Traditional application and modern pharmacological research of Artemisia annua L.

doi:10.1016/j.pharmthera.2020.107650

Pharmacology & Therapeutics

Volume 216, December 2020, 107650

https://doi.org/10.1016/j.pharmthera.2020.107650 Get rights and content

Abstract

As a Traditional Chinese Medicine, Artemisia annua L. (A. annua) has been used for the treatment of various diseases since ancient times, including intermittent fevers due to malaria, bone steaming and heat/fever arising from exhaustion, tuberculosis, lice, wounds, scabies, dysentery et al. With the discovery of artemisinin and its excellent anti-malarial activity, A. annua has received great attention. Recently, A. annua has been revealed to show inhibitory effects against parasites (e.g. Plasmodium, Toxoplasma gondii, Leishmania, Acanthamoeba, Schistosoma), viruses (e.g. hepatitis A virus, herpes simplex viruses 1 and 2, human immunodeficiency virus), fungi (Candida, Malassezia, Saccharomyces spp.) and bacteria (Enterococcus, Streptococcus, Staphylococcus, Bacillus, Listeria, Haemophilus, Escherichia, Pseudomonas, Klebsiella, Acinetobacter, Salmonella, Yersinia spp.). A. annua has also been reported to possess anti-inflammatory and anti-cancer actions and been employed for the treatment of osteoarthritis, leukemia, colon cancer, renal cell carcinoma, breast cancer, non-small cell lung cancer, prostate cancre and hepatoma. Besides, the immunoregulation, anti-adipogenic, anti-ulcerogenic, anti-asthmatic, anti-nociceptive and anti-osteoporotic activities of A. annua were also evaluated. Along these lines, this review summarizes the traditional application and modern pharmacological research of A. annua, providing novel insights of A. annua in the treatment of various diseases.

Introduction

Artemisia annua L. (A. annua), a plant belonging to the Asteraceae family, grows wild in Asia (mainly China, Japan and Korea) and it was introduced to Poland, Brazil, Spain, France, Italy, Romania, United States and Austria, where it became domesticated (Klayman, 1993). It has been used by Chinese herbalists for the treatment of various diseases since ancient times (Hsu, 2006; Liu, 2017). In 1967, a national research project against malaria was initiated in China. More than 380 herbal extracts were evaluated by Chinese scholar Tu Youyou for their anti-malarial activities and A. annua was found to be the most active herb (Tu, 2011). Then, in 1971, an endoperoxide sesquiterpene lactone named artemisinin was isolated and characterized as the active principle of A. annua against malaria. From then on, as the only commercial source of artemisinin, A. annua gained a widespread attention (de Ridder, van der Kooy, & Verpoorte, 2008).

Nowadays, there are still continuous efforts in delineating the mechanisms of action for anti-malaria activities of A. annua and artemisinin (Ding, Beck, & Raso, 2011; Wang et al., 2015). In the meantime, within the last few decades, A. annua has been investigated for its effects in various diseases, ranging from inflammatory, cancers to viral, bacterial and parasite-related infection (Alesaeidi & Miraj, 2016; Bilia, Santomauro, Sacco, Bergonzi, & Donato, 2014; Efferth, 2017). The extensive biological activities made A. annua a promising therapeutic to be widely used in clinical therapy. The aim of this review was to provide a comprehensive overview on the traditional application and the modern pharmacological research associated with A. annua, providing novel insights of A. annua in the treatment of various diseases.

Section snippets

Traditional application of A. annua

A. annua was first recorded in “52 Sickness Sides (Wu Shi Er Bing Fang)”, a medical prescription excavated in the Mawangdui Han Tombs for the treatment of haemorrhoids. Application of A. annua for the treatment of fever and chills related to malarial was first mentioned by Hong Ge (284–365 CE) in “Handbook of Prescriptions for Emergencies”. Nowadays, A. annua has been officially recognized as a medicinal plant and listed in Chinese Pharmacopeia. As recorded in ancient medical textbooks, A. annua

Malaria parasites (Plasmodium)

Infection with malaria parasites may result in a wide variety of symptoms, ranging from absent or very mild symptoms to severe disease and even death. Malaria is still a leading cause of illness and death in several countries. The World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) for the treatment of uncomplicated malaria due to Plasmodium falciparum. Nowadays, a number of herbal remedies made of A. annua are available and suggested for the prevention and

Novel components isolated from A. annua and their biological activities

A. annua had been one of the most widely investigated herbs since the isolation of artemisinin in 1972. During the past few decades, phytochemical investigations have demonstrated that sesquiterpenoids, flavonoids, coumarins, triterpenoids and phenolics were the main components existing in A. annua (Bhakuni, Jain, Sharma, & Kumar, 2001). Even though over 600 components were isolated and identified, investigators were still doing their best to fully elucidate the phytochemical profiles of A.

Current developments and limitations of A. annua

As described in this review, A. annua has been proved to possess a variety of pharmacological activities (Fig. 5). Compared with its recommended therapeutic usages recorded in ancient Chinese medical textbooks, there are still several traditional usages are not estimated by modern pharmacological researches, including wounds, dysentery, haemorrhoids, rhinopolyp, tuberculosis, et al. Further investigations are still needed to fully reveal the potential clinical application of A. annua and the

Summary

In summary, extensive in vitro and in vivo data have revealed that A. annua possess excellent anti-malarial effects and multiple other biological activities, including anti-parastic, anti-viral, anti-fungal, anti-bacterial, anti-inflammatory, anti-cancer, anti-adipogenic, anti-osteoporotic, anti-asthmatic, anti-ulcerogenic, anti-nociceptive and immunoregulation, supporting the promising therapeutic application of A. annua in various human diseases. For the next decade, more clinical indications

Declaration of Competing Interest

The authors have no conflict of interest.

Acknowledgment

This work was supported by the Technology Major Project of China “Key New Drug Creation and Manufacturing Program” (2017ZX09301012-001) and the Major State Basic Research Development Program of China (No. 2014CB560706).

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Artemisinin (ART) is a bioactive compound isolated from the plant Artemisia annua and has been traditionally used to treat conditions such as malaria, cancer, viral infections, bacterial infections, and some cardiovascular diseases, especially in Asia, North America, Europe and other parts of the world. This comprehensive review aims to update the biomedical potential of ART and its derivatives for treating human diseases highlighting its pharmacokinetic and pharmacological properties based on the results of experimental pharmacological studies in vitro and in vivo. Cellular and molecular mechanisms of action, tested doses and toxic effects of artemisinin were also described. The analysis of data based on an up-to-date literature search showed that ART and its derivatives display anticancer effects along with a wide range of pharmacological activities such as antibacterial, antiviral, antimalarial, antioxidant and cardioprotective effects. These compounds have great potential for discovering new drugs used as adjunctive therapies in cancer and various other diseases. Detailed translational and experimental studies are however needed to fully understand the pharmacological effects of these compounds.

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Traditional application and modern pharmacological research of Artemisia annua L.

Abstract

Introduction

Section snippets

Traditional application of A. annua

Malaria parasites (Plasmodium)

Novel components isolated from A. annua and their biological activities

Current developments and limitations of A. annua

Summary

Declaration of Competing Interest

Acknowledgment

Phytomedicine

Bioorganic & Medicinal Chemistry

Lancet

Journal of Ethnopharmacology

Industrial Crops and Products

African Journal of Traditional, Complementary and Alternative Medicines

Journal of Ethnopharmacology

Biomedicine & Pharmacotherapy

The Lancet Infectious Diseases

Placenta

Phytomedicine

Trends in Parasitology

LWT - Food Science and Technology

Seminars in Cancer Biology

Biotechnology Advances

Food Chemistry

Biochemical Pharmacology

Pharmacology & Therapeutics

Transactions of the Royal Society of Tropical Medicine and Hygiene

Journal of Ethnopharmacology

Fitoterapia

Journal of Ethnopharmacology

Pharmacological Research

Phytomedicine

Fitoterapia

Toxicology and Applied Pharmacology

Chinese Herbal Medicines

Pharmacological Research

Journal of Ethnopharmacology

Food Chemistry

Phytomedicine

Lancet

Transactions of the Royal Society of Tropical Medicine and Hygiene

Phytomedicine

Experimental Parasitology

A systematic review of anti-malarial properties, immunosuppressive properties, anti-inflammatory properties, and anti-cancer properties of Artemisia annua

Electronic Physician

Concentration and time dependency of artemisinin efficacy against Plasmodium falciparum in vitro

The American Journal of Tropical Medicine and Hygiene

Anti-adipogenic effect of Artemisia annua in diet-induced-obesity mice model

Journal of Veterinary Science

Secondary metabolites of Artemisia Artemisia annua and their biological activity

Current Science

Artemisinin and its derivatives in cancer therapy: Status of progress, mechanism of action, and future perspectives

Cancer Chemotherapy and Pharmacology

Essential oil of Artemisia annua L.: An extraordinary component with numerous antimicrobial properties

Evidence-Based Complementary and Alternative Medicine

Herba Artemisiae annuae tea preparation compared to sulfadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria in adults: A randomized double-blind clinical trial

Tropical Doctor

The biosynthesis of artemisinin (Qinghaosu) and the phytochemistry of Artemisia annua L. (Qinghao)

Molecules

Korean medicinal plants inhibiting to human immunodeficiency virus type 1 (HIV-1) fusion

Phytotherapy Research

Anti-inflammatory and acetylcholinesterase activity of extract, fractions and five compounds isolated from the leaves and twigs of Artemisia annua growing in Cameroon

Springerplus

New sesquiterpene and polymethoxy-flavonoids from Artemisia annua L

Pharmacognosy Magazine

Antitumor activity of artemisinin and its derivatives: From a well-known antimalarial agent to a potential anticancer drug

Journal of Biomedicine & Biotechnology

The leishmanicidal activity of artemisinin is mediated by cleavage of the endoperoxide bridge and mitochondrial dysfunction

Parasitology

Artemether exhibits amoebicidal activity against Acanthamoeba castellanii through inhibition of the serine biosynthesis pathway

Antimicrobial Agents and Chemotherapy

Artemisia annua L. as a plant with potential use in the treatment of acanthamoebiasis

Parasitology Research