Herbal Antibiotics: Natural Alternatives for Treating Drug-Resistant Bacteria (38 page)

Because this book is concentrating on the treatment of resistant bacterial organisms, many of which can have severe impacts if not treated effectively, it makes sense to me to use the isolated constituent piperine rather than the whole herb in this instance. The herb itself
can
be used; it is, however, about one-fifteenth as strong as piperine. Since piperine is, at this point, relatively easy to find, I would suggest having some on hand, just in case. If you don't have it or it becomes no longer available (see Finding Black Pepper and Piperine on opposite page) you can indeed use the pepper itself.

Both
Piper nigrum
and
Piper longum
are prepared as tinctures, 1:5, 65 percent alcohol. Dosage: 5–15 drops as needed. Piperine is not very water soluble; you need an alcohol tincture to extract it from the peppercorns. I would highly recommend using whole peppercorns, freshly ground, for making the tinctures. Previously ground pepper is much weaker.

Actions

Analgesic

Antibacterial

Anticonvulsant

Antidiarrheal

Antidysphagic (essential oil)

Antihyperlipidemic (reduces lipid levels in the blood)

Anti-inflammatory

Antimutagenic

Antioxidant

Antispasmodic

Antitumor inhibitor

CYP3A4 inhibitor

Free radical scavenger (potent)

Hepatoprotector

Immunostimulant

Increases oxygen uptake by red blood cells

Intestinal mucosa modulator

Melanocyte stimulant

Modulates thyroid hormone levels in the blood

Neural protector/stimulant

P-glycoprotein inhibitor

Reduces blood glucose levels

Reduces erythrocyte fragility

Stimulates production and release of pancreatic enzymes, bile acids, and gastric acids

Stimulates the pituitary/adrenal axis

Synergist

Testosterone antagonist

Vasodilator

You can also, if you wish, make trikatu, the traditional Ayurvedic combination that is added to herbs as a formulation synergist. It is prepared using
Piper nigrum
and
P. longum
and gingerroot in a ratio of 1:1:1; that is, equal parts of each herb or their tinctures. I prefer the tinctures. Use a tincture of fresh gingerroot, or, more preferably, the alcohol-stabilized fresh juice (as described in the ginger monograph) and tinctures of the two peppers as outlined above. Combine them in equal parts and then add that combined tincture to whatever formulation you are making. If you are making 4 ounces of an influenza formulation, then add an extra ounce of trikatu to make a total of 5 ounces. In other words, add 25 percent to any formulation you are making. It is going to be spicy.

If you wish to use pure piperine, you will need to buy it, as it is a manufactured product. It is relatively inexpensive. Normal dosing, for instance to enhance the uptake of nutrients from food, is 20 mg daily.

Note:
I would
not
use piperine as a regular supplement; in my opinion, it is indicated
only
for medical conditions that necessitate its use. If you have a systemic infection, especially if it is Gram-negative, piperine is a highly effective synergist for the herbs you will use to treat it and should be considered as a part of the treatment approach.

Dosage in acute conditions:
Piperine should be taken prior to the herbal formulation you are using so that the intestinal wall has already been altered by the time your herbs get to the GI tract. Take 20 mg piperine 15–30 minutes prior to your herbs and then again 4–6 hours later, 30 minutes before taking your herbs again. Piperine will stay strongly present in the body for about 6 hours.

So … take piperine twice daily, 20 mg each time, in acute conditions to a max of 40 mg daily. Generally, not to exceed 7 days. If you are taking your herbs six times daily, you still only need to take piperine twice, once before the first dose, and then again 4–6 hours later.

Black pepper can exacerbate gastric reflux problems, but its major side effects occur on the reproductive system. In traditional medicine it is considered a mild contraceptive. The whole herb, however, is generally pretty safe along these lines unless taken in huge doses for extended periods of time. Studies on piperine, on the other hand, have found that it does interfere with egg implantation if taken long term in high doses.

However
, the impacts on the male reproductive system are more severe. When taken as a supplement continued oral intake of piperine decreases the weight of the testes, lowers sperm production, decreases intracellular testosterone, and decreases the fertilizing capacity of sperm. Constant piperine intake has deleterious effects on the Leydig cells, epididymis, and seminiferous tubes even at doses of 1 mg/kg of body weight (that is, roughly, 70 to 80 mg daily for an adult male).

Piperine should primarily be used for short-term treatment of acute conditions. Women who are trying to become pregnant should not use it. Men with low testosterone levels should be very cautious in its use and not use it for longer than 2 weeks.

Piperine will increase the bioavailability of scores of drugs. (It will decrease the bioavailability of a few others such as diclofenac sodium.) If you are taking pharmaceuticals, you should check for synergy (the list is too long for this book) or simply not take them together. It is highly likely that the supplement
will
increase bioavailability and thus the impacts of the pharmaceutical.

Piper nigrum
contains at least 200 identified constituents with more being discovered all the time. The most important is considered to be the alkaloid piperine, which is present at levels of up to 9 percent of the dried peppercorns in black pepper. It is the primary substance responsible for the peppery taste of the spice.

Other major compounds are chavicine, coumaperine, piperidine, numerous piperidine amides, piperettine, piperanine, piperolein A, B, and C, piperonal, and so on.

Piper nigrum
is native to southern India, where it is extensively cultivated. The plant is a flowering vine that produces grape-like clusters of dark red berries, at the center of which is a large white seed. The seed, as is sometimes the case, comprises most of the berry; the pulp surrounding it is fairly thin, with the usual thinnish outer rind of the fruit covering that. Basically, it is not a very exciting berry.

The black peppercorns that we use for a spice, however, are produced from the green, unripe berries. The berries are harvested and briefly immersed in hot water, thus slightly cooking them. This ruptures the cell walls in the berry and activates a number of enzymes that will cause the outer pulp and rind that surround the white seed to blacken during drying. The fruits are then spread in the sun to dry for several days. The outer pulp and rind wrinkle and turn black. Once dried the fruits are usually sold whole to preserve the strength of the corns, then ground into the powder that we call black pepper just before use.

White pepper is simply the pepper seeds themselves absent the pulp and rind. In this case the ripe berries are soaked in water for a week until the outer rind and pulp soften and slough off the inner seed. The seed is then dried, sold, and ground into a fine powder.

Black pepper has been used in India for at least four thousand years as both spice and medicine. It is probably the most common spice in the world after salt.

Black pepper has a primary place in Ayurveda, often combined with long pepper (
Piper longum
) and ginger to form a compound called
trikatu
or the three acrids. This combination has been a primary element
of Ayurvedic compounding since at least 600
BCE
; most Ayurvedic formulations contain it.

Trikatu is considered specific for correcting imbalances in the three
doshas
, psychospiritual aspects of the human body that when out of balance lead to disease expressing itself physically. This formulation is (as are the three herbs individually) considered specific for “activating” the potency of the plants with which it is combined. This has been its main use for millennia.

As a single herb, black pepper (and long pepper) has been used for a variety of conditions (constipation, diarrhea, earache, gangrene, heart disease, hernia, hoarseness, indigestion, insect bites, insomnia, joint pain, liver problems, lung disease, oral abscesses, sunburn, tooth decay, and toothaches), but its main uses have been, internally, for disease conditions accompanied by fever and/or diarrhea, dysentery, GI tract disorders, and urinary problems, and externally for rheumatism and neuralgia.

Black pepper was incorporated into the Chinese materia medica during the Middle Ages. It is considered specific for warming the middle, dispersing cold, dispelling phlegm, for wind-cold, and for diarrhea, usually for conditions accompanied by vomiting, diarrhea, and abdominal pain. It is also considered specific for epilepsy. The synergistic actions of the plant are apparently unknown in this system.

I am splitting this section into two parts: 1) nonsynergist actions and 2) synergist actions. Most of the studies have been on the isolated constituent piperine. (There are several hundred studies on piperine; this is just a sampling; most of the studies have been in these areas.)

Black pepper does have some antibacterial activity itself. In vitro studies of a number of its constituents (not piperine) found them active against
Bacillus subtilis
,
Bacillus sphaericus
,
Staphylococcus aureus
,
Klebsiella aerogenes
, and
Chromobacterium violaceum.
The essential oil of black pepper
is effective against
Bacillus subtilis
,
Pseudomonas aeruginosa
,
Candida albicans
,
Trichoderma
spp., and
Aspergillus niger.
An aqueous solution of black pepper was tested against 12 genera of oral bacteria isolated from 200 individuals and was found to be effective against 75 percent of them (unfortunately the abstract does not list the bacteria; the full paper is regrettably elusive). Piperine itself is active against
Leishmania
spp. and
Trypanosoma cruzi
.

Here is a look at some of the studies.

In vitro:
Black pepper is a strong antioxidant, more potent than alpha-tocopherol when used at similar concentrations. One of pepper's constituents is as potent as the synthetic antioxidants BHA and BHT.

In vitro:
Black pepper inhibits cholesterol esterification in HepG2 cells; it potently inhibits binding between slCAM-1 and LFA-1 of THP-1 cells, dose dependently.

In vivo, guinea pig and rabbits:
Crude extracts of black pepper, at low doses, have a mild laxative effect in constipation. However, in larger doses they are antispasmodic, reducing contractions in the intestine, and are antisecretory and antidiarrheal. Piperine, at lower doses than the pepper extract, acts identically.

In vivo, diarrhea, mice:
Piperine inhibits castor oil and arachidonic acid–induced diarrhea.

In vivo, inflammation, mice:
1) Piperine reduces inflammation in both chronic and acute models; 2) inhibits monosodium urate crystal– induced inflammation (specific for gouty arthritis); 3) significantly reduces inflammation around joints in arthritic mice studies. It produces anti-inflammatory, antinociceptive, and antiarthritic actions. It inhibits expression of IL6 and MMP13 and production of PGE2.

In vivo, cancer, animal models:
Numerous studies have found that piperine protects animals from induced cancer, reduces tumor incidence in others, and increases life span in terminal cases.

In vivo, neuroprotection, mice/rats:
1) Piperine significantly improves memory and protects the hippocampus from neurodegeneration; 2) blocks convulsions induced by intracerebroventricular injection of kainate; 3) inhibits synchronized oscillation of intracellular calcium in rat hippocampal networks, represses spontaneous synaptic activities, and protects hippocampal neurons from apoptosis.

Human clinical trial, epilepsy in children:
Clinical trials (randomized, crossover, placebo-controlled, double-blind) with a piperine derivative in China in the treatment of epilepsy found that it reduced the number of seizures in a majority of the children who used it.

Human clinical trial, dysphagia in elderly:
Inhalation of black pepper essential oil by elderly persons suffering from difficulty or inability to swallow (dysphagia) showed remarkable effects in restoring swallowing ability.