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NOTE: These indications are only for use with embryonic plant stem cell tissues. Adult plants do not have the same constituents, actions or applications in most cases.
Artemisia Annua, also known as Annual Wormwood is a common type of wormwood that is native to temperate Asia, but naturalized throughout the world. Is a summer annual about 3-6′ tall; it is more or less erect and branches regularly. The light green stems are angular-terete, ridged, and hairless; the secondary stems are ascending or spreading. The alternate leaves are up to 6″ long and 4″ across, becoming smaller as they ascend the stems. They are green and hairless. Each leaf is pinnately divided (double or triple) into slender lobes that are narrowly lanceolate or oblong-lanceolate; some of these lobes are cleft or toothed along their margins. The lower leaves have petioles, while the upper leaves are sessile. The upper stems terminate in floral panicles up to 1½’ long and half as much across. The panicles are abundantly branched, each branch consisting of a raceme of small drooping flower heads. About 1-2 mm. across (1/8″ or less). Each flower head is about 2 mm. across (1/8″ or less); it has many tiny disk florets. At the base of each flower head, there are 6 oblong bracts that are dark green. The blooming period occurs from late summer into the fall. There is no floral scent, although the foliage has a sweet fruity fragrance. Pollination is by wind. Upon maturity, each floret is replaced by a single achene. These achenes are small enough to be carried aloft by the wind, even though they lack tufts of hair. The root system consists of a branching taproot. This plant reproduces by reseeding itself. It is a diploid plant with chromosome number, 2n=18. It is used medicinally to treat fevers for more than 2,000 years and to treat malaria for more than 1,000 years in China. Quinghao, the Chinese term for the plant, means “from the green herb.” In modern-day central China, specifically Hubei Province, the stems of this wormwood are used as food in a salad-like form. The final product, literally termed “cold-mixed wormwood” is a slightly bitter salad with strong acid overtones from the spiced rice vinegar used as a marinade. It is considered a delicacy and is typically more expensive to buy than meat. Most famous however is the mixing of the wormwood drug absinthol with anise to produce the intoxicating beverage known as absinthe. Wormwood is employed today in the making of vermouth, and accounts for this
drink’s characteristic bitter flavor.
In 1971, scientists demonstrated that the plant extracts had antimalarial activity in primate models, and in 1972 the active ingredient, artemisinin (formerly referred to as arteannuin), was isolated and its chemical structure described. Artemisinin may be extracted using a low boiling point solvent such as diethylether and is found in the glandular trichomes of the leaves, stems, and inflorescences, and it is concentrated in the upper portions of plant within new growth. With the wormwood species Artemisia Annua showing far greater antimalarial potential than extracts from over 30 other species in lab tests.
References: Duke SO, Paul RN (1993). “Development and Fine Structure of the Glandular Trichomes of Artemisia annua L.”. Int. J Plant Sci. 154 (1): 107–18. doi: 10.1086/297096.
The proposed mechanism of action of artemisinin involves cleavage of endoperoxide bridges by iron producing free radicals (hypervalent iron-oxo species, epoxides, aldehydes, and dicarbonyl compounds) which damage biological macromolecules causing oxidative stress in the cells of the parasite. Malaria is caused by the Apicomplexan, Plasmodium falciparum, which largely resides in red blood cells and itself contains iron-rich heme-groups (in the form of hemozoin).
B, Cu, Fe, K, Mg, Mn, Na, P, Su, Zn.
Vitamins and Minerals:
A, C, Calcium, E.
1,8-Cineole, Abrotamine, Absinthin, Anabsinthin (bitters), Alpha-Artelinic acid, Alpha Pinene, Alpha-Thujone, Alpha or Beta Dihydroartemisininoxy, 14 Amino acids, 38 Amorphane Sesquiterpenes are cytotoxic against a range of human tumor cell lines, Arteannuin A and B, Artemisic acid, Numerous Sesquiterpenes Artemisinin (alternatively: arteannuin) and its derivatives, Arteether, Artemether, Artesunate(all three are antimalarial), Auxins (IAA), Beta-bourbonene, Beta caryophyllene, Beta Farnesene, Beta Pinene, Beta Selinene, Beta Sitosterol, Borneol, Brassinosteroids (BR), Butyric acids, Camphene, Camphor, Caryophyllene Oxide, Copaene, 4 Coumarins, Cuminaldehyde,Cytokinins (CK), Delta Cadinene, Deoxyartemisinin, Dihydroartemisinin, Flavones (17 methoxylated flavones) such asCasticin, Chrysoplenetin, Chrysosplenol-D, and Cirsilineol in Artemesia Annua are thought to enhance the antimalarial activity of artemisinin.Gibberellins (GA), Humulene, Isoartemisia ketone, Jasmonic acid (JA), Limonene, Menthol, Methyl acetate, Meristems plant stem cells (PSC), Ocimene, Octacosanol, P-Cymene, Quercetagetin-6,7,3′,4′-Tetramethylether, Salicylates (SA), Scopoletin, Stigmasterol,Thujone, Terpinen 4-OL, Trioxane lactone, Ylangene.
Dihydroartemisinin is the reduced form and active metabolite of artemisinin. Artesunate is a water-soluble hemisuccinate derivative of artemisinin. Artemether is a lipid-soluble methyl ether derivative of artemisinin and is more active than artemisinin. Arteether is a lipid-soluble ethyl ether derivative of dihydroartemisinin. Some other important artemisinin derivatives include alpha-artelinic acid, arteanniun B, and 4-(P-Substituted Phenyl)-4(R or S)-(10 [alpha or beta]-dihydroartemisininoxy) butyric acids, which are dihydroartemisinin derivatives, as well as arteflene (a synthetic derivative) and semisynthetic artemisinin trioxanes (C-10 carbon-substituted and 10 deoxoartemisinin compounds).
There is no doubt in my mind that a synergistic advantage in using the herbal alcohol extracts the galenical prepared from the whole herb, rather than the isolated compound artemisinin or its derivatives. The highest concentration of artemisinin is found in its young shoots and early leaves prior to flowering. Artemisinin is a so-called sesquiterpene with a molecular weight of 282. It is a tetracyclic structure with a trioxane ring and a lactone ring. The trioxane ring contains a peroxide bridge, the active moiety of the molecule.
A new antioxidant. The high contents of total phenolic compounds (25.6 mg g-1) and total flavonoids (13.06 mg g-1) indicated that these compounds contribute to the antiradical and antioxidative activity. In a model system, the formation of o-semiquinone radicals from quercetin and chlorogenic acid was obtained to prove the mechanism (hydrogen donating and/or one-electron reduction) of free-radical scavenging activity.
Taiwanese researchers have found the whole herb to be as effective with fewer side effects than the isolated component. Furthermore, extracts of Artemisia annua that contained no Artemisinin were just as effective.
Plant Stem Cell Therapy Indications:
Antibiotic-resistant infections. A broad spectrum antiparasitic antibacterial Giardia and Cryptosporidium and antifungal agent. Kill parasites, particularly worms and Schistosomiasis flukes. Antimalarial even Cerebral malaria. Lyme disease especially for Babesiosis works with babesia by “exploding” oxygen molecules in the presence of malaria (and babesia – lives in RBC) and red blood cell iron molecules and work has an adjuvant antispirochetal for Borrelia burgdorferi. Antimicrobial and Antifungal properties. Antiviral Cytomegalovirus, Hepatitis B and C virus. Trypanosome, and Toxoplasma gondii – Disease Toxoplasmosis, as well as some trematodes – parasitic worms, fungi, yeast and bacteria. Gram-positive bacterium Enterococcus hirae and growth inhibition of several phytopathogenic fungi. Possesses mild antiendotoxin effects that can help in reducing Herxheimer reactions. Also effective antibacterial for Enterobacter and Klebsiella species, Streptococcus faecalis, Staphylococcus aureus, Shigella dysenteriae, Escherichia coli and Pneumocystis carinii (Chen et al, 1994), an opportunistic pathogen which causes pneumonia in AIDS and other immune compromised patients. Artemisinin derivatives are also effective against some other pathogens including those responsible for cryptosporidiosis, amoebiasis, giardiasis, clonorchiasis and leishmaniasis (Ma, Lu, Lu, Liao, & Hu, 2004; Yang & Liew, 1993). Moreover, artemisinin has been recently indicated as a potential and effective compound against a number of viruses including hepatitis B, C and others (Efferth et al., 2008).
Malaria caused by Plasmodium resistant to usual antimalarials. Incidence more common with P. falciparum. For uncomplicated and severe malaria. May occur due to improper treatment and inadequate dosage of antimalarials. Chloroquine resistant P. falciparum. More number of RBCs affected. Cause serious complications like jaundice, renal failure, cerebral malaria. Prognosis (outcome of disease) – usually grave. Artemisinin and its derivatives are renowned for their potent antimalarial activity. Immediate onset and rapid reduction of parasitaemia with complete clearance in most cases within 48 hours. Clinical recovery of the patient, e.g. defervescence is faster than with other antimalarials. Efficacy is high even in areas with multidrug resistant strains. Wormwood is the expulsion of parasitic worms. Many reference works continue to list wormwood as an effective vermifuge. Parasitic worm killer. Protozoal infections such as Leishmaniasis, Chagas’ disease, and African sleeping sickness. The free radicals attack cell membranes, breaking them apart and killing the single-cell parasite. Malaria is the world’s most important parasitic infection, causing more than a million deaths and 500 million cases annually.
In 1979, the Chinese reported that artemisinin drugs are rapidly acting, effective and safe for the treatment of patients with P. vivax or P. falciparum infection. (Tracy J. W. et al., Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 10th Ed., 2001). Artemisinin and its derivatives are toxic to the malarial parasite at nanomolar concentrations, causing specific membrane structural changes in the erythrocyte stage that kill the parasite. In general, the mechanism of action involves 2 steps: activation followed by alkylation. Iron activates artemisinin into a free radical through an iron-mediated cleavage. The second step, alkylation, involves the formation of covalent bonds between the artemisinin-derived free radicals and the malarial proteins.
Converted to dihydroartemisinin, which is a potent antimalarial compound. Exerts antimalarial activity by iron-mediated cleavage of the peroxide bridge and generation of an organic free radical. The interaction of artemisinin with haem in the parasite may turn out to be essential. Haem bound iron (but also free iron) may serve as a catalyst. The artemisinin radical binds subsequently to membrane proteins, and alkylation reactions eventually cause destruction of the parasite. They quickly arrest the ring or the trophozoite development and also prevent pathological sequelae. Fever subsides and parasites are cleared rapidly. Defervescence occurs within 2-3 days after drug administration. Ninety percent clearance of asexual erythrocytic parasitaemia is usually observed within 4 hours. Artemisinin has an endoperoxide bridge that reacts with iron in heme to form singlet oxygen and free radicals. In addition to antimalarial effects, artemisinin also effectively induces apoptosis and cell cycle arrest.
The process whereby erythrocytes containing mature forms of P. falciparum adhere to micro vascular endothelium is called cytoadherance. It thus disappears from circulation, known as sequestration.
Erythrocytes containing mature parasites also adhere to uninfected parasites, leading to the formation of “rosettes”.
Cytoadherance and rosetting lead to microcirculatory obstruction in falciparum malaria, the consequence of which are reduced oxygen and substrate supply, anaerobic glycolysis and lactic acidosis, finally leading to complications of malaria. (Manson, 1997). All artemisinin drugs prevent the development of ring stage parasites to the more mature pathogenic stages that rosette and cytoadhere to capillaries (The use of artemisinin and its derivatives as antimalarial drugs – Report of a Joint CTD/DMP/TDR- WHO, 1998).
Artesunate and artemether have been shown to clear parasitaemias more effectively than chloroquine and sulfadoxine/pyrimethamine.
Meta analysis of mortality in trials indicated that a patient treated with artemether had at least an equal chance of survival as a patient treated with quinine.
Artemisinin drugs cleared parasites faster than quinine in patients with severe malaria but fever clearance was similar.
Parenteral artemether and artesunate are easier to use than quinine and do not induce hypoglycemia. (The use of artemisinin and its derivatives as antimalarial drugs – Report of a Joint CTD/DMP/TDR- WHO, 1998)
Orally administered artemisinin or its derivatives seems to be absorbed faster from the liquid alcohol extracts than from capsules. The maximum plasma concentrations were observed after 30 minutes following intake. Artesunate is rapidly absorbed and reaches maximum plasma level within 45-90 minutes. It is metabolized in the liver by hydrolysis to dihydroartemisinin. One day in the near future I hope that we can obtain and administer these PSC in parenteral route for serious acute febrile conditions. Dosage: According to large amount of clinical study, for the treatment of malaria, use intramuscular injections of 0.3g each time each day for three days, for a total amount of 0.9 -1.2g; Double first dose for severe case.
Substantial hydrolysis of artesunate (probable complete) and artemether into dihydroartemisinin probably occurs even before absorption.
Additional support for oxygen-mediated toxicity of artemisinin is generated from other studies. The antimalarial activity of artemisinin in vitro, against P. falciparum, could be enhanced by increased oxygen tension. Drugs such as miconazole and doxorubicin, which are known to work via oxygen radical effects, enhance the activity of artesunate, a derivative of artemisinin. The effectiveness of artemisinin is reduced by catalase, dithiothreitol and alpha tocopherol. (Krungkrai SR, Yuthavong. The antimalarial action of Plasmodium falciparum of qinghaosu and artesunate in combination with agents which modulate oxidant stress. Trans. R Soc. Trop. Med Hyg 1987, 81:710-4).
Furthermore, Levander, et al. found that manipulation of the host antioxidant defense status could provide prophylactic or therapeutic enhancement for the control of malaria. In this study, mice were fed with diets deficient in vitamin E or a diet supplemented with cod liver oil, which would deplete antioxidants. Vitamin E deficiency enhanced the antimalarial action of artemisinin against P. yoelii, but selenium deficiency did not. A diet containing 5% cod liver oil had a very strong antimalarial action. (Levander OA, Ager AL, Morris VC. Qinghaosu, dietary vitamin E, selenium and cod liver oil: effect on susceptibility of mice to the malarial parasite Plasmodium yoelii. Am. J. Clin. Nutr. 1989; 5:346-52). Artemisinin is a powerful oxidant has been shown to work through oxygen and carbon based free radical mechanisms. Its structure includes an endoperoxide bridge. Peroxides generate free radicals in a Fenton type reaction when exposed to unbound ferrous iron. Malaria, which grows in the erythrocytes, has the opportunity to accumulate much excess iron which can spill into the unbound form. Electron microscopy has confirmed destruction of plasmodium membranes with morphology typical of free radical mechanisms. Elimination is mainly by hepatic metabolism (Leskovac V. et al., Comp Biochem Physiol, 1991)
Arteether has much slower elimination.
Artesunate, artemether, arteether and probably also artemisinin itself are transformed into dihydro-artemisinin, which is subsequently converted into inactive metabolites.
As a safe and effective alternative to quinine in the treatment of severe malaria.
Treatment of uncomplicated – complicated malaria – not limited to patients infected with multidrug resistant malaria.
Chloroquine and pyrimethamine may antagonize the activity of artemisinin whereas mefloquine, quinine, primaquine and tetracycline potentiate artemisinin. (Chawira A. N. et al., Trans R Soc Trop Med Hyg 1986; 80; p. 334-5).
The combination of artemisinin derivatives and mefloquine improves parasite clearance compared with either drug alone. The above combination slows down the development of resistance to mefloquine, since the residuum of parasites remaining after the action of artesunate is exposed to more slowly eliminated mefloquine.
There is little published data on combination therapy with drugs other than mefloquine.
Artemisinin and its derivatives have a significant effect on gametocytogenesis, thus reducing transmission and consequently the spread of resistant strains.
They prevent gametocyte development by their action on the ring stages and on the early (stage I-III) gametocytes. (Mehra and Bhasin, 1993).
In studies including over 5000 patients in Thailand, it was shown that gametocyte carriage was significantly less frequent after treatment with artemisinin derivatives than after treatment with mefloquine. (Price R. N. et al., Lancet, 1996)
The fast parasite killing is probably an important factor for reduction of gametocyte development.
The artemisinins are extremely well tolerated and virtually without adverse effects.
Toxicological studies in animals have shown that the toxicity of artemisinin, artemether and artesunate is much less than that of chloroquine.
CYP2C19 is increased by rifampin and artemisinin (a derivative of the herb Artemisia annua, a natural anti-malarial herb that may be used in the treatment of Babesiosis). CYP2C19 is decreased by Prilosec and ketoconazole (Nizoral, an anti-fungal).
CYP3A4 is increased by St. John’s Wort and rifampin and inhibited by grapefruit juice, Seville orange juice, the anti-fungal drugs ketoconazole (Nizoral) and itraconazole (Sporanox), and the macrolide antibiotics azithromycin (Zithromax), clarithromycin (Biaxin) and telithromycin (Ketek). The effect of grapefruit juice occurs only in the intestines, not in the liver, so it can–at high levels of consumption–increase absorption of some drugs without affecting their internal metabolism. Artemisinin is metabolized by intestinal CYP3A4, and its absorption appears to be enhanced by grapefruit juice. (van Agtmael et al, Grapefruit juice increases bioavailability the bioavailability of artemether. Eur J Clin Pharmacol 1999; 55: 405-410).
Can occur some adverse side effects but many be even less likely from the embryonic form – Headache, nausea, abdominal pain, vomiting, occasional diarrhea, symptoms that are associated with malaria and which resolve with appropriate treatment. Animal studies have demonstrated limited symptomatic and pathological evidence of neurotoxicity following the parenteral administration of high doses of either artemether or arteether.
There is no clinical evidence of serious neurotoxicity from the use of any artemisinin drug in man in prospective studies of over 10000 patients.
(The use of artemisinin and its derivatives as antimalarial drugs – Report of a Joint CTD/DMP/TDR- WHO, 1998).
Very limited data on the use of artemisinin group in pregnant women.
Artemisinin and derivatives should be avoided during first trimester of pregnancy, but in case of severe malaria the risks have to be balanced against the benefits.
No congenital malformations were detected in six children born to mothers who received intramuscular artemisinin or artemether at 17 to 27 weeks of gestation. (Wang T., J Trad Chin Med, 1989).
Also no abnormalities were observed in follow-up of 3 months to 10 years of 17 children born to mothers who took artemisinin at 16 to 38 weeks of pregnancy except 1 premature delivery at 34 weeks. (Fu L. C., et al., Clinical trials on qinghaosu and its derivatives, 1990).
Malaria kills more than 1 million children a year in the developing world, accounting for about half of all malaria deaths globally, most of them in Africa.
In malaria endemic areas – Children under age of 5 years – greater risk of dying.
Artemisinin drugs are well tolerated in children.
As per WHO recommendations, artemisinin derivatives are indicated in children over 6 months of age.
For Acute Pathogenic infections; If there is fever association you will need for the first 72 hours 100 drops 3 x a day into 8 oz water and sip over a 15 minutes period 3-4 times a day depending on response. Otherwise the Adults dosage for wide broad spectrum parasitic subacute infections would be 50 drops 3 x a day. Children 20-30 drops 3 x a day for up to 80 lbs in weight otherwise adult dosage apply. Duration is approximately for 30 days. Smaller dosages may be administered longer for chronic biofilms infections with the synergy of other antibacterial or viral infections. Especially plants that contains Humulene which is also antimalarial. A brake from taking Artemesia Annua for at least 10 days in between repeated courses of treatment is recommended. Gibberellic acid which is present in the embryonic plant stage of growth increases the artemisinin content by 24.9%. The embryonic form requires less milligrams amount dosages because of the Humulene content and other phytochemicals synergy rendering it more effective than that of monotherapy use of isolated artemisinin. Wormwood in the embryonic form with fewer side effects has been reported.
Improves liver and gallbladder function in people with liver disease. Prevent Acetaminophen-induced liver damage. Artemisia annua induced apoptosis of hepatocarcinoma. For loss of appetite, indigestion and gastrointestinal problems. Wounds in the intestines of people who have had ulcerative colitis, and from Crohn’s disease with the addition of other plants Artemesia alone is not sufficient and is more for post scar tissue and necrosis and not for acute conditions of ulcerative colitis or Crohn’s disease. Gallbladder disorders and flatulence. Use for hemorrhoids. Patients with gastrointestinal disorders or those taking antacids should not take artemisia because it increases the production of stomach hydrochloric acid. Post partum women with anemia should not take Artemisia. Patients with ulcers or gastrointestinal disorders should not take Artemisia. Adult dosage for this purpose is more in the range of 10 drops 3 x a day.
Chemotherapeutic agent. Inhibits the activation of nuclear factor kappa-B (NF-κB), an important activator protein in cancer development and progression. Inhibits inducible nitric oxide synthase activation. Artesunate activated Bax, causing cell apoptosis and inhibiting the expression of the bcl-2 protein in a concentration- and dose-dependent manner. Antiangiogenic. Lowers vascular endothelial growth factor (VEGF) Many experiments have found that Artemisinin turns deadly in the presence of iron. Cancer cells can also be rich in iron, as they often soak up the mineral to facilitate cell division. The cells bring in extra iron with the help of transferrin receptors, special receiving points that funnel the mineral into the cell. Although normal cells also have transferrin receptors, cancerous ones can have many more. To test artemisinin effect on breast cancer cells, bioengineers Henry Lai and Narendra Singh of the University of Washington, Seattle, enriched segregated normal breast cells and radiation-resistant cancerous ones with holotransferrin, a compound normally found in the body that carries iron to the cells. Then the team dosed the cells with artemisinin. As the pair reports in the 16 November 2008 issue of Life Sciences, almost all the cancer cells exposed to holotransferrin and artemisinin died within 16 hours. The compounds killed only a few of the normal cells. Lai believes that because a breast cancer cell contains five to 15 more receptors than normal, it absorbs iron more readily and hence is more susceptible to artemisinin attack. Once inside the cell, the artemisinin reacts with the iron, spawning highly reactive chemicals called “free radicals.” The free radicals attack other molecules and the cell membrane, breaking it apart and killing the cell.
It has been shown to have an antiproliferative effect on medullary thyroid carcinoma cells and induce apoptosis in a lung cancer cell line by modulating p38 and calcium signaling. Cytotoxic activities in several human tumor cell lines. Artemisinin in that treatment of human breast cancer and some form of prostate cancer cells with this plant compound disrupts estrogen responsiveness and stops cell growth. Artemisinin acts in breast cancer cells by inhibiting the production of the estrogen receptor-alpha (ERα) gene without altering the level of the related estrogen receptor-beta gene (ERα). Our hypothesis is that Artemisinin–regulated cellular pathways selectively inhibit the production of ERα and arrest the growth of estrogen responsive breast cancer cells by altering the function of nuclear cellular proteins (transcription factors) that are used by breast cancer cells to enhance the synthesis of the ERα gene. Induce apoptosis of breast cancer cells with reduced side effects. Artemisinin strongly and selectively inhibits transcription of the estrogen receptor-alpha (ER-alpha) gene without any apparent effect on expression of its isoform estrogen receptor-beta (ER-beta). Artemisinin activated signaling pathways ablate ER-alpha mediated responsiveness and estrogen-dependent growth of breast cancer cells by selectively disrupting transcription factor function on the estrogen receptor-alpha promoter. By mutagenesis of the ER-alpha promoter, and analysis of transfected promoter-luciferase reporter plasmids, it was uncovered an artemisinin-regulated region of the ER-alpha that accounts for the artemisinin sensitivity of the estrogen receptor-alpha gene expression. As a functional test, it was demonstrated that artemisinin disrupts estrogen responsiveness and growth of human breast cancer cells, as well as demonstrated that artemisinin and anti-estrogens cooperatively inhibit growth of estrogen responsive breast cancer cells. A new concept that the control of ER-alpha expression is an important and selective target of a subset of transcriptionally acting natural phytochemicals with potent anti-proliferative responses in human breast cancer cells. Therefore, the mechanistic studies directed at an understanding of the actions of artemisinin on estrogen receptor-alpha expression will provide valuable pre-clinical information in the development of artemisinin-based compounds for novel anti-breast cancer therapeutic strategies.
Wormwood plant, effectively blocked estrogen stimulated cell cycle progression induced by either β-estradiol (E2), an agonist for both estrogen receptor subtypes, or by propyl pyrazole triol (PPT), a selective ERα agonist. Art strongly down-regulated ERα protein and transcripts without altering expression or activity of ERβ. Transfection of MCF7 cells with ERα promoter-linked luciferase reporter plasmids revealed that the Art down-regulation of ERα promoter activity accounted for the loss of ERα expression. Furthermore, Art treatment ablated the estrogenic induction of endogenous progesterone receptor transcripts by either E2 or PPT, and inhibited the estrogenic stimulation of a luciferase reporter plasmid driven by consensus estrogen response elements (ERE). In vitro ERE binding assays revealed that Art treatment resulted in the loss of ERE bound ERα, whereas, the levels of ERE bound ERβ were not altered. Treatment of MCF7 cells with a combination of suboptimal combinations of Art and a pure antiestrogen, faslodex resulted in an enhanced reduction of ERα protein levels and in an enhanced G1 cell cycle arrest compared to the effects of either compound alone. Our results show that Art switches proliferative human breast cancer cells from expressing a high ERα: ERβ ratio to a condition in which expression of ERβ predominates, which parallels the physiological state linked to anti-proliferative events in both normal mammary epithelium and in breast cancer.
References: Periodical: Carcinogenesis Index Medicus: Carcinogenesis Sundar SN, Marconett CN, Doan VB, Willoughby JA Sr, Firestone GL.
For the past ten years, the Hoang medical family, with three generations of sophisticated physicians, have used artemisinin in combination with several other herbs to treat cancer, and eliminate necrosis material from the body; for example, from wounds; from intestines of people who have ulcerative colitis, and from Crohn’s disease. The efficacy of the artemisinin compound is very impressive for the treatment of breast cancer and possibly to prevent it. It is not only because of direct anticancer activity, but also due to hormonal balancing properties of the artemisinin. With the knowledge of a high accumulation of iron in cancer cells, researchers Henry Lai and Narenda Singh of the University of Washington became interested in possible Artemisinin activity against malignant cells. In 1995, they published a paper in Cancer Letters concerning the use of artemisinin against numerous cancer cell lines in vitro. This article has mobilized interest in artemisinin as an addition to anticancer treatment. (Lai H., Narendra S. Cancer Letters, 91:41-46, 1995).
There are a number of properties shared by cancer cells, which favor the selective toxicity of artemisinin against cancer cell lines, and against cancer in vivo. In addition to higher rates of iron flux via transferren receptors than normal cells, cancers are particularly sensitive to oxygen radicals. (May WS. J Membr. Biol., 88:205-215, 1985). A subsequent article appeared in Life Science in 2001 by Singh and Lai on the selective toxicity of artemisinin and holotransferrin towards human breast cancer cells. In this article, rapid and complete destruction of a radiation-resistant breast cancer cell line was achieved when the in vitro cell system was supported in iron uptake with holotransferrin. The cancer cell line was completely nonviable within 8 hours of combined incubation with minimal effect on the normal cells. (Singh NP, Lai H. Life Sci Nov 21, 70(1):49-56, 2001). Artemisinin becomes cytotoxic in the presence of ferrous iron. Since iron influx is naturally high in cancer cells, artemisinin and its analogs selectively kill cancer cells under conditions in vivo. Further, it is possible to increase or enhance iron flux in cancer cells using the conditions that increase intracellular iron concentrations. However, intact in vivo systems do not need holotransferrin; the living body provides all the necessary iron transport proteins.
A third paper, by Efferth et al., published in Oncology in 2001 stated that the antimalarial artesunate is also active against cancer.15 This article described dramatic cytotoxic activity against a wide variety of cancers including drug resistant cell lines. Artesunate (ART) is a semi-synthetic derivative of artemisinin, and has been analyzed for its anticancer activity against 55 cell lines by the Developmental Therapeutics program of the National Cancer Institute, USA. ART was most active against leukemia and colon cancer cell lines. Mean growth inhibition 50% (GI 50) 1.11microM and 2.13 microM respectively. Non-small cell lung cancer cell lines showed the highest mean (GI50 26.62 microM) indicating the lowest sensitivity towards ART. Intermediate GI 50 values were obtained for melanomas, breast, ovarian, prostate, CNS, and renal cancercell lines. Most important, a comparison of ART’s cytotoxicity with those standard cytostatic drugs showed that ART was active in molar ranges comparable to those of established antitumor drugs. Leukemia lines resistant to doxorubicin, vincristine, methotrexate, or hydroxyurea were tested. Remarkably, none of these drug resistant lines showed resistance to ART. The theorized reason for this is the absence of a tertiary amine in ART, present in virtually all other chemotherapy agents, which is required for cellular transport systems to usher the drug outside the cell. (Efferth T, Dunstan H, Sauerbrey A, Miyachi H, Chitambar CR. Antimalarial artesunate is also active against cancer, Oncology. 2001, Apr;18(4):767-73).
Cancer cells are notoriously deficient in antioxidant enzymes – forms of superoxide dismutase, the manganese form in mitochondria, and the copper zinc form in the cell cytoplasm are generally low in cancer cells. Cancer cells are grossly deficient in catalase and glutathione peroxidase, both of which degrade hydrogen peroxide. It is these deficiencies in antioxidant enzymes which lead to the use of many of the common chemotherapeutics which are superoxide generators. (Levine SA, Kidd PM. Antioxidant Adaptation: It’s Role in Free Radical Pathology. Allergy Research Group, San Leandro, California, 1985).
The higher iron fluxes, especially associated with the reproductive phase of tumor cells, should render these cells even more susceptible to oxidative damage via hydrogen peroxide and superoxide’s. Normally, the profound catalase deficiency in cancer cells is credited with creating vulnerability to oxidants, in relationship to IV vitamin C or IV hydrogen peroxide. However, since all of these protective antioxidant enzymes are most often deficient in transformed cells, the oxidant vulnerability should be enhanced dramatically, and further so, due to enhance unbound iron during cell division.
Artemisinin may be a most effective method, and certainly one of the easiest, of delivering a knockout oxidative stress to cancer cells.
Artemisinin has two semisynthetic derivatives. Artesunate is a water-soluble derivative with no reported toxicity at usual levels. However, its serum half-life is relatively short.
Artemether is a lipid soluble derivative, effective in cerebral malaria, and therefore may be more effective in brain cancers by better penetration of the blood-brain barrier. Artemether, however, has been reported to cause some neural toxicity in laboratory models in rather high doses. Artemisinin has an intermediate half life and can cross the blood-brain barrier. The two semisynthetic derivatives are available overseas in both oral and injectable for artesunate and artemether.
As mentioned, Lai used holotransferrin, which is iron-loaded transferrin, to further sensitize tumor cell lines to the oxidizing properties of dihydroartemisinin, which is derived from the parent compound metabolically in vivo. A human leukemia cell culture, Molt-4-lymphblastoid cells, and normal human lymphocytes were used in this experiment.
A significant decrease in cell count was noted with artemisinin alone, with p Lai suggests that this procedure would be most effective for the treatment of aggressive cancers, in which large numbers of transferrin receptors are expressed on the cell surface. It may not be effective for T cell leukemias, which have defective internalization of transferrin receptors, and therefore may not be susceptible to this treatment. (Lai H., Narendra S. Cancer Letters, 91:41-46, 1995).
Artesunate increased daunorabicin accumulation in CEM/E1000 cells. As artesunate and bufalin both have abilities to combat leukemia, whether it was applied alone or together with daunonrubicin in multi-resistant cells, these two drugs might be suitable for treating leukemia.
Arteminisin could prevent the spread of cancer cells and increase cytotoxicity of perarubicin and doxorubicin in P-glycoprotein-over expressing, and in MRP-over expressing, but not in their corresponding drug sensitive cell lines. (Reungpatthanaphong, P et al Modulation of MDR by Artemisinin, artesunate and DHA in K562, GLC4 Resistant cell lines, Biology Pharmacology Bull. 25(12) 1555-1561, 2002).
In this case, the patient was given artesunate injections and tablets over a period of nine months. His tumor was significantly reduced by about 70 percent just after two months of treatment. The patient also reported that he benefited much from this treatment. It actually prolonged his life and improved his quality of life. Once again, artemisinin had proven its amazing properties in killing cancer cells. (Singh and Verma, Case report of a laryngeal squamous cell carcinoma treated with artesunate, Archive of Oncology, Vol 10(4), 279-80, 2002).
Conclusion: These findings have particular relevance to the recently suggested use of Artemisia Annua, or more specifically artemisinin, as an anticancer agent. This development is based on the finding that cancer cells have a much higher concentration of iron than normal cells. (It is thought that artemisinin interacts with iron to generate reactive oxygen species (free radicals) which kill the malaria parasite.) Tests on cancer cell lines have established that artemisinin is also selectively toxic to cancer cells, presumably because their higher iron levels result in cytotoxic effects following free radical generation after contact with artemisinin.
References: Chen HH, Zhou HJ, Fang X. Inhibition of human cancer cell line growth and human umbilical vein endothelial cell angiogenesis by artemisinin derivatives in vitro. Pharmacol Res 2003; 48(3):231-236.
Efferth T, Dunstan H, Sauerbrey A et al. The anti-malarial artesunate is also active against cancer. Int J Oncol 2001; 18(4):767-773.
Woerdenbag HJ, Moskal TA, Pras N et al. Cytotoxicity of artemisinin-related endoperoxides to Ehrlich ascites tumor cells. J Nat Prod 1993; 56(6): 849-856.
Antipyretic. Appears to regulate T-cell responses and antibody production to inhibit autoimmune reactions, with artemisinin being the main active component. Artesunate, which has the same functions as artemisinin, was evaluated in laboratory animal studies and found to suppress allergic contact dermatitis and enhance specific suppressor T-cell activity. Clinically, artemisinin have been used in the treatment of systemic lupus since 1979, with claimed positive effects in recent trials. The dose of artemisinin that has been used clinically for lupus has ranged from 0.2-0.6 grams per day. Treatment time is typically about 3 months. Has also been applied in treatment of discoid lupus and was deemed successful.
References: Zhong Jiaxi, et al., 25 cases of systemic lupus erythematosus treated by integrated traditional Chinese medicine and Western medicine, Chinese Journal of Integrated Traditional Chinese Medicine and Western Medicine 1999; 19(1): 47-48.
Zhu Dayuan, Recent advances on the active components in Chinese medicines, Abstracts of Chinese Medicine 1987; 1(2): 251-266.
ENT – Pulmonary:
Pneumocystis carinii PCP. Sore infections of the throat and lungs. It numbs pain from infection in the throat and bronchial tubes and is exceptionally cooling to the throat and lungs. It is also highly antibacterial, being exceptionally effective topically.
Artemisia Annua is one of the best plants for PMS, cramping, excessive bleeding and all symptoms of hyper-estrogenemia and hyperprolactinemia anterior pituitary adenoma.
It is also an effective external antiseptic. Compresses soaked in wormwood tea are recommended for irritations, bruises, and sprains.
Although artemisinin could not be dissolved in water, it was able to cross the blood brain barrier. It might therefore be useful for curing brain tumors and other brain diseases.
During a recent experiment, an alkaloid of Artemisia was metabolized to small molecules in the digestive tract and was passed through the blood brain barrier. The results showed that it could act as an acetylcholinesterase inhibitor with a blocker of neurotoxicity induced by a beta in human beings that caused Alzheimer’s disease AD. (Heo et al, Inhibitory effects of Artemesia alkaloids on acetylcholine esterase activity from PC12 cells, molecule cells, Jun 30:10(3):253-262).
Contraindications: Post partum women with anemia should not take Artemisia. Patients with ulcers or gastrointestinal disorders should not take Artemisia. Antacids: Artemisia interferes with antacids, sucralfate, proton pump inhibitors, and histamine-receptor antagonists because it increases the production of stomach hydrochloric acid. Antiseizure medications: Artemisia can induce seizures resulting in decreased efficacy of antiseizure medications. Avoid use in women during first trimester of pregnancy because of potential teratogenicity. Avoid use. Artemisinin derivatives, in particular artemether, have a toxic effect on embryos, but no teratogenicity was described in animal studies in mice, rats, or rabbits. Thus, teratogenicity potential may be limited to early pregnancy. Clinically important effects may occur in patients because of the potent inhibition of cytochrome P-450 1A2 (CYP1A2) enzyme by artemisinin. Caution may be warranted in diabetic patients because some artemether trial patients developed hypoglycemia. Clinical trial data document prolongation of the QT interval in patients treated with artesunate and artemether, which may increase the risk of serious arrhythmias in patients receiving other drugs that prolong the QT interval. Grapefruit juice may increase the bioavailability of artemether.
Oncophytotherapy Case Studies reports:
1. Patient D.A. a 47 year-old mechanic who presented with a 4.5 cm. Non-Hodgkin’s lymphoma on the right side of his head, with gaping incision from a recent biopsy, and tremendous inflammatory erythema. Artesunate, 60mg was administered IM 14 consecutive days and he switched diets to high protein/vegetable (Kelley parasympathetic type diet). At the end of two weeks, a depression appeared at the apex of the tumor. Four weeks later, the mass was completely gone, skull surface smooth, incision totally healed and erythema virtually cleared. Apparently cancer-free as of this writing 6 months later.
2. Patient V.M. an 83 year old Toronto resident. Healthy most of her life, she now had a non-small cell lung carcinoma in the right lower lobe, considered non-resectable because of heart failure and circulatory problems. She received Artemisinin 500mg BID from Allergy Research Group and Carnivora oral, via nebulizer, 5cc BID. In 4 months the tumor shrunk to 1×2 cm and her oncologist felt this represented scar tissue and declared her cancer free. (Her heart condition improved considerably with CoQ10, 600mg daily).
3. Patient D.E., a 47 year-old Alaska resident with stage 4 breast cancer and metastases to T1 with significant pain, vertebral collapse and local neurological impairment. First seen May 2001, she received a series of IPT (insulin potentiation therapy-low dose chemotherapy), high dose vitamin C infusions, supplements, and dendritic cell vaccine, dietary management (Kelly sympathetic type diet), and detoxification strategies. Most symptoms had cleared within 4 months (October 2001). In January 2002, she received artesunate IV (source: mainland China), plus oral artemisinin 300 mg BID (ARG and Wellcare Pharma) which has been continued. Six months later she was happy to report she has no symptoms whatsoever and is living a normal life. Her local provider believes the regressed mass is now scar tissue. 4. Patient F.A., an 81 year-old Californian with multiple skin cancers including one active recurrent quarter-sized lesion that had been burned 4 times previously. Topical artemisinin (one capsule ARG artemisinin in 50% DMSO) applied twice daily caused the large lesion to fall off within 5 days and other smaller skin cancers to regress. His wife reported the same with her skin cancers.
5. L.L. is a West Coast woman in her 40’s with breast cancer and extremely painful metastasis all over her spine. She had received limited radiation therapy to reduce the pain in the thoracic spine prior to consulting me. She began artemisinin, and a variety of complementary strategies, including diet, detoxification and Kelly type proteolytic enzymes (from Allergy Research Group). Immediately, her energy exploded. Her pain level took a dive when she received treatment from an Edgar Cayce Foundation healer. Her comment after two weeks on artemisinin was “Last week I thought I was dying, and today for the first time in months, I believe I am going to live.” Four months into therapy using oral supplements alone (no IV therapy), diet and detoxification strategies, a PET scan, the most efficient and sensitive study for spread of cancer, did not show any activity anywhere in her spine, even in places that were present before and not radiated! Further, the scan did not confirm definite cancer activity anywhere else!
Current Oncology. 2006 Feb; 13(1):14-26.
Natural Health Products that Inhibit Angiogenesis: A Potential Source for Investigational
New Agents to Treat Cancer-Part 1.
Sagar, SM, et al. McMaster University, Hamilton, Ontario, Canada. Angiogenesis (the growth of new blood vessels) is a target for cancer therapy. Angiogenesis is necessary for cancer growth and a continued supply of oxygen and nutrition for cancers. Rapid tumor growth occurs after blood vessels develop.
Vascular endothelial growth factor (VEGF) is a protein formed by cancers which promotes angiogenesis. VEGF is, probably, essential for cancer cell migration and angiogenesis. The blood vessels formed are immature and can lead to bleeding and edema. Tumors sometimes increase angiogenesis after radiation therapy.
Angiogenesis is a normal process in the placenta, fetus and wound healing. Cancers take control of this normal process and use it without normal regulation. Dr. Judah Folkman promoted the use of anti-angiogenesis as anticancer therapy. One such pharmaceutical is bevacizumab (Avastin.) Avastin extends life when used with chemotherapy, but, has serious side effects.
Many natural products resist cancer through anti-angiogenesis combined with other processes. Chemicals which work by more than one pathway are often more effective than drugs which work by anti-angiogenesis, only. For example, heparin works by anti-angiogenesis and by anticoagulation. (Anticoagulation can reduce metastasis.)
Pharmacognosy is the science of natural drugs developed from plant medicines. Testing has been developed for screening herbs for anti-angiogenic activity. Ideally, an agent with strong anti-angiogenic activity at a low dose would reduce side effects. The new approach to chemotherapy is to use lower doses of organic chemicals which work in complementary ways.
Anti-angiogenesis products are Artemisia annua (Chinese wormwood), Viscum album (European mistletoe), Curcuma longa (turmeric), Scutellaria baicalensis (Chinese skullcap), resveratrol and proanthocyanidin (grape seed extract), Magnolia officinalis (Chinese magnolia tree), Camellia sinensis (green tea), Ginkgo biloba (ginkgo), quercetin, Poria cocos, Zingiber officinalis (ginger), Panax ginseng, Rabdosia rubescens hora (Rabdosia), and Chinese destagnation herbs. These herbs act as biologic modifiers, as adaptogens and as enhancers of conventional therapy.
Chinese wormwood (Artemisia annua) is an anti-malaria herb whose active chemical is artemisinin. It causes apoptosis (natural cell death) and lowers VEGF in cancer cells.