactation-promoting drug and promote the high-value utilization of H. citrina resources.

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 [...].

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.

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 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.

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.

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.

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.

Plant-derived isoquinoline alkaloids that target ergosterol biosynthesis discovered by using a novel antifungal screening tool.

The ergosterol pathway is a prime antifungal target as it is required for fungal survival, yet is not involved in human homeostasis. Methods to study the ergosterol pathway, however, are often time-consuming. The minimum inhibitory concentration (MIC) assay is a simple research tool that determines the lowest concentration at which a novel antimicrobial is active in vitro with limited scope to determine the mechanism of action for a drug. In this study, we show that by adding hydrogen peroxide, an oxidative stressor, or glutathione (GSH), an antioxidant, to modify a commonly performed MIC assay allowed us to screen selectively for new antifungal drugs that target ergosterol biosynthesis in fungi. A human pathogen and dermatophyte, Microsporum gypseum, was used as a test organism. When exposed to ergosterol targeting drugs, the hydrogen peroxide treatment significantly decreased fungal survival by reducing ergosterol in the cell wall, whereas GSH increased survival of M. gypseum. Further, by performing a series of experiments with M. gypseum and Trichophyton rubrum, it was determined that the oxidative stress from hydrogen peroxide causes cell death at different developmental stages based on fungal species. These findings allow us to describe a simple, high-throughput method for simultaneously screening new antifungal drugs for activity and effects on the ergosterol pathway. By using this tool, two isoquinoline alkaloids were discovered to be potent inhibitors of ergosterol biosynthesis in vitro by reducing the amount of ergosterol without affecting the expression of 1,3-ß-glucan. Both compounds also significantly reduced the severity of acanthosis, hyperkeratosis, spongiosis and dermal edema in vivo.

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.

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.

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 identification metabolites of Hemerocallis citrina Borani by high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry combined with a screening method.

Hemerocallis citrina Borani is an important crop and its flower buds are widely consumed in East Asian areas as a vegetable, as well as in traditional Chinese medicine, due to its health-promoting properties. Metabolites present in plant-derived foods or medicines are in part responsible for their desirable flavor profiles and health benefits. Nevertheless, detailed information about these compounds in H. citrina is scarce. Therefore, this study aimed to investigate the metabolites by high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). In this study, a total of 144 compounds, including 14 amides, 25 polyphenols, 44 flavonols, 35 anthraquinones, 15 naphthols, and 11 other components, were detected by the established screening method and were identified by their precise m/z values, characteristic tandem mass spectrometry (MS/MS) data and fragmentation pathways of references, 111 of which were reported in this plant for the first time. The distribution of identified ingredients in different parts of H. citrina was determined. Interestingly, colchicine, which had been reported as a toxic compound in the fresh flower buds in previous studies and various news reports, was not found. This work marks the first comprehensive study of metabolites from commercial flower buds and different parts of H. citrina.

Investigation of fragmentation behaviours of isoquinoline alkaloids by mass spectrometry combined with computational chemistry.

Isoquinoline alkaloids, which are one of the most important types of alkaloids, are extensively distributed in herbal medicines. However, systematic and comprehensive investigations of the fragmentation behaviours of isoquinoline alkaloids have rarely been reported. Therefore, the goal of the present study is to simultaneously investigate the collision-induced dissociation patterns and the corresponding mechanism of isoquinoline alkaloids by mass spectrometry (MS) combined with computations. Nineteen types of isoquinoline alkaloids (66 compounds) were used as references to identify the characteristic fragmentation behaviours by quadrupole time-of-flight mass spectrometry (Q-TOF/MS) in positive electrospray ionization (ESI) mode. These types of isoquinoline alkaloids were divided into three categories primarily by the characteristic [M-NHR1R2]+ (R1 and R2 represent the substituent groups of the N-atom) fragment ions. High- and low-abundance [M-NHR1R2]+ ions were observed respectively for type I (1-13) and type II (14-29) alkaloids, respectively; however, the characteristic fragments were not detected for type III alkaloids (30-66) because of the existence of a p-π conjugated system. Each type of alkaloid was further classified by its characteristic fragmentation patterns and fragment ions. In addition, isoquinoline alkaloid with vicinal methoxy and hydroxy, vicinal methoxy, methylenedioxy, methoxy, and quaternary N-methyl groups could form the characteristic fragments by the loss of CH3OH, CH4, CH2O or CO, CH3 and CO, and CH3 moieties, respectively. The mechanisms of some interesting fragmentation behaviours, such as the formation of [M-NH3]+ and [M-CH3]+ fragment ions, were further demonstrated by computational chemistry. These characteristic fragmentation behaviours and fragment ions of isoquinoline alkaloids provide a solid foundation for the rapid and high-efficiency structural elucidation of similar metabolites in plant-derived medicines.

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.

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.

The chicken gut metagenome and the modulatory effects of plant-derived benzylisoquinoline alkaloids.

BACKGROUND: Sub-therapeutic antibiotics are widely used as growth promoters in the poultry industry; however, the resulting antibiotic resistance threatens public health. A plant-derived growth promoter, Macleaya cordata extract (MCE), with effective ingredients of benzylisoquinoline alkaloids, is a potential alternative to antibiotic growth promoters. Altered intestinal microbiota play important roles in growth promotion, but the underlying mechanism remains unknown. RESULTS: We generated 1.64 terabases of metagenomic data from 495 chicken intestinal digesta samples and constructed a comprehensive chicken gut microbial gene catalog (9.04 million genes), which is also the first gene catalog of an animal's gut microbiome that covers all intestinal compartments. Then, we identified the distinctive characteristics and temporal changes in the foregut and hindgut microbiota. Next, we assessed the impact of MCE on chickens and gut microbiota. Chickens fed with MCE had improved growth performance, and major microbial changes were confined to the foregut, with the predominant role of Lactobacillus being enhanced, and the amino acids, vitamins, and secondary bile acids biosynthesis pathways being upregulated, but lacked the accumulation of antibiotic-resistance genes. In comparison, treatment with chlortetracycline similarly enriched some biosynthesis pathways of nutrients in the foregut microbiota, but elicited an increase in antibiotic-producing bacteria and antibiotic-resistance genes. CONCLUSION: The reference gene catalog of the chicken gut microbiome is an important supplement to animal gut metagenomes. Metagenomic analysis provides insights into the growth-promoting mechanism of MCE, and underscored the importance of utilizing safe and effective growth promoters.

Anticancer and Reversing Multidrug Resistance Activities of Natural Isoquinoline Alkaloids and their Structure-activity Relationship.

The severe anticancer situation as well as the emergence of multidrug-resistant (MDR) cancer cells has created an urgent need for the development of novel anticancer drugs with different mechanisms of action. A large number of natural alkaloids, such as paclitaxel, vinblastine and camptothecin have already been successfully developed into chemotherapy agents. Following the success of these natural products, in this review, twenty-six types of isoquinoline alkaloids (a total of 379 alkaloids), including benzyltetrahydroisoquinoline, aporphine, oxoaporphine, isooxoaporphine, dimeric aporphine, bisbenzylisoquinoline, tetrahydroprotoberberine, protoberberine, protopine, dihydrobenzophenanthridine, benzophenanthridine, benzophenanthridine dimer, ipecac, simple isoquinoline, pavine, montanine, erythrina, chelidonine, tropoloisoquinoline, azafluoranthene, phthalideisoquinoline, naphthylisoquinoline, lycorine, crinane, narciclasine, and phenanthridone, were summarized based on their cytotoxic and MDR reversing activities against various cancer cells. Additionally, the structure-activity relationships of different types of isoquinoline alkaloid were also discussed. Interestingly, some aporphine, oxoaporphine, isooxoaporphine, bisbenzylisoquinoline, and protoberberine alkaloids display more potent anticancer activities or anti-MDR effects than positive control against the tested cancer cells and are regarded as attractive targets for discovery new anticancer drugs or lead compounds.