The mental health issues of college students have become an increasingly prominent social problem,exerting severe impacts on their academic performance and overall well-being.Early identification of Interpersonal Sens...The mental health issues of college students have become an increasingly prominent social problem,exerting severe impacts on their academic performance and overall well-being.Early identification of Interpersonal Sensitivity(IS)in students serves as an effective approach to detect psychological problems and provide timely intervention.In this study,958 freshmen from higher education institutions in Zhejiang Province were selected as participants.We proposed a Multi-Strategy Artemisinin Optimization(MSAO)algorithm by enhancing the Artemisinin Optimization(AO)framework through the integration of a group-guided elimination strategy and a two-stage consolidation strategy.Subsequently,the MSAO was combined with the Fuzzy K-Nearest Neighbor(FKNN)classifier to develop the bMSAO-FKNN predictive model for assessing college students’IS.The proposed algorithm’s efficacy was validated through the CEC 2017 benchmark test suite,while the model’s performance was evaluated on the IS dataset,achieving an accuracy rate of 97.81%.These findings demonstrate that the bMSAO-FKNN model not only ensures high predictive accuracy but also offers interpretability for IS prediction,making it a valuable tool for mental health monitoring in academic settings.展开更多
Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug re...Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug resistance often leads to recurrence,underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates.Artemisinin(ART)has demonstrated efficacy in inhibiting the growth of drug-resistant cells,positioning art as a viable option for counteracting endocrine resistance.This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental validation.Five characterized genes(ar,cdkn1a,erbb2,esr1,hsp90aa1)and seven drug-disease crossover genes(cyp2e1,rorc,mapk10,glp1r,egfr,pgr,mgll)were identified using WGCNA crossover analysis.Subsequent functional enrichment analyses were conducted.Our findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and-sensitized patients.scRNA-seq analysis revealed high expression of key cluster genes in epithelial cells,suggesting artemisinin’s specific impact on tumor cells in estrogen receptor(ER)-positive BC tissues.Molecular target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance genes.These results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.展开更多
Artemisinin(ART)resistance has been an emerging clinical problem,severely compromising antimalarial efficacy and threatening the global malaria elimination campaign.Albeit intensive studies about the molecular mechani...Artemisinin(ART)resistance has been an emerging clinical problem,severely compromising antimalarial efficacy and threatening the global malaria elimination campaign.Albeit intensive studies about the molecular mechanism for ART resistance are under way,no effective therapeutic targets for reversing resistance have been applied.Here,we explore glutathione(GSH)as a therapeutic target to develop a thermo-responsive nanoplatform to specifically co-deliver ART and GSH synthesis inhibitor(L-buthionine sulfoximine,BSO)in a sustained manner,effectively reversing ART resistance in vivo.By combining with BSO,ART exerts increased antimalarial activity with reduced half-maximal inhibitory concentration(IC50)by 7.43-fold in ART-resistant strains.This work reveals that the GSH in ART-resistant parasites can be a promising therapeutic target for reversing ART resistance,paving the way for developing drug candidates and intelligent nanomedicines in malaria therapy.展开更多
The biotransformation of artemisinin by hairy root cultures ofRheum palmatum L. was investigated for the first time. The main product, deoxyartemisinin, was isolated and characterized on the basis of its spectral data.
The artemisinin accumulation in the hairy root cultures of Artemisia annua L. was enhanced via a treatment of three fungal elicitors separately ( Verticillium dahliae Kleb., Rhizopus stolonifer (Ehrenb. ex ...The artemisinin accumulation in the hairy root cultures of Artemisia annua L. was enhanced via a treatment of three fungal elicitors separately ( Verticillium dahliae Kleb., Rhizopus stolonifer (Ehrenb. ex Fr.) Vuill and Colletotrichum dematium (Pers.) Grove). Among these three elicitors, V. dahliae had the highest inducing efficiency, but none of them manifests any noticeable effects on the cell growth of the hairy root cultures. The artemisinin content of the hairy root cultures treated with V. dahliae elicitor was 1.12 mg/g DW, which was 45% higher than the control (0.77 mg/g DW). The results showed that elicitation was dependent on the elicitor concentration, the incubation period and the physiological stage at which the hairy root cultures were treated. In addition, the authors found that for V. dahliae , the optimum concentration was 0.4 mg carbohydrate per millilitre medium, the strongest response of A. annua hairy root cultures to the elicitation was at the late exponential growth stage, and the highest artemisinin content of the hairy root cultures was on the 4th day post treatment.展开更多
The oligosaccharide elicitor from the mycelial wall of an endophytic Colletotrichum sp. B501 promoted the production of artemisinin in Artemisia annua L. hairy root culture. When hairy roots of 22-day-old cultures (la...The oligosaccharide elicitor from the mycelial wall of an endophytic Colletotrichum sp. B501 promoted the production of artemisinin in Artemisia annua L. hairy root culture. When hairy roots of 22-day-old cultures (later growth phase) were exposed to the elicitor (20 mg/L) for 4 d, the maximum content of artemisinin reached 1.15 mg/g, a 64.29% increment over the control. The electron X-ray microanalysis disclosed the rapid accumulation of Ca 2+ in the elicited cortical cells of hairy root. The electronic microscope observation revealed the high electron density area in vacuole of elicited cells. During the first day of elicitation the peroxidase activity of hairy roots was improved sharply. Some cellular morphological changes including cell shrinkage, condensation of cytoplasm and nuclear fragmentation, coincident with the appearance of DNA ladders, were observed after the third day of elicitation. It was suggested that the oligosaccharide elicitor triggered the programmed cell death, which may provide the substance or chemical signal for artemisinin biosynthesis.展开更多
Cancer is the leading cause of human death which seriously threatens human life.The antimalarial drug artemisinin and its derivatives have been discovered with considerable anticancer properties.Simultaneously,a varie...Cancer is the leading cause of human death which seriously threatens human life.The antimalarial drug artemisinin and its derivatives have been discovered with considerable anticancer properties.Simultaneously,a variety of target-selective artemisinin-related compounds with high efficiency have been discovered.Many researches indicated that artemisinin-related compounds have cytotoxic effects against a variety of cancer cells through pleiotropic effects,including inhibiting the proliferation of tumor cells,promoting apoptosis,inducing cell cycle arrest,disrupting cancer invasion and metastasis,preventing angiogenesis,mediating the tumor-related signaling pathways,and regulating tumor microenvironment.More importantly,artemisinins demonstrated minor side effects to normal cells and manifested the ability to overcome multidrug-resistance which is widely observed in cancer patients.Therefore,we concentrated on the new advances and development of artemisinin and its derivatives as potential antitumor agents in recent 5 years.It is our hope that this review could be helpful for further exploration of novel artemisinin-related antitumor agents.展开更多
Rabies is caused by infection of rabies virus(RABV)and remains a serious threat to the global public health.Except for the requirement for cold chain and high cost of human rabies immune globulin,no small molecule dru...Rabies is caused by infection of rabies virus(RABV)and remains a serious threat to the global public health.Except for the requirement for cold chain and high cost of human rabies immune globulin,no small molecule drugs are currently available for clinical treatment of rabies.So,it is of great importance to identify novel compounds that can effectively inhibit RABV infection.Artesunate(ART)and dihydroartemisinin(DHA),two derivatives of artemisinin,are widely used for treatment of malaria in adults and children,showing high safety.In this study,we found that both ART and DHA were able to inhibit RABV replication in host cells at a low concentration(0.1μmol/L).The antiviral effects of ART and DHA were independent of viral strains and cell lines.Pre-treatment with ART or DHA for 2 h in vitro did not affect the viral replication in host cells,implying that ART and DHA neither reduced the viability of RABV directly nor inhibited the binding and entrance of the virus to host cells.Further studies revealed that ART and DHA inhibited RABV genomic RNA synthesis and viral gene transcription.Treatment with ART or DHA(5 mg/kg)by intramuscular injection improved,to some extent,the survival rate of RABV-challenged mice.Combination treatment with derivatives of artemisinin and mannitol significantly improved the survival rate of RABV-challenged mice.The results suggest that ART and DHA have a great potential to be explored as new anti-rabies agents for treatment of rabies.展开更多
Having faced increased clinical treatment failures with dihydroartemisinin-piperaquine(DHA-PPQ),Cambodia swapped the first line artemisinin-based combination therapy(ACT)from DHA-PPQ to artesunate-mefloquine given tha...Having faced increased clinical treatment failures with dihydroartemisinin-piperaquine(DHA-PPQ),Cambodia swapped the first line artemisinin-based combination therapy(ACT)from DHA-PPQ to artesunate-mefloquine given that parasites resistant to piperaquine are susceptible to mefloquine.However,triple mutants have now emerged,suggesting that drug rotations may not be adequate to keep resistance at bay.There is,therefore,an urgent need for alternative treatment strategies to tackle resistance and prevent its spread.A proper understanding of all contributors to artemisinin resistance may help us identify novel strategies to keep artemisinins effective until new drugs become available for their replacement.This review highlights the role of the key players in artemisinin resistance,the current strategies to deal with it and suggests ways of protecting future antimalarial drugs from bowing to resistance as their predecessors did.展开更多
Artemisinin（ART） is a widely used active drug for malaria, including severe and cerebral malaria. However, its therapeutic efficacy is affected by its lower bioavailability. In the present study, nanostructured lipi...Artemisinin（ART） is a widely used active drug for malaria, including severe and cerebral malaria. However, its therapeutic efficacy is affected by its lower bioavailability. In the present study, nanostructured lipid carriers（NLCs） were proposed as carrier of ART to improve pharmacokinetic properties of the drug. ART-NLC was prepared by high-pressure homogenization based on orthogonal design. The particle size, zeta potential, encapsulation efficiency（EE） and percentage of drug loading（DL） of ART-NLC were（53.06±2.11） nm,（–28.7±3.59） m V, 73.9%±0.5% and 11.23%±0.37%, respectively. ART-NLC showed the sustained release characteristics and scarcely the hemolysis effect on human red blood cells. The pharmacokinetics of ART-NLC for rats after tail intravenous injection（i.v） or intraperitoneal injection（i.p） were investigated by liquid chromatography-tandem mass spectroscopy（LC-MS/MS）. And ART solution was designed as control preparation. For rats of i.v groups, the AUC0–∞（（707.45±145.65） ng·h/m L） of ART-NLC were significantly bigger than that of ART（（368.98±139.58） ng·h/m L）. The MRT（（3.38±0.46） h） of ART-NLC was longer than that of ART（（1.39±0.61） h）. And similar results were observed for rats of i.p groups. The AUC0–∞（（1233.06±235.57） ng·h/m L） and MRT（（4.97±0.69） h） of ART-NLC were both bigger than those of ART, which were（871.17±234.03） ng·h/m L） and（1.75±0.31） h）, respectively. Compared with ART, ART-NLC showed a significant increase in AUC0–∞（P〈0.05） and MRT（P〈0.001） for both i.p and tail i.v administrations.展开更多
[Objective] The aim was to make a summary on research progresses on extraction and detection techniques of artemisinin. [Method] In the research, the concerning progress was made based on physicochemical property, sou...[Objective] The aim was to make a summary on research progresses on extraction and detection techniques of artemisinin. [Method] In the research, the concerning progress was made based on physicochemical property, source, extraction methods and detection technology of artemisinin. [Result] Artemisinin is colorless acicular crystal and easier to be dissolved in organic solvent. The extraction methods of artemisinin include organic solvent extraction, ultrasonic extraction, microwave extraction and supercritical fluid extraction; the detection technologies include ultraviolet spectrophotometry, high performance liquid chromatography and HPLC-evaporative light-scattering. [Conclusion] The research laid foundation for further exploration and global market.展开更多
Artemisinin and its derivatives represent the most important and influential class of drugs in the fight against malaria. Since the discovery of artemisinin in the early 1970s, the global community has made great stri...Artemisinin and its derivatives represent the most important and influential class of drugs in the fight against malaria. Since the discovery of artemisinin in the early 1970s, the global community has made great strides in characterizing and understanding this remarkable phytochemical and its unique chemical and pharmacological properties. Today, even as artemisinin continues to serve as the foundation for antimalarial therapy, numerous challenges have surfaced in the continued application and development of this family of drugs. These challenges include the emergence of delayed treatment responses to artemisinins in malaria and efforts to apply artemisinins for non-malarial indications. Here, we provide an overview of the story of artemisinin in terms of its past, present, and future. In particular, we comment on the current understanding of the mechanism of action (MOA) of artemisinins, and emphasize the importance of relating mechanistic studies to therapeutic outcomes, both in malarial and non-malarial contexts.展开更多
The effects of different cadmium （Cd） concentrations （0, 20, 60, and 100 μmol/L） on hydroponically grown Artemisia annua L. were investigated. Cd treatments applied for 0, 4, 12, 24, 72, 144, 216, and 336 hr were...The effects of different cadmium （Cd） concentrations （0, 20, 60, and 100 μmol/L） on hydroponically grown Artemisia annua L. were investigated. Cd treatments applied for 0, 4, 12, 24, 72, 144, 216, and 336 hr were assessed by measuring the changes in photosynthetic pigments, electrolyte leakage, malondialdehyde （MDA） and antioxidants （ascorbic acid and glutathione）, while the artemisinin content was tested after 0, 12, 144, 216, and 336 hr. A significant decrease was observed in photosynthetic pigment levels over time with increasing Cd concentration. Chlorophyll b levels were more affected by Cd than were chlorophyll a or carotenoid levels. The cell membrane was sensitive to Cd stress, as MDA content in all treatment groups showed insignificant differences from the control group, except at 12 hr treatment time. Ascorbic acid （AsA） content changed slightly over time, while glutathione （GSH） content took less time to reach a maximum as Cd concentration increased. Cd was found to promote synthesis and accumulation of artemisinin, especially at concentrations of 20 and 100 ~tmol/L. In conclusion, Cd stress can damage to photosynthetic pigments, and vigorously growing A. annua showed a strong tolerance for Cd stress. Appropriate amounts of added Cd aided synthesis and accumulation of artemisinin.展开更多
Artemisinin, also named qinghaosu, is a family of sesquiterpene trioxane lactone originally derived from the sweet wormwood plant(Artemisia annua), which is a traditional Chinese herb that has been universally used as...Artemisinin, also named qinghaosu, is a family of sesquiterpene trioxane lactone originally derived from the sweet wormwood plant(Artemisia annua), which is a traditional Chinese herb that has been universally used as anti-malarial agents for many years. Evidence has accumulated during the past few years which demonstrated the protective effects of artemisinin and its derivatives(artemisinins) in several other diseases beyond malaria, including cancers, autoimmune disorders, inflammatory diseases, viral and other parasiterelated infections. Recently, this long-considered antimalarial agent has been proved to possess anti-oxidant, anti-inflammatory, anti-apoptotic and anti-excitotoxic properties, which make it a potential treatment option for the ocular environment. In this review, we first described the overview of artemisinins, highlighting the activity of artemisinins to other diseases beyond malaria and the mechanisms of these actions. We then emphasized the main points of published results of using artemisinins in targeting ocular disorders, including uveitis, retinoblastoma, retinal neurodegenerative diseases and ocular neovascularization. To conclude, we believe that artemisinins could also be used as a promising therapeutic drug for ocular diseases, especially retinal vascular diseases in the near future.展开更多
AIM： To observe the apoptosis and oncosis of pancreatic acinar cells and secondary inflammatory reaction in pancreatic tissue from rats with acute pancreatitis （AP）, and the influences of artemisinin on them.METHOD...AIM： To observe the apoptosis and oncosis of pancreatic acinar cells and secondary inflammatory reaction in pancreatic tissue from rats with acute pancreatitis （AP）, and the influences of artemisinin on them.METHODS： AP was induced by 4 intraperitoneal iojections of caerulein at 1 h intervals. To induce apoptosis, solution of artemisinin （50 mg/kg） was given intraperitoneally 1, 12, 24 and 36 h after the last caerulein injection. Histological examination of impairment of pancreatic tissue and detection of serum amylase were performed to evaluate the severity of acute pancreatitis. Apoptosis and oncosis were detected with acridine orange （AO） and ethylene dibromide （EB） staining. Caspase-3 and myeloperoxidase （MPO） activity were measured by colorimetric assay. Nuclear factor-kappa B （NF-KB） activation was detected by flow cytometry. Macrophage inflammatory protein-lα（MIP-1α） protein was measured by Western blot. Interleukin- 1β（IL-1β） mRNA was detected by RT-PCR.RESULTS： Addition of artemisinin increased the number of apoptotic cells （11.7%±1.4% vs 6.3%± 0.7%, P 〈 0.05）, while reduced the number of oncotic cells （13.0% ±2.4% vs 17.5%±2.2%, P 〈 0.05）. The activity of caspase-3 speeded up （1.52±0.21 vs 1.03±0.08, P 〈 0.05）, the pancreas pathological impairment was relieved （3.0±0.5 vs 4.0± 0.5, P 〈 0.05） and the level of serum amylase decreased （5642±721 U/dL vs 7821±653 U/dL, P 〈 0.05）. The activation of NF-1α （29%±4.1% vs 42%±5.8%）, MIP-1α protein （3.7±0.5 vs 5.8±0.7）,MPO （0.52±0.06 U/g vs 0.68±0.09 U/g）, IL-1β mRNA （1.7 ±0.3 vs 2.4 ±0.4） in the apoptosis inducing group was obviously decreased （P 〈 0.05）.CONCLUSION： Inducing apoptosis can relieve pathological impairment and inflammatory reaction in AP rats.展开更多
Malaria is a major cause of morbidity and mortality in the developing world.This situation is mainly due to emergence of resistance to most antimalarial drugs currently available. Artemisinin-based combination treatme...Malaria is a major cause of morbidity and mortality in the developing world.This situation is mainly due to emergence of resistance to most antimalarial drugs currently available. Artemisinin-based combination treatments are now first-line drugs for Plasmodium falciparum (P.falciparum) malaria.Artemisinin(qinghaosu) and its derivatives are the most rapid acting and efficacious antimalarial drugs.This review highlights most recent investigations into the emergence of artemisinin resistance in falciparum malaria patients on the Thai-Cambodian border,a historical epicenter for multidrug resistance spread spanning over 50 years.The study presents the first evidence that highlights the parasites reduced susceptibility to artemisinin treatment by prolonged parasite-clearance times,raising considerable concern on resistance development.Although the exact mechanism of action remains unresolved,development of resistance was proposed based from both in vitro experiments and human patients.Lines of evidence suggested that the parasites in the patients are in dormant forms,presumably tolerate to the drug pressure.The World Health Organization has launched for prevention and/or containment of the artemisinin-resistant malaria parasites.Taken together,the emergence of artemisinin resistance to the most potent antidote for falciparum malaria,poses a serious threat to global malaria control and prompts renewed efforts for urgent development of new antimalarial weapons.展开更多
Artemisinin,also called qinghaosu,is originally derived from the sweet wormwood plant(Artemisia annua),which is used in traditional Chinese medicine.Artemisinin and its derivatives(artemisinins)have been widely used f...Artemisinin,also called qinghaosu,is originally derived from the sweet wormwood plant(Artemisia annua),which is used in traditional Chinese medicine.Artemisinin and its derivatives(artemisinins)have been widely used for many years as anti-malarial agents,with few adverse side effects.Interestingly,evidence has recently shown that artemisinins might have a therapeutic value for several other diseases beyond malaria,including cancers,inflammatory diseases,and autoimmune disorders.Neurodegeneration is a challenging age-associated neurological disorder characterized by deterioration of neuronal structures as well as functions,whereas neuroinflammation has been considered to be an underlying factor in the development of various neurodegenerative disorders,including Alzheimer’s disease.Recently discovered properties of artemisinins suggested that they might be used to treat neurodegenerative disorders by decreasing oxidation,inflammation,and amyloid beta protein(Aβ).In this review,we will introduce artemisinins and highlight the possible mechanisms of their neuroprotective activities,suggesting that artemisinins might have therapeutic potential in neurodegenerative disorders.展开更多
Artemisinin, also termed qinghaosu, is extracted from the traditional Chinese medicine ar- temesia annua L. （the blue-green herb） in the early 1970s, which has been confirmed for effectively treating malaria, Additi...Artemisinin, also termed qinghaosu, is extracted from the traditional Chinese medicine ar- temesia annua L. （the blue-green herb） in the early 1970s, which has been confirmed for effectively treating malaria, Additionally, emerging data prove that artemisinin exhibits anti-cancer effects against many types of cancers such as leukemia, melanoma, etc. Artemisinin becomes cytotoxic in the presence of ferrous iron. Since iron influx is high in cancer cells, artemisinin and its analogs selectively kill can- cer cells with increased intracellular iron concentrations. This study is aimed to investigate the selective inhibitory effects of artemisinin on SMMC-7721 cells in vitro and determine the effect of holotransfer- fin, which increases the concentration of ferrous iron in cancer cells, combined with artemisinin on the anticancer activity. MTT assay was used for assessing the proliferation of SMMC-7721 cells treated with artemisinin. The induction of apoptosis and inhibition of colony formation in SMMC-7721 cells treated with artemisinin were determined by TdT-mediated dUTP nick end labeling （TUNEL） and col- ony formation assay, respectively. The results showed that artemisinin at various concentrations signifi- cantly inhibited growth, colony formation and cell viability of SMMC-7721 cells （P〈0.05）, likely due to induction of apoptosis of SMMC-7721 cells. Of interest, it was found that incubation of artemisinin combined with holotransferrin sensitized the growth inhibitory effect of artemisinin on SMMC-7721 cells （P〈0.01）. Our data suggest that treatment with artemisinin leads to inhibition of viability and pro- liferation, and apoptosis of SMMC-7721 ceils. Furthermore, we observed that holotransferrin signifi- cantly enhanced the anti-cancer activity of artemisinin. This study may provide a potential therapeutic choice for liver cancer.展开更多
Malaria is a major cause of human morbidity and mortality in the tropical endemic countries worldwide. This is largely due to the emergence and spread of resistance to most antimalarial drugs currently available. Base...Malaria is a major cause of human morbidity and mortality in the tropical endemic countries worldwide. This is largely due to the emergence and spread of resistance to most antimalarial drugs currently available. Based on the World Health Organization recommendation, artemisinin-based combination therapies are now used as first-line treatment for Plasmodium falciparum malaria. Artemisinin or qinghaosu(Chinese name) and its derivatives are highly potent, rapidly acting antimalarial drugs. Artemisinin was discovered in 1971 by a Chinese medical scientist Youyou Tu, who was awarded the Nobel Prize in 2015 on her discovering the antimalarial properties of qinghaosu from the traditional Chinese qinghao plant. Nevertheless, artemisinin resistance in falciparum malaria patients has first emerged on the Thai-Cambodian border in 2009, which is now prevalent across mainland Southeast Asia from Vietnam to Myanmar. Here, we reviewed malaria disease severity, history of artemisinin discovery, chemical structure, mechanism of drug action, artemisinin-based combination therapies, emergence and spread of drug resistance, including the recent findings on mechanism of resistance in the falciparum malaria parasite. This poses a serious threat to global malaria control and prompts renewed efforts for the urgent development of new antimalarial drugs.展开更多
The present study aims at defining the differential cytotoxicity effect of artemisinin toward P815(murin mastocytoma)and BSR(kidney adenocarcinoma of hamster)cell lines.Cytotoxicity was measured by the growth inhibit...The present study aims at defining the differential cytotoxicity effect of artemisinin toward P815(murin mastocytoma)and BSR(kidney adenocarcinoma of hamster)cell lines.Cytotoxicity was measured by the growth inhibition using MTT assay.These in vitro cytotoxicity studies were complemented by the determination of apoptotic DNA fragmentation and Annexin V-streptavidin-FITC assay.Furthermore,we examined the in vitro synergism between artemisinin and the chemotherapeutic drug,vincristin.The in vivo study was investigated using the DBA2/P815(H2d)mouse model.While artemisinin acted on both tumor cell lines,P815 was much more sensitive to this drug than BSR cells,as revealed by the respective IC50 values(12 lM for P815 and 52 lM for BSR cells).On another hand,and interestingly,apoptosis was induced in P815 but not induced in BSR.These data,reveal an interesting differential cytotoxic effect,suggesting the existence of different molecular interactions between artemisinin and the studied cell lines.In vivo,our results clearly showed that the oral administration of artemisinin inhibited solid tumor development.Our study demonstrates that artemisinin caused differential cytotoxic effects depending not only on the concentration and time of exposure but also on the target cells.展开更多
文摘The mental health issues of college students have become an increasingly prominent social problem,exerting severe impacts on their academic performance and overall well-being.Early identification of Interpersonal Sensitivity(IS)in students serves as an effective approach to detect psychological problems and provide timely intervention.In this study,958 freshmen from higher education institutions in Zhejiang Province were selected as participants.We proposed a Multi-Strategy Artemisinin Optimization(MSAO)algorithm by enhancing the Artemisinin Optimization(AO)framework through the integration of a group-guided elimination strategy and a two-stage consolidation strategy.Subsequently,the MSAO was combined with the Fuzzy K-Nearest Neighbor(FKNN)classifier to develop the bMSAO-FKNN predictive model for assessing college students’IS.The proposed algorithm’s efficacy was validated through the CEC 2017 benchmark test suite,while the model’s performance was evaluated on the IS dataset,achieving an accuracy rate of 97.81%.These findings demonstrate that the bMSAO-FKNN model not only ensures high predictive accuracy but also offers interpretability for IS prediction,making it a valuable tool for mental health monitoring in academic settings.
基金supported by the National Natural Science Foundation of China(81973839)High Level Chinese Medical Hospital Promotion Project-Special Project on Formulation R&D and New Drug Translation for Medical Institutions(HLCMHPP2023037)Upgrading the Development and Promotion of about 30 Integrated Chinese and Western Medicine Diagnosis and Treatment Programs(Guidelines for the Diagnosis and Treatment of Breast Cancer with the Combination of Traditional Chinese Medicine and Western Medicine)(ZYZB-2022-798).
文摘Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug resistance often leads to recurrence,underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates.Artemisinin(ART)has demonstrated efficacy in inhibiting the growth of drug-resistant cells,positioning art as a viable option for counteracting endocrine resistance.This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental validation.Five characterized genes(ar,cdkn1a,erbb2,esr1,hsp90aa1)and seven drug-disease crossover genes(cyp2e1,rorc,mapk10,glp1r,egfr,pgr,mgll)were identified using WGCNA crossover analysis.Subsequent functional enrichment analyses were conducted.Our findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and-sensitized patients.scRNA-seq analysis revealed high expression of key cluster genes in epithelial cells,suggesting artemisinin’s specific impact on tumor cells in estrogen receptor(ER)-positive BC tissues.Molecular target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance genes.These results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.
基金supported by the National Natural Science Foundation of China(Nos.81803470 and 82173767)。
文摘Artemisinin(ART)resistance has been an emerging clinical problem,severely compromising antimalarial efficacy and threatening the global malaria elimination campaign.Albeit intensive studies about the molecular mechanism for ART resistance are under way,no effective therapeutic targets for reversing resistance have been applied.Here,we explore glutathione(GSH)as a therapeutic target to develop a thermo-responsive nanoplatform to specifically co-deliver ART and GSH synthesis inhibitor(L-buthionine sulfoximine,BSO)in a sustained manner,effectively reversing ART resistance in vivo.By combining with BSO,ART exerts increased antimalarial activity with reduced half-maximal inhibitory concentration(IC50)by 7.43-fold in ART-resistant strains.This work reveals that the GSH in ART-resistant parasites can be a promising therapeutic target for reversing ART resistance,paving the way for developing drug candidates and intelligent nanomedicines in malaria therapy.
文摘The biotransformation of artemisinin by hairy root cultures ofRheum palmatum L. was investigated for the first time. The main product, deoxyartemisinin, was isolated and characterized on the basis of its spectral data.
文摘The artemisinin accumulation in the hairy root cultures of Artemisia annua L. was enhanced via a treatment of three fungal elicitors separately ( Verticillium dahliae Kleb., Rhizopus stolonifer (Ehrenb. ex Fr.) Vuill and Colletotrichum dematium (Pers.) Grove). Among these three elicitors, V. dahliae had the highest inducing efficiency, but none of them manifests any noticeable effects on the cell growth of the hairy root cultures. The artemisinin content of the hairy root cultures treated with V. dahliae elicitor was 1.12 mg/g DW, which was 45% higher than the control (0.77 mg/g DW). The results showed that elicitation was dependent on the elicitor concentration, the incubation period and the physiological stage at which the hairy root cultures were treated. In addition, the authors found that for V. dahliae , the optimum concentration was 0.4 mg carbohydrate per millilitre medium, the strongest response of A. annua hairy root cultures to the elicitation was at the late exponential growth stage, and the highest artemisinin content of the hairy root cultures was on the 4th day post treatment.
文摘The oligosaccharide elicitor from the mycelial wall of an endophytic Colletotrichum sp. B501 promoted the production of artemisinin in Artemisia annua L. hairy root culture. When hairy roots of 22-day-old cultures (later growth phase) were exposed to the elicitor (20 mg/L) for 4 d, the maximum content of artemisinin reached 1.15 mg/g, a 64.29% increment over the control. The electron X-ray microanalysis disclosed the rapid accumulation of Ca 2+ in the elicited cortical cells of hairy root. The electronic microscope observation revealed the high electron density area in vacuole of elicited cells. During the first day of elicitation the peroxidase activity of hairy roots was improved sharply. Some cellular morphological changes including cell shrinkage, condensation of cytoplasm and nuclear fragmentation, coincident with the appearance of DNA ladders, were observed after the third day of elicitation. It was suggested that the oligosaccharide elicitor triggered the programmed cell death, which may provide the substance or chemical signal for artemisinin biosynthesis.
基金supported by CAS"Light of West China"Program([2014]91 to Z.Z.)the Basic Research Plan of Yunnan Provincial Science and Technology Department(grant number 2014FA042)+1 种基金CAS Strategic biological resources service network(ZSTH-021)the Strategic Priority Research Program of the Chinese Academy of Sciences,Grant No.XDA12030206.
文摘Cancer is the leading cause of human death which seriously threatens human life.The antimalarial drug artemisinin and its derivatives have been discovered with considerable anticancer properties.Simultaneously,a variety of target-selective artemisinin-related compounds with high efficiency have been discovered.Many researches indicated that artemisinin-related compounds have cytotoxic effects against a variety of cancer cells through pleiotropic effects,including inhibiting the proliferation of tumor cells,promoting apoptosis,inducing cell cycle arrest,disrupting cancer invasion and metastasis,preventing angiogenesis,mediating the tumor-related signaling pathways,and regulating tumor microenvironment.More importantly,artemisinins demonstrated minor side effects to normal cells and manifested the ability to overcome multidrug-resistance which is widely observed in cancer patients.Therefore,we concentrated on the new advances and development of artemisinin and its derivatives as potential antitumor agents in recent 5 years.It is our hope that this review could be helpful for further exploration of novel artemisinin-related antitumor agents.
基金We thank Dr.Xianzhu Xia(Academy of Military Medical Sciences)for providing the CVS-11 virus.We thank Dr.Zhenfang Fu(Huazhong Agricultural University)for providing the CVS-24 virus.This work was supported by the National Key Research and Development Program of China(2016YFD0500400)National Natural Science Foundation of China(31772742)Natural Science Foundation of Guangdong(2015A03031103).
文摘Rabies is caused by infection of rabies virus(RABV)and remains a serious threat to the global public health.Except for the requirement for cold chain and high cost of human rabies immune globulin,no small molecule drugs are currently available for clinical treatment of rabies.So,it is of great importance to identify novel compounds that can effectively inhibit RABV infection.Artesunate(ART)and dihydroartemisinin(DHA),two derivatives of artemisinin,are widely used for treatment of malaria in adults and children,showing high safety.In this study,we found that both ART and DHA were able to inhibit RABV replication in host cells at a low concentration(0.1μmol/L).The antiviral effects of ART and DHA were independent of viral strains and cell lines.Pre-treatment with ART or DHA for 2 h in vitro did not affect the viral replication in host cells,implying that ART and DHA neither reduced the viability of RABV directly nor inhibited the binding and entrance of the virus to host cells.Further studies revealed that ART and DHA inhibited RABV genomic RNA synthesis and viral gene transcription.Treatment with ART or DHA(5 mg/kg)by intramuscular injection improved,to some extent,the survival rate of RABV-challenged mice.Combination treatment with derivatives of artemisinin and mannitol significantly improved the survival rate of RABV-challenged mice.The results suggest that ART and DHA have a great potential to be explored as new anti-rabies agents for treatment of rabies.
文摘Having faced increased clinical treatment failures with dihydroartemisinin-piperaquine(DHA-PPQ),Cambodia swapped the first line artemisinin-based combination therapy(ACT)from DHA-PPQ to artesunate-mefloquine given that parasites resistant to piperaquine are susceptible to mefloquine.However,triple mutants have now emerged,suggesting that drug rotations may not be adequate to keep resistance at bay.There is,therefore,an urgent need for alternative treatment strategies to tackle resistance and prevent its spread.A proper understanding of all contributors to artemisinin resistance may help us identify novel strategies to keep artemisinins effective until new drugs become available for their replacement.This review highlights the role of the key players in artemisinin resistance,the current strategies to deal with it and suggests ways of protecting future antimalarial drugs from bowing to resistance as their predecessors did.
基金National Natural Science Foundation of China(Grant No.81373364)The Subject clots Project Serving Pharmaceutical Industrial Innovation of Shanxi Province
文摘Artemisinin（ART） is a widely used active drug for malaria, including severe and cerebral malaria. However, its therapeutic efficacy is affected by its lower bioavailability. In the present study, nanostructured lipid carriers（NLCs） were proposed as carrier of ART to improve pharmacokinetic properties of the drug. ART-NLC was prepared by high-pressure homogenization based on orthogonal design. The particle size, zeta potential, encapsulation efficiency（EE） and percentage of drug loading（DL） of ART-NLC were（53.06±2.11） nm,（–28.7±3.59） m V, 73.9%±0.5% and 11.23%±0.37%, respectively. ART-NLC showed the sustained release characteristics and scarcely the hemolysis effect on human red blood cells. The pharmacokinetics of ART-NLC for rats after tail intravenous injection（i.v） or intraperitoneal injection（i.p） were investigated by liquid chromatography-tandem mass spectroscopy（LC-MS/MS）. And ART solution was designed as control preparation. For rats of i.v groups, the AUC0–∞（（707.45±145.65） ng·h/m L） of ART-NLC were significantly bigger than that of ART（（368.98±139.58） ng·h/m L）. The MRT（（3.38±0.46） h） of ART-NLC was longer than that of ART（（1.39±0.61） h）. And similar results were observed for rats of i.p groups. The AUC0–∞（（1233.06±235.57） ng·h/m L） and MRT（（4.97±0.69） h） of ART-NLC were both bigger than those of ART, which were（871.17±234.03） ng·h/m L） and（1.75±0.31） h）, respectively. Compared with ART, ART-NLC showed a significant increase in AUC0–∞（P〈0.05） and MRT（P〈0.001） for both i.p and tail i.v administrations.
基金Supported by National Natural Science Foundation of China~~
文摘[Objective] The aim was to make a summary on research progresses on extraction and detection techniques of artemisinin. [Method] In the research, the concerning progress was made based on physicochemical property, source, extraction methods and detection technology of artemisinin. [Result] Artemisinin is colorless acicular crystal and easier to be dissolved in organic solvent. The extraction methods of artemisinin include organic solvent extraction, ultrasonic extraction, microwave extraction and supercritical fluid extraction; the detection technologies include ultraviolet spectrophotometry, high performance liquid chromatography and HPLC-evaporative light-scattering. [Conclusion] The research laid foundation for further exploration and global market.
基金the projects of the National Natural Science Foundation of China (81641002 and 81473548)Major National Science and Technology Program of China for Innovative Drug (2017ZX09101002-001-001-05 and 36 J. Wang et al./ Engineering 5 (2019) 32–39 2017ZX09101002-001-001-3)the Fundamental Research Funds for the Central Public Welfare Research Institutes (ZZ10-024 and ZXKT18003).
文摘Artemisinin and its derivatives represent the most important and influential class of drugs in the fight against malaria. Since the discovery of artemisinin in the early 1970s, the global community has made great strides in characterizing and understanding this remarkable phytochemical and its unique chemical and pharmacological properties. Today, even as artemisinin continues to serve as the foundation for antimalarial therapy, numerous challenges have surfaced in the continued application and development of this family of drugs. These challenges include the emergence of delayed treatment responses to artemisinins in malaria and efforts to apply artemisinins for non-malarial indications. Here, we provide an overview of the story of artemisinin in terms of its past, present, and future. In particular, we comment on the current understanding of the mechanism of action (MOA) of artemisinins, and emphasize the importance of relating mechanistic studies to therapeutic outcomes, both in malarial and non-malarial contexts.
基金supported by the National Natural Science Foundation of China (No. 81130070,81072989)the Research Projects of State Administration of Traditional Chinese Medicine of China (No. 201107009)+1 种基金the Important National Science & Technology Specific Projects (No.2009ZX09502-026,2009ZX09301-005)the Research Projects of China Academy of Chinese Medical Sciences(No. ZZ20090302)
文摘The effects of different cadmium （Cd） concentrations （0, 20, 60, and 100 μmol/L） on hydroponically grown Artemisia annua L. were investigated. Cd treatments applied for 0, 4, 12, 24, 72, 144, 216, and 336 hr were assessed by measuring the changes in photosynthetic pigments, electrolyte leakage, malondialdehyde （MDA） and antioxidants （ascorbic acid and glutathione）, while the artemisinin content was tested after 0, 12, 144, 216, and 336 hr. A significant decrease was observed in photosynthetic pigment levels over time with increasing Cd concentration. Chlorophyll b levels were more affected by Cd than were chlorophyll a or carotenoid levels. The cell membrane was sensitive to Cd stress, as MDA content in all treatment groups showed insignificant differences from the control group, except at 12 hr treatment time. Ascorbic acid （AsA） content changed slightly over time, while glutathione （GSH） content took less time to reach a maximum as Cd concentration increased. Cd was found to promote synthesis and accumulation of artemisinin, especially at concentrations of 20 and 100 ~tmol/L. In conclusion, Cd stress can damage to photosynthetic pigments, and vigorously growing A. annua showed a strong tolerance for Cd stress. Appropriate amounts of added Cd aided synthesis and accumulation of artemisinin.
文摘Artemisinin, also named qinghaosu, is a family of sesquiterpene trioxane lactone originally derived from the sweet wormwood plant(Artemisia annua), which is a traditional Chinese herb that has been universally used as anti-malarial agents for many years. Evidence has accumulated during the past few years which demonstrated the protective effects of artemisinin and its derivatives(artemisinins) in several other diseases beyond malaria, including cancers, autoimmune disorders, inflammatory diseases, viral and other parasiterelated infections. Recently, this long-considered antimalarial agent has been proved to possess anti-oxidant, anti-inflammatory, anti-apoptotic and anti-excitotoxic properties, which make it a potential treatment option for the ocular environment. In this review, we first described the overview of artemisinins, highlighting the activity of artemisinins to other diseases beyond malaria and the mechanisms of these actions. We then emphasized the main points of published results of using artemisinins in targeting ocular disorders, including uveitis, retinoblastoma, retinal neurodegenerative diseases and ocular neovascularization. To conclude, we believe that artemisinins could also be used as a promising therapeutic drug for ocular diseases, especially retinal vascular diseases in the near future.
基金the Natural Science Foundation of Heilongjiang Province,China,No. D0227
文摘AIM： To observe the apoptosis and oncosis of pancreatic acinar cells and secondary inflammatory reaction in pancreatic tissue from rats with acute pancreatitis （AP）, and the influences of artemisinin on them.METHODS： AP was induced by 4 intraperitoneal iojections of caerulein at 1 h intervals. To induce apoptosis, solution of artemisinin （50 mg/kg） was given intraperitoneally 1, 12, 24 and 36 h after the last caerulein injection. Histological examination of impairment of pancreatic tissue and detection of serum amylase were performed to evaluate the severity of acute pancreatitis. Apoptosis and oncosis were detected with acridine orange （AO） and ethylene dibromide （EB） staining. Caspase-3 and myeloperoxidase （MPO） activity were measured by colorimetric assay. Nuclear factor-kappa B （NF-KB） activation was detected by flow cytometry. Macrophage inflammatory protein-lα（MIP-1α） protein was measured by Western blot. Interleukin- 1β（IL-1β） mRNA was detected by RT-PCR.RESULTS： Addition of artemisinin increased the number of apoptotic cells （11.7%±1.4% vs 6.3%± 0.7%, P 〈 0.05）, while reduced the number of oncotic cells （13.0% ±2.4% vs 17.5%±2.2%, P 〈 0.05）. The activity of caspase-3 speeded up （1.52±0.21 vs 1.03±0.08, P 〈 0.05）, the pancreas pathological impairment was relieved （3.0±0.5 vs 4.0± 0.5, P 〈 0.05） and the level of serum amylase decreased （5642±721 U/dL vs 7821±653 U/dL, P 〈 0.05）. The activation of NF-1α （29%±4.1% vs 42%±5.8%）, MIP-1α protein （3.7±0.5 vs 5.8±0.7）,MPO （0.52±0.06 U/g vs 0.68±0.09 U/g）, IL-1β mRNA （1.7 ±0.3 vs 2.4 ±0.4） in the apoptosis inducing group was obviously decreased （P 〈 0.05）.CONCLUSION： Inducing apoptosis can relieve pathological impairment and inflammatory reaction in AP rats.
基金supported by the UNDP/ World Bank/WHO Special Programme for Research and Training in Tropical Diseasesthe National Science and Technology Development Agency of Thailand(Career Development Award)+1 种基金the Thailand Research Fund(Basic Research)the Office of Higher Education Commission (University Staff Development Consortium),Thailand
文摘Malaria is a major cause of morbidity and mortality in the developing world.This situation is mainly due to emergence of resistance to most antimalarial drugs currently available. Artemisinin-based combination treatments are now first-line drugs for Plasmodium falciparum (P.falciparum) malaria.Artemisinin(qinghaosu) and its derivatives are the most rapid acting and efficacious antimalarial drugs.This review highlights most recent investigations into the emergence of artemisinin resistance in falciparum malaria patients on the Thai-Cambodian border,a historical epicenter for multidrug resistance spread spanning over 50 years.The study presents the first evidence that highlights the parasites reduced susceptibility to artemisinin treatment by prolonged parasite-clearance times,raising considerable concern on resistance development.Although the exact mechanism of action remains unresolved,development of resistance was proposed based from both in vitro experiments and human patients.Lines of evidence suggested that the parasites in the patients are in dormant forms,presumably tolerate to the drug pressure.The World Health Organization has launched for prevention and/or containment of the artemisinin-resistant malaria parasites.Taken together,the emergence of artemisinin resistance to the most potent antidote for falciparum malaria,poses a serious threat to global malaria control and prompts renewed efforts for urgent development of new antimalarial weapons.
基金supported by the Natural Science Foundation of Beijing of China,No.7192235(to LKX)
文摘Artemisinin,also called qinghaosu,is originally derived from the sweet wormwood plant(Artemisia annua),which is used in traditional Chinese medicine.Artemisinin and its derivatives(artemisinins)have been widely used for many years as anti-malarial agents,with few adverse side effects.Interestingly,evidence has recently shown that artemisinins might have a therapeutic value for several other diseases beyond malaria,including cancers,inflammatory diseases,and autoimmune disorders.Neurodegeneration is a challenging age-associated neurological disorder characterized by deterioration of neuronal structures as well as functions,whereas neuroinflammation has been considered to be an underlying factor in the development of various neurodegenerative disorders,including Alzheimer’s disease.Recently discovered properties of artemisinins suggested that they might be used to treat neurodegenerative disorders by decreasing oxidation,inflammation,and amyloid beta protein(Aβ).In this review,we will introduce artemisinins and highlight the possible mechanisms of their neuroprotective activities,suggesting that artemisinins might have therapeutic potential in neurodegenerative disorders.
文摘Artemisinin, also termed qinghaosu, is extracted from the traditional Chinese medicine ar- temesia annua L. （the blue-green herb） in the early 1970s, which has been confirmed for effectively treating malaria, Additionally, emerging data prove that artemisinin exhibits anti-cancer effects against many types of cancers such as leukemia, melanoma, etc. Artemisinin becomes cytotoxic in the presence of ferrous iron. Since iron influx is high in cancer cells, artemisinin and its analogs selectively kill can- cer cells with increased intracellular iron concentrations. This study is aimed to investigate the selective inhibitory effects of artemisinin on SMMC-7721 cells in vitro and determine the effect of holotransfer- fin, which increases the concentration of ferrous iron in cancer cells, combined with artemisinin on the anticancer activity. MTT assay was used for assessing the proliferation of SMMC-7721 cells treated with artemisinin. The induction of apoptosis and inhibition of colony formation in SMMC-7721 cells treated with artemisinin were determined by TdT-mediated dUTP nick end labeling （TUNEL） and col- ony formation assay, respectively. The results showed that artemisinin at various concentrations signifi- cantly inhibited growth, colony formation and cell viability of SMMC-7721 cells （P〈0.05）, likely due to induction of apoptosis of SMMC-7721 cells. Of interest, it was found that incubation of artemisinin combined with holotransferrin sensitized the growth inhibitory effect of artemisinin on SMMC-7721 cells （P〈0.01）. Our data suggest that treatment with artemisinin leads to inhibition of viability and pro- liferation, and apoptosis of SMMC-7721 ceils. Furthermore, we observed that holotransferrin signifi- cantly enhanced the anti-cancer activity of artemisinin. This study may provide a potential therapeutic choice for liver cancer.
基金supported by the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (CHEMAL, TDR/WHO)the National Science and Technology Development Agency of Thailand (NSTDA Career Development Award)+1 种基金the Thailand Research Fund (TRF Basic Research)the Office of Higher Education Commission (OHEC University Staff Development Consortium), and Faculty of Medicine and Graduate School, Chulalongkorn University, Thailand
文摘Malaria is a major cause of human morbidity and mortality in the tropical endemic countries worldwide. This is largely due to the emergence and spread of resistance to most antimalarial drugs currently available. Based on the World Health Organization recommendation, artemisinin-based combination therapies are now used as first-line treatment for Plasmodium falciparum malaria. Artemisinin or qinghaosu(Chinese name) and its derivatives are highly potent, rapidly acting antimalarial drugs. Artemisinin was discovered in 1971 by a Chinese medical scientist Youyou Tu, who was awarded the Nobel Prize in 2015 on her discovering the antimalarial properties of qinghaosu from the traditional Chinese qinghao plant. Nevertheless, artemisinin resistance in falciparum malaria patients has first emerged on the Thai-Cambodian border in 2009, which is now prevalent across mainland Southeast Asia from Vietnam to Myanmar. Here, we reviewed malaria disease severity, history of artemisinin discovery, chemical structure, mechanism of drug action, artemisinin-based combination therapies, emergence and spread of drug resistance, including the recent findings on mechanism of resistance in the falciparum malaria parasite. This poses a serious threat to global malaria control and prompts renewed efforts for the urgent development of new antimalarial drugs.
文摘The present study aims at defining the differential cytotoxicity effect of artemisinin toward P815(murin mastocytoma)and BSR(kidney adenocarcinoma of hamster)cell lines.Cytotoxicity was measured by the growth inhibition using MTT assay.These in vitro cytotoxicity studies were complemented by the determination of apoptotic DNA fragmentation and Annexin V-streptavidin-FITC assay.Furthermore,we examined the in vitro synergism between artemisinin and the chemotherapeutic drug,vincristin.The in vivo study was investigated using the DBA2/P815(H2d)mouse model.While artemisinin acted on both tumor cell lines,P815 was much more sensitive to this drug than BSR cells,as revealed by the respective IC50 values(12 lM for P815 and 52 lM for BSR cells).On another hand,and interestingly,apoptosis was induced in P815 but not induced in BSR.These data,reveal an interesting differential cytotoxic effect,suggesting the existence of different molecular interactions between artemisinin and the studied cell lines.In vivo,our results clearly showed that the oral administration of artemisinin inhibited solid tumor development.Our study demonstrates that artemisinin caused differential cytotoxic effects depending not only on the concentration and time of exposure but also on the target cells.
