Herbal Antibiotics: Natural Alternatives for Treating Drug-Resistant Bacteria (33 page)

One of the more interesting developments in the medicinal chemistry of lichens is the recognition that lichens often harbor diverse fungi that themselves are highly bioactive. Some of the fungi are harbored on the outside surfaces, others are lichenicolous—they fruit from the lichen thalli. But some of the most interesting are endolichenic fungi—they live within the lichen thalli. One lichen,
Letharietum vulpinae
, has over a thousand fungal strains living on and within it. Usneas also contain numerous fungal strains and these strains also possess bioactivity when used medicinally. An associated fungus from
Usnea cavernosa
, for example, has been found to contain some unusual compounds: corynesporol, dehydroherbarin, and herbarin. Dehydroherbarin potently inhibits the migration of cancer cell lines in vitro and, along with herbarin, possesses weak antiamoebic and antimicrobial activity.

Again, plants (or lichens as in this case) are exceptionally complex; their full chemical range is unlikely to ever be completely understood. Nevertheless, they are potently synergistic in their chemical actions. Some of the actions attributable to usnea are likely from associated fungal strains.

Commonly called old man's beard, a name derived from its appearance, usnea is a lichen that grows on living and dead trees throughout the world. It is quite common in North America, Europe, Asia, and Africa (less so in South America and Australia) and this wide availability and its strong antibacterial properties make it a significant herb in treating resistant bacteria.

Usnea ranges in size from a small tuft to large hanging strands resembling hair. It may be a gray-green in the smaller species and a mild yellow-green in the larger hanging strands. As a lichen, the herb is in actuality a symbiote composed of two plants intertwined. The inner part of the plant (the cortex) is a thin white thread (a filamentous
fungi) that, when wet, stretches like a rubber band. The outer part—the sheath or thallus—(an algae) gives the herb its color and grows round the inner rubber-band-like cortex. The algae (cyanobacteria in some types of lichen) is a photobiont, providing photosynthesis for the symbiotic organism. The filamentous fungi (a mycobiont) provides water and minerals.

The distinctive method of identifying usnea is wetting it and stretching it to see if it is springy and, when it snaps apart, looking for the distinctive white thread of the inner plant. This inner band is strongly immune stimulating; the outer sheath is where most of the plant's (yeah, I know, it's a lichen) other actions (e.g., antibacterial) come from.

Usnea has been traditionally used throughout the world for skin infections, abscesses, upper respiratory and lung infections, vaginal infections, and fungal infections. The lichen (
U. longissima
in this case), sometimes soaked in garlic juice or a strong garlic decoction (sometimes not), is an older medical method of treating large gaping wounds in the body (Spanish moss was also used this way). The moss absorbs blood and provides, along with the garlic, antibacterial, anti-inflammatory, antiseptic, astringent, analgesic, and wound-healing actions directly inside the wound.

Usnea is used for abscesses in veterinary practice in Canada.

There are some 30 species of usnea that grow in India, among them
Usnea complanata
,
U. ghattensis
, and
U. emidotteries
. They have been used in traditional practice, but I can find little on the particulars.

Generally called
songluo
(sometimes
haifengteng
), usnea species, primarily
diffracta
(sometimes
longissima
), are used to clear heat in the body and to clear the liver of sthenic heat. Usnea is used for the treatment of cough due to hot phlegm, conjunctivitis, headache, carbuncle,
lymph node TB. It is considered to be antipyretic, mucolytic, detoxicant, anti-inflammatory, and analgesic.

Of ancient use in Europe but unknown in the United States until relatively recently. Indigenous cultures in the Americas used the usnea lichens primarily for wound dressings.

Most of the scientific studies have focused on usnic acid—essentially trying to develop pharmaceutical drugs given the constituent's strong antibacterial activity. Nearly all the work has been in vitro. There have been no clinical trials using the herb and very few in vivo studies. There have been a few clinical trials in China using either usnic acid or its sodium salt, sodium usnate.

In clinical trials with sodium usnate in the treatment of pulmonary and intestinal TB, clinicians found that there was rapid improvement of cough, anorexia, fever, and diarrhea. Microscopic examinations after 14 days were negative for the tubercule bacillus. In one trial with 30 cases of pulmonary TB using sodium usnate, 24 were cured, 1 had marked improvement, 5 improved. Average treatment length was 71 days, dosage was 30 mg three times daily.

In another trial, 203 cases of chronic bronchitis were effectively treated with either usnic acid or sodium usnate. The compounds showed strong antitussive, expectorant, and antiasthmatic effects.

In the treatment of surgical suppurative wounds, sodium usnate stimulated the separation of necrotic tissue and the growth of new tissue. It was strongly disinfectant and anti-erosive, stimulating the healing of second- and third-degree burns, cervical erosion, and cracked nipples. It was found effective in the treatment of trichomonas vaginitis.

In veterinary practice a 1 percent alcohol solution of usnic acid was used effectively for treating suppurative conjunctivitis, endometritis, mastitis, and suppurative wounds in cows and horses.

Usnic acid, at a dose of 20 mg once or twice daily for 6 days, then 10 mg daily for an additional 25 days, stopped the development of experimental TB in guinea pigs. It stopped the development of pathological tissues in spleen, liver, and lungs of guinea pigs who had usnic acid added to their diet.

Two studies focused on the gastric-mucosa-protective actions of two of the plant's constituents: usnic acid and diffractaic acid. Diffractaic acid inhibited gastric mucosal lesions, oxidative stress, and neutrophil infiltration. Usnic acid prevented indomethacin-induced gastric ulcers in mice and was found to be highly antioxidant. A water extract of
U. longissima
also prevented that form of induced gastric ulcer in rats and was
found to be a strong antioxidant. A methanol extract of
U. longissima
prevented pulmonary thrombosis in rats, and prevented platelet aggregation in vitro. In other studies, the anti-inflammatory activity of various usnea species has been found to be as strong as, and sometimes superior to, that of phenylbutazone and hydrocortisone hemisuccinate, the analgesic action as strong as that of noraminophenazone, and the antipyretic activity as strong as (or stronger than) that of aminophenazone. Usnea is active in both acute and chronic inflammation in rats and significantly accelerates skin wound healing, again in rats. The methanolic extract of
U. ghattensis
was found to be hepatoprotective in rats against ethanol-induced toxicity.

Usnea possesses antioxidant actions, is a strong superoxide and free radical, and is active in preventing lipid peroxidation.
Usnea barbata
extracts inhibit prostaglandin E2 synthesis and COX-2 expression in vitro and appear to be protective of keratinocytes when exposed to ultraviolet B. Usnea possesses strong wound-closure activity in vitro. Both usnic and diffractaic acid have shown antipyretic and analgesic actions in vivo.

Usnea and usnic acid, in vitro and in vivo, inhibit cancer cell formation and proliferation in breast and pancreatic cell lines and in induced colorectal cancer in rats. Crude extracts of
Usnea fasciata
showed up to 90 percent inhibition of sarcoma 180 and Ehrlich tumor cells in vitro.

In general, there has been little clinical research on the effectiveness of traditional uses of usnea. In clinical practice, however, I have found the herb very effective for topical use in the treatment of resistant bacteria, as a douche, and for urinary tract infections.

Sometimes it seems as if doses of supposed active constituents are too low to have an effect, and in the absence of clinical proof this has led sceptics to dismiss these medicines as mere placebos…. It is still routine to investigate and extract medicinal plants with a view to finding the single chemical entity responsible for the effect, and this may lead to inconclusive findings. If a combination of substances is needed for the effect, then the bioassay-led method of investigation, narrowing activity down firstly to a fraction and eventually a compound, is doomed to failure, and this has led to the suggestion that the plants are in fact devoid of activity…. When activity is thought to be lost through purification, synergy should be suspected.

—Dr. Elizabeth Williamson, “Synergy and Other Interactions in Phytomedicines” (
Phytomedicine
8, no. 5 [2001])

All investigations have shown that most of the extracts and individual constituents thereof exert multivalent or pleiotropic pharmacological effects (this multivalance of pharmacological activities can generate additive or overadditive, potentiated synergistic effects)…. The synergistic effects that have been measured exceed the effects of single compounds, or mixtures of them at equivalent concentrations, by a factor of two to four, or more.

—Dr. Hildebert Wagner, “Natural Products Chemistry and Phytomedicine in the 21st Century” (
Pure and Applied Chemistry
77, no. 1 [2005])

Synergy,
in its simplest definition, means that the combination of two (or more) things produces outcomes greater than the sum of
the individual parts and, additionally, that those outcomes
cannot
be predicted from a study of the individual parts themselves. Individual plants, because of their complex chemistry, are highly synergistic organisms by themselves. If plants are used in combination, the complexity, and resultant synergy, increases substantially.

Within older healing traditions such as traditional Chinese medicine (TCM) and Ayurveda, the inherent synergistic nature of plant medicinals and plant combinations is an integrated aspect of healing. Those systems, over millennia, developed their own language and understanding of plants as synergists. A similar understanding, using our own Western terminology and perspectives, has been lacking in our medical approaches—herbal or otherwise.

Medical technologists (usually from the younger generations) have slowly begun to move away from the dogma of monotherapy—that is, the use of a single compound to treat disease. It's not that they inherently wanted to or that they innately understood that the system in which they were trained was flawed. Their change, as it is with most of us, was driven by events occurring in the outside world that they could no longer ignore; mainly, the emergence of multidrug-resistant microorganisms and AIDS.

AIDS (along with cancer), because of its spread, its disease dynamics, and its amazing adaptability, has forced a shift from a monotherapy frame to that of a multi-target paradigm of therapeutics. Multi-target therapies not only focus on killing the disease organism—which with AIDS and cancers are often futile—but also focus deeply on activating the natural defense, protective, and repair mechanisms in the body. In other words they also stimulate immune responses to disease and, as well, the body's own highly elegant repair mechanisms.

The emergence of multidrug-resistant bacteria has also been a factor in challenging the monotherapy paradigm. As fast as new pharmaceuticals were developed for resistant organisms, new resistance emerged. Physicians learned, eventually, that if they combined therapies, for example if they used antimalarial drug combinations,
the development of malarial resistance could be delayed. (Not stopped, mind you, just delayed.) But that recognition opened up the understanding that complex drug therapies were much more effective against the disease and, as well, could slow down and, presumably if they were elegant enough, stop resistance development altogether. The use of artemisinin combination therapy (ACT) is a product of that understanding. At a very crude, simplistic level these approaches by medical technologists are beginning to mimic the actions of plant medicines, as well as older systems of healing such as TCM.

Western herbalists have never been completely captured by the monotherapy paradigm, though they have often been strongly influenced, and sometimes fully seduced, by it. Medical (and naturopathic) herbalists, for example, since they often tend to mimic a medical reductionist model, generally lean much more strongly toward monotherapeutic thinking. They often lose sight of plant complexities in the search for “active” constituents and standardized herbs.

Community herbalists, like their counterparts in all third- (and some second-) world countries, tend to be more cognizant of plant complexities and subtleties, in part simply because they haven't been trained to believe they know some ultimate truth about the nature of plant medicines or reality as a whole. Most of them consider plants to be an expression of the general intelligence and livingness of Nature. They never have felt plants to be insentient substances that can be analyzed and completely understood by science and then used however human beings wish.

All Western herbalists, no matter their orientation, do know that plants are much safer than pharmaceuticals, that they tend to produce more complex effects in the body than pharmaceuticals, and that they need to be part of a more complex treatment regimen, one that also includes immune regeneration and support for the body's natural repair mechanisms. Herbalists just naturally tend to be more
multi-target-therapy oriented than the majority of physicians. And most Western herbalists, not all, understand that whole-plant extracts are often more effective than isolated constituents and that plant combinations are often more effective than single-plant extracts.