Exploratory Systematic Review and Meta-Analysis of Panax Genus Plant Ingestion Evaluation in Exercise Endurance.

BACKGROUND: Many studies that use food containing Panax genus plants (PGPs) have been conducted but most of them have not mentioned the effective compounds ginsenosides and their composition. Therefore, we conducted a systematic review and meta-analysis of time to exhaustion as an index of exercise endurance with ingestion of PGPs or ginsenosides to reveal their effects. METHODS: We performed a systematic review with a comprehensive and structured literature search using seven literature databases, four clinical trial databases, and three general web search engines during 15-22 March 2021. A random-effects model was applied to calculate the standardized mean difference (SMD) and 95% confidence interval (CI) as the difference between the mean in the treatment and placebo groups. We evaluated the risk of bias of individual studies along with the risk of bias tool in the Cochrane handbook. This study was funded by Maruzen Pharmaceuticals Co., Ltd. (Hiroshima, Japan). The protocol for this study was registered with the UMIN-CTR (No. UMIN000043341). RESULTS: Five studies met the inclusion criteria. The number of total participants was 90, with 59 in the ingestion-PGPs group and 64 in the control group, because three studies were crossover-design trials. We found that ingestion of PGPs or ginsenosides significantly improved exercise endurance (SMD [95% CI]: 0.58 [0.22-0.95], I2 = 0%). It was suggested that ginsenoside Rg1 (Rg1) and PGPs extract containing Rg1 were significantly effective in improving exercise endurance (SMD [95% CI]: 0.70 [0.14-1.27], I2 = 30%) by additional analysis. CONCLUSIONS: This systematic review suggests that the ingestion of PGPs or ginsenosides, especially Rg1, is effective in improving exercise endurance in healthy adults. However, further high-quality randomized controlled trials are required because imprecision and publication bias cannot be ignored in this systematic review.

PUFA synthase-independent DHA synthesis pathway in Parietichytrium sp. and its modification to produce EPA and n-3DPA.

The demand for n-3 long-chain polyunsaturated fatty acids (n-3LC-PUFAs), such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), will exceed their supply in the near future, and a sustainable source of n-3LC-PUFAs is needed. Thraustochytrids are marine protists characterized by anaerobic biosynthesis of DHA via polyunsaturated fatty acid synthase (PUFA-S). Analysis of a homemade draft genome database suggested that Parietichytrium sp. lacks PUFA-S but possesses all fatty acid elongase (ELO) and desaturase (DES) genes required for DHA synthesis. The reverse genetic approach and a tracing experiment using stable isotope-labeled fatty acids revealed that the ELO/DES pathway is the only DHA synthesis pathway in Parietichytrium sp. Disruption of the C20 fatty acid ELO (C20ELO) and ∆4 fatty acid DES (∆4DES) genes with expression of ω3 fatty acid DES in this thraustochytrid allowed the production of EPA and n-3docosapentaenoic acid (n-3DPA), respectively, at the highest level among known microbial sources using fed-batch culture.

ß-Amyrin induces angiogenesis in vascular endothelial cells through the Akt/endothelial nitric oxide synthase signaling pathway.

ß-Amyrin is a pentacyclic triterpene found in various plants and has a variety of biological and pharmacological activities. However, the angiogenic effects of ß-amyrin in vascular endothelial cells have not been elucidated. Herein, we investigated the effects of ß-amyrin on angiogenesis and evaluated the underlying molecular mechanisms. ß-Amyrin treatment had no cytotoxic effect on cultured human umbilical vein endothelial cells (HUVECs). It promoted the formation of tube-like structures and enhanced HUVEC migration and the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS) in HUVECs. Pre-treatment with a PI3 kinase or NOS inhibitor blocked ß-amyrin-induced phosphorylation of Akt and eNOS. ß-Amyrin treatment significantly induced nitric oxide (NO) production in HUVECs. Furthermore, pre-treatment with a PI3 kinase or NOS inhibitor significantly inhibited ß-amyrin-induced tube-like structures formation of vascular endothelial cells and HUVEC migration. These data indicate that ß-amyrin-induced angiogenesis in vascular endothelial cells may be mediated by Akt-eNOS signaling-dependent mechanisms. These findings suggest that ß-amyrin could be a novel therapeutic agent for ischemic vascular diseases.

Planar polarization of node cells determines the rotational axis of node cilia.

Rotational movement of the node cilia generates a leftward fluid flow in the mouse embryo because the cilia are posteriorly tilted. However, it is not known how anterior-posterior information is translated into the posterior tilt of the node cilia. Here, we show that the basal body of node cilia is initially positioned centrally but then gradually shifts toward the posterior side of the node cells. Positioning of the basal body and unidirectional flow were found to be impaired in compound mutant mice lacking Dvl genes. Whereas the basal body was normally positioned in the node cells of Wnt3a(-/-) embryos, inhibition of Rac1, a component of the noncanonical Wnt signalling pathway, impaired the polarized localization of the basal body in wild-type embryos. Dvl2 and Dvl3 proteins were found to be localized to the apical side of the node cells, and their location was polarized to the posterior side of the cells before the posterior positioning of the basal body. These results suggest that posterior positioning of the basal body, which provides the posterior tilt to node cilia, is determined by planar polarization mediated by noncanonical Wnt signalling.

Expression of the circadian clock-related gene pex in cyanobacteria increases in darkness and is required to delay the clock.

The time measurement system of the unicellular cyanobacterium Synechococcus elongatus PCC 7942 is analogous to the circadian clock of eukaryotic cells. Circadian clock-related genes have been identified in this strain. The clock-related gene pex is thought to maintain the normal clock period because constitutive transcription or deficiency of this gene causes respectively longer (approximately 28 h) or shorter (approximately 24 h) circadian periods than that of the wild type (approximately 25 h). Here, the authors report other properties of pex in the circadian system. Levels of pex mRNA increased significantly in a 12-h exposure to darkness. Western blotting with a GST-Pex antibody revealed a 13.5-kDa protein band in wild-type cells that were incubated in the dark, while this protein was not detected in pex-deficient mutant cells. Therefore, the molecular weight of the Pex protein appears to be 13.5 kDa in vivo. The PadR domain, which is conserved among DNA-binding transcription factors in lactobacilli, was found in Pex. In the pex mutant, several 12-h light/12-h dark cycles reset the phase of the clock by 3 h earlier (phase advance) compared to wild-type cells. The degree of the advance in the pex mutant was proportional to the number of exposed light-dark cycles. In addition, ectopic induction of pex with an inducible Escherichia coli promoter, Ptrc, delayed the phase in the examined recombinant cells by 2.5 h (phase delay) compared to control cells. These results suggest that the dark-responsive gene expression of pex delays the circadian clock under daily light-dark cycles.

De novo formation of left-right asymmetry by posterior tilt of nodal cilia.

In the developing mouse embryo, leftward fluid flow on the ventral side of the node determines left-right (L-R) asymmetry. However, the mechanism by which the rotational movement of node cilia can generate a unidirectional flow remains hypothetical. Here we have addressed this question by motion and morphological analyses of the node cilia and by fluid dynamic model experiments. We found that the cilia stand, not perpendicular to the node surface, but tilted posteriorly. We further confirmed that such posterior tilt can produce leftward flow in model experiments. These results strongly suggest that L-R asymmetry is not the descendant of pre-existing L-R asymmetry within each cell but is generated de novo by combining three sources of spatial information: antero-posterior and dorso-ventral axes, and the chirality of ciliary movement.