Artemisinin

• Antiparasitic properties
• Anti-inflammatory effects
• Antioxidant activity
• Potential anticancer properties

• Immune system modulation
• Potential neuroprotective effects
• Liver protection
• Antimicrobial activity
• Potential anti-fibrotic effects
• Cardiovascular support

Artemisinin exerts its biological effects through multiple mechanisms, with its most well-characterized action being its antiparasitic activity against Plasmodium species that cause malaria. The primary mechanism involves the endoperoxide bridge (C-O-O-C) within artemisinin’s molecular structure, which is essential for its activity. When artemisinin encounters high concentrations of iron (Fe²⁺) in the form of heme or free iron, as found in the parasite’s food vacuole, the endoperoxide bridge undergoes reductive cleavage. This reaction generates highly reactive carbon-centered free radicals and reactive oxygen species (ROS).

These reactive intermediates then alkylate and oxidize parasite proteins and lipids, leading to cellular damage and ultimately parasite death. Artemisinin also inhibits the parasite’s calcium ATPase (PfATP6), disrupting calcium homeostasis critical for parasite survival. Additionally, artemisinin interferes with the parasite’s ability to detoxify heme, a byproduct of hemoglobin digestion, further contributing to its antiparasitic effects. Beyond its antimalarial activity, artemisinin exhibits anti-inflammatory properties through inhibition of the NF-κB signaling pathway, a master regulator of inflammatory responses.

This inhibition reduces the production of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6, and decreases the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Artemisinin also modulates immune function by affecting T-cell differentiation, promoting regulatory T-cells while suppressing Th17 cell development, which contributes to its immunomodulatory effects in autoimmune and inflammatory conditions. The antioxidant properties of artemisinin involve both direct and indirect mechanisms. While artemisinin can directly scavenge some free radicals, it primarily enhances endogenous antioxidant systems by activating the Nrf2/ARE pathway.

This activation increases the expression of antioxidant enzymes including superoxide dismutase (SOD), catalase, glutathione peroxidase, and heme oxygenase-1 (HO-1), providing comprehensive cellular protection against oxidative stress. Artemisinin’s anticancer potential stems from several mechanisms. Cancer cells typically contain higher iron concentrations than normal cells due to increased transferrin receptor expression, making them more susceptible to artemisinin’s iron-dependent cytotoxicity. The endoperoxide bridge reacts with intracellular iron to generate free radicals that damage DNA, proteins, and organelles, leading to cancer cell death.

Artemisinin also induces apoptosis through both intrinsic (mitochondrial) and extrinsic (death receptor) pathways, arrests the cell cycle primarily at the G1/S phase, and inhibits angiogenesis by reducing VEGF expression and endothelial cell proliferation. Additionally, artemisinin suppresses cancer cell migration and invasion by inhibiting matrix metalloproteinases (MMPs) and modulating epithelial-mesenchymal transition (EMT). In the context of fibrosis, artemisinin inhibits the TGF-β/Smad signaling pathway, a key driver of fibrotic processes, and reduces the production of extracellular matrix proteins such as collagen and fibronectin. It also inhibits the activation and proliferation of fibroblasts and myofibroblasts, the primary cellular mediators of fibrosis.

Artemisinin’s neuroprotective effects involve reducing neuroinflammation, inhibiting microglial activation, and protecting neurons from oxidative damage. It also modulates neurotransmitter systems and may enhance neurogenesis and synaptic plasticity. For cardiovascular protection, artemisinin improves endothelial function, reduces platelet aggregation, and modulates lipid metabolism, contributing to its potential benefits for cardiovascular health. These diverse mechanisms of action explain artemisinin’s wide range of biological effects and therapeutic potential across various disease conditions.

Artemisinin dosing varies significantly based on the specific condition being addressed and the form used. For general health maintenance and preventative purposes, lower doses ranging from 100-200 mg daily are typically used. For therapeutic purposes, higher doses ranging from 400-1000 mg daily, often divided into 2-3 doses, may be used. It’s important to note that artemisinin and its derivatives are primarily used medically for malaria treatment under healthcare supervision, with specific WHO-recommended dosing protocols.

For non-malarial applications, dosing is less standardized and should be determined in consultation with healthcare providers.

Artemisinin is typically taken with meals, particularly those containing fats, to enhance absorption. Due to its relatively short half-life, dividing the daily dose into 2-3 administrations (typically morning, midday, and evening) helps maintain more consistent blood levels. For individuals experiencing sleep disturbances, taking the last dose at least 3-4 hours before bedtime may be beneficial. For parasitic infections, timing may be coordinated with the parasite’s life cycle, though this approach requires professional guidance.

Some practitioners recommend a pulsed dosing schedule (e.g., 5 days on, 2 days off) for certain applications to prevent adaptation by parasites and minimize potential side effects.

Short Term: For acute conditions like parasitic infections, artemisinin is typically used for 5-10 days. For malaria treatment, WHO protocols typically recommend 3-7 days of artemisinin-based combination therapy.

Medium Term: For inflammatory conditions or as adjunctive cancer support, courses of 4-12 weeks may be used, often with periodic assessment of efficacy and side effects.

Long Term: Long-term use (beyond 3 months) should include periodic breaks (e.g., 1 week off after 3-4 weeks of use) and regular monitoring of liver function and blood parameters. Safety data for continuous long-term use is limited.

Artemisinin may interact with certain medications, particularly those metabolized by cytochrome P450 enzymes. Individuals with autoimmune conditions should use with caution due to immune-modulating effects. Those with known allergies to plants in the Asteraceae family may be at higher risk for allergic reactions. Individuals with G6PD deficiency should use artemisinin derivatives with caution due to potential hemolytic effects.

Artemisinin should be discontinued at least 2 weeks before scheduled surgery due to potential effects on blood clotting, though clinical significance is uncertain. Cycling artemisinin use (periods of use followed by breaks) may help prevent potential adaptation by parasites and minimize side effects during long-term use. Starting with lower doses and gradually increasing can help minimize initial side effects like digestive discomfort.

Artemisinin has relatively poor oral bioavailability, estimated at approximately 30% in humans.

This limited bioavailability is primarily due to its poor water solubility, extensive first-pass metabolism in the liver, and degradation in the acidic environment of the stomach. After oral administration, artemisinin reaches peak plasma concentrations (Cmax) within 1-2 hours, indicating relatively rapid absorption

despite the overall low bioavailability. The absorption is significantly affected by food intake, with fatty meals enhancing absorption by up to 2-3 fold compared to fasting conditions.

Artemisinin is best taken with meals, particularly those containing moderate to high amounts of fat, to significantly enhance absorption. Dividing the daily dose into 2-3 administrations throughout the day helps maintain more consistent blood levels, as artemisinin has a relatively short half-life of approximately 2-5 hours. For parasitic infections, some practitioners recommend timing doses to coincide with the parasite’s life cycle, though

this approach requires professional guidance. Taking the last dose of the day at least 3-4 hours before bedtime may help prevent potential sleep disturbances in sensitive individuals.

Primary Metabolic Pathways: Artemisinin undergoes extensive hepatic metabolism, primarily through cytochrome P450 enzymes, particularly CYP2B6, CYP3A4, and CYP2A6. The major metabolic pathways include: 1) Reduction of the endoperoxide bridge, 2) Hydroxylation at various positions, 3) Dehydrogenation reactions, and 4) Phase II conjugation reactions (glucuronidation and sulfation). The primary metabolites include deoxyartemisinin, dihydrodeoxyartemisinin, and various hydroxylated derivatives.

Enzymes Involved: CYP2B6 appears to be the primary enzyme responsible for artemisinin metabolism, with significant contributions from CYP3A4 and CYP2A6. UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) are responsible for Phase II conjugation reactions.

Elimination Routes: Metabolites are primarily excreted through the kidneys in urine (approximately 30-40%) with a larger portion eliminated via biliary excretion in feces (approximately 60-70%).

Half Life: The elimination half-life of artemisinin in humans is approximately 2-5 hours, necessitating multiple daily doses for sustained therapeutic effects. Artemisinin derivatives have varying half-lives: artesunate (0.5-1.5 hours), dihydroartemisinin (1-2 hours), artemether (3-11 hours), and arteether (23-32 hours).

After absorption, artemisinin distributes widely throughout the body tissues. Animal studies have shown significant distribution to the liver, kidneys, bile, and adipose tissue, with lower concentrations in the brain due to limited blood-brain barrier penetration. However, some artemisinin derivatives, particularly the lipid-soluble artemether and arteether, show enhanced brain penetration. The volume of distribution (Vd) is relatively large, indicating extensive tissue distribution.

Artemisinin and its metabolites have been detected in various tissues up to 24 hours after administration, despite the relatively short plasma half-life, suggesting tissue retention of certain metabolites.

Artesunate: Water-soluble derivative with improved bioavailability (60-70%) and rapid conversion to dihydroartemisinin, the active metabolite. Can be administered orally, rectally, intramuscularly, or intravenously, with intravenous administration providing 100% bioavailability and rapid action.

Artemether: Lipid-soluble derivative with improved oral bioavailability (40-60%) and longer half-life (3-11 hours). Better absorption in the presence of fats and enhanced penetration across the blood-brain barrier.

Dihydroartemisinin: Active metabolite of most artemisinin derivatives with moderate bioavailability (approximately 45%). Directly available as a pharmaceutical with more consistent absorption than artemisinin.

Arteether: Highly lipid-soluble derivative with the longest half-life (23-32 hours) among artemisinin compounds. Primarily used for intramuscular injection in specific clinical settings.

Artemisinin content in Artemisia annua (sweet wormwood) varies significantly based on plant variety, growing conditions, harvest time, and plant part used. Typical content ranges from 0.01-1.5% of dry weight. Traditional preparations like tea extractions typically yield low and variable amounts of artemisinin, with bioavailability further reduced by incomplete extraction and degradation during preparation. Studies suggest that tea preparations may extract only 10-30% of the artemisinin present in the plant material, with additional losses during digestion.

However, some research indicates that other compounds in the whole plant extract may enhance artemisinin absorption or provide synergistic effects, potentially compensating for lower artemisinin content.

No definitive upper limit has been established for non-medical use. For malaria treatment, WHO protocols typically use artemisinin derivatives at doses equivalent to 4-8 mg/kg/day for short durations (3-7 days). For non-medical applications, most practitioners recommend not exceeding 1000 mg daily for short-term use and 600 mg daily for longer-term use. Higher doses increase the risk of side effects, particularly neurotoxicity with prolonged use.

Clinical Data: Limited data exists on long-term safety beyond 3 months of continuous use. Most clinical studies have focused on short-term use for malaria treatment. Animal studies suggest potential concerns with neurotoxicity at high doses with prolonged use, particularly with oil-soluble derivatives (artemether, arteether), though human relevance is uncertain at typical supplemental doses.

Monitoring Recommendations: For long-term use (beyond 3 months), periodic monitoring of liver function, complete blood count, and renal function is recommended. Taking periodic breaks (e.g., 1 week off after 3-4 weeks of use) may reduce the risk of potential adverse effects with long-term use.

Population Differences: Safety profiles may vary across different populations. Individuals with G6PD deficiency may be at higher risk for hemolysis, particularly with artemisinin derivatives. Genetic variations in drug-metabolizing enzymes may affect individual responses and safety profiles.

Acute Toxicity: Artemisinin has relatively low acute toxicity with LD50 values >1000 mg/kg in rodent studies. Clinical experience with therapeutic doses shows good short-term safety profile.

Subchronic Toxicity: Animal studies show potential concerns with neurotoxicity at high doses with prolonged use, particularly with oil-soluble derivatives (artemether, arteether). Effects include gait disturbances, loss of righting reflex, and histopathological changes in brain stem nuclei. Human relevance is uncertain at typical supplemental doses.

Genotoxicity: Most studies indicate no significant mutagenic or genotoxic effects at therapeutic doses.

Reproductive Toxicity: Animal studies show embryotoxicity and developmental toxicity, particularly in early pregnancy. Limited human data suggests potential risk in first trimester, supporting contraindication during this period except for severe malaria when no alternatives exist.

Organ Specific Toxicity: Neurotoxicity is the primary concern with high-dose, prolonged use, particularly with oil-soluble derivatives. Mild and transient liver enzyme elevations have been reported in some cases. Hemolysis may occur in G6PD-deficient individuals, particularly with artemisinin derivatives.

Artemisinin and its derivatives have been widely used for malaria treatment with generally good safety profiles at recommended doses and durations. The WHO has conducted extensive monitoring of artemisinin-based combination therapies (ACTs) for malaria, with rare serious adverse events reported. Most concerns relate to specific derivatives, particular populations (e.g., first trimester pregnancy, G6PD deficiency), or prolonged use at high doses.

For non-medical applications, systematic post-market surveillance data is limited, highlighting the need for caution with long-term use and in special populations.

Classification: Dual status: Pharmaceutical ingredient (derivatives) and Dietary Supplement (pure artemisinin)

Approval Status: Artemisinin derivatives (artemether, artesunate) are FDA-approved for treatment of severe malaria. Pure artemisinin is not FDA-approved as a drug but may be sold as a dietary supplement.

Regulatory Framework: Artemisinin derivatives are regulated as prescription drugs under the Federal Food, Drug, and Cosmetic Act. Pure artemisinin as a supplement is regulated under the Dietary Supplement Health and Education Act (DSHEA) of 1994.

Allowed Claims: As a dietary supplement, structure/function claims related to general health maintenance are permitted with appropriate disclaimer. Disease claims, particularly regarding malaria treatment, are not permitted for supplement forms.

Manufacturing Requirements: Pharmaceutical artemisinin derivatives must be produced in compliance with Current Good Manufacturing Practices (cGMP) for pharmaceuticals. Supplement forms must comply with cGMP for dietary supplements, which are less stringent.

Safety Status: No formal FDA safety evaluation specifically for artemisinin as a supplement; considered safe when used as directed based on history of use and available research.

Completed Trials: Extensive clinical trials for malaria treatment with artemisinin derivatives, establishing safety and efficacy. Limited clinical trials for non-malarial applications including cancer, viral infections, and inflammatory conditions.

Ongoing Trials: Multiple clinical trials investigating artemisinin and derivatives for cancer (particularly colorectal cancer), COVID-19, and other viral infections. Also trials evaluating new formulations and combinations for malaria treatment.

Research Gaps: Limited large-scale clinical trials for non-malarial applications; more research needed on optimal dosing and safety for long-term use in conditions other than malaria.

Formal Evaluations: Extensive safety evaluations for pharmaceutical artemisinin derivatives by regulatory agencies worldwide. Limited formal safety evaluation specifically for artemisinin as a supplement.

Safety Data: Generally recognized as safe for short-term use at recommended doses. Concerns about neurotoxicity with high-dose, prolonged use based on animal studies, though human relevance is uncertain at typical supplemental doses.

Monitoring Systems: WHO and national pharmacovigilance programs actively monitor adverse events associated with artemisinin-based antimalarials. Supplement forms subject to standard adverse event reporting systems for dietary supplements in various countries.

Dual status as both pharmaceutical ingredient and dietary supplement creates regulatory complexity, Ensuring quality and preventing counterfeit products, particularly in malaria-endemic regions, Managing artemisinin resistance development through appropriate use guidelines, Balancing access for malaria treatment with appropriate restrictions to prevent misuse, Addressing regulatory pathways for emerging non-malarial applications, Harmonizing international regulations for both pharmaceutical and supplement forms

Potential Developments: Expanded approved indications for artemisinin derivatives beyond malaria, Development of specific regulatory frameworks for traditional antimalarials used as supplements, Increased restrictions on supplement forms to prevent inappropriate use for malaria self-treatment, Harmonization of quality standards across pharmaceutical and supplement forms, Development of specific guidelines for artemisinin use in integrative oncology

Resistance Management: Regulatory strategies to preserve artemisinin efficacy against malaria, including combination therapy requirements, quality assurance programs, and restricted access policies in some regions.

Medium to High

Range: $1.00 – $5.00 per day for standard effective dose (400-1000 mg of pure artemisinin)

Factors Affecting Cost: Purity level (pharmaceutical grade vs. supplement grade), Source (natural extraction vs. semi-synthetic production), Form (pure artemisinin vs. derivatives), Brand reputation and quality control measures, Global market fluctuations in artemisinin supply, Scale of production, Regulatory compliance costs

Price Comparison: $0.80 – $2.00 per effective daily dose, $2.00 – $3.50 per effective daily dose, $3.50 – $5.00+ per effective daily dose

Pharmaceutical Forms: Artemisinin-based pharmaceutical products for malaria treatment are typically covered by health insurance in developed countries and by national health programs or global health initiatives in endemic regions.

Supplement Forms: Rarely covered by conventional health insurance. May be eligible for purchase using Health Savings Accounts (HSAs) or Flexible Spending Accounts (FSAs) in some jurisdictions with appropriate documentation.

Integrative Oncology: Some integrative oncology programs may include artemisinin in treatment protocols with partial coverage, particularly in research settings or specialized cancer centers.

Global Health Perspective: Artemisinin-based treatments for malaria represent one of the most cost-effective health interventions globally, with economic benefits far exceeding costs in endemic regions through reduced mortality, morbidity, and lost productivity.

Supplement Market Perspective: The artemisinin supplement market represents a small but growing segment, with economic impact limited by relatively high cost and specialized applications compared to mainstream supplements.

Production Economics: Agricultural production of Artemisia annua remains the primary source of artemisinin despite advances in semi-synthetic production. Market prices have fluctuated significantly over the past decade due to varying demand for malaria treatment and variable agricultural production. Semi-synthetic production has helped stabilize supply but at potentially higher cost.

Pricing Trends: Prices for pharmaceutical-grade artemisinin have stabilized in recent years after significant fluctuations in the 2000s-2010s. Supplement-grade artemisinin prices remain relatively high but stable, with premium formulations (liposomal, nanoparticle) commanding significant price premiums.

Market Segmentation: Growing differentiation between basic artemisinin supplements and premium formulations with enhanced bioavailability or specialized delivery systems, with corresponding price stratification.

Future Projections: Potential for moderate price decreases as production scales increase and more competitors enter the supplement market. Development of improved semi-synthetic production methods may also influence pricing in the coming years.

Pure artemisinin is relatively stable

when properly stored, with a typical shelf life of 3-5 years from the date of manufacture. Artemisinin derivatives have varying stability profiles: artesunate is the least stable (1-2 years),

while artemether and dihydroartemisinin have intermediate stability (2-3 years), and arteether has the longest shelf life (3-4 years). Formulated products like tablets and capsules typically have a shelf life of 2-3 years,

while liquid formulations generally have shorter shelf lives (1-2 years). The primary factors affecting shelf life are exposure to heat, light, moisture, and oxygen, which can degrade the critical endoperoxide bridge that is essential for artemisinin’s biological activity.

High-Performance Liquid Chromatography (HPLC) for monitoring artemisinin content and detecting degradation products, Liquid Chromatography-Mass Spectrometry (LC-MS) for detailed analysis of degradation pathways and products, Fourier-Transform Infrared Spectroscopy (FTIR) for monitoring structural changes, particularly in the endoperoxide bridge, Nuclear Magnetic Resonance (NMR) spectroscopy for structural confirmation and degradation analysis, Accelerated stability testing under controlled temperature and humidity conditions (typically 40°C/75% RH) to predict long-term stability, Photostability testing under defined light conditions according to ICH guidelines, Real-time stability testing under recommended storage conditions, Bioassays against Plasmodium falciparum or cancer cell lines to confirm retention of biological activity

Artemisinin and its derivatives should be protected from extreme temperatures during transport. Prolonged exposure to temperatures above 30°C (86°F) or below freezing should be avoided. For international shipping or transport through varying climate zones, temperature-controlled shipping may be necessary, particularly for artemisinin derivatives and liquid formulations. Proper packaging with moisture barriers, temperature indicators, and protection from physical damage is important to maintain product integrity.

Bulk raw materials are particularly susceptible to damage during transport and should be packaged with desiccants and in moisture-resistant, light-protective containers. Injectable formulations often require cold chain management during transport and distribution.

Inclusion of appropriate antioxidants (e.g., butylated hydroxytoluene, ascorbic acid) in formulations to prevent oxidative degradation, Use of desiccants in packaging to control moisture exposure, pH adjustment in liquid formulations to optimize stability (typically pH 5-6), Development of specialized formulations like liposomes or nanoparticles that can protect artemisinin from degradation, Use of coating technologies for solid oral dosage forms to provide moisture and light protection, Nitrogen purging of containers to remove oxygen before sealing, Selection of appropriate excipients that do not catalyze degradation or interact with artemisinin, Development of co-crystal formulations with improved stability profiles

Natural Sources

Cultivation Methods

Extraction Methods

Synthetic Methods

Quality Considerations

Geographical Considerations

Sustainability Aspects

Commercial Considerations

Context: In 1967, during the Vietnam War, the Chinese government launched Project 523, a secret military project to find new antimalarial drugs. Malaria was causing more casualties than combat among Vietnamese soldiers, and existing drugs were losing effectiveness due to resistance.

Traditional Knowledge Role: Professor Tu Youyou was assigned to screen traditional Chinese herbs for antimalarial activity. She reviewed over 2,000 traditional Chinese medicine recipes and tested 380 herbal extracts.

Breakthrough: Tu found a reference in Ge Hong’s ‘Handbook of Prescriptions for Emergency Treatments’ from 340 CE describing the use of Qinghao (Artemisia annua) for treating intermittent fevers. Crucially, the text specified using cold extraction rather than traditional hot decoction, which Tu realized might preserve heat-sensitive active compounds.

Extraction Innovation: Based on this insight, Tu modified the extraction method to use low-temperature ether instead of the traditional hot water extraction, significantly increasing the antimalarial activity of the extract. This represented a critical innovation that bridged traditional knowledge with modern scientific methods.

Testing And Validation: The extract showed remarkable efficacy against malaria parasites in animal models and subsequently in human clinical trials. Tu and her team isolated the active compound, artemisinin (qinghaosu), in 1972 and determined its chemical structure by 1975.

Personal Sacrifice: During the Cultural Revolution period, clinical trials were conducted under difficult conditions. Tu and her colleagues volunteered to be the first human subjects to test the safety of the extract before administering it to patients.

Global Impact: The discovery of artemisinin has saved millions of lives worldwide and represents one of the most significant contributions of traditional medicine to modern pharmacology. Tu Youyou was awarded the Nobel Prize in 2015, becoming the first Chinese Nobel laureate in physiology or medicine and the first Chinese Nobel laureate in natural sciences.

China: Artemisinin (qinghaosu) is considered a national treasure in China, representing the value of traditional Chinese medicine and its contribution to global health. The discovery story is taught in schools as an example of Chinese scientific achievement and the importance of traditional knowledge.

Global Health: Artemisinin-based treatments have become the cornerstone of malaria control programs worldwide, particularly in Africa and Southeast Asia where malaria burden is highest. The compound represents a rare example of a major pharmaceutical derived directly from traditional medicine.

Scientific Recognition: The awarding of the Nobel Prize to Tu Youyou in 2015 represented significant recognition of the value of exploring traditional medicine systems for modern drug discovery, potentially changing attitudes in the scientific community.

Traditional To Modern Bridge: The artemisinin story is frequently cited as the ideal model for integrating traditional knowledge with modern scientific methods, demonstrating how ancient wisdom can be validated and refined through contemporary research.

Traditional Methods: Originally prepared as a cold water extraction of fresh Artemisia annua leaves, as described in Ge Hong’s text. This method was specifically different from the usual hot decoction method used for most Chinese herbs, suggesting early empirical recognition of artemisinin’s heat sensitivity.

Modern Extraction: Tu Youyou’s breakthrough came from using low-temperature ether extraction instead of water, which preserved the heat-sensitive endoperoxide bridge essential for artemisinin’s activity. This represented a critical bridge between traditional knowledge and modern pharmaceutical development.

Pharmaceutical Development: Evolution from crude extracts to isolated pure artemisinin, followed by development of semi-synthetic derivatives with improved pharmacokinetic properties (artemether, artesunate, dihydroartemisinin, arteether). Each generation of compounds addressed specific limitations of the previous forms.

Combination Therapies: Development of artemisinin-based combination therapies (ACTs) to prevent resistance development, representing a modern application of the traditional concept of herbal formulations with multiple active components working synergistically.

Ancient Period: Use primarily confined to China and nearby regions where Artemisia annua was native or cultivated.

Medieval Period: Knowledge of Artemisia species for medicinal use spread along trade routes to parts of Central Asia and the Middle East, though specific preparation methods for antimalarial use may not have transferred.

Colonial Period: European documentation of Chinese medicinal plants included references to Artemisia species, but the specific antimalarial application of Artemisia annua was not widely recognized or adopted in Western medicine.

Modern Period: Following the isolation of artemisinin in the 1970s and publication in international journals in the 1980s, knowledge spread globally, leading to worldwide adoption of artemisinin-based therapies for malaria by the early 2000s.

Phase II trial of oral artesunate for colorectal cancer (NCT02633098), Artemisinin derivatives for treatment of COVID-19 (multiple trials including NCT04387240), Artesunate for treatment of metastatic breast cancer (NCT03093129), Artemisinin-based therapy for autoimmune conditions including rheumatoid arthritis (NCT04446104), Artesunate as adjunctive therapy for cerebral malaria (PACTR202007653561299)

Long-term safety data for non-malarial applications, Optimal dosing strategies for anticancer applications, Comparative effectiveness studies against standard treatments for inflammatory conditions, Mechanisms of action for neurological and metabolic effects, Pharmacokinetic studies in special populations (elderly, pediatric), Development of formulations with improved bioavailability, Strategies to prevent or overcome artemisinin resistance in malaria