Fresh or dried, previously peeled, rhizomes of the Ginger species Zingiber officinale Roscoe are used.

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1 Ginger-Eco BOTANY Zingiber officinale Roscoe; Amomum zingiber L. It is one of the best-known species since ancient times, widely used in China and India. Although the wild species has not been found, it is believed to come originally from Malaysia, India, Sri Lanka and Indonesia. Zingiber officinale is a plant with an erect appearance, whose annual stalk is covered by an imbricated membranous sheath and reaches a variable height between 0.60 and 1.50 m. The plant grows on a thick short rhizome. Scaly leaves and bears cylindrical adventitious roots at its bottom part cover the rhizome. The rhizome has several horizontal ramifications bearing palmate fleshy tubers, which eventually become fibrous. This plant s aerial branches are annually renewed. Tall stalks (1.50 m) serve assimilation and short ones (20 cm) serve reproduction. Fresh or dried, previously peeled, rhizomes of the Ginger species Zingiber officinale Roscoe are used. Ginger is grown mainly in tropical and subtropical areas where temperature and humidity are high. The harvest takes place when the aerial parts turn yellow and begin to dry up, just after flowering, some 8-10 months after sowing and before the rhizomes become fibrous and hard. V02-11/

2 CHEMISTRY The most important compounds, responsible for Ginger s therapeutic activity, are grouped into nonvolatile and volatile compounds. Non-volatile compounds The non-volatile fraction consists of an oleoresin ( %). When extraction with dissolvent is performed on this fraction, pungent elements, non-pungent elements and an essential oil fraction are obtained. Those elements responsible for Ginger s spicy flavour and partly responsible for its numerous beneficial actions have been identified as 1-(3 -methoxy-4 -hydroxyphenyl)-5-hydroxyalkan-3-ones, also known as the Gingerols group, which bear a lateral chain of variable length. In relation to these chains, the isolated and identified Gingerols have been named [3]-, [4]-, [5]-, [6]-, [8]- and [10]-Gingerol. More pungent but present in lower concentrations are the shogaols (phenylalkanones), products coming from dehydration of Gingerol, whose concentration increases during the drying process and the storing. Other pungent elements, though present in lower proportion, are gingediols, gingediacetates, Gingerdione and Gingerenones. Volatile compounds The composition of the volatile fraction consists mainly of the sesquiterpene derivatives (>50%), responsible for the aroma, whose concentration seems to keep constant. Such compounds include (-)- zingiberene (20-30%), (+)-ar-curcumene (6-19%), (-)--sesquiphelandrene (7-12%) and -bisabolene (5-12%). Figure 1: Bisabolene The monoterpene derivatives are also a part of this essential oil, though in lower proportion. Among the ones, characteristic of Ginger, that have been isolated, we can mention -pinene, bornyl acetate, borneol, camphene, -cymene, cineol, citral, cumene, -elemene, farnesene, -phelandrene, geraniol, limonene, linalol, myrcene, -pinene and sabinene. V02-11/

3 Fraction Non volatile Compounds gingerols, shogaols, gingediols, gingediacetates, gingerdiones, gingerenones. Volatile (-)-zingiberene, (+)-ar-curcumene, (-)--sesquiphelandrene, -bisabolene, -pinene, bornyl acetate, borneol, camphene, -cymene, cineol, citral, cumene, -elemene, farnesene, -phelandrene, geraniol, limonene, linalol, myrcene, -pinene, sabinene. TRADITIONAL USES Its beneficial properties have been appreciated for centuries and mentioned already by the Chinese philosopher Confucius ( BC), by Dioscorides and by the Koran. The rhizome, which has been used dried as a spice or as a pickle for thousands of years in China, was most wanted in Europe during the middle Ages. In the oriental countries it is considered an essential of the daily diet to prevent illness and boost digestion. Ginger has traditionally been used as external application to treat osteoarticular inflammation, myalgia, muscle spasms, neuralgia and odontalgia. COSMETIC PROPERTIES Ginger s activity is mainly based on its action on the arachidonic acid pathway, resulting in several actions such as anti-inflammatory, analgesic, antipyretic and anti-platelet ones. It acts also as an antioxidant, antibacterial and on the immune system. Activity on Arachidonic acid pathway Eicosanoids (prostaglandins, tromboxanes, prostacyclins, leucotrienes.) are involved in numerous basic physiologic processes at the cellular level and in most cases the involved substrate is the arachidonic acid, which is metabolised in two pathways: The cyclooxygenase pathway: produces prostaglandins, prostacyclins and tromboxanes. The lipooxygenase pathway: produces HPETE, HETE, leucotrienes and lipoxins. Anti-inflammatory effects of Ginger have been evaluated on a carragenin 1% induced inflammation. The obtained results show that such an effect is directly related to the administered dose and it has been observed to have a similar activity to that of acetyl salicylic acid. The action mechanism is based on an inhibitory effect on the prostaglandin biosynthesis (Mascolo et al. 1989). Several studies have been performed to find the active principles responsible for the anti-inflammatory activity. On the one hand, it was in vitro observed that Gingerdione inhibited the production of 5-HETE (leucotrienes) and PGE 2. Additionally, it was proved that shogaol inhibited the production of 5- HETE (leucotrienes). Gingerol, as well as dehydroparadol, favoured the cyclooxygenase inhibition. It was also demonstrated that Ginger was a potent inhibitor of the prostaglandin synthesis, even stronger than indometacin. On the other hand, it was in vivo observed tat Ginger acted by inhibiting the prostaglandin synthesis and the production of free radicals during metabolism of the arachidonic acid (Mustafa et al. 1993). V02-11/

4 It has been proved that [6]-Gingerol, [6]- and [8]-Gingerdiones and [6]- and [8]-dihydroGingerdiones inhibit the prostaglandin biosynthesis as a decrement in the release of arachidonic acid, prostaglandins and leucotrienes was observed (Rosella et al. 1996). Subsequently, such an activity has been demonstrated in vitro as well as in vivo (Wendell 1998). In vitro studies have demonstrated that the water extract of Ginger inhibits the enzymatic activity of cyclooxygenase and lipooxygenase in the arachidonic acid pathway, therefore decreasing the production of prostaglandins and leucotrienes. It has also been observed to inhibit the tromboxane-synthase, thus increasing the levels of prostacyclins without increasing the levels of prostaglandins E 2 o F 2. Recently, it has been observed that two labdanum-diterpene like dialdehides isolated from Ginger extracts act as in vitro inhibitors of the human 5-lipooxygenase (WHO, 1999). Antioxidant activity Nakatani observed in 1992 that pungent compounds such as [6]-Gingerol and [6]-shogaol have a moderated antioxydant activity. It had been demonstrated that the non volatile Ginger fraction (Gingerols, shogaols and diarylheptanoids (Gingerenones) had an antioxidant activity at concentrations as low as 4 M. Some years later, Gingerols and its analogs were considered natural antioxidants. They annulated the activity of free radicals and they turned into more simple and harmless compounds (Rosella et al. 1996). Finally, water and alcohol Ginger extracts were evaluated and it was found that they protect against lipidic peroxydation (Combest 1998). Antibacterial activity Antibacterial activity has been evaluated against Gram-positive (Bacillus subtilis, B. Anthracis, Staphylococcus aureus, S.epidermidis and S. haemolyticus) and Gram-negative (Escherichia coli 7075, E. coli Bb, Proteus mirabilis, Salmonella typhi H and Pseudomonas aeruginosa) bacteria, showing inhibitory effects on the growth of microbial flora, although weaker than that of the controls (gentamycin, tetracyclin) (Mascolo N, et al. 1989). Wendell, in 1998, confirmed these results recommending its extensive use in treatments of parasitic infection. Activity on the immune system On the basis of the traditional use of Ginger as a stimulator of the immune system, Chang et al. 1995, evaluated the effects of an ethanol Ginger extraction on mononuclear blood cells by measuring the cytokines levels in order to understand the Ginger s action mechanism. The results showed that using low Ginger extract concentrations (10-30 mg/ml) a clear cytokines secretion increment was observed. Additionally, the stimulatory effect was observed to occur mainly for 18-24h and it was therefore deduced that the Ginger extract could stimulate mononuclear blood cells yielding by-products such as messager RNA, which would act by increasing the cytokines in a longer term. V02-11/

5 EFFICACY TEST Enzymatic inhibition Collagen is the main structural protein of skin, constituting about the 90% of proteins in the dermis. Skin aging is linked to deep functional alterations of these protein fibers. Collagenase is an enzyme abundantly located in skin. Its main function is to catalyse the collagen degradation. Collagenase inhibition will therefore allow maintaining protein levels and skinning flexibility. One of the methods used for the evaluation of an anti-aging product efficacy is to determine its capacity to inhibit collagenase. An assay to measure collagenase inhibition by GINGER-ECO was performed. 1. Experimental method The substrate (collagen) degradation reaction starts when it is incubated with the enzyme (collagenase from Clostridium histolycum type I-A) and with the tested substances in a bath at 37ºC. The final GINGER-ECO concentration in medium was 0.5%. After 5 hours, determination of L-leucine was performed by Ninhydrin staining and lecture at 600 nm. Buffer TES 0.05 M ph=7,5 was used as a negative control. 1,10-phenanthroline and dithiothreitol at a final 0.5 M concentration in assay medium were used as positive controls. Maximum absorbance was obtained for those tubes treated with the negative control. The collagenase inhibition would generate less L-leucine residues and therefore a lower absorbance value. 2. Results The following graphic shows the inhibition percentages calculated in relation to the negative control. % Collagenase inhibition , GINGER-ECO 5% Phenanthroline 0.5 um Dithiothreitol 0,5 um As shown in the graphic, GINGER-ECO exhibits a 100% collagenase inhibitory activity and therefore is able to totally inhibit collagen degradation, which results in beneficial effects for the skin, such as maintenance of elasticity. V02-11/

6 COSMETIC APPLICATIONS SKIN CARE treatments: rejuvenating and anti-ageing. BODY CARE treatments: refirming, modelling of silhouette, energizing and stimulant. Products for massages with soothing and muscle relaxing properties. HAIR CARE treatments: anti-dandruff. RECOMMENDED DOSE % BIBLIOGRAPHY Charles R, et al. New gingerdione from the rhizomes of Zingiber officinale. Fitoterapia 2000;71: WHO Monographs on selected medicinal plants. Volume 1.World Health Organization, 1999; Combest WL. Ginger. Pharmacist 1998; 2: (ref.3664) Teske M, et al. Herbarium Compêndio de Fitoterapia. Curitiba:Herbarium Laboratório Botänico Ltda., 1997; Muller JL. Pharmaceutical considerations of common herbal medicine. The American Journal of Managed Care 1997; 3(11): (ref.3666) Zingiberis Rhizoma. ESCOP Monographs Fascicule 1. ESCOP, March Rosella MA, et al. Jengibre (Zingiber officinales Roscoe, Zingiberaceae): Etnofarmacognosia, cultivo, composición química y farmacología. Acta Farmm Bonaerense 1996; 15(1): (ref. 3660) Pérez JL, et al. Acción estimulante del extracto fluido del Zingiber officinales Rosc. (Jengibre). Rev. Cubana Plant Med 1996; 1(1):42-45 Chang CP, et al. The effect of chinese medicinal herba Zingiberis rizhoma extract on cytokine secretion by human peripherical blood mononuclear cells. Journal of Ethnopahrmacology 1995; 48: (ref. 3656) Grauds R. Ginger (Zingiber officinale). Pharmacy Times 1995; 11: 50. (ref.3665) Guh JH, et al. J. Pharm. Pharmacol 1995; 47: (ref. 59) Mustafa T, et al. Drug development report (9): Pharmacology of ginger, Zingiber officinale. Drug Dev 1993; 6(1): (ref.3663) Nakatani N. Natural antioxidants from spices. 1992:73-85.(ref.709) British Herbal Compendium. Volume 1. BHMA, 1992; Kikuzaki H, et al. Gingerdiol related compounds from the rhizomes of Zingiber officinale- Phtytochemistry 1992; 31(5): (ref. 3658) Nakatani N. Natural antioxidants from spices. 1992:73-85.(ref.709) Kikuzaki H, et al. Diaarylheptanoids from the rhizomes of Zingiber officinale- Phtytochemistry 1991; 30(11): (ref. 3659) Mascolo N, et al. Ethnopharmacologic investigation of Ginger (Zingiber officinale). Journal of Ethnopharmacology 1989; 27: (ref.3657) V02-11/