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...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.展开更多
Artemisinin,a constituent of Artemisia annua L.,is a well-known antimalarial drug.Artemisinin-type drugs also inhibit cancer growth in vitro and in vivo.Herbal extracts of A.annua inhibit the growth of cancer cell lin...Artemisinin,a constituent of Artemisia annua L.,is a well-known antimalarial drug.Artemisinin-type drugs also inhibit cancer growth in vitro and in vivo.Herbal extracts of A.annua inhibit the growth of cancer cell lines.Here,we report on the use of capsules containing powder of Herba Artemisiae annuae to treat pet sarcoma.The surgical tumor removal as standard treatment was supplemented by adjuvant therapy with A.annua.One cat and one dog with fibrosarcoma survived 40 and 37 months,respectively,without tumor relapse.Two other dogs suffering from fibrosarcoma and hemangioendothelial sarcoma also showed complete remission and are still alive after 39 and 26 months,respectively.A.annua was well tolerated without noticeable side effects.These four cases indicate that A.annua may be a promising herbal drug for cancer therapy.展开更多
In recent years,the popularity increased for nutritional supplements and herbal products.Prescription drugs,but not herbal therapies are paid by health insurances.They are sold over-the-counter(OTC)on the patients’ow...In recent years,the popularity increased for nutritional supplements and herbal products.Prescription drugs,but not herbal therapies are paid by health insurances.They are sold over-the-counter(OTC)on the patients’own expense.However,there are potential risks of self-medication,e.g.incorrect self-diagnosis,severe adverse reactions,dangerous drug interactions,risk of addiction etc.They are often used by patients at their own discretion without knowledge of and control by their physicians.Certain users are at risk of intoxication.Multiple medications taken by older patients increase the risk for adverse drug reactions,drug-drug interactions,and compliance problems for this age group(polypharmacy).Herbals should be discontinued prior to operations to avoid interactions with anesthetics or anticoagulants.Herbal preparations may also be carcinogenic or interfere with cancer treatments.Pregnant women use various OTC preparations.However,in many cases,it is unclear whether their use is safe for mother or baby.Self-medication with herbals is also largely distributed among anxious and depressive patients,and patients with other conditions and symptoms.The popularity of herbal products has also brought concerns on quality,efficacy and safety.Cases of botanical misidentification,contaminations with heavy metals,pesticides,radioactivity,organic solvents,microbials as well as adulteration with chemical drugs necessitate the establishment of international quality control standards.Hepatotoxic effects have been reported for more than 300 plant species,and some commonly used herbs have been demonstrated to interact with Western medication.Health care professionals have a critical responsibility assessing the self-care ability of their patients.Databases are available for pharmacists with information on action,side effects and toxicities as well as herbdrug interactions.There is a need for established guidelines regarding the correct use of nutritional supplements and herbal OTC preparations(phytovigilance).Physicians,pharmacists,and other health care professionals have to counsel patients and the general public on the benefits and risks associated with herbal drugs.Information centers for consumers and general practitioners are needed,and convincing evidence on safety and efficacy of herbal products has to be demonstrated in placebo-controlled,double blind and randomized clinical trials.展开更多
The enduring discussion,why plants produce secondary metabolites with pharmacologically and toxicologically active towards mammals traces back to the eminent role of medicinal plants in the millennia-old history of ma...The enduring discussion,why plants produce secondary metabolites with pharmacologically and toxicologically active towards mammals traces back to the eminent role of medicinal plants in the millennia-old history of manhood.In recent years,the concept of an animal plant warfare emerged,which focused on the co-evolution between plants and herbivores.As a reaction to herbivory,plants developed mechanical defenses such as thorns and hard shells,which paved the way for adapted animal physiques.Plants evolved further defense systems by producing chemicals that exert toxic effects on the animals that ingest them.As a result of this selective pressure,animals developed special enzymes,e.g.cytochrome P450 monooxigenases(CYP450)that metabolize xenobiotic phytochemicals.As a next step in the evolutionary competition between plants and animals,plants evolved to produce non-toxic pro-drugs,which become toxic only after ingestion by animals through metabolization by enzymes such as CYP450.Because these sequestered evolutionary developments call to mind an arms race,the term animal plant warfare has been coined.The evolutionary competition between plants and animals may help to better understand the modes of action of medicinal plants and to foster the efficient and safe use of phytotherapy nowadays.展开更多
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/...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/EC) on March 31st, 2004.Since April 30th,2011,all herbal展开更多
Sudanese folk medicine represents a unique blend of indigenous cultures with Islamic,Arabic and African traditions.In addition,Sudan encompasses different terrains and climatic zones,ranging from desert and semi-deser...Sudanese folk medicine represents a unique blend of indigenous cultures with Islamic,Arabic and African traditions.In addition,Sudan encompasses different terrains and climatic zones,ranging from desert and semi-desert in the north to equatorial with a short rainy season(semi-aridand semi-humid)in the centre to equatorial with a long rainy season(arid-humid and equatorial-humid)in the south.This variation contributes to the immense diversity of vegetation in the region.The flora of Sudan consists of 3137 species of flowering plants belonging to 170 families and 1280 genera.It is estimated that 15%of these plants are endemic to Sudan.The intersection of diverse cultures and the unique geography holds great potential for Sudanese herbal medicine.Medicinal and aromatic plants and their derivatives represent an integral part of life in Sudan.Indigenous remedies are the only form of therapy available to the majority of poor people.It has been estimated that only 11%of the population has access to formal health care.Therefore,research on the desired pharmacological effects and possible unwanted side effects or toxicity is required to improve efficacy and safety of Sudanese herbal medicine.In the future,it would be preferable to promote the use of traditional herbal remedies by conversion of raw plant material into more sophisticated products instead of completely replacing the traditional remedies with synthetic products from industrialized countries.The present review gives an overview of traditional Sudanese medicinal and aromatic herbs and their habitats,traditional uses,and phytochemical constituents.展开更多
The Gwich’in,which belong to the Athapaskan language group of Native Americans live in the borderland between Alaska and Canada.We analyzed 29 medicinal plants of this tribe for their growth inhibitory activity again...The Gwich’in,which belong to the Athapaskan language group of Native Americans live in the borderland between Alaska and Canada.We analyzed 29 medicinal plants of this tribe for their growth inhibitory activity against CCRF-CEM T-cell acute lymphoblastic leukemia(T-ALL)cells.The anti-leukemic activity of these plants has not been investigated as yet.Considering the poor cure rates of some ALL forms,there might be a great potential for medicinal plants as resource for natural products to treat T-ALL.We found that the hexane extracts of three plants revealed considerable growth inhibition on CCRF-CEM cells.The 50%inhibition concentrations(IC50)were 6.63±0.03μg/ml for Cladina mitis,8.65±0.38μg/ml for Picea mariana(needles),and 9.67±1.36μg/ml for Artemisia frigida.Further investigations are required to isolate the active constituents of these plants.展开更多
In Jordan,Salvia ceratophylla L.is traditionally used in the treatment of cancer,microbial infections,and urinary disorders.This study aimed:(1)to chemically characterize S.ceratophylla essential oil(EO)from South Jor...In Jordan,Salvia ceratophylla L.is traditionally used in the treatment of cancer,microbial infections,and urinary disorders.This study aimed:(1)to chemically characterize S.ceratophylla essential oil(EO)from South Jordan,by gas chromatography(GC)and gas chromatography-mass spectrometry(GC-MS);and(2)to evaluate in vitro the cytotoxic,anti-inflammatory,and antiprotozoal activities of the EO,it’s predominant components,and the hexane(A),ethyl acetate(B),methanol(C)and crude-methanol extracts(D).The analysis revealed that the EO has 71 compounds,with linalool(54.8%)as main constitu-ent.Only the hexane extract(A)showed some cytotoxic activity against SK-MEL,KB,BT-549,SK-OV-3,LLC-PK1 and VERO cells lines with IC50 between 60 and>100μg/mL.The EO inhibited NO production(IC5090μg/mL)and NF-κB activity(IC5038μg/mL).The extracts A,B,and D inhibited NO production and NF-κB activity with IC50 between 32 and 150μg/mL.Linalool considerably inhibited NO production(IC5018μg/mL).The extracts tested did not exhibit antileish-manial activity.Regarding antitrypanosomal activity,the EO exhibited significant results with IC502.65μg/mL.In conclu-sion,Jordan S.ceratophylla EO represents a rich source of linalool and bears a promising therapeutic potential for further antitrypanosomal drug development.展开更多
Carnosic acid(CA)is a natural phenolic diterpene mainly occurring in some species of the Lamiaceae family.Numerous studies described the cytotoxicity of CA towards different types of cancer both in vitro and in vivo.P...Carnosic acid(CA)is a natural phenolic diterpene mainly occurring in some species of the Lamiaceae family.Numerous studies described the cytotoxicity of CA towards different types of cancer both in vitro and in vivo.Particularly,the influence of CA in combination with other drugs,vitamins or natural products through affecting various targets has raised interest.Current experimental in vivo data suggested that CA may cooperate with clinically used anticancer drugs promoting their activity against cancer.From this point of view,CA gained importance,because it may alter pharmacodynamic profiles of various agents in the case of their co-administration,and thereby,act in a potentially synergistic manner,which can provide a basis for potential applications of CA in the management of cancer.In the present review,we give an overview of CA as well as CA co-treatment regimens with a special focus on cancer.In this context,the role of CA as an adjuvant treatment alternative is highlighted.展开更多
We investigated the antioxidant potential and cytotoxicity towards human CCRF-CEM leukemia cells of 57 extracts obtained from 18 plants collected in the Erkowit region,eastern Sudan.The antioxidant activity was determ...We investigated the antioxidant potential and cytotoxicity towards human CCRF-CEM leukemia cells of 57 extracts obtained from 18 plants collected in the Erkowit region,eastern Sudan.The antioxidant activity was determined by measuring the radical scavenging effects against 2,2-diphenyl-1-picrylhydrazyl(DPPH)and N,N-dimethyl-p-phenylendi-amine(DMPD),metal-chelation capacity,ferric-reducing(FRAP)and phosphomolibdenum-reducing antioxidant power(PRAP)methods using ELISA microtiter assays.Total phenol and flavonoid amounts of the extracts were determined spectrophotometrically.Cytotoxicity towards CCRF-CEM cells was evaluated by the resazurin reduction assay.Geranium favosum followed by Kalanchoe glaucescens,Malva parviflora,Aizoon canariense,and Coleus barbatus,respectively,possessed the highest antioxidant activity among the studied plants.Chrozophora oblongifolia and K.glaucescens exerted considerable cytotoxicity against CCRF-CEM leukemia cells.These plants may serve as source for the further development of natural antioxidant and antitumor agents.展开更多
P-Glycoprotein/MDR1 represents an important component of the blood brain barrier and contributes to multidrug resistance.We investigated two derivatives of the anti-malarial artemisinin,SM616 and GHP-AJM-3/23,concerni...P-Glycoprotein/MDR1 represents an important component of the blood brain barrier and contributes to multidrug resistance.We investigated two derivatives of the anti-malarial artemisinin,SM616 and GHP-AJM-3/23,concerning their ability to interact with P-glycoprotein.The ability of the two compounds to inhibit P-glycoprotein(P-gp)activity was examined in sensitive CCRF-CEM and P-gp over-expressing and multidrug-resistant CEM/ADR5000 cells as well as in porcine brain capillary endothelial cells(PBCEC)by means of calcein-AM assays.Verapamil as well-known P-gp inhibitor was used as control drug.CEM/ADR5000 cells exhibited cross-resistance to GHP-AJM-3/23,but slight collateral sensitivity to SM616.Furthermore,SM616 inhibited calcein efflux both in CEM/ADR5000 and PBCEC,whereas GHP-AJM-3/23 did only increase calcein fluorescence in PBCEC,but not CEM/ADR5000.This may be explained by the fact that CEM/ADR5000 only express P-gp but not other ATP-binding cassette transporters,whereas PBCEC are known to express several ABC transporters and calcein is transported by more than one ABC transporter.Hence,SM616 may be the more specific P-gp inhibitor.In conclusion,the collateral sensitivity of SM616 as well as the inhibition of calcein efflux in both CEM/ADR5000 cells and PBCEC indicate that this compound may be a promising P-gp inhibitor to treat cancer therapy and to overcome the blood brain barrier.展开更多
Multidrug resistance(MDR)mediated by ATP binding cassette subfamily B member 1(ABCB1)is significantly hindering effective cancer chemotherapy.However,currently,no ABCB1-inhibitory drugs have been approved to treat MDR...Multidrug resistance(MDR)mediated by ATP binding cassette subfamily B member 1(ABCB1)is significantly hindering effective cancer chemotherapy.However,currently,no ABCB1-inhibitory drugs have been approved to treat MDR cancer clinically,mainly due to the inhibitor specificity,toxicity,and drug interactions.Here,we reported that three polyoxypregnanes(POPs)as the most abundant constituents of Marsdenia tenacissima(M.tenacissima)were novel ABCB1-modulatory pro-drugs,which underwent intestinal microbiota-mediated biotransformation in vivo to generate active metabolites.The metabolites at non-toxic concentrations restored chemosensitivity in ABCB1-overexpressing cancer cells via inhibiting ABCB1 efflux activity without changing ABCB1 protein expression,which were further identified as specific non-competitive inhibitors of ABCB1 showing multiple binding sites within ABCB1 drug cavity.These POPs did not exhibit ABCB1/drug metabolizing enzymes interplay,and their repeated administration generated predictable pharmacokinetic interaction with paclitaxel without obvious toxicity in vivo.We further showed that these POPs enhanced the accumulation of paclitaxel in tumors and overcame ABCB1-mediated chemoresistance.The results suggested that these POPs had the potential to be developed as safe,potent,and specific pro-drugs to reverse ABCB1-mediated MDR.Our work also provided scientific evidence for the use of M.tenacissima in combinational chemotherapy.展开更多
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-b...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.g.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.展开更多
Polo-like kinase(PLK1) has been identified as a potential target for cancer treatment.Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harb...Polo-like kinase(PLK1) has been identified as a potential target for cancer treatment.Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain(PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethylbenzofuran-2-carboxylic acid ethyl ester(designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1 PBD was confirmed using fluorescence polarization and microscale thermophoresis.This compound exerted specificity towards PLK1 over PLK2 and PLK3. MCC1019 showed cytotoxic activity in a panel of different cancer cell lines. Mechanistic investigations in A549 lung adenocarcinoma cells revealed that MCC1019 induced cell growth inhibition through inactivation of AKT signaling pathway, it also induced prolonged mitotic arrest—a phenomenon known as mitotic catastrophe, which is followed by immediate cell death via apoptosis and necroptosis. MCC1019 significantly inhibited tumor growth in vivo in a murine lung cancer model without affecting body weight or vital organ size, and reduced the growth of metastatic lesions in the lung. We propose MCC1019 as promising anti-cancer drug candidate.展开更多
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 ...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.展开更多
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 focu...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 their efficacy, reasonable use and unreasonable abuse specific to different patients with different symptoms. The scientific investigation on efficacy and safety of Chinese formulas will propel the acceptance and spread of TCM in the western world for the sake of patients worldwide.展开更多
Objective: To prove specific effects of acupuncture on chronic pain. It was speculated that the potential specific effectiveness of acupuncture could be better shown in more properly designed studies. Therefore, diagn...Objective: To prove specific effects of acupuncture on chronic pain. It was speculated that the potential specific effectiveness of acupuncture could be better shown in more properly designed studies. Therefore, diagnoses of both Western medicine and traditional Chinese medicine (TCM) were used as inclusion criteria to allocate acupoints more precisely to the complaints of the patients. Secondly, objectively measurable parameters of pain relief in addition to usual Visual Analogue Scale (VAS) were chosen to quantify the effects of acupuncture. Methods: The study was prospective, randomized, controlled and single-blinded. Eighteen patients with chronic back pain and TCM diagnosis of a Taiyang/Yangming syndrome received one single session of acupuncture chosen according to TCM diagnosis or acupuncture on points outside the meridian system (controls). We evaluated pain via VAS and increased mobility via inclinometry of the back. Results: Although the sample size was small, there was a statistically significant improvement in pain and mobility in the intervention group (n=13), but not in the control group (n=5). The calculated sample size adequate power was lower for inclinometry than for VAS, indicating that VAS is less probable to discriminate acupuncture effects. Conclusion: Objectively measurable physical parameters such as the angle of flexion before and after acupuncture (inclinometry) may be more suitable to measure pain relief than subjective assessment by VAS in acupuncture studies. TCM diagnosis may be a helpful inclusion criterion in studies on acupuncture, so as to potentially allocate interventions better to the complaints of patients.展开更多
文摘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.
文摘Artemisinin,a constituent of Artemisia annua L.,is a well-known antimalarial drug.Artemisinin-type drugs also inhibit cancer growth in vitro and in vivo.Herbal extracts of A.annua inhibit the growth of cancer cell lines.Here,we report on the use of capsules containing powder of Herba Artemisiae annuae to treat pet sarcoma.The surgical tumor removal as standard treatment was supplemented by adjuvant therapy with A.annua.One cat and one dog with fibrosarcoma survived 40 and 37 months,respectively,without tumor relapse.Two other dogs suffering from fibrosarcoma and hemangioendothelial sarcoma also showed complete remission and are still alive after 39 and 26 months,respectively.A.annua was well tolerated without noticeable side effects.These four cases indicate that A.annua may be a promising herbal drug for cancer therapy.
文摘In recent years,the popularity increased for nutritional supplements and herbal products.Prescription drugs,but not herbal therapies are paid by health insurances.They are sold over-the-counter(OTC)on the patients’own expense.However,there are potential risks of self-medication,e.g.incorrect self-diagnosis,severe adverse reactions,dangerous drug interactions,risk of addiction etc.They are often used by patients at their own discretion without knowledge of and control by their physicians.Certain users are at risk of intoxication.Multiple medications taken by older patients increase the risk for adverse drug reactions,drug-drug interactions,and compliance problems for this age group(polypharmacy).Herbals should be discontinued prior to operations to avoid interactions with anesthetics or anticoagulants.Herbal preparations may also be carcinogenic or interfere with cancer treatments.Pregnant women use various OTC preparations.However,in many cases,it is unclear whether their use is safe for mother or baby.Self-medication with herbals is also largely distributed among anxious and depressive patients,and patients with other conditions and symptoms.The popularity of herbal products has also brought concerns on quality,efficacy and safety.Cases of botanical misidentification,contaminations with heavy metals,pesticides,radioactivity,organic solvents,microbials as well as adulteration with chemical drugs necessitate the establishment of international quality control standards.Hepatotoxic effects have been reported for more than 300 plant species,and some commonly used herbs have been demonstrated to interact with Western medication.Health care professionals have a critical responsibility assessing the self-care ability of their patients.Databases are available for pharmacists with information on action,side effects and toxicities as well as herbdrug interactions.There is a need for established guidelines regarding the correct use of nutritional supplements and herbal OTC preparations(phytovigilance).Physicians,pharmacists,and other health care professionals have to counsel patients and the general public on the benefits and risks associated with herbal drugs.Information centers for consumers and general practitioners are needed,and convincing evidence on safety and efficacy of herbal products has to be demonstrated in placebo-controlled,double blind and randomized clinical trials.
文摘The enduring discussion,why plants produce secondary metabolites with pharmacologically and toxicologically active towards mammals traces back to the eminent role of medicinal plants in the millennia-old history of manhood.In recent years,the concept of an animal plant warfare emerged,which focused on the co-evolution between plants and herbivores.As a reaction to herbivory,plants developed mechanical defenses such as thorns and hard shells,which paved the way for adapted animal physiques.Plants evolved further defense systems by producing chemicals that exert toxic effects on the animals that ingest them.As a result of this selective pressure,animals developed special enzymes,e.g.cytochrome P450 monooxigenases(CYP450)that metabolize xenobiotic phytochemicals.As a next step in the evolutionary competition between plants and animals,plants evolved to produce non-toxic pro-drugs,which become toxic only after ingestion by animals through metabolization by enzymes such as CYP450.Because these sequestered evolutionary developments call to mind an arms race,the term animal plant warfare has been coined.The evolutionary competition between plants and animals may help to better understand the modes of action of medicinal plants and to foster the efficient and safe use of phytotherapy nowadays.
文摘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/EC) on March 31st, 2004.Since April 30th,2011,all herbal
文摘Sudanese folk medicine represents a unique blend of indigenous cultures with Islamic,Arabic and African traditions.In addition,Sudan encompasses different terrains and climatic zones,ranging from desert and semi-desert in the north to equatorial with a short rainy season(semi-aridand semi-humid)in the centre to equatorial with a long rainy season(arid-humid and equatorial-humid)in the south.This variation contributes to the immense diversity of vegetation in the region.The flora of Sudan consists of 3137 species of flowering plants belonging to 170 families and 1280 genera.It is estimated that 15%of these plants are endemic to Sudan.The intersection of diverse cultures and the unique geography holds great potential for Sudanese herbal medicine.Medicinal and aromatic plants and their derivatives represent an integral part of life in Sudan.Indigenous remedies are the only form of therapy available to the majority of poor people.It has been estimated that only 11%of the population has access to formal health care.Therefore,research on the desired pharmacological effects and possible unwanted side effects or toxicity is required to improve efficacy and safety of Sudanese herbal medicine.In the future,it would be preferable to promote the use of traditional herbal remedies by conversion of raw plant material into more sophisticated products instead of completely replacing the traditional remedies with synthetic products from industrialized countries.The present review gives an overview of traditional Sudanese medicinal and aromatic herbs and their habitats,traditional uses,and phytochemical constituents.
文摘The Gwich’in,which belong to the Athapaskan language group of Native Americans live in the borderland between Alaska and Canada.We analyzed 29 medicinal plants of this tribe for their growth inhibitory activity against CCRF-CEM T-cell acute lymphoblastic leukemia(T-ALL)cells.The anti-leukemic activity of these plants has not been investigated as yet.Considering the poor cure rates of some ALL forms,there might be a great potential for medicinal plants as resource for natural products to treat T-ALL.We found that the hexane extracts of three plants revealed considerable growth inhibition on CCRF-CEM cells.The 50%inhibition concentrations(IC50)were 6.63±0.03μg/ml for Cladina mitis,8.65±0.38μg/ml for Picea mariana(needles),and 9.67±1.36μg/ml for Artemisia frigida.Further investigations are required to isolate the active constituents of these plants.
基金supported by Foundation for Science and Technology(FCT)Portugal(Strategic Projects UID/NEU/04539/2013,and UID/NEU/04539/2019,UIDB/04539/2020 and UIDP/04539/2020(CIBB)).
文摘In Jordan,Salvia ceratophylla L.is traditionally used in the treatment of cancer,microbial infections,and urinary disorders.This study aimed:(1)to chemically characterize S.ceratophylla essential oil(EO)from South Jordan,by gas chromatography(GC)and gas chromatography-mass spectrometry(GC-MS);and(2)to evaluate in vitro the cytotoxic,anti-inflammatory,and antiprotozoal activities of the EO,it’s predominant components,and the hexane(A),ethyl acetate(B),methanol(C)and crude-methanol extracts(D).The analysis revealed that the EO has 71 compounds,with linalool(54.8%)as main constitu-ent.Only the hexane extract(A)showed some cytotoxic activity against SK-MEL,KB,BT-549,SK-OV-3,LLC-PK1 and VERO cells lines with IC50 between 60 and>100μg/mL.The EO inhibited NO production(IC5090μg/mL)and NF-κB activity(IC5038μg/mL).The extracts A,B,and D inhibited NO production and NF-κB activity with IC50 between 32 and 150μg/mL.Linalool considerably inhibited NO production(IC5018μg/mL).The extracts tested did not exhibit antileish-manial activity.Regarding antitrypanosomal activity,the EO exhibited significant results with IC502.65μg/mL.In conclu-sion,Jordan S.ceratophylla EO represents a rich source of linalool and bears a promising therapeutic potential for further antitrypanosomal drug development.
文摘Carnosic acid(CA)is a natural phenolic diterpene mainly occurring in some species of the Lamiaceae family.Numerous studies described the cytotoxicity of CA towards different types of cancer both in vitro and in vivo.Particularly,the influence of CA in combination with other drugs,vitamins or natural products through affecting various targets has raised interest.Current experimental in vivo data suggested that CA may cooperate with clinically used anticancer drugs promoting their activity against cancer.From this point of view,CA gained importance,because it may alter pharmacodynamic profiles of various agents in the case of their co-administration,and thereby,act in a potentially synergistic manner,which can provide a basis for potential applications of CA in the management of cancer.In the present review,we give an overview of CA as well as CA co-treatment regimens with a special focus on cancer.In this context,the role of CA as an adjuvant treatment alternative is highlighted.
文摘We investigated the antioxidant potential and cytotoxicity towards human CCRF-CEM leukemia cells of 57 extracts obtained from 18 plants collected in the Erkowit region,eastern Sudan.The antioxidant activity was determined by measuring the radical scavenging effects against 2,2-diphenyl-1-picrylhydrazyl(DPPH)and N,N-dimethyl-p-phenylendi-amine(DMPD),metal-chelation capacity,ferric-reducing(FRAP)and phosphomolibdenum-reducing antioxidant power(PRAP)methods using ELISA microtiter assays.Total phenol and flavonoid amounts of the extracts were determined spectrophotometrically.Cytotoxicity towards CCRF-CEM cells was evaluated by the resazurin reduction assay.Geranium favosum followed by Kalanchoe glaucescens,Malva parviflora,Aizoon canariense,and Coleus barbatus,respectively,possessed the highest antioxidant activity among the studied plants.Chrozophora oblongifolia and K.glaucescens exerted considerable cytotoxicity against CCRF-CEM leukemia cells.These plants may serve as source for the further development of natural antioxidant and antitumor agents.
文摘P-Glycoprotein/MDR1 represents an important component of the blood brain barrier and contributes to multidrug resistance.We investigated two derivatives of the anti-malarial artemisinin,SM616 and GHP-AJM-3/23,concerning their ability to interact with P-glycoprotein.The ability of the two compounds to inhibit P-glycoprotein(P-gp)activity was examined in sensitive CCRF-CEM and P-gp over-expressing and multidrug-resistant CEM/ADR5000 cells as well as in porcine brain capillary endothelial cells(PBCEC)by means of calcein-AM assays.Verapamil as well-known P-gp inhibitor was used as control drug.CEM/ADR5000 cells exhibited cross-resistance to GHP-AJM-3/23,but slight collateral sensitivity to SM616.Furthermore,SM616 inhibited calcein efflux both in CEM/ADR5000 and PBCEC,whereas GHP-AJM-3/23 did only increase calcein fluorescence in PBCEC,but not CEM/ADR5000.This may be explained by the fact that CEM/ADR5000 only express P-gp but not other ATP-binding cassette transporters,whereas PBCEC are known to express several ABC transporters and calcein is transported by more than one ABC transporter.Hence,SM616 may be the more specific P-gp inhibitor.In conclusion,the collateral sensitivity of SM616 as well as the inhibition of calcein efflux in both CEM/ADR5000 cells and PBCEC indicate that this compound may be a promising P-gp inhibitor to treat cancer therapy and to overcome the blood brain barrier.
基金supported by Health and Medical Research Fund(HHSRF Project No.08090481,Hong Kong SAR,China)from Food and Health Bureau,HKSAROne-off Funding for Joint Lab/Research collaboration(Project code:3132968,Hong Kong SAR,China)from the Chinese University of Hong KongSeed Fund for Joint Establishments from School of Biomedical Science,the Chinese University of Hong Kong(China)
文摘Multidrug resistance(MDR)mediated by ATP binding cassette subfamily B member 1(ABCB1)is significantly hindering effective cancer chemotherapy.However,currently,no ABCB1-inhibitory drugs have been approved to treat MDR cancer clinically,mainly due to the inhibitor specificity,toxicity,and drug interactions.Here,we reported that three polyoxypregnanes(POPs)as the most abundant constituents of Marsdenia tenacissima(M.tenacissima)were novel ABCB1-modulatory pro-drugs,which underwent intestinal microbiota-mediated biotransformation in vivo to generate active metabolites.The metabolites at non-toxic concentrations restored chemosensitivity in ABCB1-overexpressing cancer cells via inhibiting ABCB1 efflux activity without changing ABCB1 protein expression,which were further identified as specific non-competitive inhibitors of ABCB1 showing multiple binding sites within ABCB1 drug cavity.These POPs did not exhibit ABCB1/drug metabolizing enzymes interplay,and their repeated administration generated predictable pharmacokinetic interaction with paclitaxel without obvious toxicity in vivo.We further showed that these POPs enhanced the accumulation of paclitaxel in tumors and overcame ABCB1-mediated chemoresistance.The results suggested that these POPs had the potential to be developed as safe,potent,and specific pro-drugs to reverse ABCB1-mediated MDR.Our work also provided scientific evidence for the use of M.tenacissima in combinational chemotherapy.
文摘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.g.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.
基金partly supported by the Deutsche Forschungsgemeinschaft(DFG INST 268/281-1 FUGG and BE 4572/3-1,Germany)
文摘Polo-like kinase(PLK1) has been identified as a potential target for cancer treatment.Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain(PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethylbenzofuran-2-carboxylic acid ethyl ester(designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1 PBD was confirmed using fluorescence polarization and microscale thermophoresis.This compound exerted specificity towards PLK1 over PLK2 and PLK3. MCC1019 showed cytotoxic activity in a panel of different cancer cell lines. Mechanistic investigations in A549 lung adenocarcinoma cells revealed that MCC1019 induced cell growth inhibition through inactivation of AKT signaling pathway, it also induced prolonged mitotic arrest—a phenomenon known as mitotic catastrophe, which is followed by immediate cell death via apoptosis and necroptosis. MCC1019 significantly inhibited tumor growth in vivo in a murine lung cancer model without affecting body weight or vital organ size, and reduced the growth of metastatic lesions in the lung. We propose MCC1019 as promising anti-cancer drug candidate.
基金funded by the grant from Deutsche Forschungsgemeinschaft,(GRK2015/2)。
文摘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.
基金funded by the Deutsche Forschungsgemeinschaft,grant 2015/1(GRK"Life Science-Life Writing")
文摘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 their efficacy, reasonable use and unreasonable abuse specific to different patients with different symptoms. The scientific investigation on efficacy and safety of Chinese formulas will propel the acceptance and spread of TCM in the western world for the sake of patients worldwide.
文摘Objective: To prove specific effects of acupuncture on chronic pain. It was speculated that the potential specific effectiveness of acupuncture could be better shown in more properly designed studies. Therefore, diagnoses of both Western medicine and traditional Chinese medicine (TCM) were used as inclusion criteria to allocate acupoints more precisely to the complaints of the patients. Secondly, objectively measurable parameters of pain relief in addition to usual Visual Analogue Scale (VAS) were chosen to quantify the effects of acupuncture. Methods: The study was prospective, randomized, controlled and single-blinded. Eighteen patients with chronic back pain and TCM diagnosis of a Taiyang/Yangming syndrome received one single session of acupuncture chosen according to TCM diagnosis or acupuncture on points outside the meridian system (controls). We evaluated pain via VAS and increased mobility via inclinometry of the back. Results: Although the sample size was small, there was a statistically significant improvement in pain and mobility in the intervention group (n=13), but not in the control group (n=5). The calculated sample size adequate power was lower for inclinometry than for VAS, indicating that VAS is less probable to discriminate acupuncture effects. Conclusion: Objectively measurable physical parameters such as the angle of flexion before and after acupuncture (inclinometry) may be more suitable to measure pain relief than subjective assessment by VAS in acupuncture studies. TCM diagnosis may be a helpful inclusion criterion in studies on acupuncture, so as to potentially allocate interventions better to the complaints of patients.