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Salvia plebeia (Lamiaceae) is a valuable medicinal plant widely distributed across Asia and Oceania. However, the composition and accumulation patterns of its active ingredients in different organs during the growth and their biosynthetic mechanism remain unknown. Therefore, we conducted metabolite profiling, transcriptomic analysis, and biological functional verification to explore the distribution, accumulation, and biosynthesis mechanisms of flavonoids in S. plebeia. We identified 70 metabolites including 46 flavonoids, 16 phenolic acids, seven terpenoids, and one organic acid, of which 21 were previously unreported in S. plebeia. Combining metabolomic-transcriptomic analysis and biological functional verification, we identified the key genes involved in biosynthesis of its main active ingredients, hispidulin and homoplantaginin, including SpPAL, SpC4H, Sp4CL2, Sp4CL5, SpCHS1, SpCHI, SpFNS, SpF6H1, SpF6OMT1, SpF6OMT2, SpUGT1, SpUGT2, and SpUGT3. Using the identified genes, we reconstructed the hispidulin and homoplantaginin biosynthesis pathways in Escherichia coli, and obtained a yield of 5.33 and 3.86 mg/L for hispidulin and homoplantaginin, respectively. Our findings provide valuable insights into the changes in chemical components in different organs of S. plebeia during different growth and harvest stages and establishes a foundation for identifying and synthesizing its active components.
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BACKGROUND: Viola philippica Cav. is the only original plant for Violae Herba, as described in the Chinese Pharmacopoeia. The quality of this crude drug is affected by several adulterants from congeneric Viola species, and the authentic plant origin of Violae Herba is still controversial. Genome-based identification offers abundant genetic information and potential molecular markers that can be used for the authentication of closely related species. This study aims to investigate the certified origin of Violae Herba and to develop more effective markers for these easily confused species at the genetic level. METHODS: We compared the morphology and chemical composition of 18 batches of commercial samples and six widespread medicinal Viola plants used as Violae Herba or its substitutes by TLC and HPLC-Triple-TOF-MS/MS analyses. The complete chloroplast genomes of these species were sequenced and analyzed, including the general features, repeat sequences, mutational hotspots and phylogeny. The complete chloroplast genomes used as superbarcodes and some specific barcodes screened from mutational hotspots were tested for their ability to distinguish Viola species. RESULTS: A comparative study showed that Violae Herba is a multi-origin traditional Chinese medicine. Commercial decoction pieces and the standard reference drug were mainly derived from V. prionantha, clashing with the record in the Chinese Pharmacopoeia. Chloroplast genome analyses of V. philippica and five adulterants indicated that sequence divergence was relatively low within Viola species. By tree-based approaches, the complete chloroplast genomes showed a better discrimination ability and phylogenetic resolution for each Viola species. These results indicate that the whole chloroplast genomes can be used as superbarcodes to differentiate Viola medicinal plants. More specific DNA barcodes could be further developed from the Viola chloroplast genomes for more efficient and rapid identification of commercial Violae Herba and its adulterants. CONCLUSIONS: This study has implications for chloroplast genome-based phylogenetic analysis and the authentication of multiple Viola species used as Violae Herba. The legal origin recorded in the Chinese Pharmacopoeia should be further revised to V. prionantha, in line with the commercial Violae Herba in the TCM markets.
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The mulberry leaf is a classic herb commonly used in traditional Chinese medicine. It has also been used as animal feed for livestock and its fruits have been made into a variety of food products. Traditionally, mulberry (Morus alba L.) leaf harvesting after frost is thought to have better medicinal properties, but the underlying mechanism remains largely unsolved. To elucidate the biological basis of mulberry leaves after frost, we first explored the content changes of various compounds in mulberry leaves at different harvest times. Significant enrichment of flavonoids was observed with a total of 224 differential metabolites after frost. Subsequently, we analyzed the transcriptomic data of mulberry leaves collected at different harvest times and successfully annotated 22,939 unigenes containing 1,695 new genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed 26, 20, and 59 unigenes related to flavonoids synthesis in three different groups harvested at different times. We found that the expression levels of flavonoid biosynthesis-related unigenes also increased when harvested at a delayed time, which was consistent with the flavonoid accumulation discovered by the metabolomic analysis. The results indicated that low temperature may be a key trigger in flavonoid biosynthesis of mulberry leaves by increasing the expression of flavonoid biosynthesis-related genes. This study also provided a theoretical basis for the optimal harvest time of mulberry leaves.
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Peucedani Radix is the dry root of Peucedanum praeruptorum of the umbelliferous family, but the dry root of Angelica decursiva was also the source of Peucedani Radix in the past. As one of the most popular traditional Chinese medicinal herbs, the certified source of Peucedani Radix is still disputed. To better understand the relationship between A. decursiva and P. praeruptorum, we sequenced their chloroplast (cp) genomes. The gene structure, codon usage bias, repeat, simple sequence repeat (SSR), as well as their borders of inverted repeat (IR) regions of the two cp genomes are analyzed to identify potential genetic markers. Great variation is exhibited in the repeat sequences of IR, large single copy regions and the SSRs of the two cp genomes, which can be used as molecular markers to distinguish them. The phylogenetic analysis also indicates that they belong to two different genera in Apiaceae family: A. decursiva is an Angelica plant and P. praeruptorum is a Peucedanum plant. Our observations suggest that the two species are somewhere different in gene features, which contributes to support A. decursiva as an independent species from P. praeruptorum. The results also provide new evidence that A. decursiva should not be regarded as the certified source of Peucedani Radix in taxonomy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01097-w.
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Clerodendrum lindleyi Decne. ex Planch. is a Chinese medicinal plant in the Lingnan region of China. In this study, the complete chloroplast genome sequence of C. lindleyi was assembled and characterized from high-throughput sequencing data. The chloroplast genome is 151,678 bp in length, consisting of a large single-copy (LSC) and a small single-copy (SSC) regions of 83,043 bp and 17,311 bp, respectively, which are separated by a pair of 25,662 bp inverted repeat (IR) regions. The overall GC content of the genome is 38.18%. The genome contains 133 genes, including 88 protein-coding, 37 tRNA, and 8 rRNA genes. A phylogenetic tree reconstructed by using 16 chloroplast genomes reveals that C. lindleyi is most closely related to C. trichotomum which together forms a group that is a sister to genus Caryopteris. The work reported here is the first complete chloroplast genome of C. lindleyi which will provide useful information to the evolutionary studies on the genus of Clerodendrum.
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Peristrophe japonica (Thunb.) Bremek. is a widely distributed medicinal plant species in China and Japan. In this study, the complete chloroplast genome sequence of P. japonica was assembled and characterized from high-throughput sequencing data. The chloroplast genome is 151,374 bp in length, consisting of a large single-copy (LSC) and a small single-copy (SSC) regions of 83,395 bp and 17,073 bp, respectively, which were separated by a pair of 25,453 bp inverted repeat (IR) regions. The overall GC content of the genome is 38.07%. The genome contains 133 genes, including 88 protein-coding, 37 tRNA, and eight rRNA genes. A phylogenetic tree reconstructed using 23 chloroplast genomes reveals that Peristrophe form a separate group which is a sister of the genus Dicliptera. The work reported here is the first complete chloroplast genome of P. japonica which will provide useful information to the evolutionary studies on the genus of Peristrophe.
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Corydalis yanhusuo W.T. Wang is a classic herb that is frequently used in traditional Chinese medicine and is efficacious in promoting blood circulation, enhancing energy, and relieving pain. Benzylisoquinoline alkaloids (BIAs) are the main bioactive ingredients in Corydalis yanhusuo. However, few studies have investigated the BIA biosynthetic pathway in C. yanhusuo, and the biosynthetic pathway of species-specific chemicals such as tetrahydropalmatine remains unclear. We performed full-length transcriptomic and metabolomic analyses to identify candidate genes that might be involved in BIA biosynthesis and identified a total of 101 full-length transcripts and 19 metabolites involved in the BIA biosynthetic pathway. Moreover, the contents of 19 representative BIAs in C. yanhusuo were quantified by classical targeted metabolomic approaches. Their accumulation in the tuber was consistent with the expression patterns of identified BIA biosynthetic genes in tubers and leaves, which reinforces the validity and reliability of the analyses. Full-length genes with similar expression or enrichment patterns were identified, and a complete BIA biosynthesis pathway in C. yanhusuo was constructed according to these findings. Phylogenetic analysis revealed a total of ten enzymes that may possess columbamine-O-methyltransferase activity, which is the final step for tetrahydropalmatine synthesis. Our results span the whole BIA biosynthetic pathway in C. yanhusuo. Our full-length transcriptomic data will enable further molecular cloning of enzymes and activity validation studies.
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KEY MESSAGE: Psoralen synthase and angelicin synthase responsible for the formation of psoralen and angelicin in Peucedanum praeruptorum Dunn were identified and functionally characterized, respectively. Furanocoumarins were reported to possess several activities such as anticancer, anti-inflammatory and neuroprotective, and function as phytotoxin and allelochemical in plants. Furanocoumarins are the main bioactive ingredient in P. praeruptorum which is a commonly used traditional Chinese medicine. Phenylalanine ammonia lyase (PAL), 4-coumarate: CoA ligase (4CL), p-coumaroyl CoA 2'-hyfroxylase (C2'H) were cloned previously to elucidate the biosynthetic mechanism of coumarin lactone ring. However, the genes involved in complex coumarins in P. praeruptorum have not been explored. Herein, putative psoralen synthase CYP71AJ49 and angelicin synthase CYP71AJ51 were cloned from P. praeruptorum. In vivo and in vitro yeast assays were conducted to confirm their activities. Furthermore, the results of High Performance Liquid Chromatography-Electrospray Ionization Mass Spectrometry (HPLC-ESI-MS) verified that CYP71AJ49 catalyzed the conversion of marmesin to psoralen, and CYP71AJ51 catalyzed columbianetin to angelicin. Subsequently, the expression profile showed that CYP71AJ49 and CYP71AJ51 were easily affected by environmental conditions, especially UV and temperature. The genes tissue-specific expression and compounds tissue-specific distribution pattern indicated the existence of substance transport in P. praeruptorum. Phylogenetic analysis was conducted with 27 CYP71AJs, CYP71AJ49 and CYP71AJ51 were classified in I-4 and I-2, respectively. These results provide further insight to understand the biosynthetic mechanism of complex coumarins.
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Apiaceae/enzimología , Apiaceae/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Furocumarinas/metabolismo , Proteínas de Plantas/metabolismo , Apiaceae/genética , China , Cromatografía Líquida de Alta Presión/métodos , Coenzima A Ligasas/genética , Cumarinas/metabolismo , Sistema Enzimático del Citocromo P-450/química , Sistema Enzimático del Citocromo P-450/genética , Furocumarinas/química , Furocumarinas/genética , Regulación de la Expresión Génica de las Plantas , Cinética , Medicina Tradicional China , Fenilanina Amoníaco-Liasa/genética , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/aislamiento & purificación , Espectrometría de Masa por Ionización de Electrospray/métodos , TranscriptomaRESUMEN
Opium poppy is one of the most important medicinal plants and remains the only commercial resource of morphinan-based painkillers. However, little is known about the regulatory mechanisms involved in benzylisoquinoline alkaloids (BIAs) biosynthesis in opium poppy. Herein, the full-length transcriptome dataset of opium poppy was constructed for the first time in accompanied with the 33 samples of Illumina transcriptome data from different tissues, growth phases and cultivars. The long-read sequencing produced 902,140 raw reads with 55,114 high-quality transcripts, and short-read sequencing produced 1,923,679,864 clean reads with an average Q30 rate of 93%. The high-quality transcripts were subsequently quantified using the short reads, and the expression of each unigene among different samples was calculated as reads per kilobase per million mapped reads (RPKM). These data provide a foundation for opium poppy transcriptomic analysis, which may aid in capturing splice variants and some non-coding RNAs involved in the regulation of BIAs biosynthesis. It can also be used for genome assembly and annotation which will favor in new transcript identification.
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Papaver/genética , Transcriptoma , Bencilisoquinolinas , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Papaver/crecimiento & desarrolloRESUMEN
Cirsium setosum is a widely distributed species of edible medicinal plant around the world. Triterpenes, flavonoids, sterols, polyphenols, and glycosides are its main medicinal ingredients. In this study, the complete chloroplast genome sequence of C. setosum was assembled and characterized from high-throughput sequencing data. The chloroplast genome was 152,405 bp in length, consisting of large single-copy (LSC) and small single-copy (SSC) regions of 83,385 bp and 18,632 bp, respectively, which were separated by a pair of 25,193 bp inverted repeat (IR) regions. The genome is predicted to contain 133 genes, including 88 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The overall GC content of the genome is 37.7%. A phylogenetic tree reconstructed by 12 chloroplast genomes reveals that C. setosum is mostly related to Cirsium arvense, which is also a Cephalanoplos plant widely distributed all over the world. The work reported the firstly complete chloroplast genome of C. setosum which may provide useful information to the evolution of Cephalanoplos.
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Coumarins exhibit many biological activities and are the main specialised metabolites of Peucedanum praeruptorum Dunn, an important plant used in traditional Chinese medicine. In preliminary studies, we cloned several genes involved in coumarin biosynthesis in P. praeruptorum, such as 4-coumarate: CoA ligase (4CL), p-coumaroyl CoA 2'-hydroxylase (C2'H), feruloyl CoA 6'-hydroxylase (F6'H) and bergaptol O-methyltransferase (BMT). However, phenylalanine ammonia-lyase (PAL) in P. praeruptorum (PpPAL) has not yet been studied. In the present study, we cloned one novel PpPAL gene. Subsequently, the relationship between gene and compounds was studied using quantitative real-time PCR (qRT-PCR) and High Performance Liquid Chromatography (HPLC) analysis. Then, enzyme function was analyzed with L-phenylalanine (L-Phe) as substrate. These experiments showed that the coumarin content could be upregulated by methyl jasmonate (MeJA), UV irradiation and cold, which was consistent with increased expression levels of PpPAL. In addition, correlation analysis indicated that coumarins were partially related to PpPAL. And the recombinant protein could catalyze the conversion of L-Phe to trans-cinnamic acid (t-CA) with a Km of 120⯱â¯33⯵M and a Kcat of 117⯱â¯32 min-1. Besides, Tyr110, Phe116, Gly117, Ser206, Leu209, Leu259, Tyr354, Arg357, Asn387 and Phe403 were essential for enzymatic activity based on three-dimensional modeling and site-directed mutagenesis experiments. Altogether these results highlight the importance of PpPAL in abiotically induced coumarin biosynthesis and provide further insights regarding the structure-function relationships of this protein.
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Apiaceae/metabolismo , Cumarinas/metabolismo , Fenilanina Amoníaco-Liasa/genética , Proteínas de Plantas/genética , Dominio Catalítico , Citosol/enzimología , Escherichia coli/genética , Regulación de la Expresión Génica de las Plantas , Mutagénesis Sitio-Dirigida , Fenilanina Amoníaco-Liasa/química , Fenilanina Amoníaco-Liasa/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Relación Estructura-ActividadRESUMEN
KEY MESSAGE: A p-coumaroyl CoA 2'-hydroxylase responsible for the formation of coumarin lactone ring was identified from Peucedanum praeruptorum Dunn and functionally characterized in vitro. Coumarins are important plant secondary metabolites with a variety of biological activities. Ortho-hydroxylation of cinnamates leads to the formation of coumarin lactone ring and is generally thought to be a key step in coumarin biosynthesis. However, ortho-hydroxylases, especially p-coumaroyl CoA 2'-hydroxylase (C2'H) responsible for the biosynthesis of the most common coumarin skeleton, have received insufficient attention. Here, a putative ortho-hydroxylase PpC2'H was isolated from P. praeruptorum Dunn, a traditional Chinese medicinal herb rich in coumarins. Expression profile indicated that PpC2'H exhibited the highest transcript level in roots and could be up-regulated by MeJA elicitation. Subcellular localization of PpC2'H was demonstrated to be cytosol in planta. In order to functionally characterize PpC2'H, the purified recombinant protein was incubated with various potential substrates. HPLC-ESI-MS analysis indicated that PpC2'H catalyzed the conversion of p-coumaroyl CoA into hydroxylated intermediate, which then underwent spontaneous lactonization to generate umbelliferone. Our data also showed that light would promote the spontaneous process. In addition, based on homology modeling and site-directed mutagenesis, amino acid residues Phe-130, Lys-141, Asn-207, His-224, Asp-226, His-282 and Phe-298 were verified essential for enzymatic activity. These findings provide insight into structure-function relationship of this pivotal ortho-hydroxylase and also contribute to elucidating the biosynthetic mechanism of coumarin skeleton.
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Apiaceae/enzimología , Vías Biosintéticas , Cumarinas/metabolismo , Oxigenasas de Función Mixta/metabolismo , Secuencia de Aminoácidos , Vías Biosintéticas/genética , Cromatografía Líquida de Alta Presión , Cumarinas/química , ADN Complementario/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de la radiación , Cinética , Luz , Oxigenasas de Función Mixta/química , Modelos Moleculares , Mutagénesis Sitio-Dirigida , Especificidad de Órganos/genética , Especificidad de Órganos/efectos de la radiación , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Protoplastos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Alineación de Secuencia , Espectrometría de Masa por Ionización de Electrospray , Homología Estructural de Proteína , Fracciones Subcelulares/enzimología , Transcriptoma/genética , Transcriptoma/efectos de la radiaciónRESUMEN
Coumarins are the main bioactive compounds in Peucedanum praeruptorum Dunn, a common Chinese herbal medicine. Nevertheless, the genes involved in the biosynthesis of core structure of coumarin in P. praeruptorum have not been identified yet. 4-Coumarate: CoA ligase (4CL) catalyzes the formation of hydroxycinnamates CoA esters, and plays an essential role at the divergence point from general phenylpropanoid metabolism to major branch pathway of coumarin. Here, three novel putative 4CL genes (Pp4CL1, Pp4CL7, and Pp4CL10) were isolated from P. praeruptorum. Biochemical characterization of the recombinant proteins revealed that Pp4CL1 utilized p-coumaric and ferulic acids as its two main substrates for coumarin biosynthesis in P. praeruptorum. Furthermore, Pp4CL1 also exhibited activity toward caffeic, cinnamic, isoferulic, and o-coumaric acids and represented a bona fide 4CL. Pp4CL7 and Pp4CL10 had no catalytic activity toward hydroxycinnamic acid compounds. But they had close phylogenetic relationship to true 4CLs and were defined as 4CL-like genes. Among all putative 4CLs, Pp4CL1 was the most highly expressed gene in roots, and its expression level was significantly up-regulated in mature roots compared with seedlings. Subcellular localization studies showed that Pp4CL1 and Pp4CL10 proteins were localized in the cytosol. In addition, site-directed mutagenesis of Pp4CL1 demonstrated that amino acids of Tyr-239, Ala-243, Met-306, Ala-309, Gly-334, Lys-441, Gln-446, and Lys-526 were essential for substrate binding or catalytic activities. The characterization and site-directed mutagenesis studies of Pp4CL1 lays a solid foundation for elucidating the biosynthetic mechanisms of coumarins in P. praeruptorum and provides further insights in understanding the structure-function relationships of this important family of proteins.
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Peucedanum praeruptorum Dunn is well-known traditional Chinese medicine. However, little is known in the biosynthesis and the transport mechanisms of its coumarin compounds at the molecular level. Although transcriptomic sequence is playing an increasingly significant role in gene discovery, it is not sufficient in predicting the specific function of target gene. Furthermore, there is also a huge database to be analyzed. In this study, RNA sequencing assisted transcriptome dataset and high-performance liquid chromatography (HPLC) coupled with electrospray-ionization quadrupole time-of-flight mass spectrometry (Q-TOF MS)-based metabolomics dataset of P. praeruptorum were firstly constructed for gene discovery and compound identification. Subsequently, methyl jasmonate (MeJA)-induced gene expression analysis and metabolomics analysis were conducted to narrow-down the dataset for selecting the candidate genes and the potential marker metabolites. Finally, the genes involved in coumarins biosynthesis and transport were predicted with parallel analysis of transcript and metabolic profiles. As a result, a total of 40,952 unigenes and 19 coumarin compounds were obtained. Based on the results of gene expression and metabolomics analysis, 7 cytochrome-P450 and 8 multidrug resistance transporter unigenes were selected as candidate genes and 8 marker compounds were selected as biomarkers, respectively. The parallel analysis of gene expression and metabolites accumulation indicated that the gene labeled as 23,746, 228, and 30,922 were related to the formation of the coumarin core compounds whereas 36,276 and 9533 participated in the prenylation, hydroxylation, cyclization or structural modification. Similarly, 1462, 20,815, and 15,318 participated in the transport of coumarin core compounds while 124,029 and 324,293 participated in the transport of the modified compounds. This finding suggested that integration of a decrescent transcriptome and metabolomics dataset could largely narrow down the number of gene to be investigated and significantly improve the efficiency of functional gene predication. In addition, the large amount of transcriptomic data produced from P. praeruptorum and the genes discovered in this study would provide useful information in investigating the biosynthesis and transport mechanism of coumarins.
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Enfermedades Cardiovasculares/prevención & control , Medicamentos Herbarios Chinos/uso terapéutico , Fitoterapia , Enfermedades Cardiovasculares/complicaciones , China , Método Doble Ciego , Femenino , Humanos , Hepatopatías/complicaciones , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Factores de Riesgo , Prevención Secundaria , Factores de TiempoRESUMEN
Several previous trials from Western population studies have showed that statins may help reduce blood pressure (BP). However, randomized clinical data is limited. Xuezhikang, a partially extract of red yeast rice, contains a family of naturally occurring statins, and has a marked impact on lipids, but it is unknown whether Xuezhikang has any effect on BP during long-term follow-up in the Chinese population. This is a post-hoc subgroup analysis of a randomized, double-blinded, placebo-controlled, parallel group clinical trial, Chinese Coronary Secondary Prevention Study (CCSPS). A total of 2704 hypertensive patients with previous myocardial infarction (MI) were assigned either to placebo (n = 1341) or to Xuezhikang (n = 1363) daily for an average of 4.5 years. The primary outcome was the unadjusted changes in mean arterial pressure (MAP) from baseline to 6 months. We also assessed systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure. Analysis of covariance was used to calculate the adjusted effects of treatment on changes in these outcomes at 6, 12, 24, and 48 months post-randomization, after controlling for potential confounders. This analysis included 2704/4870 (55.5%) hypertensive patients for whom BP was measured at baseline and at least one follow-up visit after randomization. Median duration of the follow-up was 4.5 years (54 months), and 25 patients (0.92%) were lost to the last follow-up because of adverse effects. The results showed that the unadjusted and adjusted changes in MAP, SBP, DBP, or pulse pressure from baseline were not significantly different for Xuezhikang or placebo recipients at 6, 12, 24, and 48 months after randomization. In this post-hoc subgroup analysis, we failed to demonstrate any significant reducing effects of Xuezhikang on BP in Chinese hypertensive patients with previous MI, suggesting that further prospective study on the effects of statins on BP would be needed, especially in high-risk patients.
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Antihipertensivos/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Hipertensión/tratamiento farmacológico , Infarto del Miocardio/complicaciones , Adolescente , Adulto , Anciano , Presión Sanguínea/efectos de los fármacos , China , Femenino , Estudios de Seguimiento , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipertensión/complicaciones , Hipertensión/fisiopatología , Lípidos/sangre , Masculino , Persona de Mediana Edad , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/prevención & control , Adulto JovenRESUMEN
BACKGROUND: The lowering of cholesterol concentrations in individuals at high risk for cardiovascular disease improves clinical outcome. Xuezhikang has a marked impact on lipids. METHODS: In this randomized, double-blinded, placebo-controlled, parallel-group clinical trial, a total of 2704 hypertensive patients with previous myocardial infarction (MI) were assigned either to placebo (n = 1341) or to Xuezhikang (0.6 g twice daily, n = 1363) for an average of 4.5 years. The primary end-point was recurrent coronary events; the secondary end-point was all-cause mortality and other clinical events, including adverse effects. RESULTS: There were no differences between the Xuezhikang and placebo group in base-line characteristics. However, Xuezhikang treatment reduced the incidence of coronary events by 43.0% (P = 0.02), deaths from coronary heart disease (CHD) by 30.0% (P < 0.01), and all-cause mortality by 35.8% (P = 0.001). CONCLUSIONS: This study, for the first time, demonstrated that long-term Xuezhikang therapy resulted in significant reduction in cardiovascular events and death in Chinese hypertensive patients with previous MI in a safe manner.
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Enfermedad de la Arteria Coronaria/prevención & control , Medicamentos Herbarios Chinos/uso terapéutico , Hipertensión/dietoterapia , Infarto del Miocardio/complicaciones , Adolescente , Adulto , Anciano , China/epidemiología , Enfermedad de la Arteria Coronaria/etiología , Método Doble Ciego , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/mortalidad , Incidencia , Estimación de Kaplan-Meier , Lipoproteínas/sangre , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Coronary heart disease, hypertension, and dyslipidemia are highly prevalent and commonly coexist in people who are middle-aged and older. Previous data suggested that lowering cholesterol concentrations in individuals at high risk of cardiovascular disease improved clinical outcomes. Xuezhikang, a partial extract of red yeast rice containing statin, has a marked impact on lipids. The purpose of this study, therefore, was to evaluate the impact of Xuezhikang on reducing cardiovascular events and mortality in elderly Chinese hypertensive patients with a history of myocardial infarction (MI) enrolled in the Chinese Coronary Secondary Prevention Study. In this randomized trial, 1530 elderly hypertensive patients (> or = 65-years-old) with previous MI were assigned either to placebo (n = 758) or to Xuezhikang (n = 772) daily for an average of 4.5 years. The primary endpoint was recurrent coronary events; the secondary endpoint was all-cause mortality and other clinical events, including adverse effects. There were 68 cases of coronary events (8.8%) detected in the Xuezhikang group and 108 cases (14.3%) in the placebo group (38.2% risk reduction by Xuezhikang therapy). Death from coronary heart disease (CHD) totaled 49 cases in the Xuezhikang group (6.4%) and 68 cases in the placebo group (9.0%), indicating that Xuezhikang significantly decreased the risk of CHD death by 29.2%. Our study demonstrated that Xuezhikang therapy could effectively and safely reduce cardiovascular events and all-cause death in Chinese elderly hypertensive patients with previous MI. This finding may have an important implication for the treatment of elderly hypertensive patients with CHD.
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Enfermedades Cardiovasculares/prevención & control , Enfermedad Coronaria/prevención & control , Medicamentos Herbarios Chinos/uso terapéutico , Infarto del Miocardio/complicaciones , Anciano , Enfermedades Cardiovasculares/mortalidad , Enfermedad Coronaria/mortalidad , Método Doble Ciego , Medicamentos Herbarios Chinos/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/complicaciones , Hipertensión/mortalidad , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Factores de Riesgo , Resultado del TratamientoRESUMEN
OBJECTIVES: To evaluate whether lipid-lowering therapy with xuezhikang reduces the risk of coronary events and total mortality in patients with coronary heart disease (CHD) aged 65 and older. DESIGN: Subgroup analysis of the China Coronary Secondary Prevention Study, a randomized, double-blind, placebo-controlled, clinical trial. SETTING: Sixty-six hospitals in China. PARTICIPANTS: A total of 1,445 patients, aged 65 to 75, were chosen from 4,780 patients with a history of myocardial infarction. INTERVENTION: The patients were randomized to the xuezhikang (n=735) or the placebo (n=710) group and followed for a mean of 4 years. MEASUREMENTS: The primary endpoint was recurrent coronary events; the secondary endpoint was all-cause mortality and other clinical events, including adverse effects. RESULTS: Elderly patients were at greater risk for coronary events, death from coronary events, all-cause mortality, and malignancies than younger patients. Xuezhikang therapy reduced the incidence of coronary events 36.9% (P=.001), death from coronary heart disease 31.0% (P=.04), all-cause mortality 31.9% (P=.01), stroke 44.1% (P=.04), the need for a percutaneous coronary intervention or coronary artery bypass graft 48.6% (P=.07), and malignancies 51.4% (P=.03). Based on the treatment of elderly patients with xuezhikang for an average of 4 years, the number needed to treat (NNT) to prevent one coronary event, one coronary death, and one mortality due to all causes was estimated to be 18, 33, and 23, respectively. In a like manner, the estimated NNT to prevent one coronary event, one coronary death, and one mortality due to all causes in younger patients was 23, 82, and 51, respectively. There was not a significantly greater number of adverse effects in the xuezhikang group than in the placebo group. CONCLUSION: This is the first study demonstrating that treatment with xuezhikang capsules is safe and effective for the secondary prevention of CHD in older Chinese people.