Cornus officinalis with high pressure wine steaming enhanced anti-hepatic fibrosis: Possible through SIRT3-AMPK axis

Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying mechanisms.In vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-b(TGF-b).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated histopathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw form.Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)pathway.Of note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and caspase9.small interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3.In conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mechanism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

The Mechanism of Cornus officinalis Total Glycosides and Cornus Polysaccharide on Myocardial Protection in Rats with Acute Myocardial Infarction

Objective: To investigate effects of Cornus officinalis Total Glycosides (COTG) and Cornus Polysaccharide (CP) on myocardial protection and on expression of mitochondria biogenesis related gene of acute myocardial infarction (AMI) rats, Materials and Methods: Ninety-six SD rats of SPF level were randomly divided into 5 groups: sham operation group, model group, preventive treatment group, COTG treatment group, CP treatment group, and there were 12 cases in each one. By legating the left anterior descending branch of coronary artery method, acute myocardial infarction model was established. The rat of sham operation group and model group was intragastric administered with physiological saline;other groups were given with corresponding drugs. The cardiac function, the myocardial infarct area, the expression of mitochondrial biogenesis genes such as PGC-1α, PGC-1β, NRF-1mRNA and GSK-3β mRNA, GSK-3β Protein Expression were analyzed. Results: The results revealed that compared with model group, myocardial infarction size, LVDs, LVDd, LVESV, LVEDP, and -dp/dt decreased;LVSP increased in preventive treatment group, COTG treatment group, and CP treatment group (p < 0.05);LVEDV increased in preventive treatment group (p < 0.05), PGC 1 alpha, and PGC 1 beta;the NRF-1 mRNA expression increased in preventive treatment group, COTG treatment group, and CP treatment group (p < 0.05). Compared with CP and COTG treatment group, PGClpha, beta PGC 1, the NRF-1 mRNA expression increased in preventive treatment group (p < 0.05). Compared with the sham operation group, GSK-3 beta mRNA and protein expression increased in model group, preventive treatment group, COTG treatment group, and CP treatment group (p < 0.05). Compared with model group, GSK-3 beta mRNA expression reduced in preventive treatment group, COTG treatment group, and CP treatment group (p Cornus officinalis total glycosides and Cornus polysaccharides can effectively protect myocardial mitochondria of acute myocardial infarction rats by activating GSK-3β signaling pathways, and reduce the myocardial infarct size, which has great significance for improving cardiac function.

Modeling habitat distribution of Cornus officinalis with Maxent modeling and fuzzy logics in China

Aims Predicting suitable habitat distribution is an effective way to protect rare or endangered medicinal plants.Cornus officinalis is a perennial tree growing in forest edge and its air-dried pericarp is one of the traditional Chinese medicines(TCM)with significant medicinal values.In recent years,C.officinalis has undergone severe degeneration of its natural habitat owing to growing market demands and unprecedented damage to the forests.Moreover,the degeneration of suitable habitat has threatened the supply of medicinal materials,and even led to the extinction of some engendered medicinal plant species.In this case,there is a great risk to introduce and cultivate medicinal plants if planners determine the suitable cultivation regions based on personal subjective experience alone.Therefore,predicting suitable potential habitat distribution of medicinal plants(e.g.C.officinalis)and revealing the environmental factors determining such distribution patterns are important to habitat conservation and environmental restoration.Methods In this article,we report the results of a study on the habitat distribution of C.officinalis using maximum entropy(Maxent)modeling and fuzzy logics together with loganin content and environmental variables.The localities of 106 C.officinalis in China were collected by our group and other researchers and used as occurrence data.The loganin content of 234 C.officinalis germplasm resources were tested by high-performance liquid chromatography(HPLC)and used as content data.79 environmental variables were selected and processed with multicollinearity test by using Pearson Correlation Coefficient(r)to determine a set of independent variables.The chosen variables were then processed in the fuzzy linear model according to the cell values(maximum,minimum)of localities with estimated loganin content.The SDMtoolbox was used to spatially rarefy occurrence data and prepare bias files.Furthermore,combined Maxent modeling and fuzzy logics were used to predict the suitable habitat of C.officinalis.The modeling result was validated using null-model method.Important Findings As a result,six environmental factors including tmin3,prec3,bio4,alt,bio12 and bio3 were determined as key influential factors that mostly affected both the habitat suitability and active ingredient of C.officinalis.The highly suitable regions of C.officinalis mainly distribute in a‘core distribution zone’of the east-central China.The statistically significant AUC value indicated that combined Maxent modeling and fuzzy logics could be used to predict the suitable habitat distribution of medicinal plants.Furthermore,our results confirm that ecological factors played critical roles in assessing suitable geographical regions as well as active ingredient of plants,highlighting the need for effective habitat rehabilitation and resource conservation.

UPLC-Q-TOF/MS-based Metabolic Profiles of Bioactive Components in Rehmannia glutinosa and Cornus officinalis Herb Pair by Rat Intestinal Bacteria

Objective To investigate the metabolic routes and metabolites of Rehmannia glutinosa and Cornus officinalis herb pair produced by gut microbiome from rats.Methods A rapid and sensitive ultra-performance liquid chromatography/quadrupole-time-offlight mass spectrometry（UPLC-Q-TOF/MS） technique combined with Metabolynx？software was established and successfully applied to identify the metabolites of the main bioactive components in the herb pair extract by rat intestinal bacteria.Results Four parent compounds（loganin,morroniside,catalpol,and acteoside） and their eight corresponding metabolites were detected and tentatively identified by the characteristics of their protonated ions.Hydrogenated and demethylated loganetin,dehydroxylated morronisid aglycone,caffeic acid,and its methylated product were the main metabolites.These metabolites suggested that the glycosides were firstly hydrolyzed to their aglycones by hydrolytic enzymes of the enteric microbial flora and subsequently to the other metabolites through hydrogenation,（de）-methylation,and de-hydroxylation.Conclusion The results may be helpful for the further investigation of the pharmacokinetic study of R.glutinosa and C.officinalis herb pair in vivo.

Estimation of Nuclear DNA Content in Tannin-rich Medicinal Plant Cornus officinalis by Flow Cytometry

Objective The amount of nuclear DNA（C-value）is a key biodiversity character that provides strong unifying elements in revealing the phylogenetic regularity and relationship between genome size and functional traits for plant resource.The estimation of C-values could primarily extend our knowledge on the genetic background and genome diversity for medicinal plants,and thereby the variation of pharmacological constituents and phylogenetic mechanism of medicinal plant taxa will be revealed.However,a large number of medicinal plants（e.g.Cornus officinalis）typically contain a series of secondary metabolites,especially tannic acid,which would significantly affect the estimation of DNA content by flow cytometry（FCM）.Methodological discussions and improvement need to be made to solve this problem.Methods Two isolation buffers LB01 and Otto 1 were selected to prepare nuclear suspension with additional treatments of pre-soaking and centrifugation combination of gradient centrifugal force and duration.The best isolation and estimation methods were determined by FCM measurement in C.officinalis.Results The dry leaves were pre-soaked in Otto I buffer for 15 min and the Otto I nuclear suspension was centrifugated at 1.0×103 g for 2 min.The results showed that debris and nuclei were better separated and the scatterplots of good quality were obtained with low coefficient of variation（CV）.Contrarily,the nuclear DNA content of C.officinalis could not be accurately estimated for nuclei extracted by LB01 buffer.Finally,2C-value and genome size of C.officinalis were first estimated as 5.92 pg and 2893 Mbp,respectively.Conclusion The new methods proposed here are able to accurately estimate DNA content of C.officinalis,which provides valuable references for the estimation of genome size in other tannin-rich medicinal plants.

Multi-component quantitative and feed-forward neural network for pattern classification of raw and wine-processed Corni Fructus

Background:To promote the quality evaluation,clarify the processing mechanism and distinguish origins of Corni Fructus(cornus)from different regions.Methods:This study developed a high performance liquid chromatography method for simultaneous determination of 5-hydroxymethylfurfural,2 phenolic acids and 4 iridoid glycosides and the reference fingerprint of cornus from different regions.In addition,the feedforward neural network model provided a pattern classification of sample regions.Results:The content of morroniside and loganin were the highest in all raw cornus samples ranging from 9.45μg/mg to 16.3μg/mg and 6.64μg/mg to 13.7μg/mg,respectively.The level of sweroside in raw cornus from Henan(0.83μg/mg^(-1).39μg/mg)and Zhejiang(0.64μg/mg^(-1).17μg/mg)were greater than other origins.After wine-processing,the glucose or fructose were dehydrated to increase the levels of 5-hydroxymethylfurfural.The C-4 position of-COOCH3 of hot-sensitive iridoid glycosides was hydrolyzed to generate-COOH as stable components.Polyphenol derivatives may be degraded to increase the content of phenolic acid.Subsequently,an excellent feedforward neural network model for identification of raw cornus and wine-prepared cornus was established which could distinguish the sample origins.Conclusion:This work provided a trustworthy method to evaluate the quality and distinguish the sources of cornus.Meanwhile,the clear processing mechanism provided a scientific foundation for controlling the cornus quality during wine-processing.

山茱萸活性成分马钱子苷对超负荷运动大鼠心肌细胞焦亡的保护作用

本研究旨在探讨山茱萸中的活性成分马钱子苷是否对超负荷运动引起的心肌细胞焦亡具有保护作用。本研究采用递增负荷游泳法建立了超负荷运动诱导的心肌损伤大鼠模型,并将大鼠分为多个实验组,分别灌胃不同剂量的马钱子苷。通过心功能参数的检测、血清心肌损伤指标的测定和心肌组织氧化应激指标的测量,研究发现马钱子苷能够显著改善超负荷运动诱导的心肌损伤大鼠的心功能,减轻心肌损伤,并抑制心肌组织的氧化应激反应。进一步的组织学染色和RT-qPCR分析结果显示,马钱子苷可以剂量依赖性地抑制超负荷运动诱导的心肌细胞焦亡,降低TUNEL阳性率和Bax转录水平,并升高Bcl-2转录水平。通过Western blot实验,本研究证实马钱子苷可抑制超负荷运动诱导的心肌损伤大鼠心肌组织中NLRP3炎症体相关蛋白(NLRP3,cleaved caspase-1,ASC,IL-1β和IL-18)的表达水平。本研究结果初步表明,山茱萸中的活性成分马钱子苷对超负荷运动引起的心肌细胞焦亡具有显著的保护作用,可能通过抑制细胞焦亡和减轻氧化应激反应来改善超负荷运动诱导的心肌损伤。

优质药材山茱萸生产技术

中药材山茱萸具有10余种生理活性,应用范围不断扩大,市场供给矛盾日益突出,梳理其原植物栽培要点,总结优质药材山茱萸生产技术具有重要意义。首先,结合山茱萸资源自然分布特点,发现陕西秦岭和河南伏牛山、浙江天目山“一岭二山地区”是药材山茱萸道地产区,这些地区的山茱萸(Cornus officinalis Sieb et.Zucc.)生长综合生产能力强,品质优良。其次,以山茱萸为药材山茱萸唯一基原植物栽培,应选择适宜当地种植的综合抗性强、丰产稳产、品质优良的主导品种。最后,采取规范化栽培措施是优质山茱萸生产的重要环节,栽培选地、育苗管理、幼林抚育、成林管护、病虫害防治以及产地加工等过程对药材山茱萸品质均有影响。