encyclopedia

Azulene

Natural Sources:     
Matricaria recutita L. and other Matricaria species [Fam. Asteraceae]
    
     
Forms:     
Oily extract of fresh or dried chamomile flowers.    


     
Therapeutic Uses:     
– Antimicrobial
– Athlete's Foot
– Bone and Joint Problems (externally)
– Bunions
– Cardiovascular Health Maintenance
– Carpal Tunnel Syndrome
– Digestive Disorders
– Fever
– Gastrointestinal Disorders
– Gastritis
– Heart Health Maintenance
– Infections (externally)
– Insomnia
– Leg Vein Health
– Nervous Disorders
– Sciatica
– Skin Disorders
– Ulcers
– Vascular Disorders
– Vein Health     
     
    
Overview:     
Azulene is a prime component of the essential oil of chamomile flowers, Matricaria recutita L. [Fam. Asteraceae] and related plant species. Products containing azulene generally also contain the other characteristic components of chamomile's essential oil and are gaining popularity for improving leg vein health. Studies have shown that an azulene-based synthetic drug has beneficial cardiovascular effects and may be helpful in treating arrhythmias and for relaxing venous tissues thereby improving circulation. It is thought that this drug may block both Na+ and Ca2+ channels expressed in cardiac and vascular smooth muscles. The multiple ion channel blocking effects of these azulene-based drugs are thought to be largely responsible for the antiarrhythmic and vasorelaxant actions. Azulene extracts used in skin creams for reducing skin puffiness and wrinkles have also gained popularity in the health industry. However, studies have shown that azulene can be photo-reactive following irradiation with UVA and/or visible light, causing a mutagenicity 4-5-fold higher than the spontaneous background mutation. Therefore, it is not recommended to use skin creams standardized for azulene as they may cause skin irritation and mutations. Traditionally, the essential oil of chamomile has been used to help keep bunions under control and to treat Carpel Tunnel Syndrome, sciatica and bone and joint problems through its antinflammatory properties. The German Commission E monograph notes that the oil extract of Chamomile is antiphlogistic (anti-inflammatory and anti-fever) and studies have verified that several compounds contribute to this activity including: bisabolol, chamazulene, matricin and the spiro-ethers. Chamomile tea is also used to prevent and soothe gastrointestinal ulcers. One German synonym for chamomile, translated as 'roll-boil', reflects this traditional usage. To soothe ulcers, a concentrated warm tea of chamomile was drunk while lying down and slowly rolling onto all sides of the body to coat all the inner membranes with the tea.    
     
    
Chemistry:     
Azulene is a prime component of the essential oil of chamomile flowers. Chamomile flowers contain: From 0.3-1.5% essential oil containing azulene, (-)-alpha bisabolol, bisabolol oxides A, B, and C, bisabolone oxide, chamazulene, chamamviolin, spathulenol, cis- and trans-enyne dicyclo ethers (spiro-ether, polyacetylenes) as the principal components.    
     
    
Suggested Amount:     
Chamomile extracts standardized for azulene content are generally taken internally as an herbal product for treating circulatory conditions and are also used in creams for treating dry, puffy skin or wrinkles. However, it is not recommended to use creams standardized for high azulene content as these may cause skin irritation and mutations when exposed to light. The content of azulene in products for internal use should be at least equal to that recommended by the German Pharmacopoeia. German authorities recommend using a heaped tablespoon (ca. 3g) of the flowers for every 150ml of water. It is recommended that boiling water be poured over the flowers and after 5-10 minutes strained. For inflammation of the mucous membranes of the mouth and throat, a freshly prepared cup of tea is used as a gargle or wash. Externally: a 3-10% infusion is used for poultices and rinses; as a bath additive, 50 grams of flowers are used per 10 liters of water.    
     
      
Drug Interactions:     
None known.    
     
    
Contraindications:     
Persons who are allergic to daisy family plants [Fam. Asteraceae] may experience allergy symptoms to chamomile. Creams standardized for high azulene content may cause skin irritation and mutations when exposed to light.    
     
    
Side Effects:     
Allergic reactions are possible in susceptible persons. Infusions should not be used near the eyes. Creams standardized for high azulene content may cause skin irritation and mutations when exposed to light.    
     
    
References:     
     
Duke, J. 1997: The Green Pharmacy, The Ultimate Compendium of Natural Remedies from the World's Foremost Authority on Healing and Herbs. pp. 85-86; 126-127; 291; 362; 531-533. Rodale Press.
 
Saitoh M, Sugiyama A, Hagihara A, Nakazawa T, Hashimoto K. 997. Cardiovascular and antiarrhythmic effects of the azulene-1-carboxamidine derivative N1,N1-dimethyl-N2-(2-pyridylmethyl)-5-isopropyl-3, 8-dimethylazulene-1-carboxamidine. Arzneimittelforschung. 1997 Jul; 47(7): 810-5.
 
Tanaka Y, Shigenobu K. 2001. A review of HNS-32: a novel azulene-1-carboxamidine derivative with multiple cardiovascular protective actions. Cardiovasc Drug Rev. 2001 Winter; 19(4): 297-312.
 
Wang L, Yan J, Fu PP, Parekh KA, Yu H. 2003. Photomutagenicity of cosmetic ingredient chemicals azulene and guaiazulene. Mutat Res. 2003 Sep 29; 530(1-2): 19-26.
 
Wichtl M (ed). 1994. Matricariae flos Matricaria flowers (English translation by Norman Grainger Bisset). In Herbal Drugs and Phyto-pharmaceuticals. CRC Press, Stuttgart, pp. 322-325.
    
     
 
Additional Information:     
     
Wang L, Yan J, Fu PP, Parekh KA, Yu H. 2003. Photomutagenicity of cosmetic ingredient chemicals azulene and guaiazulene. Mutat Res. 2003 Sep 29;530(1-2):19-26.
Department of Chemistry, Jackson State University, Jackson, MS 39217, USA.
 
The photomutagenicity of the popular skin conditioning agents azulene and guaiazulene were tested in Salmonella typhimurium TA98, TA100 and TA102. Following irradiation with UVA and/or visible light, both azulene and guaiazulene exhibited mutagenicity 4-5-fold higher than the spontaneous background mutation. In contrary, naphthalene, a structural isomer of azulene, was not photomutagenic under the same conditions. Azulene was photomutagenic when irradiated with UVA light alone, visible light alone, or a combination of UVA and visible light. Azulene and guaiazulene are not mutagenic when the experiment is conducted with the exclusion of light. Therefore, extreme care must be taken when using cosmetic products with azulene/guaiazulene as ingredients since after applying these products on the skin, exposure to sunlight is inevitable.
 
Tanaka Y, Shigenobu K. 2001. A review of HNS-32: a novel azulene-1-carboxamidine derivative with multiple cardiovascular protective actions. Cardiovasc Drug Rev. 2001 Winter; 19(4): 297-312.
 
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, 2-2-1 Miyama, Funabashi-City, Chiba 274-8510, Japan. yotanaka@phar.toho-u.ac.jp
 
HNS-32 [N(1),N(1)-dimethyl-N(2)-(2-pyridylmethyl)-5-isopropyl-3,8-dimethylazulene-1- carboxamidine] (CAS Registry Number: 186086-10-2) is a newly synthesized azulene derivative. Computer simulation showed that its three dimensional structure is similar to that of the class Ib antiarrhythmic drugs, e.g., lidocaine or mexiletine. HNS-32 potently suppressed ventricular arrhythmias induced by ischemia due to coronary ligation and/or ischemia-reperfusion in dogs and rats. In the isolated dog and guinea pig cardiac tissues, HNS-32 had negative inotropic and chronotropic actions, prolonged atrial-His and His-ventricular conduction time and increased coronary blood flow. In the isolated guinea pig ventricular papillary muscle, HNS-32 decreased maximal rate of action potential upstroke (Vmax) and shortened action potential duration (APD). These findings suggest that HNS-32 inhibits inward Na+ and Ca2+ channel currents. In the isolated pig coronary and rabbit conduit arteries, HNS-32 inhibited both Ca2+ channel-dependent and -independent contractions induced by a wide variety of chemical stimuli. HNS-32 is a potent inhibitor of protein kinase C (PKC)-mediated constriction of cerebral arteries. It is likely to block both, Na+ and Ca2+ channels expressed in cardiac and vascular smooth muscles. These multiple ion channel blocking effects are largely responsible for the antiarrhythmic and vasorelaxant actions of HNS-32. This drug may represent a novel approach to the treatment of arrhythmias.
 

Saitoh M, Sugiyama A, Hagihara A, Nakazawa T, Hashimoto K. 997. Cardiovascular and antiarrhythmic effects of the azulene-1-carboxamidine derivative N1,N1-dimethyl-N2-(2-pyridylmethyl)-5-isopropyl-3, 8-dimethylazulene-1-carboxamidine. Arzneimittelforschung. 1997 Jul; 47(7): 810-5.
 
Department of Pharmacology, Yamanashi Medical University, Japan.
 
The azulene-1-carboxamidine derivative N1,N1-Dimethyl-N2-(2- pyridylmethyl)-5-isopropyl-3,8-dimethyl-azulene-1-carboxamidine (CAS 186086-10-2, HNS-32) is a newly synthesized compound. In the present study, direct cardiovascular effects of HNS-32 were assessed using the canine isolated, blood-perfused sinoatrial node, papillary muscle and atrioventricular node preparations, while the antiarrhythmic action was examined using the canine two-stage coronary ligation-induced arrhythmia model. Intracoronary administration of HNS-32 (1-300 micrograms) suppressed the sinus nodal automaticity and ventricular contractile force, while it increased the atrio-His and His-ventricular conduction time as well as the coronary blood flow. Intravenous administration of HNS-32 (5 mg/kg) suppressed the ventricular arrhythmia for approximately 30 min. Since HNS-32 possesses multiple cardiac direct effects which are unique compared with well-established antiarrhythmic drugs, it may become a leading compound in the search for novel antiarrhythmic agents.