PHOTOSENSITIZING HERBS – For Skin Disease and Cancers

PHOTOSENSITIZING HERBS – FOR SKIN DISEASES AND CANCERS
Jillian E Stansbury ND

Although photosensitizing herbs are a cause of concern for obvious skin damage and dermal inflammation, they also have many medicinal effects when used in appropriate dosages. The main photosensitizing herbs are in the Apiacea family, but Monarda of the Lamiacea family is photosensitizing, and the most potent photosensitizer known is hypercin in Hypericum of the Hyperiacea Family.
The Apiacea family plants have photosensitizing effects because of a certain group of coumarins known as furanocoumarins. Coumarins are ingested commonly in the diet, particularly in the Umbell family plants frequently eaten as vegetables: carrots, celery, parsnip, and parsley.
Those who had a high physical exposure to the plants, such as celery or Bergamot pickers, where noted to develop dermatitis associated with sun exposure. Records of Egyptian and Ayruvedic traditions dating back to over 1000 BC mention using plants that we now know to be high in coumarin for skin diseases

Coumarin’s and Phototoxicity
The “angular furanocoumarins”, such as athamantin and simple coumarins (umbelliferone) show no phototoxicity. The “linear furnaocoumarins “show significant phototoxicity in the following order: psoralen, bergapten, peucedanin, xanthotoxin. , The linear furanocoumarins are also sometimes referred to as furanochromones. as they are often pigmented. Furanochromones, like pigments are able to absorb UV radiation. Some research has suggested that furanochromones form photoadducts with DNA of microbes and thereby are able to kill pathogens. These photoadducts may also lead to stimulation of dermal cell activity and may be used for dematoses such as recalcitrant psoriasis and vitiligo. Other research suggests that furochromones can reduce adenylate cyclase activity when excessive, such as by pertussis toxin or in cases of excessive mitosis in cancer.
Celery and parsnips, two commonly consumed Apiacea family vegetable consistently contain photoactive coumarin compounds, particularly xanthotoxin and bergapten. Since the amounts are small, it is not commonly noted that consumption of reasonable dietary amounts of these vegetables causes photosensitivity. However, when these compounds, particularly psoralen, are isolated and applied topically to the skin, significant photosensitivity results. Psoralen combined with UV radiation has been a mainstay in the treatment of Psoriasis and variety of difficult dermatoses , particularly prior to the advent of synthetic steroids. For many decades the oral ingestion of psoralen was the main method of getting photosensitizing coumarins into the skin, however in recent years oral medication has been replaced with psoralen baths or the application of topical creams immediately prior to UV light therapy . Since the oral ingestion of psoralen compounds at the dosages required to reach effective concentrations in the skin can cause nausea, vomiting, malaise, and headaches , it is important to identify which photosensitizing psoralens or other coumarins are more effective with the least side effects. Recent research has indicated that the higher concentrations of coumarins in the skin are the most effective in clearing chronic psoriasis. The dermal penetration of topically applied xanthotoxin has been investigated for one. Xanthotoxin is reported to be reasonably well absorbed and to be retained in the stratum corneum for 24 hrs. Although great caution must be used because burns and inflammation can result, the topical application of coumarins in small doses and working upward as tolerated may help vitiligo and psoriasis, and possibly other chronic and stubborn skin conditions. Psoralen with UV A is also helpful for alopecia areata and somewhat helpful in alopecia totalis.

Photosensitization to Treat Dermatitis
Chemical research into the nature of the photosensitizing effect of coumarins began as early as the 1940s in the United States. The psoralens, a subcategory of coumarins chemically considered to be furanocoumarins, were noted to be useful in treating psoriasis. Psoriasis patients ingested psoralens for their photosensitizing effects and spent some time each day under ultraviolet light to induce a slight sunburn. This slight sunburn tends to clear psoriatic lesions and accelerate the skins’ regenerative and immunomodulatory processes. This therapy came to be known as “PUVA” therapy, a name derived from P for psoralen plus UVA from Ultraviolet A radiation. UV A is thought to be less damaging to the skin than other frequencies of the ultraviolet spectrum such as UV B. PUVA therapy has also been noted to be effective for treating of vitiligo, a condition where patches of the skin lose their pigment due to an underlying fungal infection or autoimmune condition affecting melanocytes within the dermis. One study showed a narrow band of UVB to be more effective than UVA in promoting repigmentation in cases of vitiligo.
Russian researchers have noted that both the dose of the psoralen combined with the intensity of the UV radiation determined whether the therapy was immunosuppressive to hyper-inflammatory processes, or was entirely toxic to the membrane and lysed the treated cells. It was noted that different photo-oxidation products, having differing physiologic effects resulted from the varying doses and UV intensities.
Thus, an herbal approach to treating the difficult skin conditions of psoriasis and vitiligo might include a photosensitization therapy as one prong of a broader clinical approach. The photosensitizing essential oils such as Bergamot might be put in a base of Hypericum oil and used with a sunlamp two or more times a day. As with the historical PUVA therapy, one might start with 5 minutes of controlled UV exposure the first day, 7 minutes the second, 10 mintues the 3rd day etc, building up to 30 minutes of UV exposures a minimum of once a day, possibly 3 times daily if convenient. Some essential oil companies market “Bergapten-Free” Bergamot oil to avoid photosensitizing effects, but in this circumstance, the product should contain Bergapten. Daily vegetable juices to increase the dietary intake of psoralens might also be employed such as a parsnip, celery, and carrot juice each day. Anise and Celery seed teas may also be employed to increase the intake of photosensitizing compounds. Essential oils of Anise, Celery, or other Apiacea family plants might also be included in the formula for topical application.

Photosensitizers in the Apiaceae Family
The Angelicas
There are over 60 Angelica species, members of the Umbelliferacea/Apiacea Family. This entire family is noted for circulatory and respiratory effects, including many members also containing substantial quantities of coumarin compounds. Many Angelica species have been important herbal and folkloric medicine around the world and many varied coumarin compounds have been identified as being medicinally/physiologically active such as osthole and xanthotoxin. Animal studies have noted the coumarins to affect calcium channel binding in cardiac smooth muscle.
Ammi visnaga –  Contains the coumarins khellin and visnagin, both noted to have calcium channel blocking activity in the respiratory passages, vascular smooth muscle and likely urinary musculature. Also the furocouamrins xanthotoxin and ammidin.
Pimpinella anisum – Anise seed. Coumarins include umbelliferone, umbelliprenine, bergapten, and scopoletin
Apium graveolans – Celery seeds, Contains the coumarin bergapten, and the coumarin glycoside apiumoside.

Photosensitizers in the Rutaceea Family
Citrus bergamia – Bergamot Oil. Contains the furocoumarins xanthotoxin and bergapten both well studied for phototoxicity.
Ruta graveolans is a rich source of coumarins as well as a high alkaloid content make Rue a potentially toxic plant and is a reported abortifacienct and mutagen. Contains the furocoumarins bergapten, psorelen, xanthoxanthin, xanthotoxin, isopimpenilline, and rutamarin.

Hypericum as a Photosensitizer
Most readers will be aware that Hypericum is capable of causing photophobia of the eyes if ingested repeatedly in quantity, and that Hypericum can cause horrendous burns if used topically on the skin followed by the exposure to strong direct sun. Current research is revealing that the same mechanism responsible for photosensitivity may also lend Hypericum anticancer and anti-viral activities mentioned briefly below. Hypericin in Hypericum is the most potent natural photosensitizer known. When rubbed into the skin, the absorption of UV light may increase so dramatically as to induce 3rd degree burns. The skin and eyes can also become more sensitive to light with oral ingestion if Hypericum flavonoids are consumed in quantity. As with Lomatium and furanocoumarins of the Apiacea family, this photophenomenon may also lend Hypericum anti-viral activity as the viruses can be subdued due to interactions with hypericin and viral protein as they pass through cutaneous blood vessels, close enough to skin’s surface to be affected by UV light. Furthermore, hypericin generates large quantities of singlet oxygen and other reactive oxygen species when exposed to UV light which is thought to be one mechanism by which this photodynamic therapy damages cells. The topical use of Hypericum oil may also be combined with UV light as a complementary therapy for psoriasis and vitiligo, taking care not overdue the UV light or natural sunshine and cause harm. The research will be saved for a future article, but due to these same mechanisms, Hypericum is also been explored for internal epithelial cancers where fiberoptic light can be delivered locally, such as bladder cancer and esophogeal cancers. In fact, many cancer cell types appear to intensely take up and concentrate hypericin. Researchers have reported some initial success, and we can expect more investigations to be published in the coming decade. One group of researchers is reporting some success with pituitary adenomas in rats using simple visual spectrum light via the eyes.

Topical Photosensitizers for Skin Cancer
Research published in the Czech Republic last year explored the use of hypericin in nonmelanoma skin cancer cells. Hypericum was applied topically to actinic keratoses, basal cell carcinoma and Bowens disease carcinoma in situ in 34 different patients and covered for several hours with an occlusive dressing. Hypericum application was followed by irradiation with a quantified wavelength of light 2 hours later and repeated weekly for 6 weeks. Researchers reported that 50% of actinic keratoses, 28% of basal cell cancers and 40% Bowen’s disease lesions completely resolved visually, though some cancer cells could still be detected histologically. It was reported that nodular basal cell cancers were less responsive then other types. The researchers expressed optimism that further enhancement of the technique might yield better results, or course of therapy for longer than 6 weeks might resolve such lesions entirely.

Photosensitizing Coumarins Have Anti-Microbial Effects
Psoralen and related compounds may be photosensitizing to bacteria and viruses, and plants containing these photosensitizers may be antimicrobial via a mechanism of phototoxicity involving DNA disruption in the microbes. Furocoumarins from parsley are noted to inhibit E. coli via a phototoxic mechanism. Hypericum’s and Lomatium’s anti-viral effects may occur due to this mechanism as well as the dermatitis occasionally seen with large doses of Lomatium.

Photosensitizing Coumarins and Hypericin with Anti-Tumor Effects
Coumarins and related compounds may also have anti tumor effects via a photo phenomenon. Research has noted that some coumarins may form adducts with DNA of tumor cells causing an antiproliferative effect. The early stages of some forms of cutaneous T-cell lymphoma have been shown to respond to psoralen consumption combined with ultraviolet light exposure.

Photosensitizing Coumarins and Anti-Viral Effects
As mentioned with the examples of Lomatium and Hypericum, many anti-viral compounds from plants are noted to be photosensitizers. Furanocoumarins are believed to form adducts with viral DNA, such that exposure to UV light, presumably as the virus passes close to the surface of the body in superficial cutaneous blood vessels, proves lethal to viruses. Some courmarins may show strong bondage or adducts and others, such as khellin, have been found to bind weakly. Khellin has been reported to have an affinity for thymine and may form adducts with DNA via this amino acid. Psoralen, angelicin and khellin have also all been shown to exhibit an inhibitory effect on cyclic AMP phosphodiasterase, which is often overative in cases of psoriasis.

Coumarins and Anti-inflammatory Effects
In addition to the photosensitizing effects, coumarins have numerous anti-inflammatory, circulatory enhancing, and hormonal effects that are too vast to fully detail in this space. But to summarize effects that may benefit skin diseases furanocoumarins, in general have been noted to effect prostaglandin E2s with imperatorin noted to be the most potent, and ankangelicin, phellopterin, isoimperatorin, umbelliferone and oxypeucedanin also noted to inhibit lipoxygenase activity when stimulated by prostaglanding E2. , This mechanisms may also contribute to skin healing effects in cases of psoriasis and chronic inflammatory lesions.



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