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Novel SNP markers on ginsenosides biosynthesis functional gene for authentication of ginseng herbs and commercial products

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chinese Journal of Natural medicines 2020年第10期18卷 770-778页

作者： WU Wen-Ru CHENG Chun-Song CHENG Qi-Qing LAO Chi-Chou CUI Hao TANG Zi-Yu OUYANG Yue LIU Liang ZHOU Hua state key laboratory of quality research in chinese medicine Faculty of Chinese MedicineMacao University o f Science and TechnologyMacao 999078China School of chinese Pharmaceutical Sciences Guangzhou University of Chinese MedicineGuangzhou 510006China Joint laboratory for Translational Cancer research of chinese medicine of the Ministry of Education of the People's Republic of China Macao University of Science and TechnologyMacao 999078China

Panax ginseng and Panax quinquefolius have similar bioactive components and morphological characteristics, but they are known to have different medicinal values, high-sensitive and accurate method is expected to identify the sources of ginseng products and evaluate the quality, but with a huge challenge. Our established UHPLC-TOF/MS method coupled with orthogonal partial least squares discriminant analysis(OPLS-DA) model based on 18 ginsenosides was applied to discriminate the sources of raw medicinal materials in ginseng products, and nested PCR strategy was used to discover 6 novel single nucleotide polymorphism(SNP)sites in functional dammarenediol synthase(DS) gene for genetic authentication of P. ginseng and P. quinquefolius for the first ***-DA model could identify the sources of raw ginseng materials are real or not. SNP markers were applied to identify ginseng fresh samples as well as commercial products, and proved to be successful. This established molecular method can tell exact source information of adulterants, and it was highly sensitive and specific even when total DNA amount was only 0.1 ng and the adulteration was as low as 1%. Therefore, this study made an attempt at the exploration of new type SNP marker for variety authentication and function regulation at the same time, and the combination of chemical and molecular discrimination methods provided the comprehensive evaluation and authentication for the sources of ginseng herbs and products.

关键词： Panax ginseng Panax quinquefolius UHPLC-TOF/MS Dammarenediol synthase Nested PCR SNP

Bear bile powder alleviates Parkinson’s disease-like behavior in mice by inhibiting astrocyte-mediated neuroinflammation

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chinese Journal of Natural medicines 2023年第9期21卷 710-720页

作者： WANG Lupeng BAI Yuyan TAO Yanlin SHEN Wei ZHOU Houyuan HE Yixin WU Hui HUANG Fei SHI Hailian WU Xiaojun Shanghai key laboratory of Compound chinese medicines The Ministry of Education(MOE)Key Laboratory for Standardization of Chinese MedicinesThe State Administration of TCM(SATCM)Key Laboratory for New Resources and Quality Evaluation of Chinese MedicineInstitute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China

Parkinson’s disease(PD)is a common neurodegenerative disease in middle-aged and elderly *** particular,increasing evidence has showed that astrocyte-mediated neuroinflammation is involved in the pathogenesis of *** a precious traditional chinese medicine,bear bile powder(BBP)has a long history of use in clinical *** has numerous activities,such as clearing heat,calming the liver wind and anti-inflammation,and also exhibits good therapeutic effect on convulsive ***,whether BBP can prevent the development of PD has not been ***,this study was designed to explore the effect and mechanism of BBP on suppressing astrocyte-mediated neuroinflammation in a mouse model of ***-like behavior was induced in the mice by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)(30 mg·kg−1)for five days,followed by BBP(50,100,and 200 mg·kg−1)treatment daily for ten *** stimulated rat C6 astrocytic cells were used as a cell model of *** results indicated that BBP treatment significantly ameliorated dyskinesia,increased the levels of tyrosine hydroxylase(TH)and inhibited astrocyte hyperactivation in the substantia nigra(SN)of PD ***,BBP decreased the protein levels of glial fibrillary acidic protein(GFAP),cyclooxygenase 2(COX2)and inducible nitric oxide synthase(iNOS),and up-regulated the protein levels of takeda G protein-coupled receptor 5(TGR5)in the ***,BBP significantly activated TGR5 in a dose-dependent manner,and decreased the protein levels of GFAP,iNOS and COX2,as well as the mRNA levels of GFAP,iNOS,COX2,interleukin(IL)-1β,IL-6 and tumor necrosis factor-α(TNF-α)in LPS-stimulated C6 ***,BBP suppressed the phosphorylation of protein kinase B(AKT),inhibitor of NF-κB(IκBα)and nuclear factor-κB(NF-κB)proteins in vivo and in *** also observed that TGR5 inhibitor triamterene attenuated the anti-neuroinflammatory effect of BBP on LPS-stimulated C6 ***

关键词： Parkinson's disease Bear bile powder Astrocyte Neuroinflammation Takeda G protein-coupled receptor 5

Anti-Parkinsonian Therapy:Strategies for Crossing the Blood–Brain Barrier and Nano-Biological Effects of Nanomaterials

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Nano-Micro Letters 2022年第6期14卷 350-398页

作者： Guowang Cheng Yujing Liu Rui Ma Guopan Cheng Yucheng Guan Xiaojia Chen Zhenfeng Wu Tongkai Chen key laboratory of Modern Preparation of Traditional chinese medicine Ministry of EducationJiangxi University of Chinese MedicineNanchang 330004People’s Republic of China Science and Technology Innovation Center Guangzhou University of Chinese MedicineGuangzhou 510405People’s Republic of China state key laboratory of quality research in chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078People’s Republic of China

Parkinson’s disease(PD),a neurodegenerative disease that shows a high incidence in older individuals,is becoming increasingly ***,there is no clinical cure for PD,and novel anti-PD drugs are therefore urgently ***,the selective permeability of the blood–brain barrier(BBB)poses a huge challenge in the development of such ***,through strategies based on the physiological characteristics of the BBB and other modifications,including enhancement of BBB permeability,nanotechnology can offer a solution to this problem and facilitate drug delivery across the *** nanomaterials are often used as carriers for PD treatment,their biological activity is *** studies in recent years have shown that nanomaterials can improve PD symptoms via their own nano-bio *** this review,we first summarize the physiological features of the BBB and then discuss the design of appropriate brain-targeted delivery nanoplatforms for PD ***,we highlight the emerging strategies for crossing the BBB and the development of novel nanomaterials with anti-PD nano-biological ***,we discuss the current challenges in nanomaterial-based PD treatment and the future trends in this *** review emphasizes the clinical value of nanotechnology in PD treatment based on recent patents and could guide researchers working in this area in the future.

关键词： Blood-brain barrier Parkinson’s disease Nasal delivery Biomimetic drug delivery Nano-biological effects

Post-ingestion conversion of dietary indoles into anticancer agents

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National Science Review 2022年第4期9卷 128-138页

作者： Li Ping Lin Dan Liu Jia Cheng Qian Liang Wu Quan Zhao Ren Xiang Tan state key laboratory of Pharmaceutical Biotechnology Institute of Functional BiomoleculesNanjing University state key laboratory Cultivation Base for TCM quality and Efficacy Nanjing University of Chinese Medicine

There are health benefits from consuming cruciferous vegetables that release indole-3-carbinol(I3 C), but the in vivo transformation of I3 C-related indoles remains underinvestigated. Here we detail the post-ingestion conversion of I3 C into antitumor agents, 2-(indol-3-ylmethyl)-3,3′-diindolylmethane(LTr1) and 3,3′-diindolylmethane(DIM), by conceptualizing and materializing the reaction flux derailing(RFD) approach as a means of unraveling these stepwise transformations to be non-enzymatic but p H-dependent and gut microbe-sensitive. In the upper(or acidic) gastrointestinal tract, LTr1 is generated through Michael addition of 3-methyleneindolium(3 MI, derived in situ from I3 C) to DIM produced from I3 C via the formaldehyde-releasing(major) and CO-liberating(minor) pathways. In the large intestine,‘endogenous’ I3 C and DIM can form, respectively, from couplings of formaldehyde with one and two molecules of indole(a tryptophan catabolite). Acid-producing gut bacteria such as Lactobacillus acidophilus facilitate the H+-promotable steps. This work updates our understanding of the merits of I3 C consumption and identifies LTr1 as a drug candidate.

关键词： indole-3-carbinol reaction flux derailing (RFD) approach 2-(indol-3-ylmethyl)-3,3′-diindolylmethane (LTr1) anticancer Lactobacillus acidophilus

Contrasting neuropathology and functional recovery after spinal cord injury in developing and adult rats

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Neuroscience Bulletin 2013年第4期29卷 509-516页

作者： Qiuju Yuan Huanxing Su Kin Chiu Wutian Wu Zhi-Xiu Lin Department of Anatomy The University of Hong Kong School of chinese medicine Faculty of Science The Chinese University of Hong Kong state key laboratory of quality research in chinese medicine and Institute of chinese Medical Sciences University of Macao state key laboratory of Brain and Cognitive Sciences Development and Growth Li Ka Shing Faculty of Medicine The University of Hong Kong research Center of Reproduction Development and Growth Li Ka Shing Faculty of Medicine The University of Hong Kong GHM Institute of CNS Regeneration Jinan University

Conflicting findings exist regarding the link between functional recovery and the regrowth of spinal tracts across the lesion leading to the restoration of functional contacts. In the present study, we investigated whether functional locomotor recovery was attributable to anatomical regeneration at postnatal day 1 （PN1）, PN7, PN14 and in adult rats two months after transection injury at the tenth thoracic segment of the spinal cord. The Basso, Beattie, and Bresnahan scores showed that transection led to a failure of hindlimb locomotor function in PN14 and adult rats. However, PN1 and PN7 rats showed a significant level of stepping function after complete spinal cord transection. Unexpectedly, unlike the transected PN14 and adult rats in which the spinal cord underwent limited secondary degeneration and showed a scar at the lesion site, the rats transected at PN1 and PN7 showed massive secondary degeneration both anterograde and retrograde, leaving a 〉5-mm gap between the two stumps. Furthermore, retrograde tracing with fluorogold （FG） also showed that FG did not cross the transection site in PN1 and PN7rats as in PN14 and adult rats, and re-transection of the cord caused no apparent loss in locomotor performance in the rats transected at PN1. Thus, these three lines of evidence strongly indicated that the functional recovery after transection in neonatal rats is independent of regrowth of spinal tracts across the lesion site. Our results support the notion that the recovery of locomotor function in developing rats may be due to intrinsic adaptations in the spinal circuitry below the lesion that control hindlimb locomotor activity rather than the regrowth of spinal tracts across the lesion. The difference in secondary degeneration between neonatal and adult rats remains to be explored.

关键词： neonatal spinal cord injury regeneration functional recovery rat

Fast saccharide mapping method for quality consistency evaluation of commercial xylooligosaccharides collected in China

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Journal of Pharmaceutical Analysis 2021年第3期11卷 284-291页

作者： Yong Deng Cunwu Chen Lingxiao Chen Bangxing Han Shaoping Li Jing Zhao state key laboratory of quality research in chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoMacaoChina Anhui Engineering laboratory for Conservation and Sustainable Utilization of Traditional chinese medicine Resources West Anhui UniversityLu'anAnhuiChina

Due to the extensive use of xylooligosaccharides(XOS)as functional food ingredients,many inferior goods and even adulterants are generally found in the market,which may pose a health hazard to certain *** method such as high-performance liquid chromatography(HPLC)and high-performance thin-layer chromatography(HPTLC)is traditionally applied for the quality analysis of ***,it is time consuming due to the prolonged separation and pre-or post-derivatization *** this study,a fast saccharide mapping method based on matrix-assisted laser desorption/time-of-flight mass spectrometry(MALDI-TOF-MS)was developed for the quality consistency analysis of 22 batches of XOS collected from different manufacturers in *** time needed for saccharides analysis using MALDI-MS was less than 30 min for one plate,at least 6 times faster than that by the traditional HPTLC chromatography *** addition,MALDI-MS possessed higher resolution for XOS with DP4-DP7 based on the difference of m/z,which is hardly separated using *** results showed that XOS were present only in samples XY01-XY11,samples XY12-XY14 only consisted of hex oligosaccharides,and samples XY15-XY22 were free of *** indicate that the quality consistency of XOS products in the China market was poor,which should be carefully investigated.

关键词： Xylooligosaccharides Saccharide mapping MALDI-MS quality control

Prediction of the anti-inflammatory mechanisms of curcumin by module-based protein interaction network analysis

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Acta Pharmaceutica Sinica B 2015年第6期5卷 590-595页

作者： Yanxiong Gan Shichao Zheng Jan P.A.Baak Silei Zhao Yongfeng Zheng Nini Luo Wan Liao Chaomei Fu state key laboratory Breeding Base of Systematic research Development and Utilization of Chinese Medicine ResourcesSchool of PharmacyChengdu University of Traditional Chinese Medicine School of chinese Pharmacy Beijing University of Chinese Medicine faculty of Sports Sciences and medicine Technical University Munich

Curcumin, the medically active component from Curcuma Tonga (Turmeric), is widely used to treat inflammatory diseases. Protein interaction network (PIN) analysis was used to predict its mechanisms of molecular action. Targets of curcumin were obtained based on ChEMBL and STITCH databases. Protein protein interactions (PPIs) were extracted from the String database. The PIN of curcumin was constructed by Cytoscape and the function modules identified by gene ontology (GO) enrichment analysis based on molecular complex detection (MCODE). A PIN of curcumin with 482 nodes and 1688 interactions was constructed, which has scale-free, small world and modular properties. Based on analysis of these function modules, the mechanism of curcumin is proposed. Two modules were found to be intimately associated with inflammation. With function modules analysis, the anti-inflammatory effects of curcumin were related to SMAD, ERG and mediation by the TLR family. TLR9 may be a potential target of curcumin to treat inflammation. (C) 2015 chinese Pharmaceutical Association and Institute of Materia Medica, chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

关键词： Curcumin Protein interaction network Module Anti-inflamatory Molecular mechanism Gene ontology enrichment analysis Molecular complex detection Cytoseape

A polyphenol-assisted IL-10 mRNA delivery system for ulcerative colitis

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Acta Pharmaceutica Sinica B 2022年第8期12卷 3367-3382页

作者： Zhejie Chen Wei Hao Caifang Gao Yangyang Zhou Chen Zhang Jinming Zhang Ruibing Wang Yitao Wang Shengpeng Wang state key laboratory of quality research in chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China Macao Centre for research and Development in chinese medicine University of MacaoMacao 999078China College of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu 611137China

With the development of synthesis technology, modified messenger RNA(mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 ***-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.

关键词： Polyphenol mRNA IL-10 Colitis Inflammatory bowel disease Drug delivery mRNA delivery Supramolecular binding

Triple three-dimensional MS/MS spectrum facilitates quantitative ginsenosides-targeted sub-metabolome characterization in notoginseng

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4045-4058页

作者： Ke Zhang Jinru Jia Ting Li Wenjing Liu Pengfei Tu Jian-Bo Wan Jun Li Yuelin Song Modern research Center for Traditional chinese medicine Beijing Research Institute of Chinese MedicineBeijing University of Chinese MedicineBeijing 100029China SCIEX China Beijing 100015China School of Pharmacy Henan University of Chinese MedicineZhengzhou 450046China state key laboratory of quality research in chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoTaip1Macao 999078China

Although serving as the workhorse,MS/MS cannot fully satisfy the analytical requirements of quantitative sub-metabolome *** more information intrinsically correlates to more structural and concentration clues,here,efforts were devoted to comprehensively tracing and deciphering MS/MS behaviors through constructing triple three-dimensional(3×3D)-MS/MS ***-targeted metabolomics of notoginseng,one of the most famous edible medicinal plants,was employed as a *** authentic ginsenosides were deployed to build the correlations between 3×3D-MS/MS spectra and structure/concentration *** assaying ginsenosides with progressive concentrations using QTOF-MS to configure 1st 3D spectrum,the generations of MS1 spectral signals,particularly multi-charged multimer anions,e.g.,[2Me2H]^(2-) and[2M+2HCOO]^(2-) ions,relied on both concentration and the amount of sugar *** programming progressive collision energies to the front collision cell of Qtrap-MS device to gain 2^(nd) 3D spectrum,optimal collision energy(OCE)corresponding to the glycosidic bond fission was primarily correlated with the masses of precursor and fragment ions and partially governed by the glycosidation *** quantitative relationships between OCEs and masses of precursor and fragment ions were utilized to build large-scale quantitative program for *** applying progressive exciting energies to the back collision chamber to build 3^(rd) 3D spectrum,the fragment ion and the decomposition product anion exhibited identical dissociation trajectories when they shared the same molecular *** ginsenosides-focused quantitative metabolomics,significant differences occurred for sub-metabolome amongst different parts of *** differential ginsenosides were confirmatively identified by applying the correlations between 3×3D-MS/MS spectra and ***,3×3D-MS/MS spectrum covers all MS/MS behaviors and drama

关键词： Quantitative submetabolome characterization Ginsenosides Structural identification Notoginseng Full exciting energy ramp-MS3 spectrum