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Forsythosides as Essential Components of Forsythia-based Traditional Chinese Medicines Used to Treat Inflammatory Diseases and COVID-19

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World Journal of Traditional Chinese Medicine 2022年第1期8卷 1-20页

作者： Christian bailly OncoWitan Scientific Consulting OfficeLille(Wasquehal59290)France

The dried fruits of the plant Forsythia suspensa(Forsythia Fructus: Lianqiao in Chinese) are used in many herbal preparations to treat various diseases or the associated symptoms. Forsythia extracts contain phenylethanoid glycosides(Ph Gs) such as the forsythosides(Fst A-to-P). The leading products, Fst-A,-B and-F(arenarioside), can be found also in >90 other plants inventoried here. The pharmacological properties of Fst are reviewed, with emphasis on their anticancer, antiviral, and antibacterial activities, which essentially derive from their anti-inflammatory and antioxidant effects. Fst-B functions as a potential binder of the repressor protein Kelch-like ECH-association protein 1(Keap 1), thus promoting the nuclear translocation of the transcription factor Nuclear factor erythroid 2-related factor 2(Nrf2) implicated in the subsequent activation of the production of antioxidant enzymes and repression of the oxidative stress. The regulation of the Nrf2/Heme oxygenase-1 pathway is the central piece of the multifaceted mechanism of action of Fst-A/B. Their prominent antioxidant and anti-inflammatory effects support the use of these compounds in different inflammation-related diseases and conditions, from sepsis to neuroprotection and many other pathologies discussed here. In addition, these properties contribute to the antiviral action of the compounds. Fst-A/B displays activities against the influenza A virus and different Fst-containing traditional Chinese medicinal(TCMs) have revealed beneficial effects to combat the current COVID-19 pandemic. The mechanisms whereby Fst-A/B could inhibit viral multiplication are discussed. Ph Gs likely contribute to the anti-COVID-19 activities reported with several TCM such as Shuang-Huang-Lian oral liquid, Lianhua-Qingwen capsules, and others. This review highlights the pharmacological profile of Fst and illustrates health benefits associated with the use of Forsythia Fructus.

关键词： Chinese medicine COVID-19 forsythia forsythoside mechanism of action natural products phenylethanoid glycosides

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Traditional Uses and Phytochemical Constituents of Cynanchum otophyllum C. K. Schneid (Qingyangshen)

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World Journal of Traditional Chinese Medicine 2023年第1期9卷 1-7页

作者： Christian bailly Cheng Xiang Ji-HongZhang Oncowitan Scientific Consulting OfficeLille(Wasquehal)59290France Faculty of life Science and Technology Kunming University of Science and TechnologyKunming 650500China Medical School Kunming University of Science and TechnologyKunming 650500China

The roots of the plant Cynanchum otophyllum C. K. Schneid(Apocynaceae), known as Qingyangshen in Chinese, are used for a long time as a traditional medicine by different ethnic communities in the Yunnan province(China). The multiple properties and applications of this herbal medicine have been analyzed. C. otophyllum is a perennial herbal liana, nonedible, and generally wild harvested. A cultivation method has been proposed to increase the fruit set level. Qingyangshen is used essentially to treat epilepsy, rheumatism, or other inflammatory diseases. The plant can be found also in diverse polyherbal preparations used in cosmetic or as food supplement(detox products), and in phyto-preparations claimed to reduce hair loss. The plant is a rich reservoir of C-21 steroidal glycosides. Many bioactive compounds have been isolated from this plant and some of them have been pharmacologically characterized, such as otophyllosides, cynotophyllosides, cynanotins, cynotogenins, cynanchins, all briefly evocated here. The plant presents also interesting features in other domains. In particular, leave extracts of C. otophyllum C. K. Schneid contain proteases which are exploited for the local preparation of a cheese-like milk cake. Qingyangshen herbal preparation can be useful to treat epilepsy and inflammation. It has applications beyond medicine in the cosmetic and food industry.

关键词： Cynanchum epilepsy medicinal plant steroidal glycosides

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Anticancer Properties of Lobetyolin,an Essential Component of Radix Codonopsis(Dangshen)

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Natural Products and Bioprospecting 2021年第2期11卷 143-153页

作者： Christian bailly OncoWitan 59290 Lille(Wasquehal)France

Lobetyolin(LBT)is a polyacetylene glycoside found in diverse medicinal plants but mainly isolated from the roots of Codo-nopsis pilosula,known as Radix Codonopsis or Dangshen.Twelve traditional Chinese medicinal preparations containing Radix Codonopsis were identified;they are generally used to tonify spleen and lung Qi and occasionally to treat cancer.Here we have reviewed the anticancer properties of Codonopsis extracts,LBT and structural analogs.Lobetyolin and lobetyolinin are the mono-and bis-glucosylated forms of the polyacetylenic compound lobetyol.Lobetyol and LBT have shown activi-ties against several types of cancer(notably gastric cancer)and we examined the molecular basis of their activity.A down-regulation of glutamine metabolism by LBT has been evidenced,contributing to drug-induced apoptosis and tumor growth inhibition.LBT markedly reduces both mRNA and protein expression of the amino acid transporter Alanine-Serine-Cysteine Transporter 2(ASCT2).Other potential targets are proposed here,based on the structural analogy with other anticancer compounds.LBT and related polyacetylene glycosides should be further considered as potential anticancer agents,but more work is needed to evaluate their efficacy,toxicity,and risk-benefit ratio.

关键词： Cancer therapy Natural products Mechanism of action Molecular target Terpenoids Lobetyolin Polyacetylene glycoside Glutamine metabolism

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Anticancer Activities and Mechanism of Action of Nagilactones, a Group of Terpenoid Lactones Isolated from Podocarpus Species

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Natural Products and Bioprospecting 2020年第6期10卷 367-375页

作者： Christian bailly OncoWitan 59290 Lille(Wasquehal)France

Nagilactones are tetracyclic natural products isolated from various Podocarpus species.These lactone-based compounds display a range of pharmacological effects,including antifungal,anti-atherosclerosis,anti-inflammatory and anticancer activities reviewed here.The most active derivatives,such as nagilactones C,E and F,exhibit potent anticancer activities against different cancer cell lines and tumor models.A comprehensive analysis of their mechanism of action indicates that their anticancer activity mainly derives from three complementary action:(i)a drug-induced inhibition of cell proliferation coupled with a cell cycle perturbation and induction of apoptosis,(ii)a blockade of the epithelial to mesenchymal cell transi-tion contributing to an inhibition of cancer cell migration and invasion and(iii)a capacity to modulate the PD-L1 immune checkpoint.Different molecular effectors have been implicated in the antitumor activity,chiefly the AP-1 pathway blocked upon activation of the JNK/c-Jun axis.Nag-C is a potent inhibitor of protein synthesis binding to eukaryotic ribosomes and inhibition of different protein kinases,such as RIOK2 and JAK2,has been postulated with Nag-E.The literature survey on nagilactones highlights the therapeutic potential of these little-known terpenoids.The mechanistic analysis also provides useful information for structurally related compounds(podolactones,oidiolactones,inumakilactones)isolated from Podo-carpus plants.

关键词： Cancer Natural products Mechanism of action Molecular target Terpenoids

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马辅助干预对老年人健康影响的系统综述

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International Journal of Nursing Sciences 2022年第4期9卷 542-552页

作者： Léa Badin Émilie Alibran Kristell Pothier Nathalie bailly University of Tours EA 2114 PAVEA LaboratoryToursFrance

目的马辅助干预(Equine-assisted interventions,EAI)可以改善老年人的各种健康问题,从而促进他们的福祉。本系统综述旨在综合EAI的研究,以更好地了解其对老年人健康的影响。方法按照PRISMA(2020)指南和综合评价方法,对Medline(PubMed)... 详细信息

目的马辅助干预(Equine-assisted interventions,EAI)可以改善老年人的各种健康问题,从而促进他们的福祉。本系统综述旨在综合EAI的研究,以更好地了解其对老年人健康的影响。方法按照PRISMA(2020)指南和综合评价方法,对Medline(PubMed)、Embase、PsycINFO和Cochrane Library等数据库进行检索。检索时间为建库至2022年6月,仅纳入经过同行评审的英文文献。采用改良版的Downs和Black检查表对纳入文献进行质量评价。结果共检索出244篇文章,13篇文章符合纳入标准。调查了3个健康领域:身体(平衡、步态和肌肉力量)、心理(生活质量和认知评估)和生理(激素测量、大脑和肌肉活动)。在调查身体维度的8项研究中,4项研究强调了EAI对平衡的积极影响,4项提示了对步态的积极影响,3项提示了对力量的积极影响。在调查心理维度的3项研究中,有2项研究显示EAI对生活质量有积极影响。最后,调查生理维度的4项研究都证明了EAI对激素测量、大脑和肌肉活动的积极影响。结论系统综述提供了关于EAI对老年人身体、心理和生理健康的积极影响的相关研究。建议EAI的研究应该以一种严格的方式进行,以便在老年人群中推广这种非药物干预。

关键词：动物辅助疗法老年人马辅助疗法健康促进

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ZMYM3:a new candidate gene in nonobstructive azoospermia?

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Asian Journal of Andrology 2023年第5期25卷 648-649页

作者： Morgane Le Beulze Nelly Swierkowski-Blanchardl Farah Ghieh Joanne Fortemps Carole Gerault Valerie Scrazin Anne Louboutin-Sanchez Marc bailly Francois Vialard Paris-Saclay University UVSQINRAEBREEDJouy-en-Josas F-78350France Alfort National Veterinary Scholl BREEDMaisons Alfort F-94700France Department of Gynecology and Obstetric CHI de Poissy/Saint-Germain-en-LayePoissy F-78300France Unit of Anatomo-Pathology CHI de Poissy/Saint-Germain-en-LayePoissy F-78300France Department of Genetic CHI de Poissy/Saint-Germain-en-LayePoissy F-78300France

Dear Editor,Infertility affects about 15%of couples of childbearing age.i About half of these cases can be attributed predominantly to a male factor,such as a quantitative or qualitative impairment in spermatogenesis.The etiology of male infertility is related to anatomic,genetic,and environmental causes,being sometimes multifactorial and of unknown or idiopathic origins.At present,genetic screening for nonobstructive azoospermia(NOA)is generally limited to karyotyping for the identification of chromosome abnormalities such as 47,XXY,46,X,der(X)t(X;Y)(p22.3;p11.2),chromosome rearrangements,and Y chromosome microdeletions.Whole-genome analyses have shown that over 100 gene variants are associated with a male infertility phenotype,and the list continues to grow;hence,a large number of genes are involved in spermatogenesis.The continuing identification of genes responsible for male infertility in general and azoospermia,in particular,is a major challenge in both research and the diagnosis ofmale infertility.

关键词： azoospermia obstructive diagnosis

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Xihuang Pills,a Traditional Chinese Preparation used as a Complementary Medicine to Treat Cancer:An Updated Review

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World Journal of Traditional Chinese Medicine 2020年第2期6卷 152-162页

作者： Christian bailly OncoWitan Lille(Wasquehal)59290France

The traditional Chinese medicine,Xihuang pills(XHP),has long been used for the management of cancers,both to limit tumor cells proliferation and dissemination,and to protect nontumor cells from damages induced by conventional therapeutic agents.XHP is made from two plant extracts(from Boswellia carteri and Commiphora myrrha)and two animal-derived products(from Moschus moschiferus and Calculus bovis).Recent advances into the mechanism of action of XHP and its clinical efficacy are reviewed here to highlight its potential to treat breast and colon cancers in particular.The immunoregulatory effects of XHP are underlined.Similar traditional medicinal preparations containing Boswellia and Commiphora are discussed,as well as the activities of the major natural products found in XHP including abietic acid,acetyl-keto-boswellic acid,and muscone.Pharmacological and clinical studies of XHP and similar medicinal preparations,such as the Korean medicine Hang Am Dan-B,are encouraged.

关键词： Anticancer drugs cancer therapy natural products traditional Chinese medicine

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Anticancer Properties and Mechanism of Action of Oblongifolin C,Guttiferone K and Related Polyprenylated Acylphloroglucinols

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Natural Products and Bioprospecting 2021年第6期11卷 629-641页

作者： Christian bailly Gérard Vergoten Scientific Consulting Office OncoWitan59290 LilleWasquehalFrance Inserm INFINITE-U1286Facultéde PharmacieUniversity of LilleInstitut de Chimie Pharmaceutique Albert Lespagnol(ICPAL)3 rue du Professeur LaguesseBP-8359006 LilleFrance

Polyprenylated acylphloroglucinols represent an important class of natural products found in many plants.Among them,the two related products oblongifolin C(Ob-C)and guttiferone K(Gt-K)isolated from Garcinia species(notably from edible fruits),have attracted attention due to their marked anticancer properties.The two compounds only differ by the nature of the C-6 side chain,prenyl(Gt-K)or geranyl(Ob-C)on the phloroglucinol core.Their origin,method of extraction and biological properties are presented here,with a focus on the targets and pathways implicated in their anticancer activities.Both compounds markedly reduce cancer cell proliferation in vitro,as well as tumor growth and metastasis in vivo.They are both potent inducer of tumor cell apoptosis,and regulation of autophagy flux is a hallmark of their mode of action.The distinct mechanism leading to autophagosome accumulation in cells and the implicated molecular targets are discussed.The specific role of the chaperone protein HSPA8,known to interact with Ob-C,is addressed.Molecular models of Gt-K and Ob-C bound to HSPA8 provide a structural basis to their common HSPA8-binding recognition capacity.The review shed light on the mechanism of action of these compounds,to encourage their studies and potential development.

关键词： Anticancer Autophagy HSPA8 Natural products Polyprenylated acylphloroglucinols

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生物碱bouchardatine及orirenierine与组蛋白去乙酰化酶1(SIRT1)结合的分子建模研究

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Digital Chinese Medicine 2022年第3期5卷 276-285页

作者： Gérard Vergoten Christian bailly Inserm INFINITE-U1286Institut de Chimie Pharmaceutique Albert Lespagnol(ICPAL)Faculty of PharmacyUniversity of LilleLille 59006France Scientific Consulting Office OncoWitanLille 59290France

目的Bouchardatine(1)是从植物Bouchardatia neurococca中分离得到的一种β-吲哚喹唑啉生物碱,可作为脂肪生成的一种调节剂及一种抗癌药。天然产物作为蛋白腺苷5'-单磷酸(AMP)活化蛋白激酶(AMPK)和组蛋白去乙酰化酶1(SIRT1)的激活剂发... 详细信息

目的Bouchardatine(1)是从植物Bouchardatia neurococca中分离得到的一种β-吲哚喹唑啉生物碱,可作为脂肪生成的一种调节剂及一种抗癌药。天然产物作为蛋白腺苷5'-单磷酸(AMP)活化蛋白激酶(AMPK)和组蛋白去乙酰化酶1(SIRT1)的激活剂发挥作用。我们利用分子模型研究了化合物1和各种结构类似物的SIRT1结合能力,如从药用植物Oriciarenieri中分离得到的orirenierine A(2)和orirenierine B(3)。方法我们研究了包括β-吲哚喹唑啉生物碱1−3和类似物在内的25种天然产物与人源组蛋白去乙酰化酶1(hSIRT1)的结合,并与参比产物去乙酰化酶(R和S异构体)进行了比较。从hSIRT1催化结构域的闭合和开放状态构象(PDB结构:4KXQ和4IG9)开始阐述去乙酰化酶结合模型。对于与SIRT1结合的每种化合物,我们计算了相互作用的经验能量(ΔE),并与去乙酰化酶进行比较。结果在我们的模型中,发现化合物1与SIRT1的去乙酰化酶位点适度结合。相反,喹唑啉酮部分7位酚羟基表现出更高的结合能力。化合物2提供的SIRT1蛋白复合物与去乙酰化酶观察到的一样稳定。用甲氧基(3)取代羟基取代基(2)降低了SIRT1的结合能力。我们还鉴定了其他SIRT1结合的天然产物,如生物碱orisuaveolines A和B,并讨论了结构结合关系。结论本研究强调了β-吲哚喹唑啉生物碱与SIRT1相互作用的能力。这种去乙酰化酶可以代表生物碱2的分子靶标。这种化合物在设计对SIRT1依赖性病理有活性的药物研究方面值得进一步关注。

关键词：组蛋白去乙酰化酶1 生物碱 Bouchardatine Orirenierine 天然产物癌症炎症性疾病分子建模药物设计

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Role of ethylene and proteolytic N-degron pathway in the regulation of Arabidopsis seed dormancy

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Journal of Integrative Plant Biology 2021年第12期63卷 2110-2122页

作者： Xu Wang Malaika Maraya Gomes Christophe bailly Eiji Nambara Francoise Corbineau UMR7622 Biologie du Développement Sorbonne UniversitéIBPSCNRSParis F-75005France Department of Cell and Systems Biology University of TorontoTorontoOntarioM5S 3B2Canada

Primary dormant seeds of Arabidopsis thaliana did not germinate in darkness at temperature higher than 10–15℃.Ethylene improved the germination of dormant wild-type(Col-0)seeds at 25℃ in darkness but seeds of the mutant affected in the proteolytic N-degronpathway,proteolysis6(prt6),were insensitive to ethylene suggesting that PRT6 was involved in dormancy release by ethylene.The substrates of the N-degron pathway,the Ethylene Response Factors from group VII(HRE1,HRE2,RAP2.2,RAP2.3,and RAP2.12),were identified to be involved in this insensitivity with an increased germination in prt6 rap2.2 rap2.3 rap2.12 rather than in prt6 hre1 hre2,which also indicated that the three RAPs acted downstream of PRT6,while the two HREs acted upstream of PRT6.Ethylene reduced the expression of the three RAPs in Col-0 seeds but they were maintained or induced by ethylene in prt6 seeds.The promoting effect of ethylene was associated with a down-regulation of dormancy-related genes in gibberellins(GAs)and abscisic acid(ABA)signaling,such as RGA,RGL2,and ABI5,and with a strong decrease in ABA/GA4 ratio in the presence of ethylene.In contrast,we show that the insensitivity of prt6 seeds to ethylene was mainly related to GA signaling disturbance.

关键词： abscisic acid/gibberellin Arabidopsis thaliana L dormancy Ethylene Response Factors ethylene germination N-degron pathway proteolysis6

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