Arnica extract is produced from Arnica montana L. flowers. Its chemical make up is composed of sesquiterpene lactones (Helenalin and Dihydorhelenalin), flavonoids, phenol acids and essential oils.
Anti-inflammatory activity is derived from the sesquiterpene lactones and flavonoids. It has been found that Helenalin and Dihydorhelenalin exerted anti-inflammatory effects on experimental animals, by inhibiting prostaglandin production through the blockade of the prostaglandin-synthase enzyme. Such anti-inflammatory effects were reinforced by carotenoids and flavonoids (Alonso J., 2004).
Helenalin, Dihydrohelenalin, Dhamissonolide and their ester derivatives present in arnica flower heads influence several cell processes. Lyss G. et al. (1997) and Klaas C.A. et al. (2002) carried out studies that demonstrated that Helenalin and, to a much lesser degree, Dihydrohelenalin and Chamissonolide, inhibit the activation of the FN-kappa-B and NF-AT transcription factors involved in the genesis of inflammatory processes.
Flavonoids attenuate the inflammation and the immune response through their inhibitory action on major regulatory enzymes. Certain flavonoids are powerful inhibitors of the production of prostaglandins, a group of molecules involved in the immune response. Several studies have shown that this effect is due to the flavonoid inhibition of key enzymes involved in prostaglandin biosynthesis such as lipooxygenase, phospholipase, and cyclooxygenase. Flavonoids also inhibit phosphodiesterases involved in cell activation. This inhibition mainly affects the biosynthesis of cytokines that mediate adhesion of circulating leukocytes to sites of injury. Flavonoids also inhibit another class of regulatory enzymes, the protein-kinases, by competing with ATP for binding at the enzymes catalytic sites. Thus, flavonoids exert anti-inflammatory effects by inhibiting different enzymes involved in the inflammation processes (Manthey J.A., 2000).
A homeopathic product containing Arnica montana and other plant extracts and minerals, was tested on rat models of inflammation. It was found that its main action mechanism was associated to a significant decrease of systemic interleukin-6 level. An open multi-centre clinical study revealed that 2 daily applications of an arnica-containing gel to 79 patients suffering knee-osteoarthritis, for a 3-6 weeks treatment, significantly reduced joint pain in most of the cases; the product was well tolerated in 87% of the cases (Alonso J., 2004).
Flavonoids are vein-active and vessel-protective agents because they reduce the permeability and increase the resistance of blood capillaries. Flavonoids are used in the treatment of blood vessels disorders such as varices, chronic venous insufficiency (CVI), low capillary resistance, etc. Their protective effect is due to their high affinity for proline-rich proteins, such as collagen and elastin. Since these proteins are structural components of veins, their degradation weakens the blood vessels, inducing oedema and swelling of the lower limbs.
The RELIEF study (“Reflexus asEssment and quality of life improvement with micronized flavonoids in chronic venous insufficiency”) is a controlled multi-centre study carried out between March 1997 and December 1998, in 23 countries around the world, in which more than 10,000 patients suffering CVI participated. These patients were treated with a purified flavonoid fraction for six months. The results of this study showed that the flavonoid treatment significantly improved the cases of pain, tired legs, swelling, cramps and oedema (when it was present) (Spignoli G., 2000).
Essential oils show antiseptic effects against different pathogenic bacteria, even antibiotic-resistant strains. Some essential oils are also effective against the fungi and yeasts (Candida) that cause mycosis.
Different research studies have confirmed the antimicrobial properties of essential oils, especially on antibiotic-resistant bacteria, such as Staphylococcus aureus, which resists methicillin, or Enterococcus faecium, which resists vancomycin. The antimicrobial activity of essential oils is attributed to their main chemical components: citral (aldehyde), geraniol (primary alcohol), eugenol (phenol), menthol (secondary alcohol) and cinnamic aldehyde (aldehyde) (Hartman D. & Coetzee JC., 2002).
Therefore, arnica extract is highly recommendable to formulate products with anti-inflammatory, venotonic and antiseptic activity.
Horse chestnut extract is produced from the seeds of Aesculus hippocastanum L. Its main chemical make up is composed of Triperpene saponins mainly in the form of Escin, Flavonoids and Proanthocyanidins.
Due to their Escin content, horse chestnut seeds have anti-inflammatory and venotonic properties, which decrease blood-vessels permeability and produce an important anti-oedema effect. Horse chestnut seeds extract reduces lysosomic enzymatic activity (β-glucuronidase and arylsulfatase) – which is augmented in chronic venous pathologies – thus reducing the hydrolysis of proteoglycans in the capillary walls. Furthermore, reduced vascular permeability reduces the leakage of low molecular-weight proteins, electrolytes and water to the interstitial space. These Escin properties are based on a molecular mechanism that improves calcium ions intake, which results in in vivo as well as in vitro increase in venous tension. Further mechanisms, such as prostaglandin F2 (PGF2) release, antagonism to histamine and reduction of tissue mucopolysaccharides catabolism, contribute to the former pharmacological actions (www.fitoterapia.net).
Chronic venous insufficiency is a condition that may include leg swelling, varicose veins, leg pain, itching, and skin ulcers. There is evidence from laboratory, animal, and human research that horse chestnut seed extract may be beneficial to patients with this condition. Studies report significant decreases in leg size, leg pain, itchiness, fatigue and "tenseness." There is preliminary evidence that horse chestnut seed extract may be as effective as compression stockings.
Topical applications of Escin and its aglycone, Escinol, have been demonstrated to possess non- competitive anti-hyaluronidase activity. A. hippocastanum has protective effects on the connective tissues, which surround the capillary vessels. In chronic venous insufficiency, the capillaries become highly permeable; the outcome is that water and proteins leave the vascular system, which in turn cause swelling. This may be as a result of the degradation of the extracellular matrix surrounding the capillaries. The main component of this extracellular matrix is hyaluronic acid; levels of this compound are usually regulated by the enzyme hyaluronidase, which promotes the degradation of hyaluronic acid. This inhibition of hyaluronidase should lead to the recovery of the integrity of hyaluronic acid, and consequently of the extracellular matrix surrounding the capillaries (Wilkinson, J.A. & Brown, A.M.G., 1999).
The venotonic effects of Escin were evaluated on isolated human saphenous veins. Stimulation with Escin always increased venous tone; this effect was not blocked by phentolamine and was not mediated by adrenergic receptors. PGE seemed to be the venous tone relaxing agent, while PGFα seemed to produce contraction. These findings suggested that Escin extracts exert in vitro improving effects on venous tone associated to PGFα increase (Alonso, J., 2004).
Flavonoids are active principles with a wide range of actions; remarkably, reduction of capillary fragility and permeability, anti-inflammatory action and free radical scavenging action (Wilkinson, J.A. & Brown, A.M.G., 1999).
Therefore, horse chestnut seed extract is recommended to formulate products to have venotonic properties, improve general blood circulation and reduce inflammation.