Herbal Antibiotics: Natural Alternatives for Treating Drug-Resistant Bacteria (28 page)

Hydrastis canadensis:
As a bitter tonic, mucous membrane tonic; for skin disorders including infection and inflammation, eye and ear infections, mouth ulcers, throat and mouth infections, fever, diarrhea, dysentery, catarrh, vaginal discharges, liver congestion and gallbladder problems, menstrual irregularities, ulcerative colitis, cancer.

Mahonia
spp.:
As a bitter tonic, mucous membrane tonic; for liver and blood stagnation, skin problems including inflammation and infections, GI tract infections, ulceration, fever.

Berberis
spp.:
As a bitter tonic, mucous membrane tonic; for skin inflammation and infection, GI tract problems, cholera, dysentery, diarrhea, fever, cancer, liver stagnation, poor blood, gout.

Coptis
spp.:
For abdominal problems, GI tract problems, dysentery, cholera, enteritis, typhoid, respiratory tract infections, UTIs, gynecological inflammations, ear/nose/throat infections, jaundice, fever, blood problems, eye inflammation, insomnia, abscesses, skin problems.

Corydalis
spp.:
As a bitter tonic, analgesic, mucous membrane tonic; for liver stagnation, spleen stagnation, stagnant blood, menstrual irregularities, ulcers.

Phellodendron
spp.:
As a bitter tonic; for GI tract problems, dysentery, jaundice, vaginal inflammation and discharges, urinary tract infections, pain, swelling in knees and feet, boils, sores, abscesses, ulcers, eczema, canker sores, burns, fever, night sweats.

Argemone
spp.:
As a sedative, laxative; for jaundice, skin diseases, cough, venereal disease, vaginal discharge, arthritis, kidney pain, post-partum difficulties, dropsy, swelling of the legs, malaria, fever.

Many of the other berberine-containing plants have been used similarly.

The phellodendrons are not that common in India, but the barberries are and have been used for millennia. Five species are commonly used, the main ones being
Berberis vulgaris
and
Berberis aristata
. They are used just as all berberine-containing plants are. See Traditional Uses of the Berberines,
page 171
.

Phellodendron,
known as
huang bo
or
huang bai
, is considered to be one of the 50 fundamental herbs of traditional Chinese medicine (TCM). It has been used for millennia and appears in medical texts as early as 300
BCE
. It is considered bitter and cold, affecting urinary bladder, kidney, and large intestine meridians. It is used to clear heat and dry dampness, to reduce fire and release toxins. See Traditional Uses of the Berberines,
page 171
, for specific TCM uses. Normal dosage in China is 3 to 10 grams of the dried herb (1/10 to
⅓
ounce). The plant has also been a part of traditional Korean and Japanese medicine for a very long time, used for similar diseases and conditions.

Coptis, Corydalis, Mahonia,
and
Berberis
species have all been a part of TCM for millennia and are used in similar ways.

Phellodendron
has been unknown until now.
Hydrastis
,
Berberis
species, and
Mahonia
species were all used for a very long time, in just the same ways all berberine plants are.

All the berberine plants, and berberine (in vitro studies), are highly active against a wide range of microorganisms, especially bacteria. There are literally scores if not hundreds of such studies on the compound.

Part of the problem with berberine as a systemic is that it does not move across the GI tract membranes very well; it tends to be limited to where it can touch for its activity. Researchers have been trying for years to find a way to make it broadly systemic but have not succeeded. Most of the pharmacokinetic studies have focused on injectable forms of berberine or other, similar, alkaloids. Oral administration of crude plant preparations has shown
some movement of alkaloids, e.g., berberine and palmatine, into blood plasma in rats, but the amounts are tiny, 0.31 ng/ml as compared to 18.1 ng/ml if pure berberine is injected. Tiny amounts of berberine have been found in the pancreas, heart, kidney, spleen, lung, testes, and uterus. This does have some tonic and stimulatory effects on those systems, which is reflected by the plant's traditional uses. The tiny systemic amounts do provide
some
systemic antimicrobial help, just not very much and certainly not enough to treat a resistant systemic disease.

In human volunteers (China), normal dosing produced about 0.020 ng/ml in plasma, very large doses got it up to 3.0 ng/ml in the blood, still not enough for systemic treatment of serious diseases, and this was from ingesting pure berberine. Oral intake of goldenseal (product contained 77 mg hydrastine, 132 mg berberine) produced only 0.1 ng/ml of
both
constituents (combined total) in blood plasma of human volunteers. Berberine (and presumably many of the other alkaloids in these plants) just doesn't transfer well across the GI tract membranes; however, the amounts that do are very quickly expressed into the urine for excretion, into the mucous membranes for excretion by that route, or routed to the liver, where they are expressed into the bile. The amounts expressed in the urine (about 5 percent) are what account for the use of berberine plants in the treatment of urinary tract infections (for which they do work to some extent). The amounts concentrated in the liver and then expressed into the bile (0.5 percent) are what account for the traditional uses of the herbs for sluggish liver and as a bile stimulant. Berberine is metabolized in the liver and the metabolites excreted into the bile, which then expresses them into the GI tract. The gut bacteria play a role then in the enterohepatic circulation of the metabolites. These metabolites remain more prominently in the body than berberine itself, however still at fairly low levels.

The particular substance, pervasive in the intestinal epithelium (and hepatocytes), that keeps berberine from circulating widely in the body is permeability glycoprotein, a.k.a. P-glycoprotein. P-glycoprotein distributes a great many substances across the mucous membranes of the intestinal tract, including herbal constituents. However, it is also responsible for transporting substances the body identifies as toxic out of the body, often through urine and bile—the berberine-plant alkaloids are some of them. Because P-glycoprotein (or its directors) identifies berberine-like alkaloids as toxic, they are not allowed to cross the intestinal barrier to circulate in any concentration in the bloodstream.

However, the tiny amount of alkaloids that do circulate in the bloodstream increases the level of the active immunoglobulin A antibodies (IgA) in the mucous membranes—though this action is much, much higher in the intestines because the herb is actually able to touch the membranes there. IgA is one of the most potent antibodies in the human body and it infuses the mucous membranes in order to fight infections that seek to gain entry there. In this instance the body is identifying the berberine
alkaloids and their metabolites as an infectious agent and producing IgA antibodies in response. Stimulation of the mucous membranes and the IgA antibodies helps prevent infections. This is the main source of the immune-modulating and immune-potentiating actions of the berberines and is why the herbs, if used properly, help prevent and can effectively treat viral and bacterial infections of the mouth, throat, and sinuses. Synergistically, berberine also interferes with the adherence of bacteria, e.g.,
Streptococcus pyogenes
, to epithelial cells, thus reducing disease incidence.

The berberine plants are, however, most specific for intestinal infections from pathogenic organisms. That is where their great strength lies. Berberine reduces the intestinal secretion of water and electrolytes caused by infectious intestinal bacteria such as cholera and
E. coli
organisms, inhibits cholera and other bacterial entertoxins, reduces smooth muscle contraction and intestinal motility (thus reducing cramping), delays intestinal transit time, reduces inflammation in intestinal tissues, and is directly bactericidal to cholera and other dysenteric/diarrheal organisms. Berberine specifically inhibits bacterial adherence to mucosal or epithelial surfaces, thus stopping the infection.

Because berberine is so widely antimicrobial, many people have used berberine plants (and many companies have touted them) as systemic antibacterials. They are not and are only partially effective for colds and flu, their other main use. (They are active against some viruses and do potentiate mucous membrane function, which helps the membranes fight off microorganisms.) Goldenseal is the primary berberine plant used medicinally in the United States and it is ridiculously overused, usually for the wrong things. There are much better plants for colds and flu.

Many of the berberine-containing plants have been found to contain multidrug-resistance (MDR) reversal activity, usually inhibiting efflux pumps in resistant bacteria.
Berberis
species and
Hydrastis canadensis
contain 5′-methoxyhydnocarpin-D (5′-MHC) and pheophorbide A, which inhibit the NorA efflux pump in
Staphylococcus aureus
. This is part of what makes the plants so effective in treating resistant organisms, especially MRSA. There are numerous other compounds in the berberine plants that show this kind of MDR inhibition.

The MDR inhibitors in the berberine plants have been found to be synergistic with the alkaloids in the plants. They have also been found to be synergistic with pharmaceuticals, increasing their activity and effectiveness in treating resistant organisms and lowering the necessary dose for antibacterial, antifungal, and anti-amoebic action.

In this section I am only going to look in any depth at research on the phellodendrons and berberine as an isolated constituent.

An in vivo trial in the treatment of both acute and chronic induced inflammation using an ethanol extract of
Phellodendron
and
Coptis
(in a
2:1 ratio) found the tincture to be as potent in its effects as celecoxib and dexamethasone in reducing inflammation. In vitro studies on human osteoarthritis cartilage found that the plant significantly inhibited collagen and chondrocyte destruction by inhibiting proteoglycan release and type II cartilage degradation; down-regulating aggrecanases, matrix metalloproteinase (MMP) activity, and phospho-ERK ½, JNK, and p38 MAP kinase signaling; and up-regulating TIMP-1 activity. Another found potent antioxidant activity by the plant.

Eighty people (45 completing) were enrolled in an 8-week, placebo-controlled, randomized, double-blind study of the effects of a
Phellodendron amurense
bark and
Citrus sinensis
peel combination capsule (740 mg, twice daily) on primary osteoarthritis of the knee in both overweight and normal-weight persons. Overweight participants lost an average of 5 percent of body weight, and lipid levels, blood pressure, and fasting blood glucose levels normalized. There was significantly less inflammation and fewer symptoms of osteoarthritis in all those who used the herb combination.

A clinical trial with 28 participants (premenopausal women), double-blind, placebo-controlled, and randomized, testing a combination extract of magnolia and
Phellodendron
bark found no weight gain in the extract group but gains in the placebo group. The extract group had lower cortisol levels in the evening (the placebo group, higher) and lower levels of stress.

A combination blend of
Phellodendron
and magnolia, in a randomized, parallel, double-blind, placebo-controlled, clinical trial with healthy, overweight women (40 participants, 26 completing) found the extract effective in reducing temporary, transitory anxiety.

Phellodendron
has been found effective in treating periodontal disease.

Extracts of
Phellodendron
(Nexrutine) fed to TRAMP mice for 20 weeks significantly inhibited prostate cancer cell proliferation and progression. There have been a number of studies that found similar antitumor activity of the plant for the prostate. It's strongly active on the prostate gland in vitro, inhibiting contractility. Dietary berberine and dietary
Phellodendron
extract were found to inhibit cell cycle progression and lung tumorigenesis in mice.

In vivo studies with hyperuricemic mice found a decrease in uric acid levels in mice ingesting a high-dose
Phellodendron
extract. Other studies found that the plant constituent phellodendrine suppresses autoimmune responses in mice and guinea pigs. Unlike prednisone and cyclophosphamide, the extract did not affect antibody production.

Phellodendron
extracts prevent ethanol-, aspirin-, stress-, and pylorus-ligated-induced ulcers in mice. Extracts of
P. wilsonii
were highly protective of mouse liver in CCl4-induced hepatotoxicity. Other species provided only moderate protection.

During in vitro studies
Phellodendron
was found to be antioxidant, antitumor, anti-inflammatory, antimicrobial (plaque), anti–herpes simplex 1, and antibacterial against a wide range of bacteria.

Clinical (and a few other) studies with other berberine-containing plants:

123 people with acute bacillic dysentery were treated with a decoction of Sankezhen (any of four
Berberis
species used in China:
soulieana
,
wilsoniae
,
poiretii
, or
vernae
). Of them, 113 were cured, 4 improved. In another trial with 94 people, 88 were cured.

A trial used tablets prepared from
Berberis poirettii
decoction in the treatment of 228 cases of chronic bronchitis. Of them, 12.3 percent experienced cure, 39 percent marked effects, 38 percent improved. (A tincture would have worked better.)