Mugwort (Artemisia Vulgaris, Artemisia Douglasiana

Chinese Medicine, 2012, 3, 116-123 http://dx.doi.org/10.4236/cm.2012.33019 Published Online September 2012 (http://www.SciRP.org/journal/cm) Mugwort (Artemisia vulgaris, Artemisia douglasiana, Artemisia argyi) in the Treatment of Menopause, Premenstrual Syndrome, Dysmenorrhea and Attention Deficit Hyperactivity Disorder James David Adams, Cecilia Garcia, Garima Garg University of Southern California, School of Pharmacy, Los Angeles, USA Email: [email protected] Received June 19, 2012; revised July 16, 2012; accepted July 30, 2012 ABSTRACT Mugwort has many traditional uses around the world. The Chumash Indians of California use it to treat imbalances that women may suffer such as premenstrual syndrome, dysmenorrhea and menopausal symptoms. The plant contains a sesquiterpene that appears to work through a serotonergic mechanism and may be beneficial for women. Mugwort therapy is safer for menopausal women than hormone replacement therapy. Children affected by attention deficit hyperactivity disorder benefit from mugwort therapy. There is no doubt that mugwort therapy is safer for these children than methylphenidate or amphetamine. Keywords: Mugwort; Artemisia vulgaris; Artemisia argyi; Artemisia douglasiana; Menopause; Attention Deficit Hyperactivity Disorder 1. Introduction 2. European Traditional Uses Mugwort is found in Europe (Artemisia vulgaris), Africa Mugwort, Artemisia vulgaris, is used in Europe as a bit- (Artemisia vulgaris), India (Artemisia vulgaris), Asia ter aromatic and is rarely used [1]. It is intended to (Artemisia argyi) and America (Artemisia douglasiana). stimulate gastric secretions in patients with poor appetite, This plant may have been transported throughout the is used against flatulence, distention, colic, diarrhea, consti- world by early humans who needed it for its medicinal pation, cramps, worm infestations, hysteria, epilepsy, vom- and food value. It can be easily transported as seeds. The iting, menstrual problems, irregular periods, to promote meaning of mugwort may be marsh root since it grows circulation and as a sedative. This sedative effect may be near permanent sources of water. In Chinese, mugwort is responsible for internet reports of the use of A. vulgaris lou hao. In Chumash Indian, mugwort is molush. The to induce dreams. The root has different uses, as a tonic, scientific name Artemisia comes from Artemis, Greek for psychoneuroses, neurasthenia, depression, autonomic Goddess of the hunt, wild animals, wilderness, childbirth neuroses, irritability, restlessness, insomnia and anxiety. and virginity. Artemis is capable of bringing or relieving A. vulgaris is described as an abortifacient without dis- disease in women. cussion of the preparation used [1]. The three species of mugwort differ somewhat in ap- The plant contains many active compounds including pearance, perhaps the result of growing in different habi- the monoterpenes, eucalyptol, camphor, linalool, thujone, tats for thousands of years. Mugwort is easy to grow 4-terpineol, borneol, α-cadinol, spathulenol and 21 others from seeds and likes shade. The perennial plants grow to [1]. These monoterpenes are present in the essential oil 2.5 meters high and have variably lobed oblanceolate that makes up 0.03% - 0.3% of the plant. The plant also leaves with 1 to 7 lobes. The leaves can be up to 15 cm contains sesquiterpenes and sesquiterpene lactones such long, are green on top and white, tomentose on the un- as eudesmane, vulgarin, psilostachyin and psilostachyin derside. The stem and roots are woody. The flowers grow C [1]. Flavonol glycosides are present including quercitin in panicles as small disciform heads, less than 5 mm in 3-O-glucoside, rutin and isorhamnetin 3-O-glucoside [1]. diameter, contain 5 - 9 pistillate flowers and 6 - 25 disk Coumarins are found such as aesculetin, aesculin, um- flowers. belliferone, scopoletin, coumarin and 6-methoxy-7,8- Copyright © 2012 SciRes. CM J. D. ADAMS ET AL. 117 methylene-dioxycoumarin [1]. Polyacetylenes, carote- reported to have strong anti-inflammatory activity and is noids and pentacyclic triterpenes are present such as si- topically active [15]. In other words, it penetrates the tosterol and stigmasterol [1]. skin after topical administration and relieves inflammation. The mechanism of anti-inflammatory action of a 3. Pharmacology of Artemisia Plants sesquiterpene, 7-hydroxyfrullanolide, appears to be inhibition of an NF-κB pathway [16]. IKKβ phosphorylation Many monoterpenoids are pain and anxiety relievers due was shown to be inhibited by 7-hydroxyfrullanolide, to inhibition of transient receptor potential cation chan- which resulted in inhibition of NF-κB translocation into nels [2]. These channels are found on sensory afferent the nucleus. Several sesquiterpenes inhibit the production neurons of the skin and are usually responsive to heat or of inflammatory cytokines and adipokines. 7-Hydroxy- cold. They are also found in the brain, spinal cord and frullanolide inhibits the production of inflammatory ad- lungs [2]. The involvement of the brain transient receptor hesion proteins such as ICAM-1, VCAM-1 and E-se- potential channels in anxiety has not been investigated. lectin [16]. This inhibits monocyte induced inflammation. Most of these channels have six transmembrane spanning Patchouli alcohol, a tricyclic sequiterpene, inhibits tumor units and large intracellular amino and carboxy terminal necrosis factor-α, IL-1β (interleukin-1β), cyclooxyge- portions [2]. Most of them allow sodium and calcium to nase-2, and iNOS production [17]. This results in less enter the cell. The vanilloid receptors (TRPV) have NO and PGE2 production, less inflammation and less amino terminal ankyrin repeat domains and a carboxy edema. Parthenolide, a sesquiterpene lactone present in terminal TRP box. The TRPA channels (ankyrin) have several plants, inhibits inflammation in the brain and many ankyrin repeats in the amino terminal. The TRPM other organs by decreasing IL-6, tumor necrosis factor-α channels (melastatin) have a TRP box in the carboxy ter- and cyclooxygenase-2 production [18]. This results in minal. Several drugs are available that act on these chan- lowered body temperature and occurs through an NF-κB nels, such as capsaicin (TRPV1) and menthol (TRPM8). inhibition mechanism. NF-κB activation is inhibited, More than a dozen drug candidates are in clinical trials especially in the hypothalamus. Alpha-bisabolol is an- that act on these channels to relieve pain. Typically an other anti-inflammatory sesquiterpene that is found in agonist at these channels causes transient channel open- several plants. Alpha-bisabolol has been shown to de- ing that is followed by long term channel closing and crease iNOS and cyclooxygenase-2 production by inhib- pain relief [2]. iting NF-κB activation [19]. A plant used by Native Several monoterpenoids have reported pain relieving Americans, Eupatorium perfoliatum, has been found to activity such as camphor [3-5], eucalyptol [4-6, also be anti-inflammatory due to the presence of sesquiter- called 1,8-cineole], camphene [4,5], β-pinene [4-6], bor- penes [20]. A structure-activity study of 26 sesquiterpene neol [4,5,7] and thujone [8]. Most of the pain relieving lactones was conducted to elucidate the structural re- monoterpenoids found in A. vulgaris are agonists for quirements for inhibition of iNOS production and found TRPV3 (heat sensing) including camphor [3,9,10], bor- potent inhibition down to micromolar levels [21]. This neol, thujone and eucalyptol [10]. Camphor is also an clearly indicates that sesquiterpenes are very useful antagonist for the TRPA1 (TRP ankyrin-repeat1, cold- anti-inflammatory and fever decreasing agents that have sensitive) receptor and an agonist for the TRPV1 (heat- been used for centuries in plant medicines around the sensitive) receptor [3]. Eucalyptol has been shown to also world. be a TRPM8 (cold-sensitive) receptor agonist and to ex- Flavonols can be anti-inflammatory agents. For inhibit an antinociceptive activity comparable to or greater stance, women who have higher intake of flavonol rich than that of morphine [11]. foods, especially citrus fruits, have lower blood levels of Some monoterpenoids have reported anti-inflamma- inflammatory proteins, including VCAM, C-reactive pro- tory properties such as camphene and β-pinene [12,13]. tein, soluble tumor necrosis factor receptor-2 and IL-18 The monoterpene, borneol has been shown to have high [22]. Kaempferol, kaempferol anti-inflammatory activity [14], which results from the 3-O-alpha-L-rhamnopyranosyl-(1-6)-beta-D-glucopyrano inhibition of nitric oxide (NO) and prostaglandin E2 side and quercetin 3-O-alpha-L-rhamnopyranosyl-(1-6)- (PGE2) production due to inhibition of NF-κB activation beta-D-glucopyranoside have been found to be anti-in- (nuclear factor κB). The NF-κB mechanism involves flammatory agents and can be topically active in paw increasing the expression of IKK (inhibitor of NF-κB edema tests [23]. These flavonols inhibit production of kinase), iNOS (inducible nitric oxide synthase) and de- iNOS [23]. Some flavonols, such as papyriflavonol A, creasing IκBα (inhibitor of NF-κBα) expression in are phospholipase A2 inhibitors and potently inhibit the dose-dependent manners [13,14]. enzyme with IC50 values of 4 micromolar [24]. Inhibi- Some sesquiterpenoids are anti-inflammatory agents tion of phospholipase A2 decreases leukotriene C4 pro- [12]. In fact, a sesquiterpene from Artemisia pallens is duction, decreases allergic reactions and results in

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