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Research Project: Genetic Improvement of Crop Plants for Use with Low Quality Irrigation Waters: Physiological, Biochemical and Molecular Approaches

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Title: Isolation of dihydroatemisinic acid from the artemisia annua l. by-product by combining Ultrasound-assisted extraction with response surface methodology

Author
item Liu, Shuoqian - Hunan Agricultural University
item Ferreira, Jorge
item Liu, Liuping - Hunan Agricultural University
item Yuwei, Tang - Hunan Agricultural University
item Tian, Dongming - Hunan Agricultural University
item Liu, Zhonghua - Hunan Agricultural University
item Tian, Na - Hunan Agricultural University

Submitted to: Chemical and Pharmaceutical Bulletin
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/24/2017
Publication Date: 6/1/2017
Citation: Liu, S., Ferreira, J.F., Liu, L., Yuwei, T., Tian, D., Liu, Z., Tian, N. 2017. Isolation of dihydroatemisinic acid from the artemisia annua l. by-product by combining Ultrasound-assisted extraction with response surface methodology. Chemical and Pharmaceutical Bulletin. 65(8):746-753. doi: 10.1248/cpb.c17-00192.

Interpretive Summary: Malaria is the world’s most important parasitic disease, affecting 300-500 million people worldwide, and killing over a million per year. Its parasitic agent has become resistant to quinine-derived drugs in several countries and artemisinin-derived drugs are currently the only medicine that cures quinine-resistant malaria. However, the artemisinin market has been unstable due to production-related costs. Thus, the cost-effective production of artemisinin continues to attract interest worldwide. Although currently unexplored, the use of dihydroartemisinic acid (DHAA), discarded after the commercial extraction of ART from Artemisia annua, is a potential way to increase ART yield from the plant matrix. In the present work, an ultrasound-assisted alkaline procedure for the extraction of DHAA from ART production waste was developed and optimized using response surface methodology. Our results using this methodology established that sodium hydroxide at 0.36%, an extraction time of 68 min, a solvent:solid ratio of 6.0, and ultrasonic power of 84 W were the optimal conditions to extract DHAA from ART production waste. Under these optimal conditions, a DHAA yield of approximately 3% was achieved. Finally, a validation experiment was conducted, and the results confirmed the prediction generated by the regression model developed in this study. This work provides a novel way to increase the production of ART per cultivated area and to reduce ART production costs by recycling ART commercial waste to obtain DHAA, which can then be derivatized into ART in the laboratory. This technology can be used by commercial artemisinin extraction companies to maximize the yield of this life-saving and natural antimalarial medicine.

Technical Abstract: Malaria is one of the world’s most important parasitic diseases, affecting 300-500 million people worldwide and killing more than one million per year. Artemisinin is currently the only raw material for the production of artemisinin combination therapies (ACT), the only medicine that cures drug-resistant malaria. Therefore, the cost-effective production of artemisinin (ART) continues to attract attention worldwide. Although currently unexplored, the use of dihydroartemisinic acid (DHAA), discarded after the commercial extraction of ART from Artemisia annua, is a potential way to increase ART yield from the plant matrix. In the present work, an ultrasound-assisted alkaline procedure for the extraction of DHAA from ART production waste was developed and optimized using response surface methodology. Our results using this methodology established that NaOH at 0.36%, extraction time of 67.96 min, liquid-solid ratio of 5.89, and ultrasonic power of 83.9 W were the optimal conditions to extract DHAA from ART production waste. Under these optimal conditions, a DHAA yield of 2.7% was achieved. Finally, a validation experiment was conducted, and the results confirmed the prediction generated by the regression model developed in this study. This work provides a novel way to increase the production of ART per cultivated area and to reduce ART production costs by recycling its commercial waste to obtain DHAA, which can then be derivatized into ART.