THE APIACEAE FAMILY – Medicinal Plant Research Summary

THE APIACIAE (UMBELL) FAMILY
©  Jillian Stansbury ND

The Apiaceae Family (Formerly Ubellifereae Family) includes over 300 genera and over 3,000 species. The family is most abundant in the northern hemisphere, though can be found worldwide. The common carrot, Daucus carota, subspecies sativus is probably the most well known, most widely cultivated and most important Apiacea species economically, however many family members are important culinary and medicinal plants. These include angelica, anise, caraway, celeriac, celery, chervil, coriander, cilantro, cumin, dill, fennel, lovage, parsley, and parsnip. Several poisonous species are also round within this family including poisonous hemlock – Conium, and Water Hemlock – Cicuta, which are used as homeopathic medicines.
Botanically, the Apiacea Family has been organized and categorized in different ways over the last several centuries. One such classification system breaks the family into 3 Subfamilies: The Apioideae, Saniculoideae, and Hydrocotyloideae, and then further dividing these into a series of tribes and subtribes. Modern molecular investigations, however, find that these categories do not necessarily make sense according to chemical constituent groupings. The Hydrocotyl Group includes Centella and Bupleurum, and has been referred to in botany as the “araliaceous hydrocotyloids” as in some respects they are molecularly closer to the Araliacea. (Simple leaves, different chemistry from the rest of the family)

BOTANICAL CONSIDERATIONS
The Apiacea is widely distributed about the planet but does not typically thrive in the tropics or rain forests. Otherwise, the plant produces many sturdy seeds, and many species will self seed prolifically.
One of the most note-worthy characteristics of this family is the inflorescence, the umbel. Fashioned like an upside down umbrella, numerous flowers stalks radiate out from a single point on the stems. These stalks themselves typically offer another umbel on its tip, where tiny flowers, and finally small hard aromatic seeds are borne. In this manner, the Apiacea/Umbelliferaceae display a fractal like growth pattern where tiny umbels are borne on a large umbel, which flows from a larger umbel still. The stems of these plants do not typically branch in the vicinity of the flower rather the umbels display the fractal like method of extending the growth. These infloresences may hold themselves in a shape quite spherical, a shape that is broad and disk-like, an umbel with a flat top, an umbel with a rounded top, or as an umbel with a sphere on the tip of each ray. The colors or presentations of these flowers are not typically showy or flashy, the tiny flowers usually being white, beige, and pale yellow.
The leaves are never entire or blade-like, but are usually highly divided, taking on a fine feathery appearance. Even the species having the most substantial leaves, such as Celery or Lovage, the leaves appear, small, soft, and sometimes fern-like. The appearance is more twiggy, stemmy, and seedy, although the overall habit of the plant is not to become woody. Both annuals and perennial species occur among this family, and even among the long-lived perennials, such as the Azorella that occurs in the Antarctic as a broad flat mat surviving for hundreds of years in harsh conditions, tough mineralization and a woody habit does not occur.

 
Another noteworthy character of this family is the high content of volatile oil making many of these favored spice and flavoring plants. Many of these volatile oils, medicinally, have an affinity for the respiratory system. The aromas are not highly rich or intoxicating like Rose, Lavendar, or citrus. Rather the essential oils are appetizing, sweet, mild, and light. Unlike the Labaitae which hold their volatile oils in small vesicles on the surface, the Umbelliferaceae’s volatile oils are held more tightly in the tissues of the plants. Outwardly, the plants are not highly aromatic, but crushing or chewing the leaves and seeds will release the volatile oils and thereby the aromas.

 
These plants are fairly immune to insect and slug predation, unlike other aromatic plants such as the roses. Insects and birds do not favor the seeds as they do the grasses, the asters, and the thistles. The seeds are small and dry and never fleshy or succulent.

METAPHYSICAL CONSIDERATIONS.
Because the volatile oils are held inside the leaves and seeds, not easily exuded into the atmosphere about the plant, anthroposophical traditions have viewed the Umbelliferaceae to have its sulfurous process held with in the leaves. Put another way, the sulfuric process is limited to the vegetative aspect of the Umbells. The astral or cosmic forces are taken in, but not released again outwardly. Among the members of this family that are poisons, such as Conium maculatum, it is thought that astral forces penetrate deeply and are not transmuted and released as outward sulfuric processes, but rather held within the material aspects of the plant leaves and tissues as poisons. As with the Nightshade Family, astral/cosmic energies are held within the plant and not balanced with more earthly energies in the case of umbel poisons such as coniine.
While the plant does not express outward, sulfuric or cosmic forces, neither does it strongly express earthy or highly mineral/salt processes. The plants do not become woody or highly mineralized. There is not substantial nutritional value, starch or protein content within this family, and there is not typically rich leafy growth. Furthermore, the plants are rarely succulent, juicy or rich in sap. The seeds are dry and without flesh, the stems are often smooth and dry, and flowers not showy or colorful. Therefore, the Umbells are not fiery, are not earthy, and are not particularly watery. The family seems to concentrate its energies in a subdued vegetative expression which the cosmic forces are expressed with an affinity to the air.
This is another metaphysical attribute of the Umbelliferaceae family – the expression of an air-like quality. We can observe this affinity with the air, for one, it the physical presentation of the plant. Many species, such as the Angelicas and the Coniums, possess hollow stems, where surprising large hollow tubes of an inch in diameter and a meter or so in length occur. Some of the species, such Water Dropwort (Oenanthe fistulosa) even have hollow chambers within the stems helping them to float.
Another noteworthy signature of Air expressed by the plant is the habit of being long, thin and twiggy, as much empty space as mass in the 3 dimensional area the plants occupy. The umbels themselves are fine and airy in appearance, branching out in the air in finer and finer growth.

MOLECULAR CONSIDERATIONS
Although the chemical constituent arrays are varied from species to species, chemical constituents held in common are a variety of fatty acids and organic acids, a variety of aromatic compounds, and a variety of coumarin cumpounds and precursors such as cinnamic acid. Some species also contain a variety of phytosterols such as Spinasterol, and Stigmasterol. And the seeds of many of the Apiacea species such as the culinary species are fairly nourishing containing macrominerals such as Calcium, Zinc, Iron, Sulfer Mangesium, and Potassium, and trace minerals such as phosphorus, chromium, manganese, boron, fluoride, selenium, cobalt, lithium, rubidium silicon and copper. Essential and non essential amino acids are also common in Apiacea species.
Apiaceae family plants are noted to accumulate flavinoids, mainly in the form of flavones and flavonols, many having significant antioxidant and antiinolammatory effects. The enxyme flavone synthase has been found to be high in Apiaceae plants and is looked at, by evolutionary botanists as a marker the evolutionary process. Flavone synthases are involved in in the formation of apigenin from naringenin.
Vegetables in the Apicacea family include celery, fennel, parsely, carrots, and parsnips are noted to be high in polyacetylenes including falcarinol, falcarinidiol, and panaxudiol. Carrots and Fennel have lesser amounts and celery, parsnips, and parsely have high amounts of these compounds. Current research is showing these polysacetylenes to be cytotoxic to five different cancer cell lines. Falcarinol proved to be the most active compound with a pronounced toxicity against acute lymphoblastic leukemia cell line.

A SAMPLING OF THE VARIOUS CHEMICAL CONSTITUENT GROUPS IN APIACEA

Flavinoids
Common flavinoids in the Apiacea include Rutin, Quercitin, Apigenin, Bisabolene, Luteolin, Lutein
Apigenin, has been credited with antispasmodic activity. Apigenin was more effective in alleviating muscle spasms produced from a variety of offending agents (Barium chloride, histamine, serotonin, nicotine, bradykinin, and oxytocin). Due to these antispasmodic and anti-inflammatory actions, chamomile is often used for muscle pain, stomach cramps, irritable bowel syndrome, and nausea.
Essential Fatty Acids and Organic Acids:
Linoleic acid, Linolenic acid, Oleic acid, Lauric acid, Palmitic acid, Palmitoleic acid, Petroselinic acid, Stearic acid, Myristic acids, Vanillic acid, Coumaric acid, Rosmarinic acid

Aromatic Compounds:
Limonene, Phellandrene, Pinene, Cadinen, Camphene, Carvacrol, carveol, carvone, Carophyllene, Elemene, Farnesene ,Fenchone, Camphor, Cineole, Methanol, Kaempferol Geriniol, Anethole, Turpinene, aldehydes, Thujene, Eugenol, and many many other aromatics. These essential oils have antimicrobial and many other physiologic effects.

Coumarins
Coumarin, Pyranocoumarin, Furanocoumarin,Furocoumarin
Linear furanocoumarins – psoralen, bergapten, xanthotoxin, anglicin, isopimpinellin, imperatorin and umbelliferone. Umbelliferone is the precursor to all the linear furanocoumarins.
Furanochromones – are structurally related compounds have photoactivity.

Osthole, Umbelliferone, Scopoletin, Psoralen, Columbianetin, Bergapten, Angelicin , Xanthotoxin, Apiin, Impertorin, Isoimperatorin,Pabulenol , Isooxypeucedanin, Oxypeucedanin hydrate, Decursinol angelate, Decursin, Nodakenin, Xanthotoxin, Isopimpinellin, Scoparone, Bergapten, Avicennin, Avicennol

Photosensitizing Compounds
Linear furnaocoumarins show phototoxicity in the following order – strongest photosensitizer to weakest: psoralen, bergapten, peucedanin, xanthotoxin. , Angelicin is also photosensitizing.

Coumarin Precursors
Cinnamic acid, Chlorogenic acid, Caffeic acids, Ferulic acid, Coumaric acid

NOTABLE COMPOUNDS IN SPECIFIC APIACEA SPECIES INCLUDE:

Bupleurum Saponins: Saikogenins, Saikosaponins

Carum carvi – Caraway:  Myrcene, Myristic acid, and Myristicin

Centella asiatica – Gotu Kola, Pennywort
Saponins – Beta sitosterol, capesterol, stigmasterol
Organic Acids – Asiatic acid, aspartic acid, Betulic acid, Betulinic acid, Brahmic acid, Brahminoside, Centellic acid, Eladic acid, Glutamic acid and essential fatty acids.

Coriandrum sativum – Chinese Parsley, Cilantro, Coriander
Organic Acids – Cinnamic acid, Ferulic acid, Coumaric acid, Caffeic acid, Chlorogenic acid
Flavinoids – Apigenin,
Coumarins – Scopoletin
Steroids – sitosterols

Foeniculum vulgare – Fennel
Arginine, Histidine, Glycine, Isoleucine, proline, Serine, Valine, Tryosine, Tryptophan, Threoinine
Avicularin
Benzic acid, Caffeic Acid, Glycolic acid, Glutamic acid, Ferulic acid, Malic acid, Coumaric acid
Bergapten, Imperatorin, Scopoletin, Psoralen, Xanthotoxin,
Umbelliferone
Estragole
Fenchone
Shikmic acid
Sinapic acid
Trigoneline

Petroselinum crispum – Parsley
Toluene
Coumarin, Psoralen, Iperatorin
Octadecanoic acid, Chlorgenic acid, Glycolic acid, Rosmarinic acid
Apigenin
Benzaldehyde
Bergapten,
Ligustilide
Cryptone, Graveolone
Estragole
Lutein, Luteolin

Pimpinella anisum – Anise
Zingiberene, Carvene, Eugenol, Antehole
Apigenin
Beta amyrin
Bergapten, Scopoletin, Imperatorin, Umbelliferone
Chlorgenic acid, Caffeic acid
Choline
Estragole,
Isovitexin
Mannitol
Proazulene, Squalene

Apium graveolans – Celery
Isovaeridenes
Phthalides, Ligustilide,
Umbelliferone, Psoralens,Scopoletin, Apiin
Adenine, Adenosisne, Alanine, Asparagine, Choline, Glutamine, Glycine, Histidine, Leucine Lysine, Proline
Apigenin, apigravin, apiin, Apiole, Apimetin
Humulene, elemene, Phellandrene, Pinene
Caffeic acid, Chlorogenic acid, Angelic acid, Fumaric acid, Ferulic acid, Lauric acid, galacturonic acid, gentisic acid, Malic acid, Pyruvic acid, Shikmic acid, Succinic acid, Tiglic acid, Valeric acid, Glutamic acid
Chromium
Zeatin

Angelica sinensis – Dong quai
Choline
Ligustilide, Pthalides
Osthole, Umbelliferone, Scopoletin, Bergapten
Myristic acid
Nicotinic acid, Nicotinamide, Palmitic aicd, Vanillic acid, Stearic acid
Safrole, isosafrole

Ammi visnaga – Khella
Astragalin
Cinnimaic acid
Coumarin, Furanocoumarin, Furocoumarin, Furochrome, Pyranocoumarin
Delphinidin
Glucoronic acid
Khellalactone
Khellin, Khellin, Kheinin, Khellinol, Khellinone, Khellol
Vasammidin,m Visamminol, Visandin, Visnagane, Visnagin,
Myricetin, Myristic acid
Oleic acid, Palmitic acid, Petroselinic acid
Phenylalanine
Shikimic acid, Steric acid
Stigmasterol

BACKGROUND ON COUMARIN AND RELATIVES
Apiacea plants produce coumarin compounds in response to the presence of fungal elicitors indictation these compounds may play a role the plant’s defense against microbes. Coumarin or related compounds are classified as a benzopyrone compound and is moderately common in Apiace family plants. The word for the chemical compound is derived from “coumarou”, the French word for Tonka Beans which are very high in coumarin and related compounds. Coumarins are synthesized in plants from cinnamic acid. The primary coumarin coumpounds occurring in plants are Psoralen, Umbelliferone (7-hydroxycoumarin), Aescultetin (6,7-dihydroxycoumarin with numerous others including Hernairarin, (7-methoxycoumarin), Osthole, Columbianetin, Bergapten, xanthotoxin and Imperatorin. Synonyms for coumarin include benzopyrone, coumarinic acid lactone, hydroxycinnamic acid lactone, and coumarinic anhydride. Bergapten and xanthotoxin are considered to be methoxylated psoralens and are the final products of furanocoumarin biosythesis common in both Apicacea and Rutaceae families.

More than 300 different coumarins have been identified in plants. The physiologic activity of these coumarins has been shown to relate to the molecular configuration. The more complex molecules include the dicoumarols, the alflatoxins, and the psoralens, all having strong and potentially toxic physiologic effects.
Simple coumarins, such as coumarin itself (1,2-benzopyrone) has long been noted to reduce lymphedema, even in such difficult situations such as elephantitis and postmastectomy lymphedema of the arm. The precise mechanisms by which simple coumarins reduce lymphedema is uncertain by possibilities include increased venous return and uptake of interstitial fluid into venules. Another possibilityis enhanced digestion of interstitial proteins by macrophages.  Other coumarins, as discussed in this document posess valuable vascular effects including hypotensive action and improvement in blood lipids. There has been much research on osthole, a simple coumarin common in the Apiacea family having potent anti-inflammatory and vascular protective activity, amongst other actions.
It is thought however, that oral absorption of plant-based coumarins is somewhat low due to extensive conversion for the liver into umbelliferone (7-hydroxycoumarin), which itself is then rapidly subjected to glucuronidation. Some amount however is absorbed and is physiologically active and coumarins and furanocoumarins can be detected in human uring following ingestion of plants containing these comounds indicating good oral absorption and assimilation.
In a concentrated and isolated form, coumarin is toxic due to internal hemorrhage, and liver and kidney toxicity. The various coumarin compounds are metabolized to umbelliferone, a form with the least toxicity. Due to toxicity concerns, pure coumarins have been banned as a food additive for over 50 years in the US. Coumarin is also considered to be a lung carcinogen, though this is in part due to its history as a flavorant in tobacco products.
COUMARIN CONTAINING PLANTS AND BLOOD CIRCULATION AND VISCOSITY
Whether coumarin containing plants have any significant anti-thrombotic affect, such that might actually dissolve existing thrombi like pharmaceutical anticoagulants is questionable. Some coumarins, such as those found in several Angelica species have been noted to act as platelet anti-aggregators, but not act as coumadin-like anticoagulants. Dicoumarols however, the agents which pharmaceutical Warfarin anticoagulants are based, have potent anticoagulant action. Dicoumarol is structurally similar to Vitamin K and acts as an antagonist, competing with Vitamin K and reducing the effects of this blood clotting vitamin to promote the clotting factors VII, IX, and X. Dicoumarols may form naturally from the fermentation of coumarin in plant leaves, such as decayed Sweet Clover and Sweet Vernal Grass. Therefore anticoagulant action from dried plant material such as Melilotus officianalis or Trifolium pratense is theoretically possible but not emphasized in historic or modern literature on coumarins except in the case of accidental poisoning of livestock. Instead coumarins have been noted to possess hormonal balancing and immune modulating properties, and have platelet stabilizing and anti-inflammatory effects on the vasculature. Angelica sinensis, Galium species, Foeniculum vulgare, and Viburnum prunifolium, all contain active coumarin compounds and are all thought to have hormonal balancing and blood or fluid moving effects.
Livestock who graze on large amounts of Trifolium, Red Clover or other legumes or umbels as forage are noted to develop gas and bloating, as do humans consuming a high legume diet, but blood clotting difficulties are not observed. However, livestock who graze on large amounts of spoiled Yellow clover, Melilotus officianlis, or Sweet Vernal Grass, Anthoxanthum odoratum ARE reported to suffer hematologic and bleeding disorders which can be fatal when a large amount is ingested, due to the conversion of coumarin to dicoumarol, a potent anticoagulant.
Although coumarin itself is not found to be anticoagulant like the dicoumerol category of drugs or like heparin, many plants high in coumarin-like compounds are noted to affect platelets, blood cells and the vasculature such aesculin in Aesculus, Umbelliferone in the Umbell/Apiace Family, a nd the coumarins in Melilotus officinalis. These coumarins are not claimed to inhibit necessary and appropriate blood clotting, but rather to act on capillary, venule, and vein permeability, increasing fluid uptake and return from the tissues to general circulation. Coumarins may inhibit aberrant clotting by having anti-inflammatory and platelet anti-aggregating effects. Such coumarin constituents appear to act in tandem with “Permeability factors” such as rutin and quercitin and improve venous return. High rutin plants include Ruta graveolans or Rue, Fagopyrum esculentum, Buckwheat, and Citrus peels, as well as the Apiacea plants.
Coumarins and related compounds, the isoflavones are also common in Leguminosea family plants such as Trifolium and Soy, are known to effect animal and human steroids, most notably estrogen. Ewes grazing on large amounts of Trifolium have been noted to frequently develop uterine fibroids and abnormal estrus, while rams develop low sperm counts and reduce fertility. While coumarin containing plants such as Trifolium and Melilotus can be recommended for vascular pathology, thromboxane inhibitors such as garlic, onions, and ginger are more noted for their blood thinning effects, and carry no such hormonal activities. Medicago is another legume family plant with both coumarins and isoflavones noted to have both circulatory and hormonal effects. Animal studies on a coumarin containing Melilotus officinalis was shown to reduce acute vascular inflammation. Researchers noted improved phagocytosis, total leukocyte and differential leukocyte counts compared to cortisone, without the inhibitory effects on the bone marrow.

APIACEA COUMARINS
Coumarin is fairly common in plants and widely distributed, but the Legume (Leguminoseae), Citrus (Rutaceae) and Carrot Families (Apiacea/Umbelliferae) are particularly high in coumarin. One coumarin found in many Umbells is osthole. Osthole has also been shown to have numerous vascular effects, hepatoprotective effects, hormonal effects and immune-enhancing and anti cancer effects. Similar research is mounting for Umbelliferone, another common coumarin in the Apiacea family. Some of the coumarins are photosensitizing, as discussed below, giving them antiviral properties as well as direct effects on skin disorders. Hormonal effects are also noted from many Apiacea plants – from the historical folkloric use of Fennel and Anise seed tea to promote lactation in nursing women, to the modern research on Apiacea compounds and gonadotropins activity in the central nervous system.

Apiaceae Coumarin and Vascular Effects
Coumarins from Angelica species have been noted to posess platelet anti-aggregating effects either equal to or greatly surpassing that of aspirin. The coumarin compounds also display an inability to calm arachidonic acid and thromboxane induced inflammatory and platelet aggregating activity. Mild hyperlipidemic effects have also been demonstrated by Apiaceae coumarins such as Umbelliferone.
Osthole has been demonstrated to possess antiproliferative effects on vascular smooth muscle, protecting these cells from a variety of mitogenic agents including platelet-derived growth factors and serotonin. The inhibition of proliferation was shown to involve a mechanism of enhanced cyclic AMP and GMP in the cell.  Osthole reduces platelet aggregation induced by ADP, arachidonic acid, PAF, collagen and thrombin via direct thromboxane inhibition.
Osthole can reduce the frequency of action potential in neurons via inhibition of calcium channels. In animal studies, osthole has been shown to relax the thoracic aorta by virtue of its Ca (2+)-channel blocking properties and by elevating cGMP levels in vascular smooth muscle. This is presently presumed to be the mechanism whereby some Apiacae plants such as Cnidium, Angelica, and Apium are able to reduce blood pressure. Osthole was noted to reduce hyperexcitability of the atrial electrical fibers when subjected to electrical stimulation. The protection against excessive electrical activity has been credited to calcium channel inhibition. This research suggests that Apiaciae plants might be useful for tachyarrhthmias as well as hypertension.
Cnidium tincture and the isolated coumarins osthole, imperatorin, xanthotoxin and isopimpinellin have been shown to exhibit vasodilating effects in the penis, reversing vasoconstriction of corpus cavernosum induced by epinephrine compounds . This research has implications for the treatment of hypertension in general as well as impotence. Cnidium has been used traditionally in China to improve male sexual function. Some research has suggested that osthole may promote the release of nitric oxide promoting a vasodilating effect within the corpus cavernosum. The release of nitric oxide may be mediated via phosphodiasterase inhibition which prolongs the activity of cGMP and cAMP intracellularly.
Osthole is noted to reduce interleukin-1 providing anti-inflammatory activity that may be an alternative to steroidal medications in some situations. Some researchers have reported osthole containing plants to be alternatives to steroidal medications in cases of ocular ischemia and retinal degeneration due to the involvement of interleukin driven inflammation.

Apiacie Coumarins and Hepatic Support
Osthole, a coumarin common in Apiacea is noted to have a protective and restorative effect on liver function. One study showed Osthole to protect from fatty liver in rats fed a fat-rich diet. Researchers noted increased expression of genes coding for liver detoxification as well as simple reduced lipid accumulation in the hepatocytes.
Other researchers have reported decreases in liver cholesterol and triglyerides in animals fed a diet containing 0.05% osthol by weight. It was noted that the reduction in liver lipids was associated with an increase in HMG-CoA and carnitine palmitoyl transferase, enzymes involved with hepatic lipid metabolism. These findings have been repeated by other reasearchers.

Osthole has also been shown to help protect the liver in cases of hepatitis by preventing the development of apoptosis in infected hepatocytes and preserving hepatic function. One group of researchers demonstrated hepatoprotective effects against both high fat diets and alcohol using osthole at a dose of 5-20 mg/kg. After 6 weeks serum lipids were lower and superoxide dismutase levels in the liver higher. Malondialdehyde levels decreased in alchohol fed groups and glutathione peroxidase levels decreased in the high fat groups, all indicated inmproved antioxidant and anti-inflammatory hepatoprotective activity from osthole. Histological evaluation demonstrated osthole to dramtically reduce lipid accumulation in the liver in both treated groups over controls
Patients with hepatitis C have an increased risk for developing Hepatocellular carcinoma. Agents which reduce liver inflammation and improve hepatocyte function and survival are believed to decrease the occurance of cancerous changes in the inflamed liver. Coumarins from plants are noted to lower plasma ALT, an indicator of decreased liver inflammation. Research is presently underway to find the best absorbed compounds that would be effective with oral dosing. Furanocoumarins display activity in vitro but are not well absorped orally. Furocoumarin are also active in the liver but have a low therapeutic window due to toxicity concerns. Osthole, a simple coumarin has been shown to lower plasma ALT, to be well absorped orally, and to have little toxicity. HPLC analysis has demonstrated osthole to enter the serum at pharmacologically significant levels within 20 minutes to an hour following oral dosages of whole Cnidium fruit extract.
Osthole has been shown to inhibit the secretion of hepatitis B virus surface antigens in vitro by increasing the glycosylation of HBsAg. Coumarins in general, are noted to increase liver detoxification via promotion of glucuronoconjugation in hepatocytes.

Apiaciae Coumarins and Hormonal Activity
Anethol and essential oils in Foeniculum and Pimpinella and other plants is noted to possess estrogenic activity. Osthole and other coumarins may also bind hormonal receptors and elicit hormonal effects. There has been some investigation into coumarin supplementation for improving bone density. The isolated coumarins osthole, impertorin, and bergapten from Cnidium were investigated for effects on bone metabolism. Osthole has been shown to be the most potent promoter of osteoblastic proliferation, with the related coumarins bergapten and and imperatorin having lesser effects. Osthole promoted alkaline phosphatase levels levels and osteoblast activity and proliferation as well as inhibited bone resorption by reducing activity and maturation of osteoclasts.
A comparative studying between osthole and estradiol on bone density of ovarectomized rats showed both estradiol and osthole to protect from cancellous bone loss compared to controls, while only estradiol prevented uterus atrophy. As a result of these findings researchers felt that osthole might act via a gonadotrophin pathway rather than direct estrogen receptor agonism.
Other researchers measured alkaline phosphatase, osteocalcin, osteopontin, type I collagen activity, and osteoblastic proliferation following dosing with osthole. The investigations showed that osthole promoted osteoblast via a mechanism involving bone matrix protein synthesis.
Osthol may also possess a gonadotropins-like effect. Animals studies have shown Testosterone, Luteinizing Hormone and Follicle Stimulating Hormone levels to all increase in 20 days time following daily consumption. Penile nitric oxide levels were also promoted, a mechanism that may enhance vasodilation and erectile function.
Estrogen and other hormones are increasingly being explored for their effects on neurotransmission in the central nervous system. For example, menopause and andropause are often associated with deficits in mental focus, and hormonal therapies sometimes offer improvements for patients with Alzheimer’s or other types of dementia. Research into how estrogens and adrogens might activate cholinergic activity is underway. Cnidiuim and its constituent osthole have been shown to improve spatial orientation and activate cholinergic transmission within the central nervous system in rats.
Osthol, but not xanthotoxin has been noted to have activity at TRH receptors in rats. Osthole was shown to decrease binding of TRH to its receptors in the pituitary and mitigate TRH-induced increases in calcium channel activity.
Osthole and the total coumarin fraction from Cnidium have been shown to strengthen the pituitary adrenal axis. Researchers showed that administration of these coumarins could prevent suppression of adrenal function in animals given cortisone. Oral ingestion of osthole was also noted to prevent the reduction in lymphocytes and phagocytic activity normally suppressed by cortisone. Similar research showed that Cnidium coumarins could also prevent suppression of TSH and thyroid hormones following hydrocortisone administration suggesting Apiacea coumarins could also strengthen pitutitary-thyroid axis activity.

Apiaciae Coumarins and Cognitive Function
Osthole administration is noted to improve memory and learning capacity in mice, simulataneous with an enhancement of the inflammatory enzymes glutathione peroxidase and superoxide dismutase suggesting an antioxidant mechanism and protection of neurons from peroxidation.
Anethole, an essential oil in Foeniculum and Pimpinella and other plants, is structurally similar to the catecholamines and may affect cholinergic neurotransmission. Anethole may also compete with dopamine, reducing in the ability of dopamine to inhibit prolactin secretion.

Apiaciace and Anti-Allergy Effects
Angelica species have long been used in China for allergies and asthma, and Ammi visnaga used for asthma as well as is the inspiration for the development of a synthetic bronchodilator base don one of it’s anti-inflammatory flavinoids Khellin. Furthermore Foeniculum and Pimpinella have been tradicional bronchodilators included in cough, asthma and lung formulas in western herbal medicine for centuries.
Cnidium tincture has been shown to possess anti-allergy activity reducing contact dermatitis in experimental models. Angelica has been found to have an anti-histamine and anti-serotinin effect which may be an explanation of the reported anti-allergy effects.

Apiaciae Coumarins and Diabetes
Umbelliferone has the ability to improve glycemic control in diabetics and normalize the activity of ATPases on the membranes of erythrocytes body tissues including the liver, kidneys, and heart. These membrane-bound ATPases are typically depressed in diabetics. Collagen repair and regeneration also becomes aberrant in diabetes with total collagen increasing but soluable and transportable types of collagen decreasing. Umbelliferone has been shown to have a normalizing effect on collagen, a mechanism presumed to help protect the kidneys and nerves from the contributions of excessive collagen deposition in nephropathy and neuropathy. Umbelliferone has also been noted to improve lipid profiles in diabetic rats, as well as improve insulin and glucose regulation in general. Histological analysis showed a marked ability to improve fatty, hemorrhagic, and lymphocytic infiltration in diabetic rats of the liver to near normal. Effects on renal cells and tissue were similarly impressive.

Apiaciae Coumarins and Cancer
Coumarin and Umbelliferone have anti-tumour actions in vitro and in vivo against non-small cell lung carcinoma cell lines. The anti-cancer effects include the inhibition of cell proliferation and the induction of apoptosis. The effects were apparent on all the lung carcinoma cell lines except squamous lung carcinoma cell lines.
Coumarin compounds have also shown activity against renal cell carcinoma. Researchers noted coumarins to alter phosphorylation and thereby affect protein kinase enzymes and favorably affect cellular differentiation and apoptosis.
Osthole is reported to have both in vitro and in vivo antitumor effects. Osthole inhibited the growth of the cell line of aggressive breast cancer known as HeLa in a dose dependant manner. Osthol induced apoptosis in one study while showing little cytotoxicity against normal cervical fibroblasts.
Umbelliferone may inhibit dehydrogenase enzymes in human testes, an activity which may decrease prostatic hypertrophy and have therapeutic potential for prostate and testicular cancer. Umbelliferone may also reduce overproduction of dihydrotestosterone via a reduction in alpha-5-reductase activity , providing further rationale for Apiaciae family plants to be included in formula for prostatic disease and endocrine disorders involving testosterone elevations such as Polycystic Ovarian disease.
Coumarins are also being explored for activity against bladder cancer. Forbesoside, columbiandin, esculin, decursin and umbelliferone have all shown inhibitory effects on human bladder cander cell lines.

Apiacea and Phototoxicity
The angular furanocoumarin, such as athamantin and simple coumarins (umbelliferone) show no photoxicity. The linear furnaocoumarins show significant phototoxicity in the following order: psoralen, bergapten, peucedanin, xanthotoxin. , The linear fornaocoumarins are sometimes referred to as furanochromones. Furanochromones are like pigments that appear to absorb UV radiation. Some research has suggested that furanochromones form photoadducts with DNA of microbes and therby are able to kill pathogens. These photoadducts may also lead to stimulation of dermal cell activity and are used for dematoses such as recaltirant psoriasis and vitiligo. Other research suggests that furochromones can reduce adenylate cyclase activity when when excessive, such as by pertussis toxin or in cases of cancer with its excessive, aberrant mitosis.
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 isoloated 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. 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 , investigations into the variety of photosensitizing psoralens or other coumarins is necessary to identify which are most effective with the least side affects.
In general UV A has been used, but in some circumstances UV B is used as well. Recent research has indicated that the higher the concentrations of coumarins in the skin are the most effective in clearing chronic psoriasis.
Coumarins and related compounds may 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. Psoralen and related comounds may be photosensitizing to bacteria and viruses, and plants containing these photosensitizers may be antimicrobial via a mechanim of phototoxiticy involving DNA disruption in the microbes. Furocoumarins from parsley are noted to inhibit E. coli via a phototoxic mechanism. The early stages of some forms of cutaneous T-cell lymphoma have been shown to respond to psoralen consumption combined with ultraviolet light exposure.
Psoralen with UV A is also helpful for alopecia areata and somewhat helpful in alopecia totalis. Vitiligo may also respond to psoralen combined with UV light. One study showed a narrow band of UVB to be more effective than UVA in promoting repigmentation in cases of vitiligo.
Many antiviral compounds from plants are noted to be photosensitizers. The coumarins and the prunaochromones are believed to form adducts with viral DNA. Some may show strong bondage 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 all been shown to exibit an inhibitory effect on cyclic AMP phosphodiesterase. These compounds may interfere with microbial and cancerous processes via this mechanism, as well as have vascular effects via this mechanism.  The dermal penetration of topically applied xanthotoxin has been investigated. Xanthotoxin is reported to be reasonably well absorbed and to be retained in the stratum corneum for 24 hours.
RECENT RESEARCH ON SPECIFIC APIACEA SPECIES

The Family In General
Apiaciae seeds from Foeniculum, Carum, and Pimpinella have been folkloric mainstays for treating digestive gassiness and bloating including IBS and colic in babies. One clinical trial showed a combination of Matricaria, Foeniculum, and Melissa to improve colic symptoms with one week with no reported side affects. The topical application of a Foeniculum essential oil containing emulsion has also shown efficacy for infantile colic in double-blind placebo controlled trials.
Apiaciae plants Foeniculum vulgare, Pimpinella ansium, and Carum carvi have shown activity against Helicobacter pylori. Foeniculum vulgare and Coriandrum sativum have also shown activity against E. coli and Bacillus mageterium, two standard marker microbes as well as activity against 27 patholgenic bacterial and 2 mushroom pathogens. Foeniculum also acts as a deterent to mosquitoes.
Apiacea family foods carrot, celery, fennel, parsley, and parsnip have all shown activity against lymphoblastic leukemia cell lines.

Lomatium and Ligusticum
Lomatium californicum has been shown to have activity against Staphylococcus aureus. Lomatium and a similar Apiacie family member Ligusticum both contain the coumarin relative ligustilide and the essential oil Apiol, both credited with antimicrobial activity. The seeds of these species are particularly high in these compounds. Lomatium has also been noted to have activity against the rotavirus. Suksdorfin from Lomatium suksdorfii has been shown to have anti HIV activity. Lomatium dissectum contains a relatively uncommon water soluable coumarin apiose

Foeniculum vulgare – Fennel
Fennel is high in volatile oils including the phenylpropanoid anethole. Isolate anethole is sometimes used as a flavoring agent and is credited with the carminative action of fennel seeds. Fennel seeds also contain the flavinoid rutin which is common in plants and credited with antibacterial and antiviral actions. Rutin is also known to strengthen capillaries. Fennel also contains potassium, phosphorus, calcium, and Vitamins A and C.
Fennel aromatic oils display benzene ring-like chemical structures, and may be able to bind to hormone receptors like other ring structures are noted to do (Coumestans, Isoflavones). Overall, animal studies have noted increased estrogenic activity from fennel, befitting the historical use of the plant to support fertility and lactation.
Anethole is structually similar to the catecholamines, and may also bind these neurotransmittor receptors, or otherwise affect catecholamine activity in the body. Anethole may compete with dopamine for neurotransmittors receptors, leading to a reducing in the ability of dopamine to inhibit prolactin secretion.
Foeniculum vulgare in noted to have a chemopreventative effect and is able to protect the liver from the carcinogen trichloroacetic acid. Liver enzymes improve and antioxidant activity is enhanced, not only in the liver but in the kidneys, brain and other tissues as well. Psoralen compounds in fennel seeds inhibit human liver cytochrome P450 enzyme activity.
Antifungal activities have been shown from Foeniculum essential oils. Fennel essential oil has shown efficacy placed directly in the soil to deter agricultural pathogens and may be an alternative to synthetic fungicides. Foeniculum vulgare has shown some activity agains the Tuberulosis, including some of the drug resistant strains.
Foeniculum vulgare essential oil has also shown significant anti-platelet activities preventing clotting induced by arachidonic acid, collagen, and thombin. Anethole, one of the main components of the essential oil prevent thrombin induced clotting and displays a vasodilating activity, while showing no toxicity. Furthermore, the dose that accomplishes antithrombotic activity showed no pro-hemorrhage activity, and displays a protective effect from ethanol induced gastric ulcers.
The oral consumption of Foeniculum has shown some efficacy in relieving dysmenorrhea in young women. It is suspected that Foeniculum seeds posess estrogenic activity as evidenced by increases in uterine and ovarian with in immature mice fed fennel extracts.

There have been 4 cases summarized from European literature of methemoglobinermia in infants fed fennel purees. The infants become cyanotic and responded to methylene blue therapy making full recoveries. Foeniculum vulgare coumarin relatives are noted to inhibit liver cytochrome p450.
Hirsuitism, excessive male pattern hair growth in women may respond to topical creams containing Foeniuculum. In many cases of such hirsuitism hormones, including androgens are normal and the excessive hair growth may be due to abnormal metabolism of peripheral adrogens. One clinical trial showed a reduction in hair diameter compared to placebo.
Foeniculum extracts are noted to reduce allergic inflammation as well as posess an analgesic effect. A reduction in allergic inflammation may relate to an increase in plasma superoxide dismutase. Foeniculum tea, tincture, and essential oil are noted to have bronchodilating effects and research has suggested that relaxation of the bronchi may be due to enhancement of potassium channels.
Investigations into Foeniculum vulgare toxicity have shown no teratogenicity. Although Foeniculum possesses some hormonal activity, review and investigation has shown no serious health risks to be associated with the consumption of fennel tea.

Khella – Ammi visnaga
Ammi visnaga contains a number of coumarin compounds which have been named khellin, visnadin, visnagin and khellol glycoside. Xanthoxin is also found in Ammi majus. Khellin, Visnagin and visdadin are all noted to have vasodilating effects due to smooth muscle relaxation. Research has shown visnagin and visnadin to reduce the vasoconstrictive effects induced by noreadrenaline via direct activity on vascular calcium channels. Visdadine, another compound has also been shown to have peripheral and coronary dilating abilitities via calcium channel inhibition. This is likely the same mechanism by which Ammi visnaga is bronchodilating being valuable for asthma and spastic coughing. The furnaochromones may have a positive activity on the vascular system through a variety of mechanisms. There is also evidence that khellin may act via intracellular G proteins due to effects on adenylate cyclase and GTPase. Visnagin may also interact with phosphodiasterase enzymes having a vasorelaxing effect. Visnagin has been noted to reduce blood pressure through this vascular relaxation effect.
Ammi visnaga tea has been shown to possess a significant hypoglycemic effect in diabetic rats. Blood glucose was reduced significantly 6 hours after a single oral ingestion of the tea. Insulin-like or insulin-promoting activities have been reported by Ammi extracts with measureable increases in glucose uptake.
Khellin dosed at 50 mg four times daily was noted to improve blood lipids compared to placebo after 2 weeks. The impact on blood lipids was an increase in HDL cholesterol while triglycerides and total cholesterol were unchanged. Similar findings have been reported by other researchers.
Ammi visnaga has been used traditionally to facilliatate the passage of renal calculi. Research has shown that Ammi visnaga has a spasmolytic effect on smooth muscle, including on the ureters.
The topical application of khellin in combination with UV or natural sunlight may be effective for chronic skin lesions. One study reported the method to be successful for palmar and plantar pompholyx. Another study reported topical Khella in combination with UV was helpful for vitiligo. Researchers reported that the younger the patient, the better the result.
A similar investigation on vitiligo used an encapsulated form of khellin with L-phenylalanine and phosphatidylcholine in comibination with UVA and compared this with the results of the use of UV alone. Results required a full year to manifest, but after this time, a significant repigmentation was accomplished in the group the used the oral Khellin capsules but not in the UV only control group. Other studies have reported melanocyte stimulation from the use of khella. Khellin has been shown to penetrate the stratum corneum with topical application and inotophoresis increases the concentration in the skin.
Khellin has been known to be a mast cell stabilizer for decades. A synthetic version of this compound, Sodium cromoglycate was released in the late 60s as a treatment for allergies and asthma. An inhaler version of this medication is marketed under the trade name of Intal.

Petroselinum crispum – Parsley
Petroselinum is among the vegetables with the highest content of polyphenols, well known anti-cancer, anti-inflammatory and antioxidant compounds in plants. The polyphenol contentin foods is sometimes measured in terms of gallic acid equivenlency (GAE). Parsley is noted to have a GAE of greated than 250 mg while the food most commonly referred to as having highing high polyphenol content, the berries, have around 180 mg GAE in compariason. Petrolesinum, like other Apiaceae has been shown to have antioxidant properties against a variety of different free radicals including OH.
Petroselinum also showed a protective effect on the liver when exposed to hepatotoxins. Petroselinum has been shown to exert positive histological improvements in the livers of diabetic rats. Blood glucose and liver enzymes were also noted to improve. Petroselinum has been shown to exert positive histological improvements in the livers of diabetic rats. Blood glucose and liver enzymes were also noted to improve. Some plants having an anti-diabetic effect have been shown to exhibit a supportive effect directly on the pancreas, increasing the number and activity of B cells. However, histological studies in rats have shown Petroselinium to not be among them. The blood sugar balancing effects of Petroselinum appear to be via metabolic activities alone, and not involve direct pancreatic tissue effects.
An anti-platelet aggregating effect has been demonstrated by Petroselinum. Activation of platelets by both thrombin and ADP has been shown and the activity has been credited in part to the polyphenol content.
Petroselinum has a high apigenin content. Research has been conducted on consuming parsley as a food to determine whethter or not the apigenin was absorbed and able to be assimilated in away that may have biologicial effects. Apigenin can be detected in red blood cells within a few hours after oral ingestion of apiin-rich food, and is noted to peak within 7 hours. The content of apigenin in blood is not altered by dose and appears to have a maximum saturation level. Apigenin can also be detected in the urine and shown to clear, more or less 24 hours following ingestion.
A tincture preparation of Petroselinum has been shown to reduce excessive gastric secretions and offer protective effects to the gastric mucosa in animals predisposed to ulcers and other lesions.
Petroselinum contains a phenylalanine-lysase enzyme that may be valuable for phenylketonuria patients. Although PKU patients must always attempt to avoid phenylalanine in all forms, the consumption of parsely may reduce the the harmful consequences following accidental ingestion. Research is underway in China, investigating methods to synthesize or clone these substances from Petroselinum in hopes of leading to a therapeutic drug.

Conium maculatum – Poison Hemlock
Due to its toxicity, Conium is rarely used as an herbal medicine in concentrated form, however it is used as a homeopathic, especially for vertigo, dizziness and balance issues.   “Slow Brainstem Syndrome” is the term used in neurology for the combination of tinnitus with vertigo and dizziness, sometimes associated with nystagmus. Drop dosages or homeopathic preparations of Conium may stimulate the vestibular, ocular, and acousticocortical system in a manner which normalizes activity and improves tinnitus and vertigo in the elderly.
Conium is extremetly toxic and known to promote drowsiness, headache, and abdominal pain, vomiting and diarrhea with the ingestion of substanstial amounts. Toxicity is due to a group of piperidine alkaloids including coniine and gamma-coniceine. These alkaloids are precursed by lysine. Studies have shown that the content of toxic alkaloids varies widely according to environmental habitat and age of the plant, hence the toxicity may vary greatly. When the content of coniine is high, ingestion may be fatal due to respiratory failure and paralysis of the motor nerves, which lead to coma and death. When content is low, but chronically ingested, such as by livestock over a period of time, fetal malformations are reported. The entire plant, flowers, seeds, leaves, roots contain the toxic alkaloids.
Conium was listed in the British Herbal Pharmacopea in the 1885 and 1898 editions and is often mentioned in early european herbals for pain management. The Llyod Brothers produced a specific medicine from Conium stating it to be a narcotic sedative for chorea, tetanus, whooping cough, asthma, or other conditions involving overstimulated motor responses and reflexes.  Conium has been used topically to releive the pain of cancerous growths. Conium is indicated internally for all types of pain including rheumatism, muscle spasm, glandular swellings, breast pain, and dysmenorrhea. Conium was at one time used in the treatment of chorea and mania as it acts as a motor depressant. Conium has been used as an antispasmodic for asthma and pertussis in tiny drop dosages.

Dacus carota – Wild Carrot
Daucus carota seeds are noted to inhibit the growth of some plants and have therefore been explored as a potentital organic herbacide. Crotonic acid is credited with these herbicidal effects.
Daucus carota seed extracts have also been noted to inhibit cyclooxygenase having the ability to reduce inflammatory prostaglandins. The drugs ibuprofen, naproxen, aspirin, celebrex and are popular for pain management are noted to act via this mechanism. Carrot seed extracts are noted to inhibit COX enzymes in league with these pharmaceuticals.

The ripe seeds of the wild carrot were reportedly used by Native American peoples as an agent to reduce fertility. Modern research into the chemistry and physiology of this common meadow plant has found porphyrins capable affecting the release of gonadotropins from the pituitary.

Angelica sinensis – Dong Quai
Legend has it that Angelica was so named because an angel revealed herself to a medieval European monk and taught him the medicinal virtues of Angelica. Angelica is a classic blood mover and is appropriate for amenorrhea , and may also offer significant cardiovascular benefits.
Angelica may reduce nociceptive pain by affecting nervous activity. Secondly, Angelica may reduce congestion in the tissues through enhanced blood and lymph circulation. Animal studies have shown Angelica to have a general analgesic and anti-inflammatory effect. Angelica extracts are noted to have numerous positive effects on the vasculature including vasodilating effects via both nitric oxide and calcium channel inhibition mechanisms. Angelica has been noted to have protective, antiproliferative effects on vascular smooth muscle.
Studies have shown that Angelica sinensis is useful in treating gynecological complaints including infertility, PMS, numerous menstrual complaints including cramping and irregular cycles, chronic miscarriage, and menopausal complaints. It is believed to increase the basic function of the uterine and ovarian cells. Specifically, metabolism is increased within the uterus and ovaries. This means that the internal cellular reactions such as using fuel and producing energy are increased. Studies have shown Angelica to increase the use of glucose or sugar in uterine cells, and to promote the synthesis of DNA in the uterus and ovaries. If a cell is using more glucose, the primary fuel of all cells and producing more genes, you can be certain that metabolism in those cells has been stimulated.
Although Angelica contains no steroids or hormone molecules, it does contain coumarin which may affect estrogen levels. Many women have found Angelica to improve their menstrual cramps. Interestingly, several studies have shown Angelica to act as a muscle relaxant overall, but to stimulate the uterus briefly before relaxing it. , This curious action is likely the result of two chemical constituents in Angelica that have opposite actions on the uterus. Heavier menstrual flow may be due to the blood vessel dilating effect of nicotinic acid, or may be due the ability of coumarin, ferulic acid and lugistilide in the volatile oil to inhibit platelet aggregation.
Studies also cite Angelica’s effectiveness in treating allergies and respiratory complaints. Angelica has been found to have an anhistamine and antiserotinin effect which may be an explanation of the reported anti-allergy effects.
Angelica has also been credited with enhancing the immune system, which helps the body fight off disease, as well as anti-tumor activity. The coumarins in Angelica will increase the number of white blood cells and enhance their ability to search out and destroy agents that cause disease. Angelica promotes numerous natural defense mechanisms including increased ability of the blood cells to directly engulf disease producing invaders, and ability of the cells to secrete substances that enhance immunity.

Apium graveolans – Celery

Apium graveolans is noted to reduce cholesterol without interfering with general metabolism of hepatic sterols. Researchers believe that cholesterol is diminished via enhanced biliary excretion, not by interference with the reductase enzymes. Other research suggests that a multiple active compounds in Apium lower triglycerides and cholesterol via a variety of mechanisms. Apium graveolans is also noted to have numerous anti-inflammatory effects in the blood. Apium may both promote sodium excretion and diurese, as well as contain coumarins. Traditional and homeopathic literature has reported Apium to be specific for pelvic pain associated with urinary retention, nervous anxiety and sharp sticking pains. Sharp sticking ovarian pains and tenerdess of the nipples have are included in the specific indications in tractional literature.
Centella asiatica – Gotu Kola
Centella asiatica is a nourishing succulent green leafy native to India. Centella has been used traditionally as something of panacea for general strength and longeveity. Centella has been widely used for wound healing including bone, skin, joint, and other tissues. Centella has also been specifically recommended for ulcerative and inflammatory conditions of the cystic, gastric, esophogeal, intestinal, rectal, and oral mucosal surfaces. Centella has been noted to promote healing of bladder ulcers specifically.
Skin injuries including burns, lacerations, keloid formation, excema, psoriasis and other forms of dermatitis may also respond to Centella. Recently, Centalla has been reported to improve abberant fibroblast activity in the skin and connective tissue as seen with scleroderma, Lupus and other auto-immune diseases. Earlier research has shown Centella to promote formation of new connective tissue, hyalronic acid, and chondrotin sulfate.  For this history as an ulcer and mucous membrane remedy, plus possible immune and inflammatory stabilization, Centella may benefit IC.
Centella is also appropriate for burns. Since burns destroy the protective barrier of the skin and leave the local area susceptible to secondary infections, rapid epithelization is important for both infection prevention as well as pain managements and aesthetic considerations to reduce scarring. Infection is main cause of death when there have been extensive burns. Centella has been shown useful in promoting epithelial regeneration following burns. Asiaticoside, asiatic acid, and madecassic acid are among the triterpenoid wound-healing compounds in Centella and have been shown to help reduce excessive fibrosis in situations of scleroderma, extensive scar formation and keloids. The proliferation of epithelial cells and angiogenesis are noted to be promoted by Centella as is fibroblastic growth factor, an angiogenic agent. Centella has been shown to promote the genes involved with angiogenesis, growth factors, and extracellular hyaluronic binding proteins providing an explanation for the plant’s wound healing effects. Other investigations report that Centella promotes granular tissue, the strength of the granular tissue and hydroxyproline content is both normal situations and steroid-suppressed healing response. Centella asiatica may also be specific for injury to nerves and highly innervated areas by promoting axonal regeneration. Centella tincture, but not the tea, has been shown to promote a marked increase in neurite growth.
Centella asiatica may be useful for improving cutaneous microcirculation. Diabetics with impaired microcirculation may benefit from Centella therapy and improved venoarteriolar response, blood gases, capillary permeability and general microcirculation have been reported in clinical trials.
Centella asiatica saponin asiaticoside has shown to induce type I collagen synthesis in human dermal fibroblast cells. Centella has also been noted to reduce fibrotic process in the liver in animal studies.
Centella asiatica at a dose of 100 mg per Kg has been shown to offer a protective effect to the liver when dosed prior to radiation exposure. Centella was also shown to have a protective effect from gamma radiation generated by radioactive Cobalt 60 increasing survival time and reducing radiation-induced weight loss. The most effective dose was 100 mg per kg.

Cnidim monnieri
Cnidium monnieri contains a variety of coumarin compounds including osthole, volatile oil, monoterpene polyols, glucides and sesquiterpenes. A broad review of the literature on Cnidium reports hepatoprotective, anti-tumor, and immune enhancing effects. Cnidium has been noted to have positive effects on cholesterol metabolism and improve drug tolerance via enhanced hepatic metabolism. Cnidium might be considered in formulas for impotence because studies have shown vasodilating effects in the penis . Via nitric oxide pathways, Cnidium has general vasodilating and blood moving effects making this plant, like other Apiacea members appropritate for hypertension and all manner of vascular diseases. Cnidium may also improve impotence via hormonal effects in addition to vascular effects. And like most Apiacea family plants, Cnidium has anti-allergy activity. Cnidium tincture has been shown to possess anti-allergy activity reducing contact dermatitis in experimental models.
Osthol may also possess a gonadotropins-like effect. Animals studies have shown Testosterone, Luteinizing Hormone and Follicle Stimulating Hormone levels to all increase in 20 days time following daily consumption. Penile nitric oxide levels were also promoted, a mechanism that may enhance vasodilation and erectile function.
Estrogen and other hormones are increasingly being explored for their effects on neurotransmission in the central nervous system. For example, menopause and andropause are often associated with deficits in mental focus, and hormonal therapies sometimes offer improvements for patients with Alzheimer’s or other types of dementia. Research into how estrogens and adrogens might activate cholinergic activity is underway. Cnidium and its constituent osthole have been shown to improve spatial orientation and activate cholinergic transmission within the central nervous system in rats.
Research has shown thyroid supportive activity. Osthol, but not xanthotoxin has been noted to have activity at TRH receptors in rats. Osthole was shown to decrease binding of TRH to its receptors in the pituitary and mitigate TRH-induced increases in calcium channel activity. Osthole and the total coumarin fraction from Cnidium have been shown to strengthen the pituitary adrenal axis. Researchers showed that administration of these coumarins could prevent suppression of adrenal function in animals given cortisone.

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