Right now one of the hottest areas of rosacea treatments involves topical St. John's Wort. Many manufacturers are developing topical St. John's Wort for chronic skin redness, inflammation and broken blood vessels . Recent clinical and scientific studies have shown two active ingredients of St. John's Wort to be potent blockers of uncontrolled blood vessel growth (e.g. angiogenesis):

PLoS One. 2010 Mar 9;5(3):e9558.

Tetrahydrohyperforin and octahydrohyperforin are two new potent inhibitors of angiogenesis.
Martínez-Poveda B, Verotta L, Bombardelli E, Quesada AR, Medina MA.


Abstract

BACKGROUND: We have previously shown that hyperforin, a phloroglucinol derivative found in St. John's wort, behaves as a potent anti-angiogenic compound. To identify the reactive group(s) mainly involved in this anti-angiogenic effect, we have investigated the anti-angiogenic properties of a series of stable derivatives obtained by oxidative modification of the natural product. In addition, in the present work we have studied the role of the four carbonyl groups present in hyperforin by investigating the potential of some other chemically stable derivatives.

METHODOLOGY/PRINCIPAL FINDINGS: The experimental procedures included the analysis of the effects of treatment of endothelial cells with these compounds in cell growth, cell viability, cell migration and zymographic assays, as well as the tube formation assay on Matrigel. Our study with hyperforin and eight derivatives shows that the enolized beta-dicarbonyl system contained in the structure of hyperforin has a dominant role in its antiangiogenic activity. On the other hand, two of the tested hyperforin derivatives, namely, tetrahydrohyperforin and octahydrohyperforin, behave as potent inhibitors of angiogenesis. Additional characterization of these compounds included a cell specificity study of their effects on cell growth, as well as the in vivo Matrigel plug assay.

CONCLUSIONS/SIGNIFICANCE: These observations could be useful for the rational design and chemical synthesis of more effective hyperforin derivatives as anti-angiogenic drugs. Altogether, the results indicate that octahydrohyperforin is a more specific and slightly more potent antiangiogenic compound than hyperforin.

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Best,
Geoffrey

Dr. Geoffrey Nase
Ph.D: Neuro-Vascular Physiologist

Email: drnase1000@hotmail.com
Bibliography: http://drnase.com

All posts are for informational purposes only. Please visit our Home Page to view our Medical Disclaimer.

Int J Cancer. 2005 Dec 10;117(5):775-80.

Hyperforin, a bio-active compound of St. John's Wort, is a new inhibitor of angiogenesis targeting several key steps of the process.

Martínez-Poveda B, Quesada AR, Medina MA.

Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain.

Abstract

Hyperforin, a phloroglucinol derivative found in St. John's wort related mainly to its antidepressant effects, has been reported recently to induce apoptosis in tumour cells and to inhibit cancer invasion and metastasis. We show that hyperforin inhibits angiogenesis in vitro in bovine aortic endothelial cells and in vivo in the chorioallantoic membrane assay. In a variety of experimental systems representing the sequential events of the angiogenic process, hyperforin treatment of endothelial cells resulted in strong inhibitory effects. Hyperforin inhibited the growth of endothelial cells in culture. Capillary tube formation on Matrigel was abrogated completely by addition of hypeforin at the low micromolar range. Hyperforin also exhibited a clear inhibitory effect on the invasive capabilities of endothelial cells. Zymographic assays showed that hyperforin treatment produced a complete inhibition of urokinase and a remarkable inhibition of matrix metalloproteinase 2. Our data indicates that hyperforin is a compound that interferes with key events in angiogenesis, confirming the recent and growing evidence about a potential role of this compound in cancer and metastasis inhibition and making it a promising drug for further evaluation in the treatment of angiogenesis-related pathologies. Copyright 2005 Wiley-Liss, Inc

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Best,
Geoffrey

Dr. Geoffrey Nase
Ph.D: Neuro-Vascular Physiologist

Email: drnase1000@hotmail.com
Bibliography: http://drnase.com

All posts are for informational purposes only. Please visit our Home Page to view our Medical Disclaimer.

Eur J Cancer. 2009 May;45(8):1474-84. Epub 2009 Feb 14.

Mechanisms of Hyperforin as an anti-angiogenic angioprevention agent.

Lorusso G, Vannini N, Sogno I, Generoso L, Garbisa S, Noonan DM, Albini A.


Abstract

Hyperforin, the major lipophilic compound contained in extracts of Hypericum perforatum, is responsible for the antidepressant activity associated with the extract. Recently, several other biological properties of Hyperforin have been unveiled including inhibition of tumour invasion and angiogenesis. The mechanism of the anti-angiogenic activity of Hyperforin remains to be fully elucidated. We show that treatment with non-cytotoxic concentrations of Hyperforin restrains, in a dose-dependent manner, the capacity of endothelial cells to migrate towards relevant chemotactic stimuli. Hyperforin inhibits the organisation of HUVE endothelial cells in capillary-like structures in vitro, and potently represses angiogenesis in vivo in the Matrigel sponge assay in response to diverse angiogenic agents. Immunofluorescent staining shows that in cytokine-activated endothelial HUVE cells Hyperforin prevents translocation to the nucleus of NF-kappaB, a transcription factor regulating numerous genes involved in cell growth, survival, angiogenesis and invasion. Under Hyperforin treatment in vivo, the growth of Kaposi's sarcoma - a highly angiogenic tumour - is strongly inhibited, with the resultant tumours remarkably reduced in size and in vascularisation as compared with controls. Hyperforin has also been reported to have anti-inflammatory properties. Here we show that Hyperforin inhibits neutrophil and monocyte chemotaxis in vitro and angiogenesis in vivo induced by angiogenic chemokines (CXCL8 or CCL2). These results highlight the potential for Hyperforin as an anti-inflammatory angioprevention agent, acting as a strong inhibitor of inflammation- or tumour-triggered angiogenesis, and provide new therapeutic approaches to halting pathology-associated angiogenesis.

__________________
_

Best,
Geoffrey

Dr. Geoffrey Nase
Ph.D: Neuro-Vascular Physiologist

Email: drnase1000@hotmail.com
Bibliography: http://drnase.com

All posts are for informational purposes only. Please visit our Home Page to view our Medical Disclaimer.

Phytomedicine. 2003;10 Suppl 4:31-7.

Topical treatment of atopic dermatitis with St. John's wort cream--a randomized, placebo controlled, double blind half-side comparison.

Schempp CM, Windeck T, Hezel S, Simon JC.


Abstract

BACKGROUND: Recent investigations suggest an anti-inflammatory and antibacterial effect of hyperforin, which is a major constituent of Hypericum perforatum L. (Saint John's wort).

OBJECTIVE: In the present half-side comparison study we assessed the efficacy of a cream containing Hypericum: extract standardised to 1.5% hyperforin (verum) in comparison to the corresponding vehicle (placebo) for the treatment of subacute Atopic Dermatitis. The study design was a prospective randomised placebo-controlled double-blind monocentric study.

METHODS: In twenty one patients suffering from mild to moderate Atopic Dermatitis (mean SCORAD 44.5) the treatment with verum or placebo was randomly allocated to the left or right site of the body, respectively. The patients were treated twice daily over a period of four weeks. Eighteen patients completed the study. The severity of the skin lesions on the left and right site was determined by means of a modified SCORAD-index (primary endpoint).

RESULTS: The intensity of the eczematous lesions improved on both sites of treatment. However, the hypericum-cream was significantly superior to the vehicle at all clinical visits (days 7, 14, 28) (p < 0.05). Skin colonisation with Staphylococcus aureus was reduced by both verum and placebo, showing a trend to better antibacterial activity of the hypericum-cream (p = 0.064). Skin tolerance and cosmetic acceptability was good or excellent with both the hypericum-cream and the vehicle (secondary endpoints).

CONCLUSION: Taken together, the present study shows a significant superiority of the hypericum-cream compared to the vehicle in the topical treatment of mild to moderate Atopic Dermatitis. The therapeutic efficacy of the hypericum-cream, however, has to be evaluated in further studies with larger patient cohorts, in comparison to therapeutic standards (i.e. glucocorticoids).

__________________
_

Best,
Geoffrey

Dr. Geoffrey Nase
Ph.D: Neuro-Vascular Physiologist

Email: drnase1000@hotmail.com
Bibliography: http://drnase.com

All posts are for informational purposes only. Please visit our Home Page to view our Medical Disclaimer.

hi,

ive been looking at these articles and it seems that st john's wort might be a good supplement to use post-laser to try to inhibit angiogenesis.

does anyone know of any other angiogenesis inhibitors that could be used post-laser. I know that there is some literature on clarythromycin inhibiting angiogenesis.

also, it seems that (according to the merck manual) st john's wort is a strong inducer of CYP3A4, which means it might decrease clarythromicin levels if the two are taken together. do you think this would really matter if one is taking the two together for the same reason (ie, inhibition of angiogenesis)?

thoughts anyone?

Rosadyn: Sulforaphane and OPC for Near-Complete Blockade of Angiogenesis Post Laser treatment


Hi Jaydee,

I think taking St. Johns Wort with standardized oral Hyperforin would be helpful post laser and should not have a significant impact on clarithromycin's effectiveness, especially the slow release clarithromycin XL.

The best angiogenesis inhibitor studied to date is the pure Sulforaphane found in the BroccoRaphanin in our successful Rosadyn product. This was the original intention of Rosadyn... for post-laser treatment... beause it is extremely important that you stop or reduce the "rebound" angiogenesis that always takes place 5 to 12 days post laser treatment during the wound healing response"

Rosadyn's Sulforaphane is so effective because it blocks all four steps of angiogenesis... not just one or two steps. This is important because blood vessels of different ages usually are at varying stages in the blood vessel growth process. So, if you are blocking step #1 of angiogenesis and half the blood vessels are already on step #3 of new blood vessel growth, then that will have no effect.

We also added Oligomeric Proanthodyns (OPC's) via pharmaceutical grade pine bark extract (95% isolates) to make the angiogenesis inhibition as effective as possible. With Sulforaphane and OPC's taken at the recomended dose, angiogenesis should be completely blocked.

Medically speaking I would start high dose Rosadyn (with or without St. Johns Wort) 3 days after laser treatment and continue for four weeks. Then I would wean back to the normal maintenance dose.

I hope this helps.

__________________
_

Best,
Geoffrey

Dr. Geoffrey Nase
Ph.D: Neuro-Vascular Physiologist

Email: drnase1000@hotmail.com
Bibliography: http://drnase.com

All posts are for informational purposes only. Please visit our Home Page to view our Medical Disclaimer.

Dear Dr. Nase,

This is an interesting thread. My blood vessels grow uncontrollably and are located right near the top of my skin.

Can you recommend the best oral St. Johns Wort to take for this condition?

Can I double up on a topical and if so, where can I get a topical angiogenesis inhibitor like the one you detailed at the beginning of the thread? Can I just open up St. John's Wort Gel capsules and mix it into a moisturizer?

Thanx

Aaron

Hello Aaron,

I think topical treatment with St. John's wort would be the most effective protocol for your case.

These topicals are still hard to find, especially those that utilize the two primary active ingredients listed above... these two specific isolates of St. John's Wort perform 95% of the work. These are the "angiogenesis inhibitors". Most patients suffering from atopic dermatitis, skin rashes or burns purchase this treatment through a compound pharmacy with at least 10% Tetrahydrohyperforin and octahydrohyperforin in an ointment-cream base.

Your best route would be to call your local compounding pharmacies to see if they can get these pure isolates (purified active ingredients). They should be able to because Sigma Chemicals, one of the main bio-medical extract specialists, sells this isolated, pure extract to professionals.

Make sure the pharmacy does not simply purchase generic St. John's Wort as this won't treat your symptoms. It should not require a prescription. It does show promise in the treatment of many vascular-oriented skin disorders. Please keep the forum posted on your progress if you decide to try this product.

I hope the information I supplied is of some use.

__________________
_

Best,
Geoffrey

Dr. Geoffrey Nase
Ph.D: Neuro-Vascular Physiologist

Email: drnase1000@hotmail.com
Bibliography: http://drnase.com

All posts are for informational purposes only. Please visit our Home Page to view our Medical Disclaimer.

Dear Dr. Nase,

you always offer very interesting information. This is what we need. Thanks again for your time and effort you are giving to us.

Aaron, I keep my fingers crossed that you will get a good topical. Good luck!

Barbara