Investigation of the component in Artemisia annua L. leading to enhanced antiplasmodial potency of artemisinin via regulation of its metabolism

Cai, Tianyu; Zhang, Yun-Rui; Ji, Jianbo; Xing, Jie

doi:10.1016/j.jep.2017.06.025

Cited by 28 publications

(26 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Inhibition of metabolizing enzymes through combination therapy could be of great importance to improve the efficacy of artemisinin. As noted in recent publications, arteannuin B is a strong inhibitor of CYP3A4, and the AUC and therapeutic effect of artemisinin could be enhanced by the metabolism-dependent synergistic effect with arteannuin B (Cai, Zhang, Ji, & Xing, 2017). In the present study, a higher AUC, longer t 1/2 , and lower CL in four components group suggested the inhibition of metabolism and excretion, which was in accordance with the previous report (Cai et al, 2017).…”

Section: Discussionsupporting

confidence: 93%

“…As noted in recent publications, arteannuin B is a strong inhibitor of CYP3A4, and the AUC and therapeutic effect of artemisinin could be enhanced by the metabolism‐dependent synergistic effect with arteannuin B (Cai, Zhang, Ji, & Xing, ). In the present study, a higher AUC, longer t 1/2 , and lower CL in four components group suggested the inhibition of metabolism and excretion, which was in accordance with the previous report (Cai et al, ). The pharmacokinetic study further demonstrated that malaria infection leads to decreased AUC, C max , and t 1/2 and increased CL as compared with that from healthy mice.…”

Section: Discussionmentioning

confidence: 90%

See 1 more Smart Citation

Combination of artemisinin‐based natural compounds from Artemisia annua L. for the treatment of malaria: Pharmacodynamic and pharmacokinetic studies

Zhang

Gong

et al. 2018

Phytotherapy Research

View full text Add to dashboard Cite

Currently, the most effective antimalarial is artemisinin, which is extracted from the leaves of medicinal herb Artemisia annua L. (A. annua). Previous studies showed that the complex chemical matrix of A. annua could enhance both the bioavailability and efficacy of artemisinin. The present study aims to evaluate the efficacy and pharmacokinetic properties of a combination therapy based on artemisinin and 3 components from A. annua with high content (arteannuin B, arteannuic acid, and scopoletin). In vivo antimalarial activity was assessed following a 4-day treatment in murine malaria models (Plasmodium yoelii and Plasmodium berghei). Results showed that a much sharper reduction in parasitemia (~93%) was found in combination therapy compared with pure artemisinin (~31%), indicating pharmacodynamic synergism occurring between artemisinin and arteannuin B, arteannuic acid, and scopoletin. Multiple-dose pharmacokinetics further demonstrated that combination therapy results in increased area under the curve (AUC ), C , and t by 3.78-, 3.47-, and 1.13-fold in healthy mice, respectively, and by 2.62-, 1.82-, and 1.22-fold in P. yoelii-infected mice, respectively. The calculated oral clearance of combination therapy in healthy and P. yoelii-infected mice was also reduced. These findings imply that specific components in A. annua might offer a possibility to develop new artemisinin-based natural combination therapy for malaria treatment.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 90%

Combination of artemisinin‐based natural compounds from Artemisia annua L. for the treatment of malaria: Pharmacodynamic and pharmacokinetic studies

Zhang

Gong

et al. 2018

Phytotherapy Research

View full text Add to dashboard Cite

show abstract

“…Hence, LA may be expected to exert toxicity to cultured P. falciparum via extracellular production of linoleate peroxides/epoxides (Guillaume, Calzada, Lagarde, Schrevel, & Deregnaucourt, ). Additionally, antiplasmodium potential of phenolics and flavonoids in GSO would have to be addressed via malaria parasite metabolism and development (Alson et al, ; Cai, Zhang, Ji, & Xing, ; Kusch et al, ; Palaniswamy, Pradeep, Sathya, & Angayarkanni, ).…”

Section: Discussionmentioning

confidence: 99%

Linoleic acid‐rich guava seed oil: Safety and bioactivity

Prommaban

Utama‐ang

Chaikitwattana

et al. 2019

Phytotherapy Research

View full text Add to dashboard Cite

Guava (Psidium guajava) is a widely consumed fruit and has been commercialized in markets. The seeds are by-products of the processing procedures performed by the commercial guava juice industry. They are considered a nutritional resource that has been poorly utilized as they contain essential fatty acids such as linoleic acid (LA) and phenolics in abundance. In the study, guava seed oil (GSO) was used, which was obtained by hexane extraction of guava seeds to determine composition and test toxicity, cell migration, cancer cell viability, and plasmodium growth. GSO was found to be relatively nontoxic to normal hepatocytes and peripheral blood mononuclear cells, with mice for 14 days showing median lethal dose (LD 50 ) > 10 mg/kg and rats for up to 90 days. Surprisingly, the oil inhibited the proliferation of the human erythroleukemic cells in a dose-dependent manner with the half maximal inhibitory concentration values of 155 and 137 μg/ml at 24 and 48 hr, respectively. Importantly, GSO at 500 μg/ml was found to increase the degree of migration of keratinocytes (HaCaT). These observations suggest that edible P. guajava seed oil, which is abundant with linoleic acid and antioxidants, can promote skin wound healing and inhibit the proliferation of leukemic cells.

show abstract

“…Their chemical structures are shown in Figure . These three flavonoids potentiated the antiplasmodial activity of artemisinin when used at 5 µM . However, it is not clear if the blood concentrations of these flavonoids could achieve a similar effect in vivo.…”

Section: Introductionmentioning

confidence: 97%

“…Thus, although bioavailability of intact flavonoids might be low, the large pool of flavonoids resulting from metabolism can be responsible for their potential antimalarial effect. Our preliminary study showed that three major flavonoids (CSP, CSN, and ARN) were present in vivo predominantly as glucuronidated metabolites . For understanding of the synergistic antimalarial effects of flavonoids in A. annua , the pharmacokinetic study of major flavonoids and their metabolites is necessary.…”

Section: Introductionmentioning

confidence: 99%

Liquid chromatography‐tandem mass spectrometry assay for the simultaneous determination of three major flavonoids and their glucuronidated metabolites in rats after oral administration of Artemisia annua L. extract at a therapeutic ultra‐low dose

Wang

Cai

Liu

et al. 2019

J of Separation Science

Self Cite

View full text Add to dashboard Cite

The traditional antimalarial herb Artemisia annua L., from which artemisinin is isolated, is widely used in endemic regions. It has been suggested that artemisinin activity can be enhanced by flavonoids in A. annua; however, how fast and how long the flavonoids are present in the body remains unknown. In the present study, a rapid and sensitive liquid chromatography with tandem mass spectrometry method was developed and validated for the simultaneous determination of three major flavonoids components, i.e. chrysosplenol D, chrysoplenetin, and artemetin and their glucuronidated metabolites in rats after oral administrations of A. annua extracts at a therapeutic ultra‐low dose. The concentration of the intact form was determined directly, and the concentration of the glucuronidated form was assayed in the form of flavonoids aglycones, after treatment with β‐glucuronidase/sulfatase. The method was linear in the range of 0.5–300.0 ng/mL for chrysoplenetin and artemetin, and 2–600 ng/mL for chrysosplenol D. All the validation data conformed to the acceptance requirements. The study revealed a significantly higher exposure of the flavonoid constituents in conjugated forms in rats, with only trace intact from. Multiple oral doses of A. annua extracts led to a decreased plasma concentration levels for three flavonoids.

show abstract

Investigation of the component in Artemisia annua L. leading to enhanced antiplasmodial potency of artemisinin via regulation of its metabolism

Cited by 28 publications

References 27 publications

Combination of artemisinin‐based natural compounds from Artemisia annua L. for the treatment of malaria: Pharmacodynamic and pharmacokinetic studies

Combination of artemisinin‐based natural compounds from Artemisia annua L. for the treatment of malaria: Pharmacodynamic and pharmacokinetic studies

Linoleic acid‐rich guava seed oil: Safety and bioactivity

Liquid chromatography‐tandem mass spectrometry assay for the simultaneous determination of three major flavonoids and their glucuronidated metabolites in rats after oral administration of Artemisia annua L. extract at a therapeutic ultra‐low dose

Contact Info

Product

Resources

About