Herbal Antibiotics: Natural Alternatives for Treating Drug-Resistant Bacteria (24 page)

The herb is very effective if used properly. The dose can be increased fairly high, as it is a very safe herb. Remember: The reason that this herb was discovered was that in the region of China where it is used there were few or no incidences of malaria. The secret is in the dose, as with all medications.

About 25 percent of people using
Artemisia annua
as an antimalarial report a mild nausea, which does not progress to vomiting. It may also cause occasional dizziness, tinnitus, pruritus, and mild abdominal pain.

Artemisinin itself can cause gastrointestinal upset, loss of appetite, nausea, cramping, diarrhea, vomiting. About 4 percent of people who take it experience these symptoms, usually in a more severe form than that experienced from ingesting the herbal infusion. Very high doses (5,000 mg per day of artemisinin for 3 days) have caused liver inflammation, which corrects upon stopping the supplement. Artemisinin has a slightly chronotropic effect on the heart. It causes mild hypotension. This has not been, apparently, a problem in any users.

Both the herb and the constituent should be used with caution in pregnancy, especially in the first trimester. In vivo studies have found a number of adverse effects in rats and mice if the herb is used in the first trimester. However, one clinical trial with 16 patients in the first trimester of pregnancy taking the herb found the miscarriage rate to be the same as that for the general population.

Artemisia annua
, like many antimicrobial plants, contains synergists that make its compounds more active against microbial organisms. In this instance, chrysospenol-D and chrysophlenetin, two flavonols in the plant, have been found to potentiate the activity of berberine and norfloxacin against resistant staph. Artemisinin does induce certain liver enzymes and may interact with drugs such as omeprazole.

A. annua
is native to China, western Asia, northern India, Japan, Korea, Vietnam, Myanmar, southern Siberia, and southeastern Europe. An emerging invasive plant species, it is naturalized in the United States and many other countries. It loves waste places—roadsides, fallow fields, neglected gardens—especially in eastern North America. It can grow pretty much anyplace but is stronger and more aromatic when grown in poor, dry soil. Its artemisinin content is about 20 percent higher when it grows in mildly potassium-deficient soils.

The plant, once established, grows into a large straggly bush. The leaves look a bit like celery's leaves, though
A. annua
's are much broader, bushier, and more extensive in their growth. The plant grows 4 to 6 feet (1.2 to 2 m) tall with a typical attractive, weedy, bushy look. It blooms in late summer.

Artemisia annua
is an annual (hence its species name) and cultivates easily from seed. Sow the tiny seeds outdoors in the fall or seed them indoors before the last frost. They like it best on top of well-aerated soil; they need light to germinate. Once established, the plant self-sows and will never go away.

The aerial parts should be harvested just after flowering. The flowers and leaves both contain artemisinin. The artemisinin content is higher in the fall than in spring; it takes the plant time to create the chemical. The longer you wait, the better the yield, so take even the older, dying-back leaves. The stems and root contain only very low amounts of the compound and aren't generally worth the trouble.

Once the plant is picked, let it dry in the sun for a week. The light helps the artemisinin precursors keep producing after the plant is harvested. After a week, the sun does more harm than good, so finish drying in a dry, dark spot inside.

Several hybrid plants (
Artemisia annua
var.
artemis
, var.
campinas
, var.
anamed
) have been bred for higher artemisinin content. They are available from Anamed (
www.anamed.org
) as part of an artemisia antimalarial
starter kit that includes a lot of useful information on growing and using the plant. One problem with the hybrids is that they don't reseed themselves well and the artemisinin content of those that do is poor (so it is not as sustainable an alternative as it should be). If you want a continual supply of the plant, non-hybrids are the way to go.

Artemisia annua
contains a great many chemical constituents, over 150 at last count, and that is most likely just a tiny fraction of the total. There are a minimum of 28 monoterpenes, 30 sesquiterpenes, 12 terpenoids and steroids, 36 flavonoids, 7 coumarins, 4 aromatics, and 9 aliphatic compounds.

Artemisinin is considered to be the active antiplasmodial compound but numerous other compounds with malarial activity have been found. Others, such as arteannuin B and artemisinic acid, are antibacterial and antifungal. Arteannuin B, while found to be ineffective against malarial parasites, strongly potentiates the activity of artemisinin. Many of the flavonoid compounds have been found to be antimalarial in vitro. Some of them (artemetin, casticin, chrysophlenetin, chrysosplenol-D, and cirsilineol) have been found to also potentiate artemisinin's ability to kill plasmodial parasites. Many of these flavonoids are abundant in the plant; they induce a three- to five-fold reduction in the amount of artemisinin needed to kill malarial organisms. Some of the sesquiterpene lactones are also antiplasmodial, with ridentin, some of the guainolides, and germacranolides being the most important.

The artemisinin content of
A. annua
, if the leaves and flowers are harvested in the fall before the plant goes to seed, can run anywhere from 0.75 percent to 1.4 percent (several high-yield varieties are in development or are just on the market).

A relatively new development is the finding of another strongly active antiplasmodial constituent, tehranolide, in a number of artemisia species. In vivo studies show it to be strongly antiplasmodial. Treatment with the tehranolide extracts of
Artemisia diffusa
resulted in complete clearance of parasites from the blood in mice at similar dosages to artemisinin.

Artemisia annua
(and many of the other artemisias) is somewhat unusual in its actions. The
systemic
constituents of the plant primarily act in two ways: 1) as highly potent antiparasitics for blood and liver parasites; and 2) as antitumor agents. These same constituents have two other actions that are useful: 1) they stimulate sweating and thus help reduce fever; and 2) they are emmenagogues; that is, they stimulate menstruation. The emmenagogue action is why the plant is generally not recommended in the first trimester of pregnancy. Caveat:
Artemisia annua
has much less emmenagogue activity than some of the other artemisias; the stimulatory activity has been found to be only minimal.

Although other artemisias have been used to effectively treat malaria and other blood parasites, the most potent species for this, at this time, is
Artemisia annua.

The plant has been used in Chinese medicine for over two thousand years, but its current status as an antimalarial emerged from its use by the North Vietnamese during the Vietnam War. Malarial infections
were exceptionally high among the North Vietnamese troops. Appeals to the Chinese leader Mao for help resulted in the discovery of
Artemisia annua
for use as an antimalarial.

Chinese researchers had discovered that in one region of China the people had little incidence of malaria infection. Looking closer they discovered that the local people took the herb at the first sign of symptoms. In 1972 Chinese researchers isolated artemisinin.

This plant is unknown in India, though a number of other artemisias are used.
Artemisia absinthium
is used for intermittent fevers, for stomach complaints (as a bitter and digestive), as a vermifuge for intestinal worms, and for nervous system complaints (from hysteria to depression).
Artemisia maritima
(wormseed) is specific for intestinal worms, especially ascarides and oxyuris. Most of the other artemisias are used similarly.

Called
qing-hao
in traditional Chinese medicine,
Artemisia annua
is used for clearing fevers from the blood, especially in conditions with headache, dizziness, low fever, and a stifling sensation in the chest. Also for febrile diseases, for malaria, and for scabies, pruritus, and malignant ulcers.

For many years
A. annua
was unknown, although many other artemisias have long been used.
Artemisia absinthium
was a primary herb among the Eclectics in the late ninteenth century in the United States. The herb was used for intermittent fevers, for malaria, as a vermifuge in the treatment of intestinal worms, for dyspepsia, nervous conditions, diarrhea and liver complaints, for amenorrhea and leukorrhea, for jaundice. Other artemisias were used similarly.

The indigenous peoples throughout the United States used the plants similarly.

There have been hundreds of in vitro and in vivo studies and clinical trials on the antiparasitical actions of artemisinin (and its analogues), most on malaria and schistosomiasis. I will just touch on them here.

Every one of the several hundred clinical trials shows the effectiveness of artemisinin in the treatment of malaria. (There have been a number of clinical trials with the whole herb as well; see Whole Herb vs. Artemisinin,
page 154
.)

Artemisinin has become the choice for malarial treatment worldwide because it is effective against resistant strains of the organism. Ninety-eight percent of malarial parasites are generally killed within 24 hours with use of the herb or its isolated constituent. If low, short-term doses are used (less than 5 days), however, relapse rates can be as high as 39 percent. Higher dose ranges for a longer period of time (5 instead of 3 days) lower the relapse rate considerably. Clinical trials with as many as 2,000 people (with both low and high dosages) have found 100 percent clearance rates for all participants if artemisinin is taken for 5 to 7 days. There are very few side effects when used properly in short-term treatment.

The constituents of the herb that are antiparasitic are exceptionally systemic in that they spread quickly throughout the body and easily cross the blood-brain barrier. Artemisinin is considered specific for cerebral malaria. Because it infuses the blood,
it is carried throughout the body to every cell, all of which need blood to live.

A slightly modified form of artemisinin—artesenuate—has been found effective for babesia organisms in vitro. Relatively low concentrations of the compound are effective; complete inhibition of
Babesia equi
and
B. caballi
occurred at 0.2 and 1.0 micrograms/ml respectively. (To make artesenuate, artemisinin is modified slightly in order to get patent protection.)

Use of artemisinin in clinical practice, however, has shown only moderate success for this organism; it seems to be effective in about half the people who use it for babesia. Sida and cryptolepis appear to be better alternatives.

A number of clinical trials have occurred with a synthetic form of artemisinin, artemether, in the treatment of schistosoma infections. Schistosoma are a type of blood fluke—and are a major infectious parasitic organism, second only to malaria in numbers of those infected, totaling hundreds of millions worldwide.

Artemether is normally given in a single dose of 6 mg/kg every 2 weeks. It is primarily active against the juvenile form of the parasite rather than the adult. Repeated dosing results in parasite reductions of 90 percent to 98 percent. Artesenuate has been found just as effective.

Artemisinin is also effective against
Neospora caninum
, another type of protozoa that affects both endothelial cells and macrophages. CNS involvement and carditis are common. Artemisinin is effective against a number of other organisms such as
Eimeria tenella
,
Leishmania major
(which infects macrophages),
Toxoplasma gondii
,
Schistosoma mansoni
(liver flukes), and
Clonorchis sinensis
(liver flukes), all parasitical organisms. It is antispirochetal against leptospire organisms, killing them in vitro. Artemisinin does appear to possess broad antiparasitical actions.