Artemisia Annua (Sweet Wormwood) and Artemisinin

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Mode of action: interaction with iron

Artemisinin’s anticancer activity is believed to occur when it comes in contact with iron. Cancer cells concentrate iron for use in cellular division (the malaria parasite also collects high concentrations of iron). Artemisinin’s contact with iron triggers the release of free radicals between cells that destroy cancer cells. Because of this “ferroptosis” effect, iron is often administered several hours before artemisinin to enhance targeting the cancer cells while sparing normal cells.¹Hu Y, Guo N et al. The potential mechanisms by which artemisinin and its derivatives induce ferroptosis in the treatment of cancer. Oxidative Medicine and Cellular Longevity. 2022 Jan 4;2022:1458143; Crespo-Ortiz MP, Wei MQ. Antitumor activity of artemisinin and its derivatives: from a well-known antimalarial agent to a potential anticancer drug. Journal of Biomedicine and Biotechnology. 2012;2012:247597. Some research shows that the effectiveness of artemisinin against colorectal cancer cells is enhanced by the addition of aminolevulinic acid, a clinically used heme synthesis precursor, to increase heme levels.²Wang J, Zhang J et al. Mechanistic investigation of the specific anticancer property of artemisinin and its combination with aminolevulinic acid for enhanced anticolorectal cancer activity. ACS Central Science. 2017;3(7):743–750.

Preclinical evidence

Notable preclinical evidence is presented here; clinical evidence is in How can Artemisia annua and artemisinin help you? What the research says ›

Improving treatment outcomes

Veterinary evidence of better survival than expected among pets with sarcoma treated with Artemisia annua

• Survival of 40 and 37 months without tumor relapse by a cat and a dog with fibrosarcoma, and a further dog with complete remission of fibrosarcoma and another with remission of hemangioendothelial sarcoma treated after surgical tumor removal with powder of Herba Artemisiae annuae³Breuer E, Efferth T. Treatment of iron-loaded veterinary sarcoma by Artemisia annua. Natural Products and Bioprospecting. 2014 Apr;4(2):113-8.

Preclinical evidence of less tumor growth and lower cancer cell viability, adhesion, and invasion in cancer cells treated with Artemisia annua extracts or artemisinin

Cancer as a whole

• Less tumor growth in 1321N1 astrocytoma, MCF-7 breast cancer, THP-1 leukemia, and LNCaP, Du-145, and PC-3 prostate cancer cells treated with alcohol extracts of Artemisia annua⁴Worku N, Mossie A et al. Evaluation of the in vitro efficacy of Artemisia annua, Rumex abyssinicus, and Catha edulis Forsk extracts in cancer and Trypanosoma brucei cells. ISRN Biochemistry. 2013 Sep 22;2013:910308.
• Substantially less development of solid tumors (mastocytoma) in mice treated with artemisinin⁵Tilaoui M, Mouse HA, Jaafari A, Zyad A. Differential effect of artemisinin against cancer cell lines. Natural Products and Bioprospecting. 2014 Jun;4(3):189-96.

Bladder cancer

• Artemisinin enhanced cytotoxic activity of miconazole against bladder cancer cells in preclinical studies⁶Efferth T. Cancer combination therapies with artemisinin-type drugs. Biochemical Pharmacology. 2017 Sep 1;139:56-70.
• Artemisinin enhanced anticancer activity of butyric acid against bladder cancer cells in preclinical studies⁷Efferth T. Cancer combination therapies with artemisinin-type drugs. Biochemical Pharmacology. 2017 Sep 1;139:56-70.

Brain cancer

• Artemisinin enhanced anticancer activity of curcumin against brain tumor cells in preclinical studies⁸Efferth T. Cancer combination therapies with artemisinin-type drugs. Biochemical Pharmacology. 2017 Sep 1;139:56-70.

Breast cancer

• Anticancer activity against MDA-MB-231 breast cancer cells treated with polyphenols from Korean Artemisia annua L⁹Ko YS, Lee WS et al. Polyphenols from Artemisia annua L inhibit adhesion and EMT of highly metastatic breast cancer cells MDA-MB-231. Phytotherapy Research. 2016 Jul;30(7):1180-8.
• Anticancer activity against human breast cancer cells treated with artemisinin in preclinical studies¹⁰Tin AS, Sundar SN et al. Antiproliferative effects of artemisinin on human breast cancer cells requires the downregulated expression of the E2F1 transcription factor and loss of E2F1-target cell cycle genes. Anticancer Drugs. 2012 Apr;23(4):370-9.
• Artemisinin enhanced cytotoxic activity of miconazole against breast cancer cells in preclinical studies¹¹Efferth T. Cancer combination therapies with artemisinin-type drugs. Biochemical Pharmacology. 2017 Sep 1;139:56-70.
• Artemisinin enhanced anticancer activity of butyric acid against breast cancer cells in preclinical studies¹²Efferth T. Cancer combination therapies with artemisinin-type drugs. Biochemical Pharmacology. 2017 Sep 1;139:56-70.
• Artemisinin enhanced the anticancer activity of halofuginone against breast cancer cells in preclinical studies¹³Efferth T. Cancer combination therapies with artemisinin-type drugs. Biochemical Pharmacology. 2017 Sep 1;139:56-70.

Cervical cancer

• Artemisinin enhanced anticancer activity of resveratrol against cervical cancer cells in preclinical studies¹⁴Efferth T. Cancer combination therapies with artemisinin-type drugs. Biochemical Pharmacology. 2017 Sep 1;139:56-70.

Colorectal cancer

• Artemisinin is able to target colorectal cancer cells rather than normal colon epithelial cells, an effect enhanced by the addition of aminolevulinic acid (ALA).¹⁵Wang J, Zhang J et al. Mechanistic investigation of the specific anticancer property of artemisinin and its combination with aminolevulinic acid for enhanced anticolorectal cancer activity. ACS Central Science. 2017;3(7):743–750.
• Artemisinin enhanced the anticancer activity of halofuginone against colon cancer cells in preclinical studies¹⁶Efferth T. Cancer combination therapies with artemisinin-type drugs. Biochemical Pharmacology. 2017 Sep 1;139:56-70.

Kidney cancer

• Less development of kidney adenocarcinoma in mice treated with artemisinin¹⁷Tilaoui M, Mouse HA, Jaafari A, Zyad A. Differential effect of artemisinin against cancer cell lines. Natural Products and Bioprospecting. 2014 Jun;4(3):189-96.

Liver cancer

• Anticancer activity against human hepatoma cells treated with artemisinin¹⁸Hou J, Wang D, Zhang R, Wang H. Experimental therapy of hepatoma with artemisinin and its derivatives: in vitro and in vivo activity, chemosensitization, and mechanisms of action. Clinical Cancer Research. 2008 Sep 1;14(17):5519-30.
• Artemisinin enhanced anticancer activity of resveratrol against liver cancer cells in preclinical studies¹⁹Efferth T. Cancer combination therapies with artemisinin-type drugs. Biochemical Pharmacology. 2017 Sep 1;139:56-70.

Lung cancer

• Artemisinin inhibited lymph node and lung metastasis and prolonged survival without retarding tumor growth in mouse Lewis lung carcinoma (LLC) models.²⁰Wang J, Zhang B et al. Artemisinin inhibits tumor lymphangiogenesis by suppression of vascular endothelial growth factor C. Pharmacology. 2008;82(2):148-55. 
• Artemisinin enhanced cytotoxic activity of chloroquine against lung cancer cells in preclinical studies²¹Efferth T. Cancer combination therapies with artemisinin-type drugs. Biochemical Pharmacology. 2017 Sep 1;139:56-70.
• Artemisia dried leaf extract led to lower colony formation and less tumor growth in preclinical studies.²²Cheong DHJ, Tan DWS, Wong FWS, Tran T. Anti-malarial drug, artemisinin and its derivatives for the treatment of respiratory diseases. Pharmacological Research. 2020 Aug;158:104901. 
• Artemisinin led to lower colony formation, less metastasis, less microvessel formation, lower VEGF, greater apoptosis, and other anticancer activity in preclinical studies.²³Cheong DHJ, Tan DWS, Wong FWS, Tran T. Anti-malarial drug, artemisinin and its derivatives for the treatment of respiratory diseases. Pharmacological Research. 2020 Aug;158:104901. 

Nasopharyngeal cancer

• Artemisinin enhanced the anticancer activity of BMI siRNA against nasopharyngeal cancer cells in preclinical studies²⁴Efferth T. Cancer combination therapies with artemisinin-type drugs. Biochemical Pharmacology. 2017 Sep 1;139:56-70.

Optimizing body terrain

Blood sugar imbalance and insulin resistance: preclinical evidence of lower levels of blood glucose, insulin, and insulin resistance in animals treated with Artemisia annua L. extract

• Lower levels of blood glucose, insulin, and HOMA-AD in diabetic mice treated with various doses of Artemisia annua L. extracted in hot water, cold water, or alcohol; in many cases, the effects were comparable to treatment with metformin²⁵Ghanbari M, Lamuki MS, Habibi E, Sadeghimahalli F. Artemisia annua L. extracts improved insulin resistance via changing adiponectin, leptin and resistin production in HFD/STZ diabetic mice. Journal of Pharmacopuncture. 2022 Jun 30;25(2):130-137.
• Lower HOMA-IR in diabetic mice treated with various doses of Artemisia annua L. extracted in hot water, cold water, or alcohol, with the strongest effects (stronger than metformin) when using the highest dose of cold-water extracts²⁶Ghanbari M, Sadeghimahalli F. Aqueous and alcoholic extracts of Artemisia annua L. improved insulin resistance via decreasing TNF-alpha, IL-6 and free fatty acids in high-fat diet/streptozotocin-induced diabetic mice. Avicenna Journal of Phytomedicine. 2022 Jan-Feb;12(1):54-66.
• Lower insulin resistance in mice fed a high-fat diet and treated with an Artemisia annua L. extract²⁷Kim KE, Ko KH et al. Artemisia annua leaf extract attenuates hepatic steatosis and inflammation in high-fat diet-fed mice. Journal of Medicinal Food. 2016 Mar;19(3):290-9.

Body weight: preclinical evidence of lower markers of body fat and obesity in cells and animals treated with Artemisia annua L.

• Lower body weight gain, adipose tissue mass, and adipocyte cell size in high-fat diet-induced obese rats treated with Artemisia annua L. leaves²⁸Song Y, Lee SJ et al. Annual wormwood leaf inhibits the adipogenesis of 3T3-L1 and obesity in high-fat diet-induced obese rats. Nutrients. 2017 May 28;9(6):554.
• Lower accumulation of lipid droplets and lower expressions of obesity-related proteins in 3T3-LI cells treated with Artemisia annua L. essential oil²⁹Hwang DI, Won KJ et al. Anti-adipocyte differentiation activity and chemical composition of essential oil from Artemisia annua. Natural Product Communications. 2016 Apr;11(4):539-42.
• Lower adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells treated with artemisinic acid isolated from Artemisia annua L.³⁰Lee J, Kim MH, Lee JH, Jung E, Yoo ES, Park D. Artemisinic acid is a regulator of adipocyte differentiation and C/EBP δ expression. Journal of Cellular Biochemistry. 2012 Jul;113(7):2488-99.

Hormone imbalance: preclinical evidence of lower levels of leptina hormone that helps regulate energy balance by inhibiting hunger and higher levels of adiponectina hormone and signaling protein involved in regulating glucose levels and fatty acid breakdown in diabetic animals treated with Artemisia annua L. extracts

• Lower levels of leptin and higher levels of adiponectin in diabetic mice treated with various doses of Artemisia annua L. extracts, with stronger effects from hot water extracts compared to cold water or alcohol extracts; the effects with hot water extracts were comparable to treatment with metformin³¹Ghanbari M, Lamuki MS, Habibi E, Sadeghimahalli F. Artemisia annua L. extracts improved insulin resistance via changing adiponectin, leptin and resistin production in HFD/STZ diabetic mice. Journal of Pharmacopuncture. 2022 Jun 30;25(2):130-137.

Immune function: preclinical evidence of immune function activation with treatment with Artemisia annua or artemisinin

• Activation (upregulation) of TGF-β signaling proteins in HCT116 colorectal cancer cells treated with Artemisia annua L. polyphenols³²Jung EJ, Paramanantham A et al. Identification of growth factors, cytokines and mediators regulated by Artemisia annua L. polyphenols (pKAL) in HCT116 colorectal cancer cells: TGF-β1 and NGF-β attenuate pKAL-induced anticancer effects via NF-κB p65 upregulation. International Journal of Molecular Sciences. 2022 Jan 29;23(3):1598.
• Fewer tumor infiltrated regulatory T cells (Treg), which suppress immune responses and are linked to poorer cancer prognosis, in mammary tumors from mice treated with artemisinin compared to either cyclophosphamide or controls³³Langroudi L, Hassan ZM et al. A comparison of low-dose cyclophosphamide treatment with artemisinin treatment in reducing the number of regulatory T cells in murine breast cancer model. International Immunopharmacology. 2010 Sep;10(9):1055-61.

Inflammation: preclinical evidence of less inflammation in animals treated with Artemisia annua L. extracts, dried leaves, or artemisinin

• Lower markers of inflammation (TNF-alpha and IL-6) in diabetic mice treated with various doses of Artemisia annua L. extracted in hot water, cold water, or alcohol, with the strongest effects (stronger than metformin) when using the highest dose of cold-water extracts³⁴Ghanbari M, Sadeghimahalli F. Aqueous and alcoholic extracts of Artemisia annua L. improved insulin resistance via decreasing TNF-alpha, IL-6 and free fatty acids in high-fat diet/streptozotocin-induced diabetic mice. Avicenna Journal of Phytomedicine. 2022 Jan-Feb;12(1):54-66.
• Greater distribution of artemisinin to tissues and organs in rats treated with dried leaves of Artemisia annua compared to pure artemisinin in a preclinical study³⁵Desrosiers MR, Mittelman A, Weathers PJ. Dried leaf Artemisia annua improves bioavailability of artemisinin via cytochrome P450 inhibition and enhances artemisinin efficacy downstream. Biomolecules. 2020 Feb 7;10(2):254.
• Greater attenuation of proinflammatory cytokine production among male rats treated with dried leaves of Artemisia annua compared to pure artemisinin, but no clear difference noted among female rats in a preclinical study³⁶Desrosiers MR, Mittelman A, Weathers PJ. Dried leaf Artemisia annua improves bioavailability of artemisinin via cytochrome P450 inhibition and enhances artemisinin efficacy downstream. Biomolecules. 2020 Feb 7;10(2):254.
• Less inflammation in mice fed a high-fat diet and treated with an Artemisia annua L. extract³⁷Kim KE, Ko KH et al. Artemisia annua leaf extract attenuates hepatic steatosis and inflammation in high-fat diet-fed mice. Journal of Medicinal Food. 2016 Mar;19(3):290-9.
• Lower markers of inflammation in mice treated with artemisinin in preclinical studies³⁸Cheong DHJ, Tan DWS, Wong FWS, Tran T. Anti-malarial drug, artemisinin and its derivatives for the treatment of respiratory diseases. Pharmacological Research. 2020 Aug;158:104901. 

Oxidation: preclinical evidence of less oxidative stress-mediated damage in liver cancer cells treated with a water extract of Artemisia annua

• Less oxidative stress-mediated damage in human hepatocarcinoma cells treated with a water extract of Artemisia annua³⁹Choi EY, Choi JO, Park CY, Kim SH, Kim D. Water extract of Artemisia annua L. exhibits hepatoprotective effects through improvement of lipid accumulation and oxidative stress-induced cytotoxicity. Journal of Medicinal Food. 2020 Dec;23(12):1312-1322. 

Your microbiome: preclinical evidence of antimicrobial activity against necrotic enteritis in birds fed n-hexane extract from fresh Artemisia annua leaves

• More weight gain (indicating less serious disease) in livestock chickens (broilers) with necrotic enteritis fed n-hexane extract from fresh Artemisia annua leaves compared to controls or birds fed dried Artemisia annua leaves⁴⁰Engberg RM, Grevsen K et al. The effect of Artemisia annua on broiler performance, on intestinal microbiota and on the course of a Clostridium perfringens infection applying a necrotic enteritis disease model. Avian Pathology. 2012;41(4):369-76.

Managing side effects and promoting wellness

Preclinical evidence of less fatty liver disease in mice fed a high-fat diet and treated with an Artemisia annua L. extract

• Less fatty liver disease (hepatic steatosis) in mice fed a high-fat diet and treated with an Artemisia annua L. extract⁴¹Kim KE, Ko KH et al. Artemisia annua leaf extract attenuates hepatic steatosis and inflammation in high-fat diet-fed mice. Journal of Medicinal Food. 2016 Mar;19(3):290-9.
• Less weight gain and hepatic lipid accumulation in mice fed a high-fat diet to induce fatty liver, and treated with a water extract of Artemisia annua⁴²Choi EY, Choi JO, Park CY, Kim SH, Kim D. Water extract of Artemisia annua L. exhibits hepatoprotective effects through improvement of lipid accumulation and oxidative stress-induced cytotoxicity. Journal of Medicinal Food. 2020 Dec;23(12):1312-1322. 

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