how can we benefit from bioactivity in icelandic herbs sigmundur gudbjarnason professor emeritus of chemsitry and bio

1. How can we benefit from bioactivity in Icelandic herbs?

2. Bioactive Phytochemicals in Icelandic Herbs

4. Research on Icelandic medicinal herbs

5. Steps in research on phytochemicals Extraction and isolation of phytochemicals by column chromatography and TLC Identification of natural products by GC-MS, HPLC, NMR 3. Determination of bioactivity Anti-viral products, active against Coxsackie and cold viruses Anti-bacterial natural products Phytochemicals that inhibit cell proliferation, tested on: a) Human cancer cells: colon-, breast- and pancreas-cancer cells b) Lymphocytes Products that stimulate the immune system a) Anti-complement activity b) Stimulation of lymphocyte proliferation

6. Angelica increases energy and well-being Increases energy: Substances present in Angelica (furanocoumarins) increase energy production from sugar or carbohydrates in the body. These compounds increase also the breakdown of fat to free fatty acids and the oxidation of these fatty acids to produce energy. Angelica increases thus energy production both from sugar and fat. Increases well-being: A furanocoumarin in Angelica has activity similar to diazepam or valium and reduces anxiety. Substances in Angelica (coumarins and furanocoumarins) dilate blood vessels in various organs and can increase blood flow to these organs. This is also the effect of an aphrodisiac but Angelica archangelica was used in aphrodisiacs during the Middle Ages.

7. AngelicaIncreases energy and well-being The bioactive coumarins and furanocoumarins mentioned in the research articles below are also present in the Angelica tincture. References. Energizer effects. 1. Cyclic AMP phosphodiesterase inhibition by coumarins and furanocoumarins. Sardari S. et al. Pharmazie 1999; 54: 554-556. 2. Effects of various coumarins from roots of Angelica dahuria on action of adrenaline, ACTH and insulin in fat cells. Kimura Y. et al. J of Medicinal Plant Research 1982; 45: 183-187. Anxiolytic effects. 3. Furanocoumarins with affinity to brain benzodiazepine receptors in vitro. Bergendorf O. et al. Phytochemistry 1997; 44: 1121-1124. Aphrodisiacs: 4. Vasorelaxing effect of coumarins from C. Monnieri on corpus cavernosum. Chiou WE. et al. Planta Medica 2001; 67: 282-284.

8. Anti-viral phytochemicals in AngelicaHelpful in prevention of cold and respiratory problems Extracts from Angelica archangelica contain natural products with anti-viral activity. These extracts prevent the growth of cold viruses, Coxsakie viruses and RS-virus without harming the cells where viruses proliferate. Among the anti-viral substances are flavonoids and furanocoumarins (prangenin, imperatorin). The anti-viral activity of the extract is expressed as an increase in lifetime of cells infected with the virus that has been exposed to the substance being tested. Normally infected cells are dead within 4-5 days after viral infection but with the anti-viral treatment the lifetime may be increased to 12-13 days or to the lifetime of normal cells that were not infected with the virus.

10. The furanocoumarin Imperatorin inhibits HIV-1 virus Reference: Imperatorin inhibits HIV-1 replication through an Sp1-dependent pathway. R Sancho et al. Journal of Biological Cemistry 279: 37349-37359, 2004. Furanocoumarins are abundant in citrus fruits, umbelliferous vegetables, certain herbal medicines and Angelica archangelica. “Furanocoumarins might have a potential therapeutic role in management of AIDS”.

11. Angelica is good for the stomachAnti-bacterial activity in Angelica Extracts (tinctures) from the seeds and leaves of Angelica archangelica have anti-bacterial activity. Activity was tested on the following bacteria and fungus: S. aureus E. coli E. faecalis P. aeruginosa and the fungus Candida albicans Angelica archangelica contains polysaccharides that promote healing of stomach ulcers.

12. Angelica Good for the stomach References: Effect of polysaccharides from Angelica sinensis on gastric ulcer healing. Yen YN. et al. Life Sciences 2003; 72: 925-932. Antiulcerogenic effect of some gastrointestinally acting plant extracts and their combinations. Khayal MT. et al. Arzneimittelforschung 2001; 51: 545-553. Isolation and identification of antimicrobial furanocoumarins from parsley. Manderfeld MM. et al. J Food Prod 1997; 60: 72-77.

13. Influence of phytochemicals on cancer cell proliferation Cell proliferation is measured by the incorporation of radioactive thymidine into DNA of proliferating cells. When cell division and cell proliferation is inhibited by drugs or phytochemicals there is reduced incorporation of thymidine into DNA and reduced radioactivity in the cell samples.

14. Angelica oil influences growth of cancer cells Fruits or seeds: Essential oils contain many terpene compounds, small and volatile compounds that give the aromatic smell, used in Aromatherapy. The next graph shows the bioactivity of three different samples of oils from A. archangelica seeds, two oils from plants growing in different locations in Iceland (A and S) and one oil sample from England (commercial sample). The graph shows that with increasing amount of oil there is increased inhibition of cancer cell growth or proliferation. This activity is observed in oil samples from Iceland but not in the sample from England. The bioactivity of herbs may thus be quite variable and in some cases the activity is greater then expected in herbs growing in a harsh and cold environment.

18. Effect of an extract from A. archangelica leaves on tumor growth in mice Mice were divided into two groups, a control group and an experimental group fed a diet supplemented with an extract from leaves. Both groups of mice were injected with Crl breast cancer cells from mice. After one week the tumors in the control mice were growing rapidly and after 5 weeks both groups of mice were sacrificed and examined. In the experimental group most of the animals developed very small tumors or no tumors at all.

21. How can we explain the antitumor activity in Angelica archangelica ? There are compounds (furanocoumarins) in the herb that inhibit proliferation of cancer cells. There are compounds (polysaccharides, flavonoids) in the herb that prevent injected cancer cells from building tumors. These compounds may inhibit the formation of new blood vessels in the tumor and thereby starve the tumor and prevent it from growing. Can these compounds reduce cell proliferation in psoriasis ?

22. Arctic Angelica Chemoprevention of cancer Coumarins and furanocoumarins that can prevent development and growth of cancer are present in Angelica. References: Oral administration of naturally ocurring coumarins leads to altered phase I and II enzyme activities and reduced DNA adduct formation by polycyclic aromatic hydrocarbons in various tissues of SENCAR mice. Kleiner HE et al. Carcinogenesis 2001; 22(1): 73-82. Imperatorin, a furanocoumarin from Angelica dahuria (Umbellifarae), induces cytochrome c-dependent apoptosis in human promyelocytic leukemia, HL-60 cells. Pae HO. et al. Pharmacology & Toxicology 2002; 91:40-48. Antiproliferative effect of isopentenylated coumarins on several cancer cell lines. Kawaii S. et al. Anticancer Research 2001; 21: 1905-1912. Cytostatic activity of coumarins in vitro. Gawron A. and Glowniak K. Planta Medica 1987; 53: 526-529. Antimutagenic properties of Angelica archangelica. Salikova RA. and Poroschenko GG. Vestn. Ross Akad Nauk. 1995; 1: 58-61.

23. Angelica arch. for enlarged prostate glands Several compounds (isoquercitrin and other flavonoids, other polyphenols and furanocoumarins) may be responsible for the rapid positive effects of SagaPro (SagaProst)

25. AngelicaPrevention of cardiovascular diseases Atherosclerosis is a complex process involving high blood cholesterol (LDL) and chronic inflammation of blood vessel walls. Heart attack is usually related to narrowing of coronary arteries due to atherosclerosis and/or blood clots preventing normal blood flow to parts of the heart muscle. Angelica may favorably influence several of these processes. Anti-platelet effects of imperatorin and bergapten. Coumarins and antiplatelet aggregation constituents from Formosan Peucedanum japonicum. Chen IS. et al. Phytochemistry 1996; 41: 525-530. Anti-inflammatory effects of osthole, xanthotoxin, imperatorin and isoimperatorin, reduce chronic inflammation. Anti-inflammatory and analgesic activities from roots of Angelica pubecens. Chen YE. et al. Planta Medica 1995; 61: 2-8. 3. Effects of furanocoumarins from C. trifida on some macrophage functions. Abad MJ. et al. J Pharmacy & Pharmacology 2001; 53: 1163-1168.

26. Angelica archangelica Inhibition of proliferation and growth of fast growing cells (cancer and psoriasis) by furanocoumarins (Angelica ticture). Inhibition of tumor growth by inhibition of Angiogenesis? Polysaccharides and flavonoides prevent formation of new blood vessels in a tumor (that would starve the tumor and prevent it from growing). a) Isolation of polysaccharides and testing in an in vitro model. b) Isolation of flavonoides and testing in the same way. 3. Inhibition of cell proliferation by terpenes (in essential oils).

30. Effect of Angelica on tumors in people Case reports: Use of Angelica has favorably influenced the outcome for some patients, tumor growth has stopped, patients are in remission. Skin cancer. Brain tumor (neurofibroma). Adenocarcinoma (gall bladder). Pancreas cancer. Hodgkin´s disease (Patient: “I´ve experimented at times being off the Angelica, and I find I have more energy, have less suseptibility to colds and flu´s and feel calmer while I am taking it”). Clinical trials of Angelica have not been carried out.

31. Immunostimulatory activity in herbs Assays for immuno-stimulatory activity. I. Anticomplement activity. Normal serum from a healthy adult was used. Various dilutions of the sample in water were incubated with serum for 30 min. at 37 C. Red blood cells (from sheep) sensitized with antigen-binding were added to the serum previously incubated with the test solution. Hemolysis was measured spectrophotometrically after 30 min. Activity is expressed as percent inhibition of hemolysis. II. Lymphocyte proliferation assay. Lymphocytes were isolated from blood and cultured for 70 hours in the presence of various dilutions of the sample. Radioactive thymidine was added and incorporated into DNA of proliferating cells. Activity is expressed as an increase in radioactivity of isolated lymphocytes, a measure of lymphocyte proliferation.

34. Angelica products: quality and safety Quality: Angelica archangelica is either wildcrafted in unpolluted areas or grown on organic farms. The Agricultural University at Hvanneyri is developing the optimal growth conditions for the herb and advicing future growers. Safety: Angelica was tested on mice for 6 months. The mice were given more than 5000 times the levels of furanocoumarins that is recommended for humans. Toxicological studies did not indicate any toxicity or abnormality in the various tissues examined. Volunteeres used Angelica for up to 12 months before it was marketed. There were no signs of side effects, except in one individual who complained about too much stimulation. This individual does not tolerate coffee or tea. SagaPro was used by volunteers for more than two years before it was marketed. Angelica has been on the market for >3 years without any complaints. SagaPro has been on the market for 6 months without side effects.

37. Phytonutrients, bitter taste and the consumer Dietary phytonutrients found in vegetables and fruit appear to lower the risk of cancer and cardiovascular disease. Studies on the mechanisms of chemoprotection have focused on the biological activity of plant-based phenols and polyphenols, terpenes and furanocoumarins, flavonoids and isoflavonoids. Most of these bioactive compounds are bitter and unpleasant to the consumer. The food industry routinely removes these compounds from plant foods through selective breeding and a variety of debittering processes. Increasing the content of bitter phytonutrients in plant food for health may be wholly incompatible with consumer acceptance. Herbs provide the bitter phytonutrients for health in the form of pills or tinctures.

38. SummaryInfluence of Angelica products on people What do people say ? Angelica has been helpful in treatment or prevention of: Chronic fatique syndrome (increases energy production) Stress (reduces anxiety) Depression (reduces anxiety, MAO inhibition and ? ) Stomach ailments (anti-bacterial activity, polysaccharides) Cold and influenca (anti-viral activity) Coronary artery disease (antiarrhythmic-, antianginal-, antiplatelet activity, vasodilation, calcium blockers) Erectile dysfunction (vasodilation, increased blood flow) Nocturia (reduces frequency of urination at night in men with BPH)

39. Summary Studies on Angelica archangelica have demonstrated bioactive natural products such as: Terpenes in essential oils (anti-proliferative, anti-bacterial) Coumarins (vasodilation, and ?). Furanocoumarins (vasodilation, anti-inflammatory, anti-tumor, anti-viral, antiplatelet effects, anti-bacterial, anxiolytic effects, MAO-inhibitors (depression), acetylcholinesterase inhibitors (Alzheimers)). Flavonoids (anti-viral, antioxidant effects). Polysaccharides (immunostimulation, anti-tumor, anti-ulcerogenic). Scientific research confirms the empirical knowledge of Angelica archangelica obtained by our anchestors.

40. Thank you