Multiomics analyses of two Leonurus species illuminate leonurine biosynthesis and its evolution.

The Lamiaceae family is renowned for its terpenoid-based medicinal components, but Leonurus, which has traditional medicinal uses, stands out for its alkaloid-rich composition. Leonurine, the principal active compound found in Leonurus, has demonstrated promising effects in reducing blood lipids and treating strokes. However, the biosynthetic pathway of leonurine remains largely unexplored. Here, we present the chromosome-level genome sequence assemblies of Leonurus japonicus, known for its high leonurine production, and Leonurus sibiricus, characterized by very limited leonurine production. By integrating genomics, RNA sequencing, metabolomics, and enzyme activity assay data, we constructed the leonurine biosynthesis pathway and identified the arginine decarboxylase (ADC), uridine diphosphate glucosyltransferase (UGT), and serine carboxypeptidase-like (SCPL) acyltransferase enzymes that catalyze key reactions in this pathway. Further analyses revealed that the UGT-SCPL gene cluster evolved by gene duplication in the ancestor of Leonurus and neofunctionalization of SCPL in L. japonicus, which contributed to the accumulation of leonurine specifically in L. japonicus. Collectively, our comprehensive study illuminates leonurine biosynthesis and its evolution in Leonurus.

[Trait-based responses and adaptation of Artemisia sacrorum to environmental changes].

The paper focused on Artemisia sacrorum in the stable natural plant community in three vegetation zones (forest, forest steppe and steppe) in the Yanhe River catchment. The following plant functional traits were measured at each sample site, i.e., specific leaf area (SLA), leaf tissue density (LTD), leaf nitrogen concentration (LNC), leaf phosphorus concentration (LPC), leaf nitrogen phosphorus ratio (LNP), specific root length (SRL), root tissue density (RTD), root nitrogen concentration (RNC), root phosphorus concentration (RPC) and root nitrogen phosphorus ratio (RNP). These 10 plant functional traits were chosen because they were easily measurable and adequately reflected plant survival strategies. We analyzed intraspecific differences in A. sacrorum functional traits in the different habitat zones, and the influence of climate and terrain factors on A. sacrorum functional traits. We also studied the relationships among A. sacrorum plant functional traits. The results showed that some A. sacrorum functional traits were significantly different among sample sites, such as LPC, LNP, SRL, RTD and RNP, while the other 5 functional traits had no significant differences. The functional traits were not significantly different between sites with different slopes and aspects. SLA was very significantly negatively correlated with LTD, SRL was significantly negatively correlated with RTD and RNP, RTD was significantly positively correlated with RNC and RNP, and there were no significant relationships among LTD, LNC and LNP and the other functional traits. This showed that A. sacrorum adapted to the environment by coordinating adjustment among leaf and root functional traits. Different climate factors had different effects on plant traits, with the effects of mean annual precipitation > mean annual temperature > annual average evaporation capacity.

[Relationships among leaf traits and their expression in different vegetation zones in Yanhe River basin, Northwest China].

This article selected zonal plant communities as the research objects in different vegetation zones in Yanhe River basin. We measured six leaf traits of the dominant species and main accompanying species in each community, and then analyzed the relationships and their changes along with environmental gradients between these traits in order to understand the plant adaptation strategies to the environment changes. The results showed that the specific leaf area was significantly negatively correlated to leaf tissue density, area-based leaf nitrogen and phosphorus concentrations, and significantly positively correlated to mass-based leaf phosphorus concentration. Both the scaling relationships among these traits and plant life strategies were different among the three vegetation zones, the scaling-dependent relationship between leaf tissue density and specific leaf area was stronger in steppe and forest-steppe zones than in forest zone, but the correlations among area-based leaf nitrogen/phosphorus concentrations and specific leaf area and leaf tissue density were more significant in forest zone than in steppe zone. In the arid grassland and forest-steppe zone, plants give priority to defensive and stress resistance strategies, and in relatively moist nutrient-rich forest zone, plants give priority to fast growth and resource optimization allocation strategies.

A systematic review of vinorelbine for the treatment of breast cancer.

The purpose of this study was to investigate the efficacy and safety profile of vinorelbine-based chemotherapy in different settings for the treatment of breast cancer. We performed a computerized search using combinations of the following keywords: "breast cancer", "breast neoplasms", "trial", "vinorelbine" and "navelbine". A total of 20 trials were included in this analysis, with a total of 5,080 patients accrued. Taxane was associated with enhanced overall survival (OS; p = 0.027) and response rate (RR; p = 0.037) as compared with vinorelbine in monotherapy, but did not show significantly favored progression-free survival (PFS; p = 0.136). Vinorelbine alone was equivalent to fluoropyrimidine treatment in RR (p = 0.79) for the treatment of metastatic breast cancer. For vinorelbine-combined regimens, the analysis showed that the vinorelbine group gave similar results as other regimens for OS (p = 0.849) and PFS (p = 0.143). The RR of vinorelbine-combined regimens was slightly better than that of the other regimens (OR, 1.17), but the difference was not statistically significant. In neoadjuvant setting, vinorelbine treatment was as active as AC (doxorubicin, cyclophosphamide) or DAC (doxorubicin, cyclophosphamide, docetaxel) regimens with respect to RR (p = 0.76) and pathologic complete response (pCR; p = 0.77), but showed lower occurrence of grade 3/4 adverse effects. The analysis also demonstrated that vinorelbine-containing therapy is effective as adjuvant, front-line or salvage therapy of metastatic breast cancer, even for patients who were previously treated with anthracyclines or taxanes.

[Clinical study on the treatment of abnormal blood lipids complicated with carotid atherosclerosis with lipid-reducing red rice minute powder: a randomized controlled trial].

OBJECTIVE: To observe the clinical effects of lipid-reducing red rice minute powder (LRRMP) on the levels of blood lipids, carotid artery intima-media thickness (IMT), and the plaque integral of hyperlipidemia patients complicated with carotid atherosclerosis. METHODS: This study was conducted from April 2005 to April 2006 according to inclusion criteria. Sixty hyperlipidemia patients complicated with carotid atherosclerosis were randomly assigned to the treatment group (20 cases), the Chinese medicine control group (CM control group, 20 cases), and the Western medicine control group (WM control group, 20 cases). They were recruited from the community of secondary machine tool factory of Jinan. Patients in the treatment group took LRRMP (175 mg/pill), one pill each time, twice daily. Patients in the CM control group took Xuezhikang Capsule (300 mg/pill), 2 pills each time, twice daily. Patients in the WM control group took Lovastatin Tablet (20 mg/tablet), 1 tablet each time, once daily. The course of treatment was 6 successive months for all. They avoided taking any lipid-regulating or anti-atherosclerotic drugs during the therapeutic course. The changes of Chinese medicine symptom scores, serum TC, TG, LDL-C, and HDL-C levels, IMT of the carotid artery, and the plaque integral before and after treatment were observed. RESULTS: After 6 months of treatment the Chinese medicine symptom scores reduced in each group ( P<0.05 or P<0.01), and the treatment group was superior to WM control group (P<0.05). Serum TC, TG and LDL-C levels were significantly lowered (P<0.05 or P<0.01), showing no significant difference in inter-group comparison (P>0.05). There was no statistical significance of the serum HDL-C level in each group (P>0.05). The IMT and the plaque integral significantly reduced (P<0.05, P<0.01), showing no statistical difference among all groups. One patient in the WM control group dropped out because of transaminase elevation. No serious adverse reaction correlated with the drugs occurred during the therapeutic course in the rest two groups. CONCLUSIONS: LRRMP showed definite effects on lipid-regulating and anti atherosclerosis. Its effects were equivalent to Xuezhikang Capsule and Lovastatin Tablet. Besides, it was safe and economic, and deserved further studies.

Phytoestrogen α-zearalanol improves vascular function in ovariectomized hyperhomocysteinemic rats.

Previous studies have showed that phytoestrogen α-zearalanol (α-ZAL) could antagonize homocysteine (Hcy) induced endothelin-1 (ET-1) expression, oxidative stress and apoptosis in human umbilical vein endothelial cells in vitro, however, its effect on vascular function in vivo remains to be determined. This study was designed to investigate the effects of α-ZAL on vascular function in ovariectomized (OVX) hyperhomocysteinemia (HHcy) rats and explore the mechanisms involved primarily. HHcy rat model was induced by diets containing 2.5% methionine (Met) for 12 weeks. Forty adult female Wistar rats were assigned randomly into five groups: (1) Con; (2) Met; (3) OVX+Met; (4) OVX+Met+α-ZAL; (5) OVX+Met+17ß-E(2) (17ß-estradiol). Blood was collected to analyze plasma estradiol, Hcy and ET-1. Thoracic aortas were isolated to detect its response to phenylephrine (PE) and acetylcholine (ACh) or sodium nitroprusside (SNP). Aortas eNOS expression was determined by Western blot. Thoracic aortas histological characterization was analyzed by optical microscope and scanning electron microscope (SEM). Rat plasma Hcy was significantly elevated after fed with 2.5% methionine diets, and ovariectomy aggravated this elevation. Phytoestrogen α-ZAL or 17ß-E(2) could attenuate this elevation. Plasma ET-1 levels increased significantly in ovariectomized HHcy rats, and supplement with α-ZAL or 17ß-E(2) could reverse these changes. In rats of OVX+Met group, PE elicited significantly greater contraction in a dose-dependent manner in endothelium-intact thoracic aortas rings; ACh elicited significantly less percentage relaxation. These effects were significantly attenuated by supplement with α-ZAL or 17ß-E(2). There was no significant difference between groups in relaxation induced by SNP whether endothelium intact or not. Thoracic aortas morphology study also showed severe endothelium injury in ovariectomized HHcy rats, both α-ZAL and 17ß-E(2) could attenuate this change. Aortas eNOS expression was decreased in ovariectomized HHcy rats, and supplement with α-ZAL or 17ß-E(2) could reverse these changes. These findings demonstrated that α-ZAL could effectively alleviate the impairment of endothelial cells and improve vascular function in ovariectomized HHcy rats by decreasing plasma Hcy and antagonizing decreasing of aortas eNOS expression. This protective effect is somewhat similar with 17ß-E(2).

[Identification of the different cultivated Magnolia biondii].

OBJECTIVE: To distinguish Magnolia biondii of ten different cultivated. METHODS: The original species can be identified by the morphological characteristics and microscopic characteristics. The volatile oil is determinated by the method of Chinese pharmacopoeia. RESULTS: The ten cultivated Mangolia biondii have obviously differents in morphological characteristics, microscopic characteristics and volatile oil. CONCLUSION: It is important for development application of Magnolia biondii and variety improvement.

[Simultaneous determination of multi-components in Chinese herbal medicine with UV spectrometry by virtual components-artificial neural network].

In the present paper, the simultaneous determination of multi-components in Chinese herbal medicine was performed by artificial neural network-UV spectrometry. The interference of other components was eliminated by self-revising and self-simulation of the virtual component. The double ANN including training and simulation network was established, and the capabilities of self-recognition and self-studying were improved. Therefore, the prediction accuracy of multicomponent content was improved greatly in the complicated Chinese herbal medicine system. The contents of aesculin and aesculetin, which were extracted from 21 Cortex Fraxinis, were predicted. Comparing the results with those of HPLC, the prediction accuracy was more than 90% within the relative errors less than 10%. The measurement precisions of aesculin and aesculetin were 0. 37% and 1. 5% respectively.

Catalpol increases hippocampal neuroplasticity and up-regulates PKC and BDNF in the aged rats.

Rehmannia, a traditional Chinese medical herb, has a long history in age-related disease therapy. Previous work has indicated that catalpol is a main active ingredient performing neuroprotective effect in rehmannia, while the mechanism underlying the effect remains poorly understood. In this study, we attempt to investigate the effect of catalpol on presynaptic proteins and explore a potential mechanism. The hippocampal levels of GAP-43 and synaptophysin in 3 groups of 4 months (young group), 22-24 months (aged group) and catalpol-treated 22-24 months (catalpol-treated group) rats were evaluated by western blotting. Results clearly showed a significant decrease in synaptophysin (46.6%) and GAP-43 (61.4%) levels in the aged group against the young animals and an increase (45.0% and 31.8% respectively) in the catalpol-treated aged rats in comparison with the untreated aged group. In particular, synaptophysin immunoreactivity (OD) in the dentate granule layer of the hippocampus was increased 0.0251 in the catalpol-treated group as compared with the aged group. The study also revealed a catalpol-associated increase of PKC and BDNF in the hippocampus of the catalpol-treated group in comparison with the aged rats and highly correlated with synaptophysin and GAP-43. Such positive correlations between presynaptic proteins and signaling molecules also existed in the young group. These results suggested that catalpol could increase presynaptic proteins and up-regulate relative signaling molecules in the hippocampus of the aged rats. Consequently, it seemed to indicate that catalpol might ameliorate age-related neuroplasticity loss by "normalizing" presynaptic proteins and their relative signaling pathways in the aged rats.

[Investigation of constituents in siwu tang fractions by chromatographic and ESI-MS methods].

OBJECTIVE: In order to discuss the chemical foundation of hematopoietic effect of Siwu Tang, three fractions of different polarities (C1, C2 and C3) were prepared from Siwu Tang and the characteristics of these fractions' constituents were investigated. METHOD: Fraction C1, C2 and C3 of Siwu Tang and corresponding fractions of Siwu Tang's four ingredient drugs were analyzed and compared, synthetically using the three methods of high-performance thin layer chromatography (HPTLC), high-performance liquid chromatography (HPLC) and direct infusion electrospray ionization mass spectrometry (ESI-MS). RESULT: Fraction C1 of Siwu Tang contained various types of compounds, including ferulic acid, paeoniflorin and supposedly ligustilide, etc. Saccharide content in fraction C1 was very little. The major constituents in fraction C2 of Siwu Tang were paeoniflorin, monosaccaride and disaccharide. The major constituents in fraction C3 of Siwu Tang were monosaccaride and disaccharide. CONCLUSION: With synthetical chromatographic and direct infusion ESI-MS methods, abundant information on composition of fractions of traditional Chinese medicine formulas can be obtained. The results gained with different methods can be compared with each other and corroborate each other, so that the obtained information can be more comprehensive and more definite than that gained with single method. The results of this study are important as references for the discussion of the chemical foundation of hematopoietic effect of Siwu Tang.

[Saccharide analysis of si-wu-tang by automated multiple development and off-line coupling thin layer chromatography electrospray ionization mass spectrometry techniques].

OBJECTIVE: To make qualitative analysis on saccharide spots in thin layer chromatography (TLC) chromatogram of SI-WU-TANG extract C, which possesses blood-enrichment activity. METHOD: TLC chromatogram of SI-WU-TANG extract C was obtained by using Automated Multiple Development (AMD) method. 4 major spots in the chromatogram were analyzed by off-line coupling TLC electrospray ionization mass spectrometry (ESI-MS) technique. Moreover, composition of monosaccharides in the fraction was analyzed by AMD technique. RESULT: Main constituents of substances from the 4 spots were monosaccharide, disaccharide, trisaccharide and tetrasaccharide respectively. Monosaccharide was mainly composed of fructose and glucose. CONCLUSION: Off-line coupling TLC ESI-MS can simply and rapidly provide qualitative examination of saccharide spots in TLC chromatogram of Traditional Chinese Medicine. AMD method can make good separation of 8 frequently-observed monosaccharides in a regular 10 cm silica gel plate, the process of which was automated, AMD and off-line coupling TLC ESI-MS techniques show good value in saccharides analysis.