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Biotechnology Applications of Plant Callus Cultures

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Engineering 2019年第1期5卷 50-59页

作者： Thomas Efferth Department of Pharmaceutical Biology Institute of Pharmacy and Biochemistry Johannes Gutenberg University Mainz Mainz 55128 Germany

In ethnopharmacology, and especially in traditional Chinese medicine, medicinal plants have been used for thousands of years. Similarly, agricultural plants have been used throughout the history of mankind. The recent development of the genetic engineering of plants to produce plants with desirable features adds a new and growing dimension to humanity’s usage of plants. The biotechnology of plants has come of age and a plethora of bioengineering applications in this context have been delineated during the past few decades. Callus cultures and suspension cell cultures offer a wide range of usages in pharmacology and pharmacy (including Chinese medicine), as well as in agriculture and horticulture. This review provides a timely overview of the advancements that have been made with callus cultures in these scientific fields. Genetically modified callus cultures by gene technological techniques can be used for the synthesis of bioactive secondary metabolites and for the generation of plants with improved resistance against salt, draft, diseases, and pests. Although the full potential of callus plant culture technology has not yet been exploited, the time has come to develop and market more callus culture-based products.

关键词： Antibody production Embryogenesis Gene technology Organogenesis Pharmacology Phytochemistry Plant regeneration Secondary metabolites Stem cells

Perspectives for Globalized Natural Medicines

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中国天然药物 2011年第1期9卷 1-6页

作者： Thomas Efferth Department of Pharmaceutical Biology Institute of Pharmacy and BiochemistryUniversity of Mainz

Natural medicines provide valuable resources to meet the requirements for global health care at affordable prices.Therefore,safety and efficacy need to be proven in a comparable manner to conventional drugs.Evidence-based natural and western medicine may merge to a "one-world medicine" for the sake of all patients in industrialized and developing countries.In the present review,we discuss strategies for (1) preservation of traditional knowledge on natural medicines,(2) sustainability of medicinal herbs and natural products,and (3) standardization and quality control.Novel technologies will impact research on natural medicines in the years to come,e.***.remote sensing to map medicinal plant locations,DNA barcoding for plant authentication,hollow fiber extraction,high-end techniques for chemo-profiling of plant constituents in medicinal products and blood serum of patients as well as systems biological approaches.

关键词：生物多样性草药的治疗生药学 Phytomedicine 植物治疗法质量控制可持续性

Drug targets and resistance mechanisms in multiple myeloma

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Cancer Drug Resistance 2018年第2期1卷 87-117页

作者： Janine Nass Thomas Efferth Department of Pharmaceutical Biology Institute of Biochemistry and PharmacyJohannes Gutenberg UniversityMainz 55128Germany

Multiple myeloma(MM),a malignancy of plasma cells,is the second most prevalent blood cancer(10%).A PubMed search has been conducted for English research papers and reviews published until January 2018.Numerous drugs are used in treatment of MM.These include the antineoplastic alkylating agents cyclophosphamide,busulfan and melphalan,immunomodulators such as lenalidomide and thalidomide,corticosteroids including dexamethasone,microtubule-targeting agents,such as paclitaxel and vinca alkaloids,as well as the proteasome inhibitors bortezomib and carfilzomib.Despite the considerable number of treatment options,MM is still difficult to treat,which is mirrored by the poor 10-year survival rate of 3%.Resistance to chemotherapy is often the cause for therapy failure.These resistances can be due to the overexpression of efflux pumps,genetic and epigenetic aberrations and the microenvironment of MM.With the gain of knowledge regarding genetic and molecular changes,many molecular targeted therapies including cell signaling targeted therapies are being developed against relapsed/refractory MM.Additionally,epigenetic aberrations such as DNA methylation and histone modifications steered MM management in new directions.Amongst these novel targeted therapies,inhibitors of histone deacetylase,Aurora kinase,inhibitors of the PI3K/AKT/mTOR pathway and cyclin dependent kinases are promising.

关键词： Cancer drug resistance drug targets chemotherapy genetics immunotherapy

Selected Secondary Plant Metabolites for Cancer Therapy

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World Journal of Traditional Chinese Medicine 2015年第1期1卷 24-28页

作者： Simone Fulda Thomas Efferth Institute of Experimental Cancer Research in Pediatry Goethe-Universitat Frankfurt Department of Pharmaceutical Biology Institute of Pharmacy and BiochemistryJohannes Gutenberg-Universitat Mainz

Secondary plant metabolites reveal numerous biological activities making them attractive as resource for drug development of human diseases.As the majority of cancer drugs clinically established during the past half century is derived from nature, cancer researchers worldwide try to identify novel natural products as lead compounds for cancer therapy. Natural products are considered as promising cancer therapeutics,either as single agents or in combination protocols, to enhance the antitumor activity of additional therapeutic modalities. Most natural compounds exert pleotrophic effects and modulate various signal transduction pathways. A better understanding of the complex mechanisms of action of natural products is expected to open new perspectives in coming years for their use alone or in combination therapies in oncology.Two major strategies to identify novel drug candidates from nature are the bioactivity-guided fractionation of medicinal plant extracts to isolate cytotoxic chemicals and the identification of small molecules inhibiting specific targets in cancer cells. In the present review, we report on our own efforts to unravel the molecular modes of action of phytochemicals in cancer cells and focus on resveratrol, betulinic acid,artesunate, dicentrine and camptothecin derivatives.

关键词： Apoptosis Bioactivity-guided fractionation Drug development Drug resistance Epidermal growth factor receptor Phytochemicals Targeted tumor therapy

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欧洲草药禁令对草药疗法的影响(英文)

中西医结合学报 2012年第4期10卷 357-361页

作者： Thomas Efferth Henry Johannes Greten Department of Pharmaceutical Biology Institute of Pharmacy and BiochemistryJohannes Gutenberg UniversityStaudinger Weg 555128 MainzGermany Heidelberg School of Chinese Medicine Karlsruher Straβe 1269126 HeidelbergGermany Biomedical Sciences Institute Abel Salazar University of PortoPortoPortugal

The European Parliament and Council enacted a directive on traditional herbal medicinal products (THMPD;Directive 2004/24/EC) as an amendment to an earlier directive on the use of medicinal products(Directive 2001/83/... 详细信息

关键词：植物药用补充疗法药物相互作用药物非处方质量控制欧盟

Tonic Herbs and Herbal Mixtures in Chinese Medicine

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World Journal of Traditional Chinese Medicine 2016年第1期2卷 10-25页

作者： Thomas Efferth Letian Shan Zhuo-Wen Zhang Department of Pharmaceutical Biology Institute of Pharmacy and Biochemistry Johannes Gutenberg University Zhejiang Chinese Medical University

This review results from a Pub Med-based data-mining of scientific literature concerning typical tonic herbs and formulas of Chinese herbal medicine and their application principle under the theory of CM. We have focused on two aspects of tonic activity: body tonification against qi气-, blood血-, yin阴-and yang阳-deficiency, respectively, and organ(Zang 脏and Fu腑) tonification against heart-, liver-, spleen/stomach-,lung-, and kidney-deficiency, respectively.Body-tonifying herbs are: Astragalus Membranaceus Radix(Huang-qi黄芪) and Panax Ginseng Radix(Ren-shen人参) for qi-tonification;Angelicae Sinensis Radix(Dang-gui当归) and Rehmannia Glutinosa Radix Preparata(Shu-di熟地) for blood-tonification; Ophiopogon Japonicus Radix(Mai-dong麦冬) and Scrophularia Ningpoensis Radix(Xuan-shen玄参) for yin-deficiency; Myristica Fragrans Semen(Roudou-kou肉豆蔻) and Psoralea Corylifolia Fructus(Bu-gu-zhi补骨脂) for yang-deficiency. The corresponding CM formulas are: Bu-zhong-yi-qi decoction(补中益气汤) for qi-tonification; Si-wu decoction(四物汤) for blood-tonification; Zeng-ye decoction(增液汤) for yin-tonification;Si-shen pill(四神丸) for yang-tonification.Organ-tonifying herbs are: Glycyrrhizae Uralensis Radix Preparata(Zhi-gan-cao炙甘草) and Rehmannia Glutinosa Radix(Di-huang地黄) for heart-tonification; Lycium Barbarum Fructus(Gou-qi-zi枸杞子) and Angelicae Sinensis Radix(Dang-gui当归) for liver-tonification; Panax Ginseng Radix(Ren-shen人参) and Atractylodis Macrocephala Rhizoma(Bai-zhu白术) for spleen/stomach-tonification; Panax Ginseng Radix(Ren-shen人参) and Astragalus Membranaceus Radix(Huang-qi黄芪) for lung-tonification; Cornus Officinalis Fructus(Shan-zhu-yu山茱萸)and Dioscorea Opposite Rhizoma(Shan-yao山药) for kidney-tonification. The corresponding CM formulas are: Zhi-gan-cao decoction(炙甘草汤) for heart-tonification; Yi-guan decoction(一贯煎) for liver-tonification; Shen-ling-bai-zhu powder(参苓白术散) for spleen/stomachtonification; Bu-fei decoction(补肺汤) for lung-tonification; Liu-wei-di-huang pill(六味地黄丸) for kidney tonification.These herbs and formulas were described regarding t

关键词： Chinese herbal medicine Chinese formula Medicinal herbs Theory of Chinese medicine

Artemisinin-Second Career as Anticancer Drug?

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World Journal of Traditional Chinese Medicine 2015年第4期1卷 2-25页

作者： Thomas Efferth Johannes Gutenberg University Institute of Pharmacy and Biochemistry Department of Pharmaceutical Biology

Artemisinin represents a showcase example not only for the activity of medicinal herbs deriving from traditional chinese medicine, but for phytotherapy in general. Its isolation from Sweet Wormwood(qinhao, Artemisia annua L.) represents the starting point for an unprecedent success story in the treatment of malaria worldwide. Beyond the therapeutic value against Plasmodium parasites, it turned out in recent years that the bioactivity of artemisinin is not restricted to malaria. We and others found that this sesquiterpenoid also exerts profound anticancer activity in vitro and in vivo. Artemisinin-type drugs exert multi-factorial cellular and molecular actions in cancer cells. Ferrous iron reacts with artemisinin, which leads to the formation of reactive oxygen species and ultimately to a plethora anticancer effects of artemisinins, e.***.expression of antioxidant response genes, cell cycle arrest(G1 as well as G2 phase arrests), DNA damage that is repaird by base excision repair,homogous recombination and non-homologous end-joining, as well as different modes of cell death(intrinsic and extrinsic apoptosis,autophagy, necrosis, necroptosis, oncosis, and ferroptosis). Furthermore, artemisinins inhibit neoangiogenesis in tumors. The signaling of major transcription factors(NF-κB, MYC/MAX, AP-1, CREBP, mTOR etc.) and signaling pathways are affected by artemisinins(e.g. Wnt/β-catenin pathway, AMPK pathway, metastatic pathways, nitric oxide signaling, and others). Several case reports on the compassionate use of artemisinins as well as clinical Phase I/II pilot studies indicate the clinical activity of artemisinins in veterinary and human cancer patients.Larger scale of Phase II and III clinical studies are required now to further develop artemisinin-type compounds as novel anticancer drugs.

关键词： Artemisia annua Artemisinin Cancer Chemotherapy Qinhaosu Malaria Phytotherapy

Nanocarriers to Enhance Solubility, Bioavailability, and Efficacy of Artemisinins

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World Journal of Traditional Chinese Medicine 2020年第1期6卷 26-38页

作者： Anna Rita Bilia Maria Camilla Bergonzi Joelle CBoulos Thomas Efferth Department of Chemistry University of FlorenceFlorenceItaly Department of Pharmaceutical Biology Institute of Pharmacy and BiochemistryJohannes Gutenberg UniversityMainzGermany

The therapeutic potential of artemisinin (ART) and its derivatives (ARTs) is not limited to malaria but has been recently expanded to other infections with protozoans, trematodes, or viruses as well as to cancer. Due to their limited poor water and oil solubility, rapid degradation by the liver, and short half-life, they have a low bioavailability after oral administration. Consequently, there is a pressing necessity to formulate new ART preparations to raise its bioavailability and efficacy. Nanosized drug delivery systems represent important tools in modern medicine with wide clinical applications, because of their potential modulation of pharmacokinetic and biodistribution. This review focuses on polymer-based systems, lipid-based systems, and inorganic nanoparticles loaded with ARTs. The overall goal of this field of research is to enhance their solubility and stability to improve bioavailability at much lower doses and to increase long-term safety. In addition, the opportunity to reach highly specific site-targeted delivery by these nanocarriers confers a high medicinal value. Remarkably, most of the reported nanoparticulate drug delivery systems are biologically inactive or marginally immunogenic, generating no antigenic or pyrogenic reactions but only partial intrinsic toxicity. As clinical studies in human patients are available so far, there is a pressing need to translate preclinical results on ART-based nanosystems into clinical settings.

关键词： Artemisinin Asteraceae derivatives inorganic nanocarriers lipid nanocarriers nanotechnology polymeric nanocarriers sesquiterpene lactones

Can eastern wisdom resolve western epidemics? Traditional Chinese medicine therapies and the opioid crisis

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Journal of Integrative Medicine 2021年第4期19卷 295-299页

作者： Thomas Efferth An-long Xu Roxana Damiescu Mita Banerjee Norbert W.Paul David Y.W.Lee Department of Pharmaceutical Biology Institute of Pharmacy and BiochemistryJohannes Gutenberg University55128 MainzGermany School of Life Science Beijing University of Chinese MedicineBeijing 100029China Obama Institute of Transnational American Studies Department of English and LinguisticsJohannes Gutenberg University55128 MainzGermany Institute for the History Philosophyand Ethics of MedicineJohannes Gutenberg University Medical Center55131 MainzGermany Harvard Medical School McLean HospitalBostonMA 02115USA

The widespread use of opioids to treat chronic pain led to a nation-wide crisis in the United States. Tens of thousands of deaths annually occur mainly due to respiratory depression, the most dangerous side effect of opioids. Non-opioid drugs and non-pharmacological treatments without addictive potential are urgently required. Traditional Chinese medicine(TCM) is based on a completely different medical theory than academic Western medicine. The scientific basis of acupuncture and herbal treatments as main TCM practices has been considerably improved during the past two decades, and large metaanalyses with thousands of patients provide evidence for their efficacy. Furthermore, opinion leaders in the United States favor non-pharmacological techniques including TCM for pain management to fight the opioid crisis. We advocate TCM as therapeutic option without addictive potential and without lifethreatening side effects(e.g., respiratory depression) to treat chronic pain patients suffering from opioid misuse. The evidence suggests that:(1) opioid misuse cannot be satisfactorily managed with standard medication;(2) opinion leaders in the United States favor to consider non-opioid and nonpharmacological treatment strategies including those from TCM to treat acute and chronic pain conditions;(3) large meta-analyses provide scientific evidence for the clinical activity of acupuncture and herbal TCM remedies in the treatment of chronic pain. Future clinical trials should demonstrate the safety of TCM treatments if combined with Western medical practices to exclude negative interactions between both modalities.

关键词： Traditional Chinese medicine Acupuncture Addiction Opioid crisis Pain