Analysis of the Coptis chinensis genome reveals the diversification of protoberberine-type alkaloids.
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ABSTRACT:
SUBMITTER: Liu Y
PROVIDER: S-EPMC8172641 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Protoberberine alkaloids are a group of tetracyclic isoquinoline compounds known for their well-established antimicrobial and anti-inflammatory properties. The richness and diversity of protoberberine alkaloids accumulated in the Coptis genus necessitate a comprehensive examination of the biosynthetic machinery to understand their ecological significance. Here, from Coptis chinensis we identified CcCYP719A1, which could install a methylenedioxy bridge on either ring A or ring D of the protoberberine backbone, thus diverging metabolite flux towards the biosynthesis of various protoberberine components. We also obtained CcCYP719A2 and CcCYP719A3, which underwent positive selection after diverging from CcCYP719A1 and maintained specific catalytic activity on ring D. Further, we resolved the biosynthetic pathway of jatrorrhizine by identifying two demethylases, which could also modulate protoberberine composition by removing the C-3 methyl group and methylenedioxy bridge of ring D, allowing demethylated metabolites to be redirected into different routes. Moreover, we characterized 2-O-methyltransferase CcOMT1 and flavin-dependent oxidase CcTHBO, respectively responsible for the commonly observed 2-O-methylation and aromatic ring-C assembly in protoberberine alkaloids. Overall, this study reveals an interconnected metabolite network from which diverse protoberberine alkaloids originate. It provides valuable insights into the existence of undiscovered protoberberine components, and paves the way for the targeted production of desired protoberberine components for potential therapeutic development.
| S-EPMC10812381 | biostudies-literature
Project description:Coptis chinensis Franch. (Huanglian in Chinese) is an important economic crop with medicinal value. Its rhizome has been used as a traditional herbal medicine for thousands of years in Asia. Protoberberine alkaloids, as the main bioactive component of Coptis chinensis, have a series of pharmacological activities. However, the protoberberine alkaloids content of C. chinensis is relatively low. Understanding the molecular mechanisms affecting the transcriptional regulation of protoberberine alkaloids would be crucial to increase their production via metabolic engineering. WRKY, one of the largest plant-specific gene families, regulates plant defense responses via the biosynthesis of specialized metabolites such as alkaloids. Totally, 41 WRKY transcription factors (TFs) related to protoberberine alkaloid biosynthesis were identified in the C. chinensis genome and classified into three groups based on phylogenetic and conserved motif analyses. Three WRKY genes (CcWRKY7, CcWRKY29, and CcWRKY32) may regulate protoberberine alkaloid biosynthesis, as suggested by gene-specific expression patterns, metabolic pathways, phylogenetic, and dual-luciferase analysis. Furthermore, the CcWRKY7, CcWRKY29, and CcWRKY32 proteins were specifically detected in the nucleus via subcellular localization. This study provides a basis for understanding the regulatory mechanisms of protoberberine alkaloid biosynthesis and valuable information for breeding C. chinensis varieties.
| S-EPMC10076542 | biostudies-literature
Project description:BackgroundCoptis chinensis Franch is extensively used in traditional Chinese medicine to treat diabetes and dementia. Alkaloids are the main active ingredients of C. chinensis.PurposeThis study was designed to probe the effects and possible mechanisms of the total alkaloids from C. chinensis (TAC) on cognitive deficits in type 2 diabetic rats.MethodsCognitive deficits were induced in rats by streptozotocin and high glucose/high fat diet. After treatment with TAC (80, 120, and 180 mg/kg) for 24 weeks, the behavioral parameters of each rat were assessed by Morris water maze and Y-maze tests. The indexes of glucose and lipid metabolism, pathological changes of brain tissue, and the phosphorylation levels of insulin signaling related proteins were also evaluated.ResultsThe type 2 diabetic rats showed significantly elevated levels of fasting blood glucose, glycosylated hemoglobin and glycosylated serum protein, as well as apolipoprotein B, free fatty acid, triglyceride and total cholesterol but decreased the content of apolipoprotein A1, and TAC treatment dose-dependently reversed these abnormal changes. Furthermore, the behavioral results showed that TAC alleviated the cognitive deficits in type 2 diabetic rats. Moreover, immunohistochemical and histopathologic examinations indicated that the diabetic rats showed significant Aβ deposition, and neuronal damage and loss, which can be reversed by TAC treatment. The western blot results showed that TAC treatment markedly increased the phosphorylation of IRS, PI3K, and Akt, and inhibited the overactivation of GSK3β in the brain of type 2 diabetic rats.ConclusionThese findings conclude that TAC prevents diabetic cognitive deficits, most likely by ameliorating the disorder of glucose and lipid metabolism, attenuating Aβ deposition, and enhancing insulin signaling.
| S-EPMC6124445 | biostudies-literature
Project description:HPLC-DAD-directed isolation and purification of the methanol extract of stems of Arcangelisia gusanlung H. S. Lo. led to the isolation of a new protoberberine alkaloid, gusanlung E (1), along with fourteen known derivatives 2-15, seven of which were obtained from the genus Arcangelisia for the first time. The structures and absolute stereochemistry of these compounds were elucidated on the basis of spectroscopic analyses, including 1D and 2D NMR, mass spectrometry, and CD analyses. Gusanlung E (1) expressed weak cytotoxic activity against the SGC 7901 cell line with an IC50 value of 85.1 µM.
| S-EPMC6271463 | biostudies-literature
Project description:Coptidis alkaloids are the primary active components of Coptis chinensis Franch. Clinical and pharmacodynamic studies have confirmed that Coptidis alkaloids have multiple therapeutic effects including anti-inflammatory, antioxidant and antitumor effects, and they are usually used to treat various inflammatory disorders and related diseases. Mouse bone marrow cells (BMCs) were isolated from BALB/c mice. Immune-mediated destruction of BMCs was induced by interferon (IFN) -γ. High-performance liquid chromatography-electrospray ionization/ mass spectrometry was used to analyze the ingredients of the aqueous extract from Coptis chinensis Franch. The results confirmed that Coptidis alkaloids were the predominant ingredients in the aqueous extract from Coptis chinensis. The functional mechanism of Coptidis alkaloids in inhibiting immune-mediated destruction of BMCs was studied in vitro. After Coptidis alkaloid treatment, the percentages of apoptotic BMCs and the proliferation and differentiation of helper T (Th) cells and regulatory T (Treg) cells were measured by flow cytometry. The expression and distribution of T-bet in BMCs were observed by immunofluorescence. Western blotting analysis was used to assay the expression of key molecules in the Fas apoptosis and Jak/Stats signaling pathways in BMCs. We identified five alkaloids in the aqueous extract of Coptis chinensis. The apoptotic ratios of BMCs induced by IFN-γ were decreased significantly after Coptidis alkaloid treatment. The levels of key molecules (Fas, Caspase-3, cleaved Caspase-3, Caspase-8 and Caspase-8) in Fas apoptosis signaling pathways also decreased significantly after treatment with low concentrations of Coptidis alkaloids. Coptidis alkaloids were also found to inhibit the proliferation of Th1 and Th17 cells and induce the differentiation of Th2 and Treg cells; further, the distribution of T-bet in BMCs was decreased significantly. In addition, the levels of Stat-1, phospho-Stat-1 and phospho-Stat-3 were also reduced after Coptidis alkaloid treatment. These results indicate that Coptidis alkaloids extracted by water decoction from Coptis chinensis Franch could inhibit the proliferation and differentiation of T lymphocytes, attenuate the apoptosis of BMCs, and suppress the immune-mediated destruction of the BMCs induced by pro-inflammatory cytokines.
| S-EPMC7380622 | biostudies-literature
Project description:Coptis chinensis has been long used as the potential herbal remedy for the treatment of influenza A infection. The six isoquinolone alkaloids extracted from C. chinensis rhizomes are reported to have good inhibition activity on neuraminidase (NA) of Clostridium perfringens, A/H1N1/1918, and recombinant NA-1; however, the study of the effect of these candidates on other NAs of threatening influenza A causing pandemic and seasonal flu recently has not considered yet. The purpose of this study is to investigate the interaction between these compounds and NAs of different wild and mutant subtypes of influenza A. This process involved the molecular docking of 3D structures of those compounds (ligand) into target proteins NA of A/H1N1/1918, A/H1N1/2009pdm, H3N2/2010 wild type, H3N2/2010 D151G mutant, H5N1 wild type, and H5N1 H274Y mutant. Then, the Protein-Ligand Interaction Profiler (PLIP) was utilized to demonstrate the bond formed between the ligand and the binding pocket of receptors of interest. The results showed that six candidates including palmatine, berberine, jatrorrhizine, epiberberine, columbamine, and coptisine have a higher affinity to all six selected proteins than commercial drugs such as oseltamivir, zanamivir, and natural binding ligand sialic acid. The results could be explained via the 2D picture, which showed the hydrophobic interaction and hydrogen bonding forming between the oxygen molecules of the ligand with the free residue of proteins.
| S-EPMC7689928 | biostudies-literature
Project description:The Coptis chinensis Franch. is an important medicinal plant from the Ranunculales. We used next generation sequencing technology to determine the complete chloroplast genome of C. chinensis. This genome is 155,484?bp long with 38.17% GC content. Two 26,758?bp long inverted repeats separated the genome into a typical quadripartite structure. The C. chinensis chloroplast genome consists of 128 gene loci, including eight rRNA gene loci, 28 tRNA gene loci, and 92 protein-coding gene loci. Most of the SSRs in C. chinensis are poly-A/T. The numbers of mononucleotide SSRs in C. chinensis and other Ranunculaceae species are fewer than those in Berberidaceae species, while the number of dinucleotide SSRs is greater than that in the Berberidaceae. C. chinensis diverged from other Ranunculaceae species an estimated 81 million years ago (Mya). The divergence between Ranunculaceae and Berberidaceae was ~111 Mya, while the Ranunculales and Magnoliaceae shared a common ancestor during the Jurassic, ~153 Mya. Position 104 of the C. chinensis ndhG protein was identified as a positively selected site, indicating possible selection for the photosystem-chlororespiration system in C. chinensis. In summary, the complete sequencing and annotation of the C. chinensis chloroplast genome will facilitate future studies on this important medicinal species.
| S-EPMC5494076 | biostudies-literature
Project description:Coptis chinensis (CC) is widely used to treat diabetes in traditional Chinese medicine due to its significant hypoglycemic and hypolipidemic effects. It was reported that CC powders are more effective than CC decoctions. In this study, a rat model of type 2 diabetes was established and treated with supercritical-extracted CC and gastric juice extracted CC, respectively. Body weight, fasting plasma insulin, insulin resistance index, and lipid profiles were measured along with oral glucose tolerance tests (OGTTs). In addition, the levels of plasma proteins were compared between type 2 diabetic rats and CC-treated rats using an iTRAQ-based quantitative proteomic analysis. The results showed that the plasma levels of triglyceride (TC), total cholesterol (TG), and low-density lipoprotein (LDL) in rats of both CC-treated groups were significantly decreased. In addition, the proteomic analysis identified 929 proteins, while 15 proteins were selected from these 929 proteins based on their expression levels and bioinformatic results. Among these 15 proteins, 9 proteins (IGF-1, Igfbp4, Igfbp-6, Igfals, C2, C4, Cfi, Prdx-2, and Prdx-3) were upregulated in the two CC-treated groups, while 6 proteins (Pla2g7, Pcyox1, ApoC-1, ApoC-3, ApoB-100, and ApoE) were downregulated. The functions of these proteins are associated with glucose metabolism, insulin action, immunity, inflammation, lipid metabolism, oxidation, and antioxidation. The two differently extracted CC did not show significant differences in terms of their treatment efficacy. This research expanded our understanding on the therapeutic effects and mechanisms of CC in the treatment of type 2 diabetes.
| S-EPMC6158947 | biostudies-literature
Project description:BackgroundUnderstanding the spatial distribution of active compounds can effectively evaluate the quality of decoction pieces of traditional Chinese medicine (TCM). Traditional methods are economical and practical but lack chemical information on the original distribution. Time-of-flight secondary ion mass spectrometry (TOF-SIMS), with the advantage of non-destructive detection of samples, can directly analyze the distribution of chemical compounds on the surface of various samples.MethodsIn this study, TOF-SIMS image analysis technology was used to detect TCM for the first time. Taking Coptis rhizome (CR) as an example, a commonly used TCM, the distribution of the compounds in the cross-section of CR was studied. Meanwhile, ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLCQQQ-MS/MS) was used to verify the results of TOF-SIMS.ResultsThe distribution of nine active compounds: berberine, epiberberine, coptisine, palmatine, columbamine, jatrorrhizine, tetrahydricheilanthifolinium, and oxyberberine, was well imaged in the cross-section of CR by TOF-SIMS. The content of berberine and epiberberine was the highest; Palmatine distribution in the pith was more than that in other parts; Oxyberberine was mainly concentrated in the cork and xylem rays. Normalization analysis showed contents of these compounds increased along with the growth years. The result was consistent with UPLC-QQQ-MS/MS.ConclusionThe TOF-SIMS method can display the spatial distribution status of the active compounds of herbs, providing a basis for selecting the medicine site with non-destructive and fast detection.
| S-EPMC9816869 | biostudies-literature
Project description:Coptis chinensis is a traditional Chinese medicinal herb used for more than 2,000 years. Root rot in C. chinensis can cause brown discoloration (necrosis) in the fibrous roots and rhizomes, leading to plants wilting and dying. However, little information exists about the resistance mechanism and the potential pathogens of the root rot of C. chinensis plants. As a result, in order to investigate the relationship between the underlying molecular processes and the pathogenesis of root rot, transcriptome and microbiome analyses were performed on healthy and diseased C. chinensis rhizomes. This study found that root rot can lead to the significant reduction of medicinal components of Coptis, including thaliotrine, columbamine, epiberberin, coptisine, palmatine chloride, and berberine, affecting its efficacy quality. In the present study, Diaporthe eres, Fusarium avenaceum, and Fusarium solani were identified as the main pathogens causing root rot in C. chinensis. At the same time, the genes in phenylpropanoid biosynthesis, plant hormone signal transduction, plant-pathogen interaction, and alkaloid synthesis pathways were involved in the regulation of root rot resistance and medicinal component synthesis. In addition, harmful pathogens (D. eres, F. avenaceum and F. solani) also induce the expression of related genes in C. chinensis root tissues to reduce active medicinal ingredients. These results provide insights into the root rot tolerance study and pave the way for process disease resistance breeding and quality production of C. chinensis. IMPORTANCE Root rot disease significantly reduces the medicinal quality of Coptis chinensis. In the present study, results found that the C. chinensis fibrous and taproot have different tactics in response to rot pathogen infection. Diaporthe eres, Fusarium avenaceum, and Fusarium solani were isolated and identified to cause different degrees of C. chinensis root rot. These results are helpful for researchers to further explore the mechanism of resistance to rhizoma Coptis root rot.
| S-EPMC10101010 | biostudies-literature