Abstract

The World Health Organization’s statistics show that there are 212 million malaria cases and 429000 deaths, half of the world’s population is at risk of malaria, and 91 countries and regions have persistent malaria transmission in 2015. Artemisinin was selected as the most safe and effective antimalarial first-line drug by the WHO, with significant medical and commercial value. Artemisia annua (Qinghao in Traditional Chinese Medicine), is the main natural plant source of artemisinin. However, the content of artemisinin in A. annua widely varied between countries, and the wild germplasms resources in most areas are unsuitable for extraction. In this review, the global geo-distribution, the suitability of origin, and the breeding and cultivation of A. annua were summarized and analyzed, the extraction technology, biosynthesis and chemical synthesis of raw material were reviewed as well. Using geographic information system for global medicinal plants(GMPGIS), we report that the most suitable area of high quality A. annua (content of artemisinin >0.8%) is in the south of China’s Qinling-Huaihe River dividing line with the areas of 1.54×106 km2 worldwide, accounting for 77.08% of the total areas. The Brazil and United States also share a certain potential distribution with areas of 1.49×105 km2 (7.43%) and 1.30×105 km2 (6.47%), respectively. Vietnam and Japan are sporadic. The ecological sub-suitable areas for high quality A. annua include Southeastern Asia, Western Europe, Southern North America and central South America. China is still the largest ecological sub-suitable area of high quality A. annua with areas of 2.03×106 km2 accounting for 70% of the world; followed by the United States and Brazil with an area of 3.11×105 km2 (10.22%), 2.21×105 km2 (7.26%). All the above results suggest that China is the main producing nation of high quality A. annua resources. In the past 50 years, China has made great progress for discovery of artemisinin, treatment of malaria and artemisinin raw material production. There are eight new varieties of A. annua with high artemisinin that have been tested since 2006 in China, and other four new breeding varieties are underway. Organic chemists around the world have developed a variety of methods to achieve the artemisinin total synthesis using citronellal, menthol derivatives, β -pinene, cyclohexenone etc. Arteannuic acid, artemisinin B and artemisitene biosynthesis have been industrially produced, and semi-synthetic based on these precursor substances accelerate the artificial preparation of artemisinin. However, many questions still remained unanswered in the field of artemisinin production. Additionally, the global rational distribution of production and layout of high quality A. annua based on ecological adaptation is necessary. This paper provides the theoretical basis for the selection of regional suitable planting areas. The resources regeneration and the production of raw materials for artemisinin play an important role in the sustainable development of artemisinin industry worldwide as well as the implementation of “the Belt and Road” global strategy on the Traditional Chinese Medicines.

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