Materia Medica, Pharmacology & Bio-Prospecting

Huang Hua Hao, Artemisinin, and Malaria

The Bencao Gangmu or Compendium of Materia Medica is a compilation of Chinese medical matter and natural history up to the 16th century. Written by Li Shizhen, a Chinese acupuncturist, herbalist, naturalist, pharmacologist, physician, and writer of the Ming dynasty (1368–1644 AD), it is a nine volume encyclopedia, first published around 1596, containing thousands of observations, manipulations, and applications of various plants, earth, and animals for human health. When writing the Bencao Gangmu, Li Shizhen traveled across China and studied a variety of sources, making this not just a medicinal guide but also a summary of accumulated Chinese medical history.

By studying the texts of ancient Chinese physicians, modern-day scientists were able to discern Huang Hua Hao (黄花蒿), or Artemisia annua L (Sweet Wormwood), as a possible treatment for Malaria. Records from the third century CE claim that Artemisia annua L. primarily grew in “wastelands,” though today they can be found on mountain slopes, riverbeds, roadsides, and open fields throughout southern and northern China. In the Bencao Gangmu, Artemisia annua L.is classified as “Aromatic plants” and later placed in the order Campanulales for modern taxonomy (Sung et al. 1995). Li Shizhen categorized Materia Medica into 16 categories based on “natural properties, such as water, fire, earth, metal and mineral, grass, cereal, vegetable, fruit, wood, insect, scale, crab shell, bird, animal and human beings” (Li and Liang 2015). These major categories are then divided and arranged into inorganic to organic and lower to higher.

Qing Hao (青蒿), or Artemisia carvifolia, is another species of Artemisia that is often confused with Huang Hua Hao due to different taxonomic methods in traditional Chinese texts. Due to the confusion in the naming of Qing Hao and Huang Hua Hao, Qing Hao is often used to describe Huang Hua Hao when looking at antimalarial treatment. 

Artemisinin (青蒿素 Qing Hao Su) was later isolated as the active component for the antimalarial properties of the plant and used to develop modern treatments for Malaria. Huang Hua Hao is used most often in research as it is the only Artemisia species with appreciable levels of artemisinin and as such will be the focus of our research.

Artemisinin first gathered attention as a treatment for malaria in 1967 when it was isolated from Huang Hua Hao by Chinese pharmaceutical chemist and malariologist, Tu Youyou, and her colleagues. Tu was financed by the People’s Republic of China under Project 523, which was a secret military project designed to discover antimalarial treatments to prevent excess death during the Vietnam War.

Tu and her colleagues investigated old texts for traditional Chinese herbs and treatments, including a 3rd century work by Ge Hong and Li Shizhen’s Bencao Gangmu (Compendium of Materia Medica, 1578). This work contained information about the treatment of intermittent fevers, a characteristic of a Malarial infection, using "Qing Hao" (the traditional medical-nosological terms of the ingredient). In the original text, whole, fresh Huang Hua Hao was soaked and made into juice for ingestion. Since the text did not provide details on the exact species or parts of the plant that needed to be extracted, Tu and her team attempted various ways of preparing different types of Qing Hao in order to find the most effective solution. Through this, Artemisinin was developed as the current most effective treatment for Malaria. Tu’s work with Artemisinin later won the Nobel Prize in Physiology and Medicine, fueling interest in both Huang Hua Hao and Chinese Materia Medica.

In this project, we will be looking at Artemisia annua L and how traditional Chinese medicine is documented and categorized. Additionally, we would like to explore how that information has been used when discovering new drugs and developing treatments. Through this, we will elaborate on the effects of traditional Chinese Materia Medica used in conjunction with Western techniques to advance our understanding of medicine.

Due to its antiviral properties, chemists from Max Planck Institute of Colloids collaborated with virologists from Freie Universität Berlin to research the potential effects of Artemisia annua L. on SARS-CoV-2. In May of 2020, the University of Kentucky initiated a clinical trial to test the efficacy of Artemisia annua L. extract and its derivative, Artesunate, which is a known antiviral treatment for malaria. The Artemisia annua L. extract is attractive to researchers due to its excellent safety profiles, availability and low costs. In the future, the team would like to conduct a placebo-control clinical trial to test the efficacy of the extract.

Additionally, the University of Kentucky and UK Markey Cancer Center have collaborated with ArtemiLife to study the extent of the plant’s anti-cancer properties. In the case of ovarian cancer, patients in remission have the greatest risk of recurrence, often highest within the first two years. Gynecologic oncologist Dr. Frederick Ueland at the UK Markey Cancer Center predicts that Artemisia annua L. extract could be an “innovative therapy for advanced-stage cancer.” A study published by UK Markey Cancer Center showed evidence that Artesunate is effective against multiple cancer types resistant to standard treatments. Researchers would like to replicate this study and elaborate further.

Works Cited 

"Artemisia Annua Could Be Promising Treatment for COVID-19." UK College of Medicine. Last modified July 18, 2020. https://research.med.uky.edu/news/artemisia-annua-could-be-promising-treatment-covid-19.

ArtimisiaLiu. "[2015 Nobel Prize] What is the Relationship Between Artemisinin, Artemisia Annua and Artemisia Annua?" Editorial. Guo Kang. https://www.guokr.com/article/440801/.

Hsu, Elisabeth. "The History of Qing Hao in the Chinese Materia Medica." Transactions of the Royal Society of Tropical Medicine and Hygiene 6, no. 100 (June 2006): 505-08. https://doi.org/10.1016/j.trstmh.2005.09.020.

Linnaeus, Carl. "Artemisia annua." In Species Plantarum, 653-91. Vols. 20-21. Stockholm, Sweden:Laurentius Salvius, 1753. http://www.efloras.org/fl

Sung, Jung Sook, Kang Tae Suh, Sung Gi Moon, and Chung Kyu Lee. "Classification of Entries in Bon-cho-kang-mok (Ben Cao Gang Mu) - I. Entries in the Part of Herbs." Kor. J. Pharmacogn 3, no. 26 (1995): 276-306.

University of Kentucky College of Medicine. "Preventing Cancer Recurrence with Coffee? Markey Launches Unique Clinical Trial." UK College of Medicine. Last modified April 26, 2021. https://research.med.uky.edu/news/preventing-cancer-recurrence-coffee-markey-launches-unique-clinical-trial.

Zhang, Zhibin, and Paul U. Unschuld. "1. The Ben cao gang mu Project." Introduction to Chinese Historical Illness Terminology, 9-43. Vol. 1 of Dictionary of the Ben Cao Gang Mu. 2014. https://content.ucpress.edu/chapters/12851.ch01.pdf.

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