Integration of network pharmacology and bone marrow mesenchymal stem cells experimental research to reveal the molecular mechanisms for Hai Honghua medicinal liquor against osteoporosis

Background:Hai Honghua medicinal liquor(HHML)formula has been used in clinical practice for a long time,mainly for the treatment of freshly closed fractures,to promote osteogenesis,to increase bone mass,and thus to promote fracture healing.However,the underlying mechanisms of HHML in the treatment of osteoporosis(OP)are still unclear.Methods:Firstly,Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform and The Encyclopedia of Traditional Chinese Medicine were used to screen the targets of the active compounds of HHML.At the same time,OP targets were identified through GeneCards,Online Mendelian Inheritance in Man,DisGeNET,Therapeutic Target Database,Comparative Toxicogenomics Database and Human Phenotype Ontology databases.Next,protein-protein interaction and pathway networks were constructed for compound-disease common targets,and core targets and compounds were screened for molecular docking.Furthermore,rat bone marrow mesenchymal stem cells were extracted as model cells,and the osteogenic effects of HHML were verified via in vitro experiments.Results:Total of 343 common targets of HHML-OP and the top 10 target proteins in the protein-protein interaction network are TP53,AKT1,STAT3,HSP90AA1,ESR1,TNF,IL6,MAPK1,MAPK3 and MAPK8.Enrichment analysis yielded that the key molecular pathway was the PI3K/Akt signaling pathway.Molecular docking analysis showed that baicalein,erysodienone and naringenin docked with the target proteins AKT1,STAT3 and TP53,respectively,with low binding energy and high affinity.In addition,In vitro experiments demonstrated that HHML promoted the proliferation of bone marrow mesenchymal stem cells;compared with the control group,HHML-treated cells showed enhanced alkaline phosphatase staining,promoted the expression of OCN,RUNX2,BSP,and COL1 mRNAs as well as the expression of PI3K and AKT phosphorylated proteins.Secondly,the expression of target proteins revealed that HHML promoted the phosphorylation of STAT3 protein and inhibited the expression of P53.Conclusions:Our study investigated that HHML treatment with OP promotes bone formation possibly through activation of the PI3K/Akt signaling pathway and may involve STAT3 and TP53 target interactions.

The mechanistic study on Wa medicine Niang-Mu-Liang medicinal liquor mitigating diabetes mellitus erectile dysfunction in rats by inhibiting ferroptosis

Background:This study aims to investigate the therapeutic effect of Wa medicine Niang-Mu-Liang medicinal liquor(NML)on rats with diabetes mellitus erectile dysfunction(DMED)and its impact on the ferroptosis signaling pathway.Methods:Thirty Sprague-Dawley rats were randomly divided into three groups:Control,DMED,and NML.After establishing the DMED model,treatments were administered for 8 weeks.After the administration,apomorphine hydrochloride tests were conducted to measure the mass and organ index of testes and epididymides,sperm concentration and viability in each group.Penile corpus cavernosum tissues were stained with hematoxylin and eosin.Nitric oxide and cyclic guanosine monophosphate levels in the penile corpus cavernosum tissues were determined using biochemical kits and enzyme-linked immunosorbent assay,while the expression of proteins related to the ferroptosis signaling pathway was measured by Western blot.Results:Compared to the DMED group,the DMED rats treated with NML showed significantly increased erection frequency,testicular and epididymal mass and index,sperm count and viability,along with noticeable improvement in the pathological morphology of penile corpus cavernosum.The content of nitric oxide and cyclic guanosine monophosphate,and the expression of ferritin heavy chain,ferritin light chain,and glutathione peroxidase 4 proteins in penile corpus cavernosum tissue were elevated,while the expression of transferrin and STEAP3 proteins was reduced.Conclusion:NML can improve erectile function in DMED rats by inhibiting the ferroptosis signaling pathway.

Improved Algorithm for Efficient Extraction of Relaxation Parameter Values from Wideband Permittivity of Baijiu

The complex permittivity of baijiu varies with frequency,and dielectric spectroscopy has been used to evaluate the quality.To simplify the analysis and reduce the number of the parameters,a dielectric relaxation model is often used to fit the permittivity data.However,existing fitting methods such as the least squares and particle swarm optimization methods are often computationally complex and require preset initial values.Therefore,a simpler calculation method of the relaxation parameters considering the geometric characteristics of the permittivity spectrum is proposed.It is based on the relationship between the Cole-Cole relaxation parameters and the Cole-Cole diagram,which is fitted by a geometric method.First,the concepts of the Cole-Cole parameters and the diagram are introduced,and then the process of obtaining the parameters from the complex permittivity measurement data is explained.Taking baijiu with 56%alcohol by volume(ABV)as an example,the fitting is better than the least squares method and similar to the particle swarm optimization.This method is then used for the parameter fitting of baijiu with ABV of 42-52%,and the average error is less than 1%,demonstrating its wider applicability.Finally,a prediction model is used for baijiu with 53%ABV,and the error is only 1.51%.Hence,the method can be applied to the measurement of ABV of baijiu.

Characterization and comparison of the aroma-active compounds on different grades of sesame-flavor Baijiu by headspace solid-phase microextraction and gas chromatography-olfactometry-mass spectrometry

This study investigated the aroma-active compounds and compared the differences of three different grades of sesame-flavor Baijiu by headspace solid-phase microextraction(HS-SPME)coupled with gas chromatography-olfactometry-mass spectrometry(GC-O-MS).A total of 54 aroma-active compounds were detected.Principal component analysis showed that JZ1,JZ2,and JZ3 were well separated from each other.JZ1 as the premium-grade Baijiu had the highest aroma intensities,concentrations.According to aroma intensities and concentrations,dimethyl trisulfide,butanoic acid,phenylacetaldehyde,2-furylmethanethiol,ethyl hexanoate,2,6-dimethylpyrazine,etc.could be potentially applied as volatile makers to distinguish the three different grades of sesame-flavor Baijiu as their significant difference(P<0.05)in three Baijiu samples.Roasted aroma had the significant difference(P<0.05)in three sample base on aroma profiles.Meanwhile,2-furylmethanethiol,2,6-dimethylpyrazine were related to the roasted aroma,they may be had a significant contribution to the differences of three different grades of sesame-flavor Baijiu.This study has provided a comprehensive understanding of the differences of three different grades of sesame-flavor Baijiu.

Wine,beer and Chinese Baijiu in relation to cardiovascular health:the impact of moderate drinking

Excessive alcohol consumption(≥15 drinks per week)causes chronic diseases and multiple other health conditions.Nevertheless,alcohol beverages have been used as a vital medicine ingredient in various cultures since ancient times.A wealth of epidemiological and experimental research has shown that light-moderate alcohol consumption,regardless of beverage type,is associated with reducing cardiovascular incidence and mortality rate.Due to the disparities in raw materials,fermentation techniques,production environment,etc.,alcoholic beverages tend to possess different non-ethanol component profiles,thus resulting in varying degrees of health effects.Furthermore,bioactive compounds in alcohol are continuously discovered as well as the mechanisms underlying their cardioprotective contributions at a molecular level.This article elucidates the epidemiology of moderate alcohol consumption and various cardiovascular conditions,along with the limitations and controversies of current studies.In addition,protective effects and putative mechanisms of both ethanol and non-ethanol components of wine,beer,and Chinese Baijiu,the three most representative alcoholic beverages worldwide,are to be evaluated within the context of a rational drinking pattern.

Characterization of terpenoids and norisoprenoids from base and retail Qingke Baijiu by GC×GC-TOFMS and multivariate statistical analysis

Qingke(highland barley)Baijiu is a special Chinese Baijiu which is mainly produced from Qinghai-Tibet Plateau.Since the pine board is used as the bottom of the fermentation pit,we deduced that the terpenoids and norisoprenoids in pine board might be introduced into Qingke Baijiu.Thus,the terpenoids and norisoprenoids in Qingke Baijiu were investigated by headspace solid phase microextraction(HS-SPME)combined with comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry(GC×GC-TOFMS).The results showed thatγ-terpinene(0.70-530.72μg/L),α-phellandrene(0.34-256.66μg/L),longicyclene(0-38.55μg/L),α-pinene(1.21-35.54μg/L)and limonene(0.93-23.69μg/L)were the top 5 terpenoids/norisoprenoids in Qingke Baijiu.Pulegone was detected and reported for the first time in Baijiu,and the concentrations in Qingke Baijiu were 0.78μg/L(fresh)and 3.90μg/L(7 years old).According to the principal component analysis(PCA)plot,young,aged,and retail Qingke Baijiu could be differentiated clearly.Fold change(FC)and t-tests analysis indicated thatβ-pinene,γ-terpinene,andα-selinene were the most different terpenoids/norisoprenoids between young and aged Qingke Baijiu,and longifolene was the most different terpenoids/norisoprenoids between base and retail Qingke Baijiu.The terpenoids and norisoprenoids,such as(E)-β-ionone,isoborneol andβ-cyclocitral,could be potential markers indicating the ageing process of Qingke Baijiu.

Characterization of Formacell Lignin Derived from Black Liquor as a Potential Green Additive for Advanced Biocomposites

Black liquor is obtained as a by-product of the pulping process,which is used to convert biomass into pulp by removing lignin,hemicelluloses and other extractives from wood to free cellulose fibers.Lignin represents a major constituent in black liquor,with quantities varying from 20%to 30%,of which a very low share is used for manufacturing value-added products,while the rest is mainly burned for energy purposes,thus underestimating its great potential as a raw material.Therefore,it is essential to establish new isolation and extraction methods to increase lignin valorization in the development of bio-based chemicals.The aim of this research work was to determine the effect of KOH or ethanol concentration as an isolation agent on lignin yields and the chemical characteristics of lignin isolated from formacell black liquor of oil palm empty fruit bunch(OPEFB).Isolation of lignin was carried out using KOH with various concentrations ranging from 5%to 15%(w/v).Ethanol was also used to precipitate lignin from black liquor at concentrations varying from 5%to 30%(v/v).The results obtained showed that the addition of KOH solution at 12.5%and 15%concentrations resulted in better lignin yield and chemical properties of lignin,i.e.,pH values of 3.86 and 4.27,lignin yield of 12.78%and 14.95%,methoxyl content of 11.33%and 10.13%,and lignin equivalent weights of 476.25 and 427.03,respectively.Due to its phenolic structure and rich functional groups that are favorable for modifications,lignin has the potential to be used as a green additive in the development of advanced biocomposite products in various applications to replace current fossil fuel-based material,ranging from fillers,fire retardants,formaldehyde scavengers,carbon fibers,aerogels,and wood adhesives.

Research of the molecular mechanism of Hai Honghua medicinal liquor in the treatment of fracture based on network pharmacology combined with molecular docking

Background:Hai Honghua medicinal liquor(HHML),a famous hospital formula composed of 19 traditional Chinese medicines,has been successfully applied in treating soft tissue injury,fresh closed fracture,limb dysfunction after fracture healing,shoulder,neck and leg pain,knee joint pain and other clinical multiple diseases for 30 years in clinical.However,research on the material basis of HHML for the treatment of fracture healing-related disorders is still in a gap.Therefore,it is particularly important to explore the active ingredients,core targets and potential pharmacological mechanisms of HHML to promote fracture healing.Methods:We screened the core active components of each traditional Chinese medicine in formula and its action targets through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Encyclopedia of Traditional Chinese Medicine database.The fracture related targets were retrieved from several different public databases,including GeneCards,Online Mendelian Inheritance in Man,DisGeNET and Therapeutic Target Database.Bioinformatics analysis to obtain key bioactive components,underlying targets and signaling pathways,containing the Venn diagram of the intersection with components and diseases gene targets,protein–protein interaction,as well as the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis,and finally molecular docking.Results:A total of 249 bioactive ingredients of HHML and 325 HHML-fracture-related targets were screened.The network analysis revealed that quercetin,luteolin,kaempferol,Licochalcone A,naringenin and 8-Isopentenyl-kaempferol may be potential candidate agents.Multiple targets are involved including TP53,MAPK3,STAT3,AKT1,MAPK1,HSP90AA1,ESR1 and PIK3CA may be closely linked targets.PI3K-AKT signaling pathway may play a significant role of HHML in treatment of fracture.What’s more,molecular docking suggested that 8-isopentenyl kaempferol,glycyrrhiza chalcone A,and naringenin bound to AKT1,PIK3CA,and ESR1,respectively,exhibiting lower energy and more stable characteristics.Conclusions:The findings indicate the potential active ingredients,target proteins and molecular mechanisms of HHML for the treatment of fractures to provide the exact idea for the next research on the mechanism of action of HHML formula for fracture treatment.

Effects of Rice Straw Steam-explosion Spent Liquor on the Growth of Cabbage Seedlings

The direct use of spent liquor from pulping and papermaking engineering,which is abundant in active organic matter,can avoid resource wastage and environmental pollution.In this study,the effects of soaking solution and filtrate from steam-exploded rice straw on seed germination and the early development of cabbage were investigated.The results have shown that soaking solution and filtrate stimulated early cabbage growth at low concentrations.Optimal germination potential and the rate of soaking solution-treated cabbage seeds increased by 8%and 5%,respectively;meanwhile,that of the filtrate-treated cabbage seeds increased by 11%and 5%,respectively.Promotion of root growth by steam-exploded rice straw spent liquor was expressed in lateral root multiplication.The fresh weight of cabbage seedlings treated with the soaking solution/filtrate increased by more than 50%and the dry weight over 20%.Comparatively,the stimulation of filtrate on seed germination and early development of cabbage is superior to that of the soaking solution.Steam-exploded rice straw spent liquor is rich in bioactive lignin and oligosaccharides,which makes it a promising biostimulant for promoting crop growth.

白酒中风味成分的检测分析技术研究进展

白酒历史悠久,是中国的国酒。白酒中的风味成分虽然含量较低,但其类别、组成及比例对产品口感、风味及香气极为重要。近年来,对风味成分的研究已成为白酒领域的热点,本文综述了白酒风味成分检测分析方面的研究进展,介绍了风味成分检测前处理技术与分析方法,总结了各大香型白酒中的风味挖掘及分析的最新成果,探讨了研究中存在的局限与不足,并展望了未来技术发展的方向和趋势。

价键原子指数用于酱香型习酒香气成分保留性质研究

酱香型习酒是一种风味极其独特的酱香型白酒,具有风味醇厚、幽雅细腻和回味悠长的香气,香气成分繁多而复杂.为探究酱香型白酒的主要挥发性物质的组成及香气风味成分的差异,研究建构酱香型习酒香气成分保留指数的定量结构-保留相关性模型,根据酱香型习酒香气成分分子中原子的空间与电性结构,基于拓扑理论,提出了一种新的结构参数-价键原子指数~mA.另计算了酱香型习酒香气成分的电拓扑状态指数(Em),优化筛选了指数中的~0A、E_(1)、E_(2)、E_(14),将4种结构参数作为神经网络三层结构的输入节点数,色谱保留指数作为三层结构的输出节点数,网络结构采用4-12-1方式.建立的预测香气成分保留指数模型的相关系数达到0.9965,计算得到的酱香型习酒香气成分保留指数RI预测值的平均相对误差为1.41%.结果表明,酱香型习酒挥发性香气成分的保留指数,与价键原子指数和电拓扑状态指数之间具有很好的非线性关系,非氢原子结构及—CH_(3)、>CH_(2)、—O—等基团,是影响酱香型习酒香气成分保留指数的主要因素.

浓香型白酒不同窖龄窖池微生物群落特征研究

浓香型白酒生产一直有“千年老窖万年糟,酒好全凭窖池老”的说法,说明窖池是生产优质浓香型白酒的重要前提条件。本研究采用宏基因组技术解析不同窖龄窖泥微生物群落结构特征,研究结果表明,窖泥细菌群落结构在门水平下主要分布在厚壁菌门、广古菌门和拟杆菌门三类微生物,其中厚壁菌门相对丰度最高;属水平下以己酸菌、甲烷短杆菌、乳酸杆菌属、甲烷杆菌属、甲烷囊菌属和一种产氢产乙酸细菌等为主导菌群;随着窖龄增加,窖泥细菌群落多样性减小,窖龄达10年以上窖泥的微生物群落结构趋于稳定。本研究为窖泥功能微生物资源的开发和窖池维护保养提供了技术支撑。

白酒酿造微生物酯化酶的研究进展

酯化酶是一类具有催化酯类物质合成活性的酶类。广义上的酯化酶被广泛应用于食品,化工,医药、军工及环保等领域中。白酒酿造微生物酯酶在白酒发酵生香过程中具有重要作用,其代谢产生的乙酸乙酯、乳酸乙酯、丁酸乙酯和己酸乙酯等酯类物质是中国白酒最为重要的风味物质。因此,深入研究中国白酒酿酒微生物酯化酶,对提高白酒优质品率、提升酿酒原料利用率具有重要意义。从微生物酯化酶的来源、特性、分子进化以及在白酒酿造中的应用进行了综述,旨在为中国白酒微生物资源的深入研究和发掘提供一定的思路。

高温堆积在老白干香型白酒生产中的应用研究

高温堆积是酱香型白酒必不可少的典型工艺环节,具有富集微生物、丰富白酒香味成分的作用。将高温堆积工艺应用于老白干香型白酒传统老五甑工艺,对堆积发酵过程中堆积方式、酒醅水分、酸度、淀粉、还原糖、酒精度指标和微生物数量的变化情况进行了初步研究,结果表明,该工艺的应用明显提高了老白干香型白酒的酸酯含量和感官质量。

白酒内源性甲醛的研究进展及监测建议

白酒是中国居民餐桌上喜闻乐见的重要饮品。大量研究表明,许多食品中都含有不同浓度的内源性甲醛,白酒也不例外。目前,我国白酒相关标准中没有规定甲醛限量,这可能同白酒甲醛的内生特性有关。但是,白酒甲醛的控制技术、风险评估和贮存期间的转化规律研究,仍有待于生产者、研究者、监管部门共同参与,为相关标准颁布实施提供依据。本文从白酒甲醛的来源、限量标准、检测方法、相关成分变化规律等角度进行了系统分析,并提出后续的发展重点,以期促进白酒产业的健康发展。

白酒酿造酵母菌研究进展

白酒作为一种极具中国特色的发酵产品,其独特的风味和深厚的文化底蕴,深受中国人民的喜爱。酵母菌是白酒生产中的一大类重要功能微生物菌群,对风味化合物的代谢及酒体品质的形成具有重要影响。本文综述了白酒酿造领域中酵母菌的研究进展,以期为筛选优良酵母菌株并应用于白酒生产、提高酒体品质提供参考和借鉴。

酒瓶挂珠和材质分析及其对白酒中钠浓度的影响分析

本研究分析了挂珠和不同材质酒瓶的玻璃成分、表面和接触角,在此基础上,用其贮存不同档次的白酒,对货架期的白酒定期进行钠(Na)浓度检测,分析其变化规律。结果表明:选取的酒瓶玻璃主要成分SiO_(2)含量为82~83mol%,密度为2.50~2.52g/cm^(3),质地均匀;存储过程中,挂珠现象对白酒中Na浓度变化几乎无影响;初探表明接触角大的酒瓶长时间存储白酒可能会引起白酒中Na浓度增加。研究结果可为相关企业把控产品质量和白酒储藏提供重要参考。

己酸菌发酵液酯化合成己酸乙酯的研究

己酸乙酯是浓香白酒的特征香气成分,其含量的多少决定着浓香型白酒的品质。本研究对己酸菌发酵液酯化合成己酸乙酯的最佳条件进行探究,研究了不同条件下的酯化pH、不同酸调节pH以及乙醇、己酸浓度对己酸菌发酵液中己酸乙酯转化率的影响。结果表明,pH在3~4时己酸乙酯转化率较高,用乳酸调节p H效果最优,增加酯化体系中乙醇、己酸浓度均有利于提高己酸乙酯的转化率;使用己酸含量为18.86 g/L的浓缩己酸菌液,加入30%的无水乙醇,0.15%的酯化酶,用乳酸调节pH至4,34℃酯化24 h,己酸乙酯含量达到8962.99 mg/L,转化率为49.77%。

从元代“汗酒”看中国蒸馏酒起源

元代的蒸馏酒虽有“汗酒”“烧酒”“重酿酒”等汉语名称,但一度流行的“阿剌吉酒”等音译名称,使得中国蒸馏酒起源成为颇具争议的国际性学术问题。本文在系统梳理史籍所载“汗酒”及其制备用具的基础上,结合考古发现的相关资料,通过“汗酒”名称和蒸馏器具渊源的探析,认为“汗酒”之名理应源自历史典故“汗出如浆”,而制备“汗酒”的酒铛实乃釜、甑等多件套甗式蒸馏器。尤其“酒铛”与古代蒸馏器实物的相互对应,有助于重新审视中国蒸馏酒、蒸馏器的起源及演化历程。

草苁蓉急性经口毒性和遗传毒性研究

目的:通过草苁蓉(酒用原料)急性经口毒性试验和遗传毒性试验,为草苁蓉配制酒开发提供食用安全性依据。方法:选用Wistar大鼠、ICR小鼠以10.0g/kg·BW剂量进行草苁蓉急性经口毒性试验。鼠伤寒沙门氏菌回复突变试验(Ames试验)设5000、1000、200、40和8μg/皿5个剂量组,另设未处理对照组、溶剂对照组和阳性对照组,试验在±S9条件下进行,每组作3个平行皿,重复1次;哺乳动物红细胞微核试验设5.34g/kg·BW、2.67g/kg·BW和1.34g/kg·BW 3个剂量组,另设空白对照组和阳性对照组;小鼠精母细胞染色体畸变试验设5.34g/kg·BW、2.67g/kg·BW和1.34g/kg·BW 3个剂量组,另设空白对照组和阳性对照组。结果:草苁蓉大鼠、小鼠急性经口LD50均大于10.0g/kg·BW;在±S9条件下,TA97a、TA98、TA100、TA102、TA15355个株菌株5个剂量组的回变菌落数均未超过未处理对照组的2倍;哺乳动物红细胞微核试验和小鼠精母细胞染色体畸变试验结果为阴性。结论:在本研究条件下,草苁蓉属实际无毒级,未见遗传毒性。