Panax notoginseng

三七
  • 文章类型: Journal Article
    根系和根区土壤微生物群落结构的组成和稳定性对植物的健康生长起着关键作用。我们检查了酚酸和皂苷的分布特征,以及根空间中的微生物群落(根内圈,根际平面土壤,根际土壤,和散装土壤)健康和受根腐病影响的三七。结果表明,感染根腐病后,根际平面土壤显示有机质和可水解氮显著减少,有效磷显著增加,有效钾,和总氮。根内圈中的酚酸(苯甲酸除外)和人参皂苷Rg2的含量显着增加。根际平面土壤中的阿魏酸和对羟基苯甲酸明显增加。红球菌在根内圈显著增加,根际平面,和根际土壤;根际平面中的硝基螺旋体明显减少,根际,和块状土壤;根际和根际平面土壤中的斑纹菌显着减少。此外,大多数自体毒素的积累可以促进病原体的生长。总之,三七根中的空间自毒物质和微生物群落差异共同诱导了根腐病的发生。IMPORTANCEPanax三七在种植过程中极易受到土壤传播疾病的影响,和根腐病,通常发生在植物的根和茎部分,是最严重的。我们将三七的根系环境分为四个部分(根内圈,根际平面土壤,根际土壤,和散装土壤),并以未种植的土壤为对照进行了研究。在这项研究中,我们研究了三七根空间中自毒物质含量的变化,以及这些物质和微生物之间的相互作用。该研究揭示了三七根腐病的发生机理,为减轻三七连作障碍提供了理论依据。
    The composition and stability of the microbial community structure of roots and root zone soils play a key role in the healthy growth of plants. We examined the distribution characteristics of phenolic acids and saponins, as well as microbial communities in the root space (root endosphere, rhizoplane soil, rhizosphere soil, and bulk soil) of healthy and root rot disease-affected Panax notoginseng. The results showed that after infection with root rot, the rhizoplane soil exhibited significant decreases in organic matter and hydrolyzable nitrogen and significant increases in available phosphorus, available potassium, and total nitrogen. The contents of phenolic acids (except benzoic acid) and ginsenoside Rg2 in the root endosphere significantly increased. Ferulic acid and p-hydroxybenzoic acid in the rhizoplane soil significantly increased. Rhodococcus increased significantly in the root endosphere, rhizoplane, and rhizosphere soil; Nitrospira decreased significantly in the rhizoplane, rhizosphere, and bulk soil; and Plectosphaerella decreased significantly in the root endosphere and rhizoplane soil. Moreover, the accumulation of most autotoxins can promote the growth of pathogens. In summary, the spatial autotoxic substances and microbial community differences in P. notoginseng roots jointly induce the occurrence of root rot.IMPORTANCEPanax notoginseng is highly susceptible to soil-borne diseases induced during planting, and root rot, which usually occurs in the root and stem parts of the plant, is the most severe. We divided the root environment of P. notoginseng into four parts (root endosphere, rhizoplane soil, rhizosphere soil, and bulk soil) and studied it with unplanted soil as the control. In this study, we examined the changes in the content of autotoxic substances in the root space of P. notoginseng, along with the interplay between these substances and microorganisms. This study revealed the mechanism underlying root rot and provided a theoretical basis for alleviating continuous cropping obstacles in P. notoginseng.
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  • 文章类型: Journal Article
    脱发的病因是如此复杂,以至于目前的疗法在长期使用过程中具有单一机制和伴随的副作用,不足以治疗。三七总皂苷(PNS)被认为具有多种治疗脱发的机制,但由于水溶性难以有效渗透皮肤。这里,我们使用霍霍巴油设计了油包水微乳液(PNSME),分馏椰子油,RH40+Span80和助表面活性剂D-泛醇,帮助PNS穿透皮肤。特别是,D-泛醇不仅扩大了微乳面积,减少表面活性剂的使用量,从而减轻皮肤刺激,但刺激真皮乳头细胞(DPC)的迁移,在抗脱发方面表现出协同作用。PNSME通过高亲和力脂质融合穿透富含皮脂的角质层,目标毛囊(HFs),它驻留在皮肤中持续释放药物,加速血管生成,为HFs建立营养良好的环境,并促进DPCs在体外的增殖和迁移。PNSME显著改善头发密度,皮肤色素沉着,新的头发重量,蒙皮厚度,和静止原脱发小鼠的胶原生成。此外,PNS对雄激素性脱发小鼠也有显著疗效。经过进一步的探索,PNSME引起β-catenin的急剧上调,VEGF和Ki67,提示其可能通过触发Wnt/β-catenin通路,加速船只的形成,激活毛囊干细胞。值得注意的是,PNSME比米诺地尔tin剂具有更长期的安全性。一起,PNSME为脱发提供了全面的策略,特别是避免了传统微乳液中高比例表面活性剂的缺陷,表现得更温和、更安全,显示了应用微乳液促进头发生长的广阔前景。
    The etiology of alopecia is so complex that current therapies with single-mechanism and attendant side-effects during long-term usage, are insufficient for treatment. Panax notoginseng saponins (PNS) is supposed to treat alopecia with multiple mechanisms, but difficult to penetrate skin efficiently due to water-solubility. Here, we designed water-in-oil microemulsion (PNS ME) using jojoba oil, fractioned coconut oil, RH 40 + Span 80 and cosurfactant D-panthenol, to help PNS penetrating the skin. Particularly, D-panthenol not only enlarges the microemulsion area, reduces the usage amounts of surfactants thus relieves skin irritation, but stimulates the migration of dermal papilla cells (DPCs), displaying cooperative effects on anti-alopecia. PNS ME penetrates through sebum-rich corneum via high-affinity lipid fusion, targets to hair follicles (HFs), where it resides in skin for sustained drug release, accelerates angiogenesis to build well-nourished environment for HFs, and facilitates the proliferation and migration of DPCs in vitro. PNS ME markedly improved hair density, skin pigmentation, new hair weight, skin thickness, and collagen generation of telogen effluvium mice. Moreover, PNS also took outstanding curative effects on androgenetic alopecia mice. Upon further exploration, PNS ME caused dramatic upregulations of β-catenin, VEGF and Ki67, suggesting it might function by triggering Wnt/β-catenin pathway, accelerating vessels formation, and activating the hair follicle stem cells. Notably, PNS ME indicated longer-term safety than minoxidil tincture. Together, PNS ME provides a comprehensive strategy for alopecia, especially it avoids defects by high-proportioned surfactants in traditional microemulsion, exhibiting milder and safer, which shows bright prospect of applying microemulsion in hair growth promotion.
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  • 文章类型: Journal Article
    三七,中国的一种药草,在培养过程中被几种病原体攻击。Dazomet(DZ)是一种土壤熏蒸剂,可有效控制土壤传播的病原体,但其对三七生长和土壤性质的长期影响尚不清楚。
    我们连续两年进行了田间试验,以评估三种浓度的DZ熏蒸(35kg/666.7m2,40kg/666.7m2和45kg/666.7m2)对土壤理化性质的影响,微生物多样性,和三七的生长。进行了微生物群落变化与土壤特性之间的相关性分析,并对土壤微生物进行了功能预测。
    DZ熏蒸增加了总氮,总磷,总钾,有效磷,有效钾,和土壤中的氨氮水平。DZ熏蒸促进三七养分积累和农艺性状的改善,产量提高2.83-3.81倍,最高的总皂苷含量增加了24.06%。40kg/666.7m2处理对三七生长和皂苷积累影响最大。DZ熏蒸后,镰刀菌等病原真菌的相对丰度下降,Plectosphaerella,和Ilyonectria,而有益菌如Ramlibacter,伯克霍尔德利亚,和红藻增加。熏蒸对土壤微生物和土壤理化性质的影响持续了18个月。DZ熏蒸提高了参与次生代谢产物和丛枝菌根真菌生物合成的细菌的相对丰度,降低了动植物病原真菌的相对丰度,减少了土传疾病的发生。
    总而言之,DZ熏蒸增强土壤理化性质,增加了土壤中有益细菌的比例,重新平衡土壤微生物种群,从而改善三七的生长环境,促进其生长,产量,和质量。本研究为DZ熏蒸作为解决三七等多年生药用植物连作问题的潜在解决方案提供了理论基础。
    UNASSIGNED: Panax notoginseng, a medicinal herb in China, is attacked by several pathogens during its cultivation. Dazomet (DZ) is a soil fumigant that is effective in controlling soil-borne pathogens, but its long-term effects on P. notoginseng growth and soil properties are unknown.
    UNASSIGNED: We conducted field experiments over two consecutive years to assess the impact of three concentrations of DZ fumigation (35 kg/666.7 m2, 40 kg/666.7 m2, and 45 kg/666.7 m2) on soil physicochemical properties, microbial diversity, and P. notoginseng growth. Correlation analyses were performed between microbial community changes and soil properties, and functional predictions for soil microorganisms were conducted.
    UNASSIGNED: DZ fumigation increased total nitrogen, total phosphorus, total potassium, available phosphorus, available potassium, and ammonia nitrogen levels in the soil. DZ fumigation promoted the nutrient accumulation and improvement of agronomic traits of P. notoginseng, resulted in a 2.83-3.81X yield increase, with the highest total saponin content increasing by 24.06%. And the 40 kg/666.7 m2 treatment had the most favorable impact on P. notoginseng growth and saponin accumulation. After DZ fumigation, there was a decrease in the relative abundance of pathogenic fungi such as Fusarium, Plectosphaerella, and Ilyonectria, while beneficial bacteria such as Ramlibacter, Burkholderia, and Rhodanobacteria increased. The effects of fumigation on soil microorganisms and soil physicochemical properties persisted for 18 months post-fumigation. DZ fumigation enhanced the relative abundance of bacteria involved in the biosynthesis of secondary metabolites and arbuscular mycorrhizal fungi, reduced the relative abundance of plant-animal pathogenic fungi, reduced the occurrence of soil-borne diseases.
    UNASSIGNED: In conclusion, DZ fumigation enhanced soil physicochemical properties, increased the proportion of beneficial bacteria in the soil, and rebalanced soil microorganism populations, consequently improving the growth environment of P. notoginseng and enhancing its growth, yield, and quality. This study offers a theoretical foundation for DZ fumigation as a potential solution to the continuous cropping issue in perennial medicinal plants such as P. notoginseng.
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  • 文章类型: Journal Article
    五种以前未描述的原人参三醇型皂苷,三七皂苷Ta-Te(1-5),从三七的根中分离出18种已知的三萜皂苷(6-23)。通过HRESIMS和NMR光谱分析和化学方法确定了新化合物的结构。化合物1和2是具有来自Panax物种的6-脱氧-β-d-葡萄糖部分的人参皂苷的第一个实例。化合物1-4、7、10、12、21-22对L02细胞具有抗对乙酰氨基酚(APAP)损伤的保护作用。其中,三七皂苷R1(12),人参皂苷Rg1(21),人参皂苷Re(22)是最有效的,细胞活力>80%。此外,化合物12和22可显着减轻APAP诱导的小鼠肝损伤。这些皂苷是潜在的肝保护剂。
    Five previously undescribed protopanaxatriol-type saponins, notoginsenosides Ta-Te (1-5), together with eighteen known triterpenoid saponins (6-23) were isolated from the roots of Panax notoginseng. The structures of new compounds were determined by HRESIMS and NMR spectroscopic analyses and chemical methods. Compounds 1 and 2 were the first examples of ginsenosides featuring a 6-deoxy-β-d-glucose moiety from Panax species. Compounds 1-4, 7, 10, 12, 21-22 showed protective effects on L02 cells against the injury of acetaminophen (APAP). Among them, notoginsenoside R1 (12), ginsenoside Rg1 (21), and ginsenoside Re (22) were the most potent ones, with cell viabilities >80%. Moreover, compounds 12 and 22 remarkably alleviated APAP-induced liver injury in mice. These saponins are potential hepatoprotective agents.
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  • 文章类型: Journal Article
    背景:三七,三七的根,长期以来,它对心血管疾病的治疗作用已被公认。皂甙,包括人参皂苷和三七皂苷,是三七的主要生物活性成分。皂苷的生物合成与内源性激素协调的防御反应密切相关。
    结果:为了提供对植物激素茉莉酸(JA)在皂苷合成和调节中的潜在作用的新见解,我们对2-4岁三七的不同组织进行了超高效液相色谱分析。此外,通过联合评价各组织的皂苷含量和转录组分析,分析了皂苷的时空分布。三七皂苷R1、人参皂苷Rb1和人参皂苷Rd在地下组织中积累,包括根,图奇,原纤维和根茎。与这些数据一致,内源激素JAs的相应基因,尤其是冠状动脉不敏感蛋白1(COI1)和粒细胞瘤病蛋白2(MYC2),主要在地下组织中表达。皂苷的组织和年龄特异性分布与参与JA生物合成的基因表达一致,代谢和信号通路。
    结论:本研究揭示了内源性植物激素在三七皂苷合成和调节中的时空效应。这将对提高生态种植技术产生重大影响,培育优质新品种,保护药用三七的稀有资源。©2024化学工业学会。
    BACKGROUND: Sanqi, the root of Panax notoginseng, has long been recognized for its therapeutic effects on cardiovascular diseases. Saponins, including ginsenosides and notoginsenosides, are the main bioactive components of P. notoginseng. The biosynthesis of saponins is closely related to the defense responses orchestrated by endogenous hormones.
    RESULTS: To provide new insights into the underlying role of phytohormone jasmonic acid (JA) in the synthesis and regulation of saponins, we performed an ultra-performance liquid chromatography analysis of different tissues of P. notoginseng aged 2-4 years. Moreover, by combined evaluation of saponin content and transcriptome profiling of each tissue, the spatial and temporal distribution of saponins was analyzed. N notoginsenoside R1, ginsenoside Rb1 and ginsenoside Rd accumulated in the underground tissues, including the root, tuqi, fibril and rhizome. In agreement with this data, the corresponding genes of the endogenous hormone JAs, especially coronatine insensitive 1 (COI1) and myelocytomatosis proteins 2 (MYC2), were predominantly expressed in the underground tissues. The tissue- and age-specific distribution of saponins was consistent with the expression of genes involved in JA biosynthetic, metabolic and signaling pathways.
    CONCLUSIONS: The present study has revealed the temporal and spatial effects of endogenous phtohormones in the synthesis and regulation of notoginsenosides, which will provide a significant impact on improving the ecological planting technology, cultivating new high-quality varieties and protecting the rare resources of medicinal P. notoginseng. © 2024 Society of Chemical Industry.
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  • 文章类型: Journal Article
    胃癌前病变(GPL)是胃癌发生发展的关键阶段。特征为不完全的肠上皮趋化和异质性增生,具有高恶性潜能。GPL的早期干预对于预防胃癌至关重要。此外,肿瘤和冠心病(CHD)之间存在共同的危险因素和发病机制,随着越来越多的肿瘤患者GPL并发CHD,生存率提高。冠心病的再灌注治疗可导致心肌缺血再灌注损伤(MIRI)。中药活血化瘀在治疗GPL和MIRI方面表现出独特的优势。人参总皂苷(PNS),中医的一个组成部分,以其血液循环的好处而闻名,具有抑制肿瘤生长和改善心肌缺血的积极作用。本研究利用GPL-MIRI小鼠模型来研究PNS在治疗中的作用。结果表明,PNS显着改善小鼠典型的GPL病变,如不完全的肠上皮化和异型增生,也减少了心肌梗塞。在分子水平上,PNS在GPL-MIRI模型中表现出双向调节作用。通过抑制PI3K/Akt/mTOR信号通路增强胃黏膜细胞自噬过程,同时抑制心肌细胞过度自噬。这些发现为使用中药复方PNS管理GPL和MIRI提供了新的见解和治疗策略。
    Gastric precancerous lesion (GPL) is a crucial stage in the development of gastric cancer, characterized by incomplete intestinal epithelial chemotaxis and heterogeneous hyperplasia with high malignant potential. Early intervention in GPL is vital for preventing gastric cancer. Additionally, there are shared risk factors and pathogenesis between tumors and coronary heart disease (CHD), with an increasing number of tumor patients GPL complicated with CHD due to improved survival rates. Reperfusion therapy in CHD can result in myocardial ischemia-reperfusion injury (MIRI). Traditional Chinese medicine (TCM) has demonstrated unique advantages in treating GPL and MIRI by promoting blood circulation and removing blood stasis. Panax ginseng total saponin (PNS), a component of TCM known for its blood circulation benefits, has shown positive effects in inhibiting tumor growth and improving myocardial ischemia. This study utilized a GPL-MIRI mouse model to investigate the effects of PNS in treatment. Results indicated that PNS significantly improved typical GPL lesions in mice, such as incomplete intestinal epithelialization and heteroplasia, and also reduced myocardial infarction. At the molecular level, PNS exhibited a bidirectional regulatory role in the GPL-MIRI model. It enhanced the autophagic process in gastric mucosal cells by inhibiting the PI3K/Akt/mTOR signaling pathway, while suppressed excessive autophagy in cardiomyocytes. These findings offer new insights and treatment strategies for managing GPL and MIRI using the TCM compound PNS.
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  • 文章类型: Journal Article
    三七和西洋参是重要的经济植物,利用干根进行药用和食品双重用途;对它们的茎和叶的研究仍然不足。其中还含有三萜皂苷。三七叶(PNL)和西洋参叶(PQL)提取物的总皂苷含量分别为12.30±0.34%和12.19±0.64%,分别。PNL和PQL皂苷提取物表现出良好的抗氧化性能,抗高血压药,低血糖,和体外抗炎特性和RAW264.7细胞。在PNL和PQL皂苷提取物中总共鉴定出699种代谢物,大多数是三萜皂苷,类黄酮和氨基酸。14种人参皂苷,18类黄酮或生物碱,两种皂苷提取物中均富集了16种氨基酸。总的来说,已经开发了药用植物PNL和PQL中的皂苷的利用,以促进功能食品和天然产品工业的系统研究。
    Panax notoginseng and Panax quinquefolium are important economic plants that utilize dried roots for medicinal and food dual purposes; there is still insufficient research of their stems and leaves, which also contain triterpenoid saponins. The extraction process was developed with a total saponin content of 12.30 ± 0.34% and 12.19 ± 0.64% for P. notoginseng leaves (PNL) and P. quinquefolium leaves (PQL) extracts, respectively. PNL and PQL saponin extracts showed good antioxidant, antihypertensive, hypoglycemic, and anti-inflammatory properties in vitro and RAW264.7 cells. A total of 699 metabolites were identified in PNL and PQL saponin extracts, with the majority being triterpenoid saponins, flavonoids and amino acids. Fourteen ginsenosides, 18 flavonoids or alkaloids, and 16 amino acids were enriched in both saponin extracts. Overall, the utilization of saponins from medicinal plants PNL and PQL has been developed to facilitate systematic research in the functional food and natural product industries.
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  • 文章类型: Journal Article
    植物衍生的纳米囊泡已成为对抗肿瘤的潜在药物。在这项研究中,我们研究了三七衍生纳米囊泡(PnNVs)对鳞状细胞癌增殖和迁移的抑制作用。此外,我们探索了植物块茎大小与物理性质之间的关系,这些纳米囊泡的组成和生物活性。
    我们从不同大小的三七块茎中分离出PnNVs:小型(s_PnNVs),中型(m_PnNVs)和大型(l_PnNVs),并评估大小,潜力,和形态学。使用共聚焦显微镜和流式细胞术评估细胞摄取效率。使用平板克隆评估了不同PnNVs抑制口腔鳞状细胞癌细胞的能力,CCK8测定,和划痕愈合试验。脱靶代谢组学用于比较不同PnNVs的代谢化合物。
    我们的发现表明,s_PnNVs表现出更低的潜能,但具有最高的细胞摄取效率,而m_PnNVs的特征是最小的大小和最低的细胞摄取效率。值得注意的是,m_PnNVs显示出最有效的抑制鳞状细胞癌的生长和迁移。组成分析表明,PnNV富含蛋白质,含有较低水平的RNA,其中l_PnNVs具有最高的蛋白质含量。此外,非靶向代谢组学分析显示,与s_PnNVs和l_PnNVs相比,m_PnNVs中特异性抗肿瘤相关代谢物的表达显着增加。
    总的来说,我们的结果强调了植物块茎大小对纳米囊泡生物活性的影响,强调其对实验设计和研究可重复性的重要性。
    UNASSIGNED: Plant-derived nanovesicles have emerged as potential agents for combating tumors. In this study, we investigated the inhibitory effects of Panax notoginseng-derived nanovesicles (PnNVs) on the proliferation and migration of squamous cell carcinoma. Additionally, we explored the relationship between plant tuber size and the physical properties, composition and bioactivity of these nanovesicles.
    UNASSIGNED: We isolated PnNVs from Panax notoginseng tubers of varying sizes: small-sized (s_PnNVs), medium-sized (m_PnNVs) and large-sized (l_PnNVs), and evaluated for size, potential, and morphology. Cellular uptake efficiency was assessed using confocal microscopy and flow cytometry. The ability of different PnNVs to inhibit oral squamous cell carcinoma cells was evaluated using plate cloning, CCK8 assay, and scratch healing assay. Off-target metabolomics was used to compare metabolic compounds of different PnNVs.
    UNASSIGNED: Our findings revealed that s_PnNVs exhibited lower potential but had the highest cellular uptake efficiency, whereas m_PnNVs were characterized by the smallest size and lowest cellular uptake efficiency. Notably, m_PnNVs demonstrated the most effective inhibition of squamous cell carcinoma growth and migration. Compositional analyses showed that PnNVs were rich in proteins and contained lower levels of RNA, with l_PnNVs having the highest protein content. Furthermore, untargeted metabolomics analysis revealed a significant increase in the expression of specific antitumour-related metabolites in m_PnNVs compared to s_PnNVs and l_PnNVs.
    UNASSIGNED: Overall, our results underscore the influence of plant tuber size on the bioactivity of the nanovesicles from which they are derived, emphasizing its importance for experimental design and study reproducibility.
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  • 文章类型: Journal Article
    腐植酸(HA)可以大大促进植物生长并改善土壤健康。目前,HA浓度变化对林下三七发育和土壤质量的影响尚不清楚。在这项研究中,以不同浓度(2、4和6ml/L)向三七根施用外源HA。随后,通过高通量测序技术评价细菌和真菌的多样性和群落结构。调查进一步涉及分析三七生长之间的相互作用,土壤侵蚀因素,和微生物网络的稳定性。我们的发现表明,中等浓度(4ml/L)的HA改善了三七的新鲜/干重和NO3--N水平。与对照相比,中等浓度的HA对细菌和真菌群落组成有显著影响.然而,细菌和真菌的α和β多样性没有显着差异。此外,4ml/LHA时,有益菌(缓生根瘤菌)和有害菌(黄杆菌科)的丰度增加和减少,分别,同时增强了细菌和真菌网络的稳定性。结构方程模型(SEM)表明,在中等浓度的HA下,三七鲜重、细菌和真菌群落是直接影响微生物网络稳定性的因素。总之,4ml/L的HA有利于促进三七生长和土壤质量。本研究为提高三七产量和三七-松农林复合体系的可持续发展提供了参考。
    Humic acid (HA) can substantially enhance plant growth and improve soil health. Currently, the impacts of HA concentrations variation on the development and soil quality of Panax notoginseng (Sanqi) from the forest understorey are still unclear. In this study, exogenous HA was administered to the roots of Sanqi at varying concentrations (2, 4, and 6 ml/L). Subsequently, the diversity and community structure of bacteria and fungi were assessed through high-throughput sequencing technology. The investigation further involved analyzing the interplay among the growth of sanqi, soil edaphic factors, and the microbial network stability. Our finding revealed that moderate concentrations (4 ml/L) of HA improved the fresh/dry weight of Sanqi and NO3--N levels. Compared with control, the moderate concentrations of HA had a notable impact on the bacterial and fungal communities compositions. However, there was no significant difference in the α and β diversity of bacteria and fungi. Moreover, the abundance of beneficial bacteria (Bradyrhizobium) and harmful bacteria (Xanthobacteraceae) increased and decreased at 4 ml/L HA, respectively, while the bacterial and fungal network stability were enhanced. Structural equation model (SEM) revealed that the fresh weight of Sanqi and bacterial and fungal communities were the factors that directly affected the microbial network stability at moderate concentrations of HA. In conclusion, 4 ml/L of HA is beneficial for promoting Sanqi growth and soil quality. Our study provides a reference for increasing the yield of Sanqi and sustainable development of the Sanqi-pine agroforestry system.
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  • 文章类型: Journal Article
    背景:三七总皂苷(PNS)是三七(Burk)的主要有效成分。PNS在中国被广泛用于治疗缺血性脑卒中。病理性低剪切应力是内皮炎症和血栓形成的一个诱因。然而,PNS对低剪切相关内皮炎症的作用机制尚不清楚。
    本研究旨在研究PNS对低剪切应力诱导的内皮炎症的影响,并探索潜在的机械和生物学机制。
    方法:建立小鼠颈动脉部分结扎诱导低内皮切应力模型,探讨了PNS通过Piezo1对低剪切应力诱导的内皮炎症的药效学作用及其机制。在静态条件下测定Yoda1诱发的人脐静脉内皮细胞(HUVECs)中Piezo1的活化和表达。使用微流体通道系统对HUVEC和Piezo1siRNAHUVEC施加剪切应力,以确定PECAM-1,p-YAP和VCAM-1表达。将富血小板血浆(PRP)引入低剪切处理的内皮细胞表面,通过荧光成像和流式细胞术观察其粘附和活化。
    结果:PNS通过影响Piezo1和PECAM-1的表达,在颈动脉部分结扎小鼠模型中以合理的剂量反应模式减轻内皮炎症并改善血流,同时抑制Yes相关蛋白(YAP)核易位。我们发现Piezo1感应到异常的剪切应力,并通过不同的途径在HUVEC中转换这些机械信号,PNS通过Piezo1缓解了低剪切应力诱导的内皮炎症。我们还发现Piezo1信号在低剪切应力下与PECAM-1相互作用,参与血小板与内皮细胞的粘附。低剪切应力增加了YAP核易位,并增加了HUVECs中VCAM-1的表达,这可能会激活血小板。PNS抑制HUVECs中低剪切诱导的Piezo1和PECAM-1表达和YAP核易位,此外,还抑制了低剪切应力诱导的功能失调的内皮细胞上的血小板粘附和活化。
    结论:PNS通过调节Piezo1通道改善了低剪切应力诱导的内皮炎症和血栓形成,PECAM-1表达,和YAP核易位。PNS可能是改善由异常血液剪切应力引起的内皮炎症的潜在治疗候选药物。
    BACKGROUND: Panax notoginseng saponins (PNS) are the major effective components of Panax notoginseng (burk) F.H.Chen which is one of the classic promoting blood circulation herbs in traditional Chinese medicine. PNS is widely used in China for the treatment of cerebral ischemic stroke. Pathological low shear stress is a causal factor in endothelial inflammation and thrombosis. However, the mechanism of PNS against low shear related endothelial inflammation is still unclear.
    UNASSIGNED: This study aims to investigate the effects of PNS against endothelial inflammation induced by low shear stress and to explore the underlying mechanical and biological mechanisms.
    METHODS: Mouse model of carotid partial ligation for inducing low endothelial shear stress was established, the pharmacodynamic effect and mechanism of PNS against endothelial inflammation induced by low shear stress through Piezo1 were explored. Yoda1-evoked Piezo1 activation and expression in human umbilical vein endothelial cells (HUVECs) were determined at static condition. Microfluidic channel systems were used to apply shear stress on HUVECs and Piezo1 siRNA HUVECs to determine PECAM-1, p-YAP and VCAM-1 expression. And platelet rich plasma (PRP) was introduced to low shear treated endothelial cells surface to observe the adhesion and activation by fluorescence imaging and flowcytometry.
    RESULTS: PNS attenuated endothelial inflammation and improved blood flow in a reasonable dose response pattern in carotid partial ligation mouse model by influencing Piezo1 and PECAM-1 expression, while suppressing yes-associated protein (YAP) nuclear translocation. We found Piezo1 sensed abnormal shear stress and transduced these mechanical signals by different pathways in HUVECs, and PNS relieved endothelial inflammation induced by low shear stress through Piezo1. We also found Piezo1 signalling has interaction with PECAM-1 under low shear stress, which were involved in platelets adhesion to endothelial cells. Low shear stress increased YAP nuclear translocation and increased VCAM-1 expression in HUVECs which might activate platelets. PNS inhibited low shear induced Piezo1 and PECAM-1 expression and YAP nuclear translocation in HUVECs, furthermore inhibited platelet adhesion and activation on dysfunctional endothelial cells induced by low shear stress.
    CONCLUSIONS: PNS ameliorated endothelial inflammation and thrombosis induced by low shear stress through modulation of the Piezo1 channel, PECAM-1 expression, and YAP nuclear translocation. PNS might serve as a potential therapeutic candidate for ameliorating endothelial inflammation induced by abnormal blood shear stress.
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