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Motor learning dysfunction and its association with neurotransmitters and gut microbiota dysbiosis in hepatic encephalopathy mice 肝性脑病小鼠运动学习功能障碍及其与神经递质和肠道菌群失调的关系
Pub Date : 2022-12-01 DOI: 10.1016/S2707-3688(23)00002-X
Yunqi SHAN , Haidan DENG , Baojun SHAN , Jiaying HUANG , Xinshu FENG , Xiaoming SUN

Objective

This study aims to investigate the potential mechanisms underlying motor learning dysfunction in hepatic encephalopathy (HE) mice using gut microbiota and neurochemicals.

Methods

C57BL/6 mice were intraperitoneally treated with thioacetamide to induce the HE model. Cytokines of TNF-α and ammonia in serum and motor cortex were tested using the ELISA kit. Rota-rod was used to assess the motor learning behavior of HE mice. The 16S rDNA analysis revealed gut microbiota species and abundance changes in HE mice. The 26 neurochemicals of control and HE mice were quantified and analyzed with different microbiota using the UPLC-TQ-MS technique.

Results

LEfSe analysis revealed that 25 genera differed significantly between healthy and HE mice. Correlation analysis revealed that the Escherichia_Shigella, Allobaculum, and Muribaculaceae were associated with higher adrenaline levels of hydrochloride, 4-aminobytyric acid, and L-glutamic acid and lower levels of L-histidine and histamine.

Conclusion

The neurotransmitter changes in motor cortex have some relationship with gut microbiota disturbances. This correlation may pave the way to explain the cognitive and motor learning dysfunction in HE mice.

目的利用肠道微生物群和神经化学物质探讨肝性脑病(HE)小鼠运动学习功能障碍的潜在机制。方法用硫乙酰胺腹腔注射sc57bl /6小鼠,建立HE模型。采用ELISA试剂盒检测血清和运动皮层中TNF-α和氨的细胞因子。采用旋转棒法评价HE小鼠的运动学习行为。16S rDNA分析揭示了HE小鼠肠道菌群种类和丰度的变化。采用UPLC-TQ-MS技术对对照组和HE小鼠的26种神经化学物质进行定量分析。结果fse分析显示,25个属在健康小鼠和HE小鼠之间存在显著差异。相关分析显示,志贺氏杆菌、异源杆菌和鼠耳杆菌科菌的肾上腺素水平较高,盐酸、4-氨基丁酸和l -谷氨酸水平较高,l -组氨酸和组胺水平较低。结论运动皮层神经递质变化与肠道菌群紊乱有一定关系。这种相关性可能为解释HE小鼠的认知和运动学习功能障碍铺平道路。
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引用次数: 0
Antiseptic property screening for 18 natural plants and efficiency–toxicity research of Coptis chinensis fermentation 18种天然植物防腐性能筛选及黄连发酵药效毒性研究
Pub Date : 2022-12-01 DOI: 10.1016/S2707-3688(23)00004-3
Fang ZHAO , Yan WANG , Yongyan PEI , Jun SHI , Ping ZHAO , Limin ZHAO

Objective

This study aimed to compare the antibacterial performance of 18 natural plants against six types of microorganisms that tend to grow in cosmetics and select the best natural antiseptic herbs with low toxicity and a broad antibacterial spectrum. The safety performance and effects of the antioxidant, whitening, and reduced inflammation of Coptis chinensis fermentation were explored.

Methods

The inhibition performance of the alcoholic extracts for the 18 natural plants against six microorganisms was compared by using the cylinder plate method. The MTT assay was used to determine the cell viability of C. chinensis extract and fermentation products. DPPH, hydroxyl, and ABTS radical scavenging rates as well as iron reduction ability were used to evaluate the antioxidant efficacy. In addition, the activity inhibition rate of tyrosinase and hyaluronidase indicated the whitening and anti-inflammatory properties of C. chinensis extract and fermentation broth.

Results

Results showed that among the 18 natural plants, C. chinensis extract had the most prominent inhibition circles and the smallest minimum inhibitory concentration (MIC) value against six microorganisms. After fermentation, the IC50 value of C. chinensis alcoholic extract increased significantly with the cell survival rate, indicating its low biosafety. The free radical scavenging rate, tyrosinase inhibition rate, and hyaluronidase inhibition rate of fermented C. chinensis extract increased significantly, showing better antioxidant activity, whitening activity, and anti-inflammatory activity than alcohol extract.

Conclusion

Among the 18 natural plants, C. chinensis has the most substantial antibacterial ability. After fermentation by yeast, the cytotoxicity of C. chinensis decreases, and the antioxidant, whitening, and anti-inflammatory activities increase, indicating that microbial fermentation attenuates toxicity and enhances the effect of plant preservatives.

目的比较18种天然植物对6种易在化妆品中生长的微生物的抑菌性能,筛选出低毒、抗菌谱广的天然抗菌草药。探讨了黄连发酵的安全性能及其抗氧化、美白、消炎作用。方法采用柱皿法比较18种天然植物醇提物对6种微生物的抑菌效果。采用MTT法测定五味子提取物和发酵产物的细胞活力。以DPPH、羟基和ABTS自由基清除率和铁还原能力评价其抗氧化效果。此外,酪氨酸酶和透明质酸酶的活性抑制率表明,五味子提取物和发酵液具有美白和抗炎作用。结果18种天然植物中,五倍子提取物对6种微生物的抑制圈最显著,最小抑制浓度(MIC)值最小。发酵后,五味子醇提物的IC50值随细胞存活率显著升高,表明其生物安全性较低。发酵五味子提取物的自由基清除率、酪氨酸酶抑制率和透明质酸酶抑制率显著提高,具有较好的抗氧化、美白和抗炎活性。结论在18种天然植物中,紫草的抑菌能力最强。经酵母发酵后,五味子的细胞毒性降低,抗氧化、美白和抗炎活性增强,说明微生物发酵可以减轻毒性,增强植物防腐剂的作用。
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引用次数: 0
Molecular mechanisms of RNA m6A-modifying enzymes in cardiovascular diseases RNA m6a修饰酶在心血管疾病中的分子机制
Pub Date : 2022-12-01 DOI: 10.1016/S2707-3688(23)00009-2
Xiangyu GAO , Mingyi XU , Jiaming LIU , Mingzhu XIAO

Cardiovascular diseases are the leading causes of death globally. Their pathological mechanisms are complex and have not yet been fully clarified. With the development of epigenetics research in recent years, the epigenetic modification N6-methyladenosine (m6A) has been demonstrated to play an important role in the occurrence and development of cardiovascular diseases. Moreover, m6A methyltransferases, demethylases, and recognition proteins can regulate m6A methylation levels in the RNA, affecting various biological processes such as RNA splicing, nuclear export, protein translation, and degradation. In this paper, we focus on the biological functions of m6A and investigate its role in the biological processes of apoptosis, inflammation, oxidative stress, energy metabolism, and lipid metabolism. Furthermore, we describe the current findings on the mechanisms involving m6A in cardiovascular diseases and discuss potential drugs targeting m6A for therapy.

心血管疾病是全球死亡的主要原因。其病理机制复杂,尚未完全阐明。近年来,随着表观遗传学研究的深入,表观遗传修饰n6 -甲基腺苷(m6A)在心血管疾病的发生发展中发挥了重要作用。此外,m6A甲基转移酶、去甲基化酶和识别蛋白可以调节RNA中的m6A甲基化水平,影响RNA剪接、核输出、蛋白质翻译和降解等多种生物过程。本文针对m6A的生物学功能,探讨其在细胞凋亡、炎症、氧化应激、能量代谢和脂质代谢等生物学过程中的作用。此外,我们描述了m6A参与心血管疾病的机制的最新发现,并讨论了靶向m6A治疗的潜在药物。
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引用次数: 0
Analgesic monoterpene indole alkaloids from Gelsemium elegans stems 菖蒲茎中的镇痛类单萜吲哚生物碱
Pub Date : 2022-09-01 DOI: 10.1016/S2707-3688(23)00047-X
Pengfei JIN , Guijuan ZHENG , Lang HUANG , Xinghua YUAN , Xiaomin MA , Guanqun ZHAN , Adila ABUDUREXITI , Guangmin YAO

Objective

The aim of this study is to search for potent analgesics from the stems of Gelsemium elegans.

Methods

Alkaloids were isolated from the samples of G. elegans and purified using column chromatograph and High-Performance Liquid Chromatography. The chemical structures of the isolated alkaloids were determined using extensive high resolution electrospray ionization mass spectroscopy (HRESIMS) and nuclear magnetic resonance (NMR) spectroscopic data analyses, 13C NMR DP4+ analysis and electronic circular dichroism (ECD) calculations, and Rh2(OCOCF3)4-induced ECD data analysis. The analgesic activities of all the isolates were analyzed using an acetic acid-induced writhing test in mice.

Results

Two new monoterpene indole alkaloids, elegansine A (1) and 14-hydroxysempervirine (2), and seven known monoterpene indole alkaloids were isolated from the stems of G. elegans. Elegansine A (1) represents the first example of sarpagine-type alkaloids with a Δ15(20) double bond. All the alkaloids (1–9) showed potential analgesic activities. Three alkaloids, namely 14-hydroxysempervirine (2), 14β,20α-dihydroxydihydrorankinidine (4), and 14-hydroxygelsenicine (6), exhibited significant analgesic activities in the acetic acid-induced writhing test in mice at a dose of 5.0 mg/kg with the writhing inhibition rates of 69.5%, 69.2%, and 72.7%, respectively.

Conclusion

These results enlarged the diversity of monoterpene indole alkaloids and also provided a new basis to develop novel potent analgesics.

目的从秀丽隐杆草茎中寻找强效镇痛药。方法从秀丽隐杆线虫样品中分离提取生物碱,采用柱层析和高效液相色谱法进行纯化。采用广泛的高分辨率电喷雾电离质谱(HRESIMS)和核磁共振(NMR)光谱数据分析、13C NMR DP4+分析和电子圆二色性(ECD)计算以及Rh2(OCOCF3)4诱导ECD数据分析来确定分离生物碱的化学结构。用醋酸致小鼠扭体实验分析了各分离物的镇痛活性。结果从秀丽隐杆线虫茎中分离到2个新的单萜吲哚类生物碱,分别为秀丽隐杆线虫素A(1)和14-羟锥虫碱(2),以及7个已知的单萜吲哚类生物碱。Elegansine A(1)是具有Δ15(20)双键的sarpagine型生物碱的第一个例子。所有生物碱(1-9)均表现出潜在的镇痛活性。在5.0 mg/kg的醋酸致小鼠扭体实验中,14-羟基贝贝virine(2)、14β、20α-二羟基二氢兰基定(4)和14-羟基格尔西尼汀(6)对小鼠的扭体抑制率分别为69.5%、69.2%和72.7%,表现出明显的镇痛作用。结论扩大了单萜吲哚类生物碱的多样性,为开发新型强效镇痛药提供了新的依据。
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引用次数: 0
Novel phenylacetate derivatives isolated from the fungus Penicillium canescens 从癌变青霉中分离的新型苯乙酸酯衍生物
Pub Date : 2022-09-01 DOI: 10.1016/S2707-3688(23)00045-6
Yi ZANG, Yingli SONG, Zhe WANG, Mengmeng YU, Honghui ZHU

Two undescribed phenylacetate derivatives (compounds 1 and 2) with a known analog were isolated from a soil-derived fungus Penicillium canescens through the “one strain-many compounds” method. The new structures were assigned using extensive 1D and 2D NMR spectra, high-resolution electrospray ionization mass spectrometry, and the comparison of coupling cleavages of known compounds, which are two pairs of racemic mixtures of aromatic polyketides with a terminal butan-2,3-diol group. In the bioassay, the biological screening signifies no cytotoxic activities against several human cancer cell lines (HL-60, A549, SMMC-7721, MCF-7, and SW480) at a concentration of 40.0 µM.

通过“一种菌株-多化合物”的方法,从土壤来源的真菌青霉菌中分离出两个具有已知类似物的未描述的苯乙酸酯衍生物(化合物1和2)。新的结构是通过广泛的一维和二维核磁共振光谱,高分辨率电喷雾电离质谱,以及已知化合物的偶联裂解比较来确定的,这些化合物是两对芳香族聚酮的外消旋混合物,末端有-2,3-二醇基团。在生物测定中,生物筛选表明,在浓度为40.0µM时,对几种人类癌细胞系(HL-60、A549、SMMC-7721、MCF-7和SW480)没有细胞毒活性。
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引用次数: 0
Peniciisoquinoline A: A new tetrahydroisoquinoline from mangrove-derived fungus Penicillium sp. DM27 青霉异喹啉A:一种新的四氢异喹啉,来源于红树真菌青霉菌
Pub Date : 2022-09-01 DOI: 10.1016/S2707-3688(23)00046-8
Liming HE , Zifang ZHAO , Mengke ZHANG , Zhijie XIANG , Kui HONG , Fengkai FAN , Yousheng CAI

Objective

This study aims to search for structurally novel, natural bioactive products from mangrove-derived fungi.

Methods

Compounds were isolated and purified by column chromatography on HP20 macroreticular resin, silica gel, Sephadex LH-20 gel, and high performance liquid chromatography. The structures of the isolates were analyzed using NMR and MS data, and the absolute configuration of 1 was determined by calculated ECD spectroscopic methods. The cytotoxicity of all the isolates was tested against HCT-116, HepG2, HEK 293t, and 5637 cancer cell lines using CCK-8 assay.

Results

A new tetrahydroisoquinoline named peniciisoquinoline A (1) was obtained from Penicillium sp. DM27 along with five known compounds. Peniciisoquinoline A (1) was inactive against the four cancer cell lines.

Conclusion

This study conducted chemical research on Penicillium sp. DM27 and tested the cytotoxic activity of the new alkaloid (1), which will assist in the further development and utilization of mangrove-derived fungi.

目的从红树林衍生真菌中寻找结构新颖的天然生物活性产物。方法采用HP20大孔树脂柱层析、硅胶柱层析、Sephadex LH-20凝胶柱层析和高效液相层析对化合物进行分离纯化。利用核磁共振和质谱分析了分离物的结构,利用计算ECD方法确定了1的绝对构型。采用CCK-8法检测各分离株对HCT-116、HepG2、HEK 293t和5637癌细胞的细胞毒性。结果从Penicillium sp. DM27中分离得到一种新的四氢异喹啉,命名为peniciisoquinoline A(1)。青霉素异喹啉A(1)对四种癌细胞均无活性。结论本研究对红树源真菌青霉菌DM27进行了化学研究,并检测了其细胞毒活性(1),为红树源真菌的进一步开发利用提供了依据。
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引用次数: 0
Mangrove soil-derived Streptomyces: an important resource of pharmaceutical active natural products 红树林土源链霉菌:药用活性天然产物的重要资源
Pub Date : 2022-09-01 DOI: 10.1016/S2707-3688(23)00050-X
Xuefeng ZHOU

The mangrove soil-derived microbes, especially genus Streptomyces strains, have proven to be a rich source of bioactive secondary metabolites and play a critical role in the development of pharmaceutical researches. To understand the structural diversity and bioactivities of the metabolites from the mangrove soil-derived Streptomyces strains, this review for the first time provides a comprehensive overview of 168 natural products isolated from the mangrove soil-derived Streptomyces strains with their bioactivities, up to the end of 2021. Most of the structural types of these compounds are alkaloids, lactones, xanthones, and quinones. The pharmacological mechanisms of some representative lead compounds are well studied, revealing that they have important medicinal potential. This review provides an important reference for the research status of natural products isolated from mangrove soil-derived genus Streptomyces, and reveals that mangrove soil-derived Streptomyces is an important resource of pharmaceutical molecules.

红树林土壤微生物,特别是链霉菌属,已被证明是生物活性次生代谢产物的丰富来源,在药物研究的发展中起着至关重要的作用。为了解红树林土源链霉菌代谢产物的结构多样性和生物活性,本文首次对截至2021年底从红树林土源链霉菌中分离到的168种天然产物及其生物活性进行了综述。这些化合物的结构类型大多是生物碱、内酯、山酮和醌类。一些具有代表性的先导化合物的药理机制已经得到了很好的研究,揭示了它们具有重要的药用潜力。本文综述为红树林土源链霉菌属天然产物的研究现状提供了重要参考,揭示了红树林土源链霉菌是药物分子的重要资源。
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引用次数: 1
Macrocyclic polyketides from microorganisms: structural diversities and bioactivities 微生物的大环聚酮:结构多样性和生物活性
Pub Date : 2022-09-01 DOI: 10.1016/S2707-3688(23)00049-3
Peng ZHOU , Qin LI , Chunmei CHEN , Hucheng ZHU , Yonghui ZHANG

Microorganisms are a seemingly inexhaustible source of bioactive secondary metabolites, which play a crucial role in discovering potential drug candidates and expanding the structural diversity of natural products. Polyketides are a large group of secondary metabolites mainly derived from microorganisms, harboring architecturally distinct scaffolds and diverse bioactivities. This review highlights the roles of macrocyclic polyketides isolated from bacteria and fungi, as well as their sources, structure diversity, and biological activities. Total 242 macrocyclic polyketides mainly reported in recent two decades were covered in this review, including 165 ones from bacteria and 77 ones from fungi. Their structures could be divided into macrolactams, macrolides in bacteria, and macrolides, polyesters in fungi. And these compounds displayed cytotoxic, antibacterial, antifungal, and also some other activities, such as antimalarial and antitrypanosomal activities.

微生物是生物活性次生代谢物的取之不尽的来源,在发现潜在的候选药物和扩大天然产物的结构多样性方面发挥着至关重要的作用。聚酮类化合物是一类主要来源于微生物的次生代谢产物,具有结构独特的支架和多种生物活性。本文综述了从细菌和真菌中分离的大环聚酮化合物的作用,以及它们的来源、结构多样性和生物活性。本文综述了近20年来报道的242种大环聚酮类化合物,其中细菌类化合物165种,真菌类化合物77种。它们的结构可分为细菌中的大环内酯类和真菌中的大环内酯类。这些化合物具有细胞毒性、抗菌、抗真菌和抗疟疾、抗锥虫等活性。
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引用次数: 0
Seladoeneolignan A, a new neolignan from Selaginella doederleinii Hieron. Seladoeneolignan A,一种新木聚糖属植物。
Pub Date : 2022-09-01 DOI: 10.1016/S2707-3688(23)00042-0
Minyu CHEN , Ni ZHENG , Wenqi LIU , Dingrong WAN , Rumei LU , Xinzhou YANG

Objective

To study the chemical compositions from Selaginella doederleinii Hieron.

Methods

The petroleum ether and ethyl acetate fractions of 80% ethanol extract of S. doederleinii were separated and purified by macroporous resin, silica gel, Sephadex LH-20 and semi-preparative HPLC, and then the structures of obtained compounds were identified by physicochemical properties and spectroscopical data.

Results

A total of 7 compounds were isolated and identified as seladoeneolignan A (1), ethoxy-ferulate (2), 11-dien-19-oic acid (3), aurantiamide (4), 9,16-dioxo-10,12,14-octadeca-trienoic acid (5), amentoflavone (6), and 7,4’-di-0-methylrobustaflavone (7).

Conclusion

Compound 1 was a new neolignan obtaind from S. doederleinii for the first time. Compounds 1, 6 and 7 were screened for antitumor activity in vitro, and the testing results showed that 3 compounds had low inhibitory activity on Hep-2 and Eca-109 tumor cells.

目的研究卷柏的化学成分。方法采用大孔树脂、硅胶、Sephadex LH-20和半制备高效液相色谱法对菟丝子80%乙醇提取物的石油醚和乙酸乙酯组分进行分离纯化,通过理化性质和波谱数据对化合物结构进行鉴定。结果共分离得到7个化合物,鉴定为seladoeneolstanan A(1)、乙氧基阿魏酸(2)、11-二烯-19-酸(3)、金酰胺(4)、9,16-二氧基-10,12,14-十八烯-三烯酸(5)、amentoflavone(6)和7,4′-二-0-甲基robustadflavone(7)。结论化合物1为首次从菟丝子中分离得到的新木脂素。对化合物1、6、7进行体外抗肿瘤活性筛选,结果表明3个化合物对Hep-2和Eca-109肿瘤细胞具有较低的抑制活性。
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引用次数: 0
Two new phenylpropanoids from the leaves of Rauvolfia vomitoria 两种新的苯丙素类化合物的研究
Pub Date : 2022-09-01 DOI: 10.1016/S2707-3688(23)00044-4
Fuxin ZHANG , Rongkun MIAO , Kailing YANG, Tao YANG, Ruixi ZHOU, Guanqun ZHAN, Zengjun GUO

Objective

Study on the non-alkaloid chemical constituents with novel structure and their biological activities from the w-butanol fraction of the leaves of Rauvolfia vomitoria.

Methods

The w-butanol fraction of R. vomitoria was separated by silica gel, ODS, and Sephadex LH-20 chromatography column, as well as semi-preparative HPLC to obtain five compounds. Their structures were identified by extensive spectroscopic analysis, including HRESIMS, 1D and 2D NMR, and ECD analysis. All the isolated compounds were evaluated their AChE inhibitory activities by Ellman’s method with slight modification, their vasorelaxant activities against phenylephrine-induced contraction of rat mesenteric arteries, and their inhibitory activity of a-glucosidase employing pNPG as substrate.

Results

Two new phenylpropanoids (1-2) along with three known compounds, methyl trans-3,4,5-trimethoxycinnamate (3), methyl cis-3,4,5-trimethoxycinnamate (4), and 3,4,5-trimethoxybenzoic acid methyl ester (5), were isolated from the leaves of R.vomitoria. The five isolated compounds did not show significant tested activity.

Conclusion

Chemical investigation of the leaves of R. vomitoria led to the isolation and identification of two new phenylpropanoids (1–2), expanding the study of non-alkaloids in the genus of Rauvolfia and enriching the chemical diversity of this genus.

目的研究苦参叶w-丁醇组分中具有新结构的非生物碱类化学成分及其生物活性。方法采用硅胶、ODS、Sephadex LH-20色谱柱和半制备高效液相色谱法对吐粪草的w-丁醇部分进行分离,得到5个化合物。通过广泛的光谱分析,包括hresms, 1D和2D NMR以及ECD分析,确定了它们的结构。采用Ellman 's法(稍作修改)测定各化合物的乙酰胆碱酯酶抑制活性、对苯肾上腺素诱导的大鼠肠系膜动脉收缩的血管松弛活性以及以pNPG为底物对a-葡萄糖苷酶的抑制活性。结果从呕吐草叶中分离得到2个新的苯丙素(1-2)和3个已知化合物:甲基反式-3,4,5-三甲氧基肉桂酸酯(3)、甲基顺式-3,4,5-三甲氧基肉桂酸酯(4)和3,4,5-三甲氧基苯甲酸甲酯(5)。这5个分离的化合物没有显示出显著的活性。结论通过对呕吐草叶的化学研究,分离鉴定出两种新的苯丙素(1-2),拓展了对呕吐草属非生物碱的研究,丰富了呕吐草属植物的化学多样性。
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引用次数: 0
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Journal of Holistic Integrative Pharmacy
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