Isorhynchophylline improves lipid metabolism disorder by mediating a circadian rhythm gene Bmal1 in spontaneously hypertensive rat.

Hypertension is a progressive metabolic disease characterized by circadian regulation of lipid metabolism disorder. Identifying specific lipid components and maintaining circadian homeostasis of lipid metabolism might be a promising therapeutic strategy for hypertension. Isorhynchophylline (IRP) can regulate lipid metabolism; however, the underlying mechanism of IRP in improving lipid metabolism rhythm disorder is still unclear. The lipid circadian biomarkers and abnormal metabolic pathways intervened by IRP were investigated using diurnal lipidomic research methods. The 24-h circadian changes in mRNA and protein expression levels of circadian genes, including Bmal1, Clock, Cry1, Cry2, Per1, and Per2, and lipid metabolism-related factors (PPARα and LPL) were determined using RT-PCR and western blot analyses, respectively. The underlying mechanisms were intensively investigated by inhibiting Bmal1. Molecular docking and drug affinity responsive target stability analyses were performed to assess the binding affinity of IRP and Bmal1. IRP treatment could effectively improve 24-h blood pressure, ameliorate the lipid metabolic rhythm disorder, reverse the expression levels of circadian rhythm genes, and regulate lipid metabolism-related genes (PPARα and LPL) by mediating Bmal1. This study highlighted the potential effects of IRP in maintaining the circadian homeostasis of lipid metabolism and the treatment of hypertension.

Variations and driving factors of leaf functional traits in the dominant desert plant species along an environmental gradient in the drylands of China.

Leaf functional traits (LFTs) of desert plants are responsive, adaptable and highly plastic to their environment. However, the macroscale variation in LFTs and driving factors underlying this variation remain unclear, especially for desert plants. Here, we measured eight LFTs, including leaf carbon concentration (LCC), leaf nitrogen concentration (LNC), leaf phosphorus concentration (LPC), specific leaf area (SLA), leaf dry matter content (LDMC), leaf mass per area (LMA), leaf thickness (LTH) and leaf tissue density (LTD) across 114 sites along environmental gradient in the drylands of China and in Guazhou Common Garden and evaluated the effect of environment and phylogeny on the LFTs. We noted that for all species, the mean values of LCC, LNC, LPC, SLA, LDMC, LMA, LTH and LTD were 384.62 mg g-1, 19.91 mg g-1, 1.12 mg g-1, 79.62 cm2 g-1, 0.74 g g-1, 237.39 g m-2, 0.38 mm and 0.91 g cm-3, respectively. LFTs exhibited significant geographical variations and the LNC, LMA and LTH in the plants of Guazhou Common Garden were significantly higher than the field sites in the drylands of China. LDMC and LTD of plants in Guazhou Common Garden were, however, considerably lower than those in the drylands of China. LCC, LPC, LTH and LTD differed significantly among different plant lifeforms, while LNC, SLA, LDMC and LMA didn't show significant variations. We found that the environmental variables explained higher spatial variations (3.6-66.3 %) in LFTs than the phylogeny (1.8-54.2 %). The LCC significantly increased, while LDMC and LTD decreased with increased temperature and reduced precipitation. LPC, LDMC, LMA, and LTD significantly increased, while SLA and LTH decreased with increased aridity. However, leaf elements were not significantly correlated with soil nutrients. The mean annual precipitation was a key factor controlling variations in LFTs at the macroscale in the drylands of China. These findings will provide new insights to better understand the response of LFTs and plants adaptation along environmental gradient in drylands, and will serve as a reference for studying biogeographic patterns of leaf traits.

Deciphering the Mechanism of the Anti-Hypertensive Effect of Isorhynchophylline by Targeting Neurotransmitters Metabolism of Hypothalamus in Spontaneously Hypertensive Rats.

Essential hypertension is a major risk factor for cardiovascular disease that can lead eventually to structural and functional alterations in the brain. Accumulating evidence has suggested that the increased activities in renin-angiotensin system and sympathetic nerve participated in the pathogenesis of hypertension that is related to the imbalance between neurotransmitters. The potential role in essential hypertension arising from alterations of neurotransmitters in the central nervous system remains understudied. Isorhynchophylline is a major oxindole alkaloid extracted from Uncaria rhynchophylla, which has been widely used for treating hypertension and neurodegenerative diseases. Whether isorhynchophylline acts on neurotransmitters to lower blood pressure has been hypothesized but rarely demonstrated unequivocally. Here, we studied the metabolic neurotransmitter profiles in the hypothalamus using a targeted metabolomic approach in spontaneously hypertensive rats after isorhynchophylline intervention. Our study demonstrated that isorhynchophylline exhibited a strong anti-hypertensive effect in spontaneously hypertensive rats by improving the neurotransmitter imbalance in the hypothalamus and inhibiting the overactivation of the renin-angiotensin system and sympathetic nerve system. Overall, this study played an essential role in enhancing our understanding of the mechanism of isorhynchophylline in essential hypertension and in providing theoretical evidence for future research and clinical application.