Antihypertensive activity of different components of Veratrum alkaloids through metabonomic data analysis.

BACKGROUND: Hypertension is a serious global public health issue. Blood pressure (BP) is still not effectively controlled in about 20 - 30% of hypertensive patients. Therefore, it is imperative to develop new treatments for hypertension. Veratrum alkaloids were once used for the clinical treatment of hypertension, the mechanism of which is still unclear. It was gradually phased out due to adverse reactions. PURPOSE: This study aimed to investigate the short-term and long-term hypotensive profiles of different components of Veratrum alkaloids in spontaneously hypertensive rats (SHRs) to unveil their mechanisms of action. RESULTS: Total Veratrum alkaloid (V), component A (A), and veratramine (M) quickly decreased BP within 30 min of treatment, reduced renal and cardiovascular damage, and improved relevant biochemical indicators (nitric oxide [NO], endothelin-1 [ET-1], angiotensin II [Ang II)], noradrenaline [NE], etc) in SHRs to delay stroke occurrence. Thereinto, A exhibited excellent protective effects in cardiovascular disease. The metabolomic profiles of SHRs treated with V, A, and M were significantly different from those of SHRs treated with vehicle. Thirteen metabolites were identified as potential pharmacodynamic biomarkers. Through Kyoto Encyclopedia of Genes and Genomes analysis, V, A, and M-induced hypotension was mainly related to alterations in nicotinate and nicotinamide metabolism, GABAergic synapses, linoleic acid metabolism, ketone body synthesis and degradation, arginine and proline metabolism, and urea cycle, of which nicotinate and nicotinamide metabolism was the key metabolic pathway to relieve hypertension. CONCLUSION: This work shows that A is an effective and promising antihypertensive agent for hypertension treatment to reduce BP and hypertensive target organ damage, which is mainly mediated through modulating nicotinate and nicotinamide metabolism, RAS, and NO-ET homeostasis.

Mass spectrometry investigation of nucleoside adducts of fatty acid hydroperoxides from oxidation of linolenic and linoleic acids.

The widespread presence of lipid hydroperoxides in foodstuffs and biological samples has aroused great attentions in recent years, while it remains challenging for analysis of the fragility of O - O bond linkage of peroxides. In this present study, we explored the utility of electrospray ionization mass spectrometry (ESI-MS) for characterization of two fatty acid hydroperoxides from oxidation of linoleic acid and α-linolenic acid, which are the essential fatty acids abundant in many seeds and vegetable oils. The results indicated that in-source fragmentation occurred in the detection of the two fatty acid hydroperoxides in both positive and negative ion modes, which yielded characteristic fragments for ESI-MS analysis. In addition, the genotoxicity of fatty acid hydroperoxides for generation of nucleoside adducts was investigated. It was found that a variety of nucleoside adducts were formed from the reactions of fatty acid hydroperoxides and nucleosides. Furthermore, the decomposition products of the fatty acid hydroperoxides were determined, which provided evidence to elucidate the reaction mechanism for formation of nucleoside adducts.

Genome-wide identification, characterization and expression profiles of the CCD gene family in Gossypium species.

Carotenoid cleavage dioxygenases (CCDs) are a group of enzymes that catalyze the selective oxidative cleavage steps from carotenoids to apocarotenoids, which are essential for the synthesis of biologically important molecules such as retinoids, and the phytohormones abscisic acid (ABA) and strigolactones. In addition, CCDs play important roles in plant biotic and abiotic stress responses. Till now, a comprehensive characterization of the CCD gene family in the economically important crop cotton (Gossypium spp.) is still missing. Here, we performed a genome-wide analysis and identified 33, 31, 16 and 15 CCD genes from two allotetraploid Gossypium species, G. hirsutum and G. barbadense, and two diploid Gossypium species, G. arboreum and G. raimondii, respectively. According to the phylogenetic tree analysis, cotton CCDs are classified as six subgroups including CCD1, CCD4, CCD7, CCD8, nine-cis-epoxycarotenoid dioxygenase (NCED) and zaxinone synthase (ZAS) sub-families. Evolutionary analysis shows that purifying selection dominated the evolution of these genes in G. hirsutum and G. barbadense. Predicted cis-acting elements in 2 kb promoters of CCDs in G. hirsutum are mainly involved in light, stress and hormone responses. The transcriptomic analysis of GhCCDs showed that different GhCCDs displayed diverse expression patterns and were ubiquitously expressed in most tissues; moreover, GhCCDs displayed specific inductions by different abiotic stresses. Quantitative reverse-transcriptional PCR (qRT-PCR) confirmed the induction of GhCCDs by heat stress, salinity, polyethylene glycol (PEG) and ABA application. In summary, the bioinformatics and expression analysis of CCD gene family provide evidence for the involvement in regulating abiotic stresses and useful information for in-depth studies of their biological functions in G. hirsutum. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02805-9.

Visualization of lipids in cottonseeds by matrix-assisted laser desorption/ionization mass spectrometry imaging.

The cotton plant is an essential crop cultivated globally for its fiber and seeds. In this study, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was used to study the spatial distribution patterns of lipids in cottonseeds. 448 lipid ions were identified by LC-MS/MS, and 24 of which were precisely visualized by using MALDI-MSI. The lipids, including phosphatidylcholines (PC), phosphatidylethanolamines (PE) and triacylglycerols (TG) showed heterogeneous distribution patterns within the cotyledonary and radicle tissues. Additionally, the roles these lipids played in the metabolic pathways were analyzed, and relationship of the spatial distribution of LPC (lysophosphatidylcholine) and corresponding PC was studied. The unique distribution patterns of these lipid metabolites revealed by MSI can provide new insights into areas relating to the spatial compartmentation of lipid metabolism in plants. We believe that the results of MSI, if combined with transcriptomics and proteomics, may offer significant help in genetic engineering work.

Chemical compounds with a neuroprotective effect from the seeds of Celosia argentea L.

Oxidative stress plays a central role in the common pathophysiology of neurodegenerative diseases such as Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. Antioxidant therapy has been suggested for the prevention and treatment of neurodegenerative diseases. Compounds derived from natural sources may offer the potential for new treatment options. Semen Celosiae is a traditional Chinese edible herbal medicine with a long history in China and exhibits wide-reaching biological activities such as hepatoprotective, anti-tumor, anti-diarrheal, anti-diabetic, anti-oxidant, etc. In this study, nine saponins and two phenylacetonitrile glycosides were isolated from Semen Celosiae and their structures were identified using ESI-MS and NMR techniques. Among them, compounds 1 and 2 have not been previously reported. The total concentrations of the five triterpenoid saponins and the two phenylacetonitrile glycosides were 3.348 mg g-1 and 0.187 mg g-1, respectively, suggesting that Semen Celosiae is a novel viable source of the two kinds of compounds. These compounds were observed to significantly attenuate t-BHP-induced neuronal damage by effectively enhancing cell viability and decreasing reactive oxygen species generation and cell apoptosis rate in NSC-34 cells. Furthermore, compounds 1 and 7 reduced the ratios of cleaved caspase-3: caspase-3 and cleaved caspase-7: caspase-7 and the level of cytochrome C, while they increased the levels of SOD1 and Beclin 1. These findings suggest that compounds 1-11 are potent inhibitors of neuron injury elicited by t-BHP, possibly via inhibition of oxidative stress and apoptosis, and activation of autophagy; therefore they may be valuable leads for future therapeutic development.

A Structure-Activity Relationship between the Veratrum Alkaloids on the Antihypertension and DNA Damage Activity in Mice.

Veratrum plant contains a family of compounds called steroidal alkaloids which have been previously reported to cause DNA damage and blood pressure decrease in vivo. In this study, the antihypertensive effects and DNA damage in brain cells of 12 steroidal alkaloids separated from Veratrum plant were all evaluated to develop a relationship among chemical structure, antihypertensive activity and neurotoxicity by utilization of chemical principal component analysis (PCA) and hierarchical cluster analysis (HCA). Twelve steroidal alkaloids markedly reduced high blood pressure of hypertensive mice and also similarly induced varying degrees of DNA single-strand breaks in mouse cerebellum and cerebral cortex after oral administration. On the basis of the PCA and HCA results, it was suggested that the 3-carboxylic esters and benzene group play a core role in the DNA damage of brain cells, while more hydroxy groups in the A-ring and B-ring structure of jervine-type alkaloid led to stronger antihypertensive activity. The primary structure, activity and neurotoxicity relationship were discussed briefly.

A new aurone glycoside from Veratrum dahuricum (Turcz.) Loes. f.

To study the chemical constituents of Veratrum dahuricum (Turcz.) Loes. f., a new aurone glycoside named as (Z)-7, 4'-dimethoxy-6-hydroxyl-aurone-4-O-ß-glucopyranoside was isolated from the 95% ethanol extracts of the rhizomes and roots of Veratrum dahuricum (Turcz.) Loes. f. by repeated column chromatography on silica gel and recrystallization. Its structure was established by extensive spectroscopic analyses, and its cytotoxicities against HepG-2, MCF7 and A549 cell lines were measured in vitro.

[Chemical constituents and antitumor activity on leukemia K562 cell of Leonurus heterophyllus].

The chemical constituents of Leonurus heterophyllus were separated and purified by repeated column chromatography on silica gel, HPD 100, Sephadex LH-20, and PHPLC. Each compound was characterized by spectroscopic and physical data. Eight compounds have been purified and identified to be quercetin 3-O-robinobioside (1), rutin (2), isoquerci trin (3), hyperoside (4), quercetin (5), apigenin (6), genkwanin (7), and benzoic acid (8). Among them, compounds 2, 5-7 were isolated from L. heterophyllus for the first time; Compounds 1, 3, 4, 8 were obtained for the first time from the genus Leonurus. The in vitro activities against leukemia K562 Cells of pure components were evaluated by testing their IC50. Compounds 1-6, 8 exhibited in-vitro inhibitory activities against leukemia K562 cells in different extent.