What is Artemisinin?

It was determined in 1972 that artemisinin is an active compound extracted from the plant Artemesia annua L. (sweet wormwood, and has a long history of use as an anti-malarial remedy It also known as the Chinese herbal Qinghao

The compound artemisinin isn't new. It was extracted from the plant Artemesia annua L., commonly known as wormwood, thousands of years ago by the Chinese, who used it to combat malaria. However, the treatment was lost over time. Artemisinin was rediscovered during an archaeological dig in the 1970s that unearthed recipes for ancient medical remedies, and has become widely used in modern Asia and Africa to fight the mosquito-borne disease

The artemisinin molecule contains two oxygen atoms linked
together in what is known as an endoperoxide bridge, which could react with an iron atom to form free radicals. Artemisinin is toxic to malaria parasites because the parasite contains a high amount of iron. Artemisinin has been extensively researched for malaria, and has been used on over a million patients, mostly in China and Vietnam. It is very helpful for drug resistant malaria.

Artemisinin is also widely recommended by the World Health Organization (WHO) for treatment of malaria.

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.

Why is it indicated in cancer patients?

Compared to normal cells, cancer cells sequester relatively large amount of iron mainly in the form of holotransferrin. 
Artemisinin has been shown to cause rapid and extensive damage and death in cancer cells and have relatively low toxicity to
normal cells.  Artemisinin had been analyzed for its activity against 55 cancer cell lines. It was most active against leukemia
and colon cancer cell lines and active for melanomas, breast, ovarian, prostate, CNS, and renal cancer cell lines.

Is it Toxic?

When artemisinin was tested with monkeys, they showed no toxicity after they received up to 292 mg/kg of artemether over
1 to 3 months. High oral doses of artemisinin can produce neurotoxicity such as gait disturbances, loss of spinal and pain
response, respiratory depression, and ultimately cardiopulmonary arrest in large animals and limited and unique, selective brain
stem neuronopathy in laboratory animals.

Artemisinin is appealing for oral use in that the pharmacodynamics, dosage and toxicity have been well studied for use in relationship to the treatment of malaria. Artemisinin is relatively safe with little side effects even at high dosages (70 mg/kg per day) in short term malaria use.

Test Tube Results with Artemisinin

The breast cancer cell research resulted in a 28% reduction of breast cancer cells treated only with artemisinin, and a staggering 98% decrease in breast cancer cells that were treated with artemisinin and an iron-enhancing molecule, transferrin, within 16 hours. These same treatments had no significant effect on normal human breast cells. This research pointed to the involvement of free iron in the toxic effect of artemisinin toward cancer cells, while basically sparing healthy cells. ("Selective toxicity of dihydroartemisinin and holotransferrin toward human breast cancer cells," Life Sciences 70 {2001) 49-56)
These results become even more potentially important because the breast cancer cells used in the study were radiation resistant, a difficult situation to overcome.
An earlier study with human leukemia cells demonstrated 100% cancer cell destruction in half the time (8 hours) as the breast cancer cells, probably due to the rapid cell division and higher iron concentration of leukemia cells. ("Selective cancer cell cytotoxicity from exposure to dihydroartemisinin and holotransferrin," Cancer Letters 91 {1995} 41-46)
These results were encouraging, but often test tube results do not carry over into animal testing.

The Rat Study
Rats that were implanted with cancer (fibrosarcoma) and given iron (ferrous sulfate) followed by a form of artemisinin (dihydroartemisinin) had a significant reduction in the growth rate of the implanted tumors. There appeared to be no tumor growth reduction in rats that were given either substance alone, iron or artemisinin. The researchers concluded in their abstract that "An artemisinin analog-ferrous salt combination may provide a novel approach for cancer therapy." ("Oral administration of dihydroartemisinin and ferrous sulfate retarded implanted fibrosarcoma growth in the rat," Cancer Letters 98 {1995} 83-87)

Forms of Artemisinin

is the active natural extract from the herb. It is not at all water-soluble and has poorer absorption than some other forms. It is quickly absorbed and reaches its peak concentration in the blood within 40 minutes. This form is broken down very quickly into its metabolites in the liver and excreted somewhat quickly, but still has some metabolic effects for as long as four hours. Human studies have shown this form to have a somewhat poor and erratic absorption, although it is the preferred form of some doctors.

Artesunate is a semi-synthetic form that is more water-soluble. This form tends to break down easily when being stored in hot climates, which is certainly a consideration for treating malaria. All the artemisinin compounds are light-sensitive; they decompose when exposed to light.
One study reported that the absorption of artesunate is about 61%, and it has the shortest activity period in the body of the three forms.
Some sources claim that artesunate is the most active form, but this has not been proven.

Artemether is a semi-synthetic, more fat-soluble form that is the longest lasting in the blood stream. Due to the fat-soluble nature of this compound, it passes more readily through the blood brain barrier. It is also metabolized fairly rapidly to dihydroartemisinin (DHA), and blood tests show that after 6 hours the DHA metabolite has higher plasma concentrations than the parent compound artemether.

Dr. Lai speculates that longer acting compounds such as artemether may be better for cancer treatment.

Important Note

No artesminin should be taken within 30 days of radiation therapy because of possible free iron leaks to the surrounding tissues after radiation therapy.
Artemisinin protocol for dogs as recommended by Dr. Narendra P. Singh, Dept. of Bioengineering, University of Washington, Seattle.

1 to 2 mg/lb body weight per day in a capsules in a piece of bread around 10PM (bed time) can be tried. Or better suspend in whole milk and fill up in a syringe to give orally. Please contact your vet for any side effects or animal related complaints. We are simply inventors of the therapy and trying to help you through your vet.
Add antioxidants, specifically vitamin A, vitamin C and vitamin E at breakfast and lunch but not at diner.Let the animal drink plenty of water during therapy and let have plenty of pleasant, playful exercise, particularly after diner for two to three hour.  Inactive and old animals with poor health respond poorly to treatment

Observations to be made:
  1. Keep a record of animalís weight, before therapy, during therapy at a weekly interval.
  2. Biopsy/Xray reports before and after 2 months of treatment.
  3. Measurements of maximum and minimum (length and breadth) tumor sizes before and after 2 months of therapy.
  4. Observe for fever on 2nd and 3rd days and make a note to give enough water during night
  5. Iron capsules are not  necessary
  6. Keep artemisinin in dark/indirect light Keep in cold, 4 degree C
Avoid iron rich food such as meat 3 to 4 hours before artemisinin dose.  Artemisinin suspended in small volume of milk filled in syringe may be the best way to administer drug.  Make sure your dog does enough exercise and has adequate supply of vitamin AD. 
Convey the progress to your vet soon after two months, and get the dog evaluated before and after this treatment (ultrasound, biopsy, X-rays etc) to see if the treatment is effective.

This is a short presentation on artemisinin that was put together by Dr. Singh. I highly recommend checking it out.