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Comparative histology,transcriptome,and metabolite profi ling unravel the browning mechanisms of calli derived from ginkgo(ginkgo biloba L.)

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Journal of Forestry Research 2023年第3期34卷 677-691页

作者： Xiaoming Yang Qi Xu Linlin Le Tingting Zhou Wanwen Yu Guibin Wang Fang-Fang Fu Fuliang Cao Co-Innovation Center for Sustainable Forestry in Southern China Nanjing Forestry UniversityNanjing 210037People’s Republic of China

Gingko biloba accumulates high levels of secondary metabolites of pharmaceutical value.ginkgo calli develop a typical browning that reduces its regenerative capacity and thus its usefulness.To elucidate the browning mechanism,histological,transcriptomic,and metabolic alterations were compared between green and browning calli derived from immature ginkgo embryos.Histological observations revealed that browning calli had a more loosely arranged cell structure and accumulated more tannins than in green calli.Integrated metabolic and transcriptomic analyses showed that phenylpropanoid metabolism was specifi-cally activated in the browning calli,and 428 diff erentially expressed genes and 63 diff erentially abundant metabolites,including 12 fl avonoid compounds,were identifi ed in the browning calli compared to the green calli.Moreover,the expression of fl avonol synthase(FLS)and UDP-glucuronosyl-transferase(UGT)genes involved in the fl avonoid pathway was more than tenfold higher in browning calli than in green calli,thus promoting biosynthesis of fl avonol,which serves as a substrate to form glycosylated fl avonoids.Flavonoid glycosides constituted the major coloring component of the browning calli and may act in response to multiple stress conditions to delay cell death caused by browning.Our results revealed the cellular and biochemical changes in browning callus cells that accompanied changes in expression of browning-related genes,providing a scientifi c basis for improving ginkgo tissue culturability.

关键词： ginkgo Callus browning Histology Transcriptome Metabolite Flavonoid biosynthesis

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Analysis of spontaneous adverse drug reactions to echinacea, valerian,black cohosh and ginkgo in Australia from 2000 to 2015

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Journal of Integrative Medicine 2019年第5期17卷 338-343页

作者： Claire L.Hoban Roger W.Byard Ian F.Musgrave Discipline of Pharmacology The University of AdelaideAdelaideSA 5005Australia Discipline of Anatomy and Pathology The University of AdelaideAdelaideSA 5005Australia

Objective: Assessing adverse drug reactions(ADRs) is a proven method to estimate the safety of medicines. The ADRs to herbal medicines in Australia(and by inference, the safety of herbal medicines in Australia) remain unknown. This study examines spontaneous ADR cases to four of the most popular herbs in Australia from 2000 to 2015: echinacea(Echinacea purpurea), valerian(Valeriana officinalis), black cohosh(Actaea racemosa) and ginkgo(ginkgo biloba).Methods: ADRs of echinacea, valerian, black cohosh and ginkgo reported to the Australian Therapeutic Goods Administration(TGA) between 2000 and 2015 were obtained from the TGA database. Data were collated and analysed according to age, sex, severity, type of ADR and body system affected. Statistics were calculated using Graph Pad Prism software.Results: Most ADRs were mild or moderate. However, every herbal medicine was associated with lifethreatening ADRs. In each life-threatening case, the herbal medicine was taken concomitantly with prescription medications. Black cohosh was associated with a significant number of severe ADRs(30.3% of the total), with 39.4% of these ADRs being associated with abnormal hepatic function, hepatitis or hepatotoxicity.Conclusion: This study highlights the lack of public awareness with regard to herb–drug interactions,since most of the severe ADRs involved a herb–drug interaction.

关键词： Herbal medicine Adverse drug reaction Actaea racemosa Echinacea purpurea ginkgo biloba Valeriana officinalis

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ginkgo Huolinhensis sp.nov.from the Lower Cretaceous of Huolinhe Coal Field,Inner Mongolia,China

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Acta Geologica Sinica(English Edition) 2012年第1期86卷 11-19页

作者： DONG Man SUN Ge Research Center of Palaeontology and Stratigraphy Jilin UniversityChangchun 130026China Key Lab for Evolution of Past Life and Environment in NEAsia Ministry of EducationChina(Jilin University)Changchun 130026China Palaeontological Institute Shenyang Normal UniversityShenyang 110034China

A new species, ginkgo huolinhensis sp. nov., with well-preserved cuticle from the Lower Cretaceous, Huolinhe Formation of Huolinhe Coal Field in Inner Mongolia, China, was studied morphologically and anatomically. The main characters of the new species are found in the leaves which are deeply dissected with narrow lobes, trichomes developed on both upper and lower epidermal cells, a media papilla developed on the periclinal walls for each cell in upper cuticle, and no trichomes on the cuticle of the petioles. These characters of G. huolinhensis sp. nov. distinguish from the known species of ginkgo previously reported. This study of the new species is beneficial for the taxonomic research of fossil ginkgo, and should be helpful for a better understanding the paleoenvironment of ginkgo living in northeastern China during the Early Cretaceous.

关键词： new species ginkgo Early Cretaceous Huolinhe Inner Mongolia

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Pharmacokinetics of the prototype and hydrolyzed carboxylic forms of ginkgolides A, B, and K administered as a ginkgo diterpene lactones meglumine injection in beagle dogs

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Chinese Journal of Natural Medicines 2017年第10期15卷 775-784页

作者： WANG Shu-Yao A Ji-Ye FEI Fei GENG Jian-Liang PENG Ying OUYANG Bing-Chen WANG Pei JIN Xiao-Liang ZHAO Yu-Qing WANG Jian-Kun GENG Ting LI Yan-Jing HUA NG Wen-Zhe WANG Zhen-Zhong XIAO Wei WANG Guang-Ji School of Chinese Pharmacy Beijing University of Chinese Medicine Beijing 100102 China Jiangsu Kanion Modern Chinese Medicine Institute Nanjing 210017 China State Key Labonatory of Pharmaceutical New-Techfor Chinese Medicine Jiangsu Kanion Pharmaceutical Co. Ltd. Lianyungang222001 China Key Lab of Drug Metabolism and Pharmacokinetics State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009 China

ginkgo diterpene lactones meglumine injection(GDLI)is a commercially available product used for neuroprotection.However,the pharmacokinetic properties of the prototypes and hydrolyzed carboxylic forms of the primary components in GDLI,i.e.,ginkgolide A(GA),ginkgolide B(GB),and ginkgolide K(GK),have never been fully evaluated in beagle dogs.In this work,a simple,sensitive,and reliable method based on ultra-fast liquid chromatography-tandem mass spectrometry(UFLC-MS/MS)was developed,and the prototypes and total amounts of GA,GB,and GK were determined in beagle dog plasma.The plasma concentrations of the hydrolyzed carboxylic forms were calculated by subtracting the prototype concentrations from the total lactone concentrations.For the first time,the pharmacokinetics of GA,GB,and GK were fully assessed in three forms,i.e.,the prototypes,the hydrolyzed carboxylic forms,and the total amounts,after intravenous administration of GDLI in beagle dogs.It was shown that ginkgolides primarily existed in the hydrolyzed form in plasma,and the ratio of hydrolysates to prototype forms of GA and GB decreased gradually to a homeostatic ratio.All of the three forms of the three ginkgolides showed linear exposure of AUC to the dosages.GA,GB,and GK showed a constant half-life approximately 2.7,3.4,and 1.2 h,respectively,which were consistent for the forms at three dose levels(0.3,1.0,and 3.0 mg·kg^(-1))and after a consecutive injection of GDLI for 7 days(1.0 mg·kg^(-1)).

关键词： Hydrolysates of ginkgolides LC-MS/MS Pharmacokinetics ginkgo diterpene lactones Beagle dog

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Potential hepatic and renal toxicity induced by the biflavonoids from ginkgo biloba

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Chinese Journal of Natural Medicines 2019年第9期17卷 672-681页

作者： LI Yun-Ying LU Xiao-Yan SUN Jia-Li WANG Qing-Qing ZHANG Yao-Dan ZHANG Jian-Bing FAN Xiao-Hui Tianjin University of Traditional Chinese Medicine Tianjin 301617China Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Zhejiang University-Wanbangde Pharmaceutical Group Joint Research Center for Chinese Medicine Modernization Hangzhou 310058China

Evidence continues to grow on potential health risks associated with ginkgo biloba and its constituents.While biflavonoid is a subclass of the flavonoid family in ginkgo biloba with a plenty of pharmacological properties,the potential toxicological effects of biflavonoids remains largely unknown.Thus,the aim of this study was to investigate the in vitro and in vivo toxicological effects of the biflavonoids from ginkgo biloba(i.e.,amentoflavone,sciadopitysin,ginkgetin,isoginkgetin,and bilobetin).In the in vitro cytotoxicity test,the five biflavonoids all reduced cell viability in a dose-dependent manner in human renal tubular epithelial cells(HK-2)and human normal hepatocytes(L-02),indicating they might have potential liver and kidney toxicity.In the in vivo experiments,after intragastrical administration of these biflavonoids at 20 mg·kg^–1·d^–1 for 7 days,serum biochemical analysis and histopathological examinations were performed.The activity of alkaline phosphatase was significantly increased after all the bifl avonoid administrations and widespread hydropic degeneration of hepatocytes was observed in ginkgetin or b ilobetin-treated mice.Moreover,the five biflavonoids all induced acute kidney injury in treated mice and the main pathological lesions were confirmed to the tubule,glomeruli,and interstitium injuries.As the in vitro and in vivo results suggested that these biflavonoids may be more toxic to the kidney than the liver,we further detected the mechanism of biflavonoids-induced nephrotoxicity.The increased TUNEL-positive cells were detected in kidney tissues of biflavonoids-treated mice,accompanied by elevated expression of proapoptotic protein BAX and unchanged levels of antiapoptotic protein BCL-2,indicating apoptosis was involved in biflavonoids-induced nephrotoxicity.Taken together,our results suggested that the five biflavonoids from ginkgo biloba may have potential hepatic and renal toxicity and more attentions should be paid to ensure ginkgo biloba preparations safety.

关键词： Biflavonoids ginkgo biloba Potential toxicity Liver Kidney Apoptosis

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Effects of ginkgo biloba extract EGb761 on neural differentiation of stem cells offer new hope for neurological disease treatment

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Neural Regeneration Research 2019年第7期14卷 1152-1157页

作者： Chao Ren Yong-Qiang Ji Hong Liu Zhe Wang Jia-Hui Wang Cai-Yi Zhang Li-Na Guan Pei-Yuan Yin Department of Neurology and Suzhou Clinical Research Center of Neurological Disease the Second Affiliated Hospital of Soochow University Department of Neurology Affiliated Yantai Yuhuangding Hospital of Qingdao University Department of Nephrology Affiliated Yantai Yuhuangding Hospital of Qingdao University Department of Clinical Laboratory Affiliated Yantai Yuhuangding Hospital of Qingdao University Department of Central Laboratory Affiliated Yantai Yuhuangding Hospital of Qingdao University Department of Emergency and Rescue Medicine Xuzhou Medical University Department of Neurosurgical Intensive Care Unit the Affiliated Yantai Yuhuangding Hospital of Qingdao University Department of Blood Supply Yantai Center Blood Station

Stem cell transplantation has brought new hope for the treatment of neurological diseases.The key to stem cell therapy lies in inducing the specific differentiation of stem cells into nerve cells.Because the differentiation of stem cells in vitro and in vivo is affected by multiple factors,the final differentiation outcome is strongly associated with the microenvironment in which the stem cells are located.Accordingly,the optimal microenvironment for inducing stem cell differentiation is a hot topic.EGb761 is extracted from the leaves of the ginkgo biloba tree.It is used worldwide and is becoming one of the focuses of stem cell research.Studies have shown that EGb761 can antagonize oxygen free radicals,stabilize cell membranes,promote neurogenesis and synaptogenesis,increase the level of brain-derived neurotrophic factors,and replicate the environment required during the differentiation of stem cells into nerve cells.This offers the possibility of using EGb761 to induce the differentiation of stem cells,facilitating stem cell transplantation.To provide a comprehensive reference for the future application of EGb761 in stem cell therapy,we reviewed studies investigating the influence of EGb761 on stem cells.These started with the composition and neuropharmacology of EGb761,and eventually led to the finding that EGb761 and some of its important components play important roles in the differentiation of stem cells and the protection of a beneficial microenvironment for stem cell transplantation.

关键词： nerve regeneration ginkgo biloba extract ginkgolide B traditional Chinese medicine stem cells induction of differentiation stem cell transplantation synaptic plasticity pharmacological effect neurological diseases nervous systems neural regeneration

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Effect of Western medicine therapy assisted by ginkgo biloba tablet on vascular cognitive impairment of none dementia

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Asian Pacific Journal of Tropical Medicine 2012年第8期5卷 661-664页

作者： Shi-Jin Zhang Zhan-You Xue Department of Traditional Chinese Medicine People's Hospital of Zhengzhou Department of Neurology the First Affiliated Hospital of Zhengzhou University

Objective:To discuss the clinical effects of Western medicine therapy assisted by ginkgo biloba tablet(GBT) on patients with vascular cognitive impairment of none dementia(VCIND).Methods: A total of 80 patients with VCIND were divided into two groups randomly:Conventional treatment group(control group) and combined treatment group.Conventional treatment group was given conventional treatment with anti-platelet aggregation.In this group,75 mg aspirin was given three times a day for 3 months.While in combined treatment group,19.2 mg CRT was given three times a day for 3 months together with conventional treatment(anti-platelet aggregation drugs). Montreal cognitive assessment(MoCA) and transcranial Doppler(TCD) were used to observe changes of cognitive ability and cerebral blood flow in VCIND patients before and after treatment in both groups.Then the clinical data were analyzed so as to compare the efficacy in two groups. Results:After 3 month-treatment in combined treatment group,the scores of executive ability, attention,abstract,delayed memory,orientation in the MoCA were significantly increased compared with those before treatment and those in control group after treatment.Besides,blood flow velocity of anterior cerebral artery increased significandy than that before treatment and that in control group after treatment.Conclusions:CBT tablet can improve the therapeutic efficacy as well improve cognitive ability and cerebral blood flow supply of patients with VCIND.

关键词： Combination of traditional Chinese and Western medicine Cognitive impairment ginkgo tablet Clinical evaluation

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Efficacy and safety of ginkgo injections in the treatment of angina pectoris caused by coronary heart disease in China: a network Meta-analysis and systematic review

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Journal of Traditional Chinese Medicine 2019年第3期39卷 285-296页

作者： Tan Di Wu Jiarui Jing Zhiwei Duan Xiaojiao Cui Yingying Liu Shi Department of Clinical Pharmacology of Traditional Chinese Medicine School of Chinese Materia Medica Beijing University of Chinese Medicine Beijing 100102 China China Academy of Chinese Medical Sciences Beijing 100700 China

OBJECTIVE:To assess the clinical efficacy and safety of ginkgo injections(GIs)combined with conventional treatment(CT)against angina pectoris(AP)due to coronary heart disease(CH D).METHODS:Randomized controlled trials(RCTs)that used GIs to treat AP were searched in SinoMed,PubMed,China National Knowledge Infrastructure Database,Chinese Scientific Journals Database,Wanfang Database,Embase and Cochrane Library until March 2017.The Cochrane "risk of bias" method was used to evaluate the methodological quality of RCTs.Data were analyzed using Stata v13.1 and WinBUGS v1.4.3.RESULTS:A total of 73 RCTs involving 7621 patients were included.A Bayesian network Meta-analysis of RCTs was undertaken,and the advantages of four types of Gl-supplemented CT in AP treatment were determined.CONCLUSION:Gl-assisted CT was more effective against AP than CT alone.However,based on the limitations of the study,additional high-quality RCTs are required to confirm our findings.

关键词： ginkgo injections Angina pectoris Network Meta-analysis Systematic review

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Influence of ginkgo biloba extract on the proliferation,apoptosis of ACC-2 cell and Survivin gene expression in adenoid cystic carcinoma of lacrimal gland

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Asian Pacific Journal of Tropical Medicine 2012年第11期5卷 897-900页

作者： Li-Xiao Zhou Yu Zhu Department of Ophthalmology First Affiliated Hospital of Zhengzhou University

Objective:To explore the influence of extract of ginkgo biloba（EGB） on the proliferation, apoptosis of ACC-2 cell and Survivin gene expression in adenoid cystic carcinoma（ACC） of lacrimal gland.Methods:ACC-2 cell in human with ACC of lacrimal gland was in vitro cultured. MTT method was used for cell proliferation detection.Annexin V/PI double-staining flow cytometer was used to detect cell apoptosis and cell cycle.Survivin gene expression was analyzed by RT-PCR and Western blotting.Results:EGB had inhibitory effect on the proliferation of ACC-2 cell with significant dose-effect relationship,and there was statistical difference when compared with the control group（P50) is 88 mg/L. The flow cytometer test indicated that CGB can gradually increase ACC-2 cell in G0-G1 stage and decrease it in G2-M and S stage.With the increase of dose,the apoptosis rate of ACC-2 cell was obviously increased（P<0.05 or P<0.01）.EGB had certain inhibitor)’ effect on Survivin gene expression of ACC-2 cell,and Survivin gene expression was decreased with the increasing of the EGB concentration（P<0.01）.Conclusions:EGB can effectively inhibit Survivin gene expression of ACC-2 cell in human with ACC of lacrimal gland,induce the apoptosis of ACC-2 cell and inhibit tumor cell proliferation.

关键词： ginkgo biloba extract ACC-2 cell Proliferation Apoptosis Survivin gene

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ginkgo paste improves tinea corporis in a guinea pig model

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BIOCELL 2020年第4期44卷 649-653页

作者： LIHUA CAO MINGSAN MIAO YAN ZHENG HUIYAUN HUANG RUI ZHANG DANDAN LIU Academy of Chinese Medical Sciences Henan University of Chinese MedicineZhengzhou450046China Department of Pharmacology Henan University of Chinese MedicineZhengzhou450046China

To investigate the effects of ginkgo paste for external use on tinea corporis in a guinea pig model.The guinea pig tinea corporis model were induced by infection with Trichophyton mentagrophytes strains.And then,high and low doses of ginkgo water-paste and alcohol-paste were administrated to the animals.The symptom,tinea corporis skin lesions and histopathological aspects of guinea pig were analyzed.High and low doses of ginkgo alcohol-paste and ginkgo water-paste could significantly reduced the tinea corporis symptom(Pginkgo alcohol paste group.These results suggest that ginkgo paste exhibits the efficacy to treat tinea corporis in a guinea pig model.

关键词： ginkgo Alcohol paste Tinea corporis Guinea pig

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