博士 / 國立臺灣大學 / 藥學研究所 / 90 / The purpose of this thesis was the development of novel non-steroidal inhibitors against 5a-reductase for the treatment of benign prostatic hyperplasia due to the disorder of dihydrotestosterone. There were three parts in the thesis: (i), the study was to synthesize compounds according to the concept of bioisosterism in which the amide bond of ONO3805 was replaced by the 1,2,4-oxadiazole moiety. Four synthesized 1,2,4-oxadiazole derivatives 4-[2-[5-[4-[1-(4-isobutylphenyl)ethoxy]-2,3-dimethylphenyl]-[1,2,4]oxadiazol-3-yl]phenoxy] butanoic acid (1), 4-[2-[3-[4-[1-(isobutylphenyl)ethoxy]-2,3-dimethylphenyl]-[1,2,4]oxadiazol-5-yl]phenoxy]butyric acid (2), 4-[2-[5-[4-[1-(4-isobutylphenyl) ethoxy]-2,3-dimethylphenyl]-[1,2,4]oxadiazol-3-yl]phenoxy]butanoic acid ethyl ester (19), and 2-[3-[3-[4-[1-(isobutylphenyl)ethoxy]-2,3-dimethylphenyl]-[1,2,4]-oxadiazol-5-yl]propoxy] benzoic acid (34) were evaluated in vitro against 5a-reductase of rat liver microsome. Targets 1 and 2 possessed similar binding affinity to that of ONO3805. These results successfully demonstrated the use of 1,2,4-oxadiazole ring as surrogate of the amide bond in ONO3805. It leads not only to enhance chemical stability but also to maintain meaningful inhibitory activity. The butyric acid moiety of these inhibitors is considered to play an important role to mimic the phosphoric acid portion of the coenzyme-NADPH in interacting with the active site of 5a-reductase. (ii), the crystal structure of 5a-reductase is not available due to the fact that it is a membrane-associated enzyme. Therefore, the direct structure-based drug design approach is impossible in this case. Consequently, we generated hypothetical pharmacophore by the Catalyst program. It provided a ligand template for 3D database search and facilitated the lead compound discovery. Employing the pharmacophore, eight isoflavone derivatives were characterized as novel potential non-steroidal inhibitors (7-49 mM). This investigation has demonstrated a practical approach toward the development of lead compounds through hypothetic pharmacophore via 3D database searching. (iii), on the basis of some isoflavonoidal extracts as phytotherapeutic agents, we were promoted to explore the potentiality of isoflavone derivatives as the 5a-reductase inhibitors. According to our hypothetic pharmacophore of 5a-reductase, we designed and synthesized a series of isoflavone derivatives to fit the five features. Since our pharmacophore, at this stage, cannot illustrate the hydrophobic group which was designed to mimic the steroid role, we still kept a lipophilic group at the 4’ position of the isoflavone skeleton. In general, two synthetic procedures were employed in this study. For the 7-alkoxy substituted isoflavone derivatives, the 7-hydroxy isoflavone core was built first, and it was then alkylated. However, for the 7-benzyl substituted derivatives, it is necessary to complete the side chain preparations at the beginning to form deoxybenzoin which was then cyclized to afford the target compounds.

EVALUATION OF PHYTOCHEMICAL COMPOSITION OF PLANTS OF GENUS HAWTHORN (CRATAEGUS L.) GROWING IN LITHUANIA INTRODUCTION For the last fifteen years, the attention of doctors and their patients on drugs and food supplements of herbal origin has been continuously increasing. The growing interest in raw plant materials is expanding the possibilities of use of these materials in the industries of medicine, cosmetics and food as well as encouraging assessment and description of natural resources using new modern methods. Scientific research on natural herbal resources has bee receiving special attention in the European Union. In recent years, a number of important documents have been published in the European Union, which declare the aims of ensuring the use and quality of natural herbal resources, such as Good Agricultural Practice document, Points to consider on Good agricultural and collection practice for starting materials of herbal origin, a long term vision of the future of herbal biotechnology in Europe Plants for the Future. Cardiovascular system diseases constitute one of the most urgent health problems. The range of effective herbal preparations for the target phytotherapy of cardiovascular system diseases is not wide. Hawthorn preparations are a promising drug for the treatment of cardiovascular system diseases, whose pharmacological effects have been substantiated by scientific studies. Throughout the territory of Lithuania, three kinds of hawthorn can be found growing... [to full text]

Dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Homoeopathy, Durban University of Technology, 2012. / INTRODUCTION Attention-Deficit/Hyperactivity Disorder (ADD/ADHD) is a multifactorial and clinically heterogeneous disorder that is associated with tremendous financial burden, stress to families and adverse academic and vocational outcomes (Bierderman, 2005). ADD/ADHD is currently one of the most researched childhood conditions, yet there is still much controversy and misunderstanding surrounding it. It is also one of the most commonly diagnosed disorders of childhood development (Picton, 2005) and the prevalence of this disorder in adults is increasingly recognized (Bierderman, 2005). Parents are seeking alternatives, as they are concerned with the side effects of Methylphenidate hydrochloride and other conventional medication used to treat the symptoms of ADD/ADHD. AIM The aim of this research was to document the current practices of registered homoeopathic practitioners, with regard to ADD/ADHD. In addition, their perceptions regarding aetiology, treatment, management and success rate was investigated. This research took the form of a qualitative survey targeting homoeopaths practicing within the KwaZulu- Natal region. METHOD A total of 42 practitioners were contacted, 35 practitioners initially agreed to participate in the study, and the questionnaires were electronically sent to them via email. Of these 35 homoeopaths, 22 participated in the survey, i.e. giving an overall response rate of 62 percent. The questionnaires were electronically distributed and collected via email. The raw data was coded and captured by Google docs and the results were analysed by utilizing the SPSS for Windows version 18 SPSS/PASW 2009. RESULTS The majority of the responding homoeopaths practiced in the more urban areas of KwaZulu-Natal, more specifically within the eThekwini Durban area. The majority of these homoeopaths had qualified from the Durban University of Technology, were English speaking females and were between the ages of 25-35 years old. The homoeopaths within this study found that most patients who present with ADD/ADHD symptoms are previously diagnosed by paediatrician’s neurologists or psychologists. According to the homoeopaths participating in the study, the general consensus is that the diagnosis of ADD/ADHD is given far too easily, and without proper assessment, 86 percent of the homoeopaths are of the opinion that ADD/ADHD is misdiagnosed, and ninety one percent stated that ADD/ADHD is over diagnosed. The majority of the practitioners prescribe a simplex remedy, or the Simillimum, whereas only a few practitioners prescribe a complex remedy. It was found that the most common complex prescribed is Nervoheel®. Some practitioners prefer to make up their own complexes, which would be patient specific. In this study it was found that 68 percent of the practitioners reported the sycotic miasm to be most common, and 54 percent of the practitioners reported the tubercular miasm to be the second most common presenting miasm. The homoeopaths in this study stated that they prefer to use a holistic approach to obtain optimal well being, thus advice, lifestyle adjustments, education and counselling all form part of the treatment and management of a patient with ADD/ADHD, making it unique and specific to each case. Of the adjunctive therapies, Vitamins, supplements, and nutritional changes are recommended, especially if a deficiency has been identified. The most commonly prescribed supplements for ADD/ADHD are the Essential Fatty Acids (EFA’s) followed by Vitamin B Complexes, Multi-vitamins and Magnesium, Zinc, and Calcium. CONCLUSION The majority of the homoeopaths in this study reported that they are having a moderate to great success in treating and managing patients with ADD/ADHD. Many of these practitioners thought there to be no single cause for ADD/ADHD, however many of them found there to be a few significant contributing factors to the development or aetiology of ADD/ADHD. These factors include; genetics, environment, diet, vaccinations and family dynamics. The majority of the practitioners believe that ADD/ADHD is far too easily diagnosed and that further assessment of the mental, emotional, and physical symptoms of the patient need to be taken into consideration. The majority of the homoeopaths in this study prefer to use Simplex treatment, and consider diet, lifestyle changes, and phytotherapy the most successful adjunctive therapies when treating and managing a patient with ADD/ADHD. Many of the practitioners within this study reported that homoeopathy should be considered a primary treatment option for patients with ADD/ADHD, as the focus of the treatment is on determining the cause of the symptoms, and then managing the patient as a whole, focusing on changing the diet, altering the lifestyle, and treating the totality of the mental, emotional and physical symptoms.

Le diabète est reconnu comme un problème majeur de santé publique causant des conséquences humaines et économiques redoutables. La phytothérapie s’offre comme une nouvelle avenue thérapeutique pour le contrôle de la glycémie. Le grenadier, Punica granatum, a servi de remède contre le diabète dans le système Unani de la médecine pratiquée en Inde et au Moyen Orient. Des études ont démontré un effet hypoglycémiant des extraits de grenadier via divers mécanismes notamment par une amélioration de la sensibilité à l’insuline et la régénération des cellules béta-pancréatiques. Cependant, aucune étude n’a démontré à ce jour, l’effet de grenadier sur le transport de glucose dans le muscle, étape cruciale dans la régulation de l’homéostasie glucidique postprandiale. De plus, l’effet de la maturation sur le potentiel antidiabétique du fruit de grenadier n’a pas été étudié. Ainsi, le but de ce projet est d’évaluer l’effet antidiabétique des extraits de grenadier sur le transport de glucose dans les cellules musculaires C2C12 en fonction de la variété et du stade de maturation du fruit et d’élucider les mécanismes d’action. Le choix des variétés du grenadier tunisien (Espagnoule [EP] et Gabsi [GB]) a été orienté pour leur pouvoir antioxydant et leur consommation locale. Deux parties de la plante ont été utilisées, les fleurs et les fruits à 3 stades de maturation soit 2, 4 et 6 mois. Les résultats ont montré que seule la variété du grenadier Gabsi stimule significativement le transport de glucose par rapport au contrôle (DMSO), et ceci sans être toxique. Cet effet est plus prononcé au stade de fruit mûr (à 6 mois) que celui de la fleur. De plus, l’extrait de fleurs stimule la voie insulino-indépendante de l’AMPK et augmente le niveau d’expression des transporteurs spécifiques de glucose (GLUT-4). Par contre, l’extrait de fruits mûrs, en plus de ces deux mécanismes, active fortement aussi la voie insulino-dépendante de l’AKT. En conclusion, cette étude présente un nouveau mécanisme d’action antidiabétique de grenadier (plus particulièrement du fruit mûr) qui est dépendant de la variété. / Diabetes is a major public health problem worldwide with astounding human and economic consequences. The seed and the flower of pomegranate (Punica granatum), a native plant of Central Asia and the Mediterranean regions, exhibited a hypoglycaemic effect in in vivo studies. However, the underlying mechanisms have not yet been elucidated. The aim of this project was to evaluate the effect of the flower and the fruit (at 3 maturation stages) of pomegranate on glucose transport in skeletal muscle cells and to determine the molecular mechanisms involved in this effect. To accomplish this, we chose two varieties of pomegranate cultivated in Tunisia (Gabsi [GB] and Espagnoule [EP]), which have been shown to be highly consumed in that area and to possess high antioxidant activity. Differentiated C2C12 cells were treated for 18 hours with 80% ethanolic extract of the flowers and fruits (at 2, 4, and 6 months) of each variety. Our results showed that the Gabsi variety of pomegranate significantly enhances glucose uptake, without any toxicity. This effect is more pronounced in the ripe fruit (6 months) than in the flower. In parallel, the ripe fruit stimulated both the insulin-dependent pathway (Akt) and the insulin-independent pathway (AMPK), while the flower stimulated the latter only. In addition, both flower and ripe fruit treatment resulted in enhanced expression level of GLUT-4 glucose transporter in the muscle. Hence, these results suggest that regulation of glucose transport in skeletal muscle is one of the components involved in the anti-diabetic effect of Tunisian pomegranate.

1. GENERAL CHARACTERICTICS OF THE WORK First drugs were of herbal origin. Today, preparations of this kind are highly appreciated. Social and economic changes have been influencing public health. The rhythm of life and nervous strain have negative effects on the human body. Many ailments are caused by emotional variations. Illnesses of the nervous system and related disorders of the digestive system raise an important concern nowadays. The potential of phytopreparations in the treatment of such ailments is capable of completing the gaps of their treatment. Phytopreparations can be used for treatment for an extensive period of time. Critics of phytotherapy can argue that existence of modern synthetic medicine supersedes phytopreparations. It must be noted, though, that this medicine is effective and easily digested. It does not compete with, but only complements pharmacotherapy. Phytopreparations are often used in the treatment of chronic disorders of the digestive system such as higher sensitivity, atony, ailments of bile bladder and duct. Functional disorders of intestine cause diarrhea, spasmodic pains, stomach rumble, and loose bowels. In case of functional stomach and intestine disorders, treatment with sedative and peristalsis regulating medicine is applied in addition to a rational daily routine and diet. Digestive disorders are well eliminated with the help of herbal drugs. At present, medicinal herbs and preparations from herbal materials have been receiving a lot of... [to full text]

Fitoterapija (gr. phyton – augalas, therapeia – gydymas) – tai ligų profilaktika ir gydymas, vartojant augalų dalis ar jų preparatus. Nuo seno lietuvių liaudies medicinoje gerai žinomi sidabražolinių (Potentilla) genties augalai. Lietuvoje auga 17 Potentilla genties augalų rūšių, kai kurios iš jų kultūrinės. Šio darbo tikslas yra atlikti biologiškai veiklių medžiagų – flavonoidų ir raugų – išskyrimą iš Potentilla genties augalų (Potentilla anserina L., Potentilla erecta L., Potentilla fruticosa L.) nustatyti veikliųjų medžiagų kiekio kitimus skirtingu augalų vegetacijos metu (birželio – rugsėjo mėnesiais) ir atlikti šių augalinių žaliavų antioksidacinio bei antimikrobinio poveikio tyrimus. Tyrimo medžiaga ir metodai. Tyrime naudota Potentilla genties augalinė žaliava surinkta Šiaulių rajone, Gruzdžių miške (P.anserina žolė, P.erecta šakniastiebiai ir žolė) bei Šiaulių universiteto botanikos sode (P.fruticosa žolė). Permanganatometrinio titravimo metodu buvo nustatytas rauginių medžiagų kiekis tirtuose Potentilla genties augalinėse žaliavose. Naudojant parūgštintą vandenilio chlorido rūgštimi 70% etanolį ir 70% etanolį spektrofotometriniu ir efektyviosios skysčių chromatografijos (ESC) metodu buvo nustatyti bendri flavonoidų kiekiai tirtose augalinėse žaliavose. Antioksidaciniam aktyvumui įvertinti buvo taikomas fotometrinis 2,2-difenil-1-pikrilhidrazilo (DPPH•) laisvojo radikalo sujungimo metodas. Antimikrobinis poveikis įvertintas atliekant tyrimus su triptozės sojos agare 2... [toliau žr. visą tekstą] / Phytotherapy (Greek origin phyton – plant, therapeia – treatment) means the prevention of disease and medical treatment using parts of plants or their extracts. Since ancient times Cinquefoil (Potentilla) family plants have been well-known in Lithuanian non-traditional medicine, comprising over 17 species, some of them are cultivated. Aims and Objectives. To extract biologically active substances – flavonoids and tannins – from Potentilla plants (Potentilla anserina L., Potentilla erecta L., Potentilla fruticosa L.) in order to determine the quantity changes at different times of plant vegetation (June – September), and to research antioxidant and antibacterial effect of those plants. Materials and Methods. Potentilla raw material was collected in the region of Šiauliai, Gruzdžiai forest (Herba Potentillae anserinae, Rhizoma et herba Potentillae erectae) and Šiauliai University Botanical Garden (Folium cum flore Potentillae fruticosae). Permanganatometric titration method was used to find out how much tannin the selected Potentilla contained. Also, spectrophotometric and HPLC methods allowed to measure flavonoid while using 70% of ethanol with hydrochloric acid and 70% of ethanol in the raw vegetation. To evaluate the anti-oxidizing activity photometric 2,2-difenil-1-pikrilhydrosil (DPPH•) free radical method was applied. Antibacterial impact was evaluated with triptosis on soya crop in a hangar for 24 hours at 35 - 37º C using cultivated microorganisms. Results. The tested... [to full text]

In natural dendroflora of Lithuania willow genus (Salix L.) is abundant in species amount. Its bark contains active materials which are known as possessing anti-inflammatory properties since former times. Bark extracts are contained in analgesic as well as antirheumatic preparations. Its therapeutic effectiveness is associated with salicine which turns into salicylic acid. Willow bark is a know phytotherapeutic precursor of aspirin. To use more natural and not synthetic materials in the 21st century the methods for extraction of active materials for medicine are being sought. Thus, the studies on plant groups possessing the most intense anti-inflammatory properties became urgent. The amount of salicin varies among different species. Acording to the European Pharmacopoea, minimal amount of 1,5% of salicin is required in Willow bark. The aim of the study was to investigate salicylates amount variation in willow bark of different Salix species growing in Lithuania. The studies were carried out using the routine methods of pharmacopeia. After extraction analysis was performed by high performance liquid chromatography (HPLC) method. The first step of study was made among 3 samples of each plant, colected at different growing period (1-st year autumn, 2-nd year autumn and 2-nd year spring). Comparison of the quantities of the salicylic derivatives depending upon age of the plant and time of collection shows, that plants at two years of growth and collected in autumn accumulate... [to full text] / Natūralioje Lietuvos floroje gluosnių (Salix L.) rūšys yra plačiai paplitusios. Gluosnio žievė – nuo seno žinoma kaip priešuždegiminiu poveikiu pasižyminti vaistinė augalinė žaliava. Jos ekstraktai įeina į priešreumatinių ir analgezinių preparatų sudėtį. Terapinis veikimas yra susijęs su salicinu, kuris organizme virsta salicilo rūgštimi. Gluosnio žievė yra fitoterapinis aspirino pirmtakas. XXI amžiuje vis didesnis dėmesys krypsta į natūralius, o ne sintetinius preparatus. Tokiu būdu, augalų, pasižyminčių terapinėmis savybėmis tyrimai įgyja didelę reikšmę. Skirtingų rūšių gluosnių žievėje, kaupiamas salicino kiekis skiriasi. Europos farmakopėjoje reglamentuojamas minimalus salicino kiekis yra 1,5%. Šio tyrimo tikslas buvo Ištirti Lietuvoje augančių gluosnio rūšių salicilatų kiekio įvairavimą vaistinėje augalinėje žaliavoje (žievėje). Darbo uždaviniai- atlikti įvairių Lietuvoje augančių gluosnio rūšių salicilatų kiekio analizę, palyginti salicilatų kiekį gluosnio žievėje, atsižvelgiant į augalo amžių bei rinkimo laiką bei įvertinti gautus rezultatus, numatomą terapinį veikimą. Tyrimai atlikti naudojant farmakopėjinius analizės metodus. Žievės ekstraktai buvo tiriami efektyviosios skysčių chromatografijos metodu.Šio tyrimo pirmo etapo metu išanalizuota 12 gluosnių taksonų. Buvo ištirti vienerių ir dviejų metų, taip pat pavasarį ir rudenį rinkti žievės pavyzdžiai. Didesni kiekiai aktyvių medžiagų rasta rudenį ir 2 metų amžiaus gluosnių žievės pavyzdžiuose. Antrajame tyrimo... [toliau žr. visą tekstą]

Fenolinės rūgštys ir fenilpropanoidai pasižymi reikšmingu biologiniu aktyvumu ir yra vaistinių žaliavų veiklieji komponentai. Įteisintų tyrimo metodikų vystymas šių junginių nustatymui (kokybiniam ir kiekybiniam žaliavų tyrimui) yra ypač svarbus augalinių vaistinių preparatų efektyvumo, saugumo ir kokybės kontrolei. Iš skirtingų Lietuvos regionų buvo surinkta 18 propolio pavyzdžių. Atlikto darbo tikslas - analitiniais metodais ištirti Lietuvoje surinktų propolio pavyzdžių cheminę sudėtį, bei kiekybiškai ir kokybiškai įvertinti šias fenolines rūgštis ir fenilpropanoidus: chlorogeno rūgštį, cinamono rūgštį, galo rūgštį, ferulo rūgštį, kavos rūgštį, kumaro rūgštį, protokatecho (3,4-dihidroksibenzoinę) rūgštį, rozmarino rūgštį, vaniliną ir vanilino rūgštį. Atlikti tyrimai paprastos ir greitos atvirkštinių fazių efektyviosios skysčių chromatografijos metodikos optimizavimui ir įtiesinimui. Sukurto crhromatografinio metodo judrioji skystoji fazė yra metanolis ir 0,5 procento acto rūgšties tirpalas vandenyje. Esant optimalioms atskyrimo sąlygoms (aprašytoms skyriuje „Tyrimo metodas“), analizė atliekama 27 min., sulaikymo laikas 4,04 min (galo rūgštis), 6,93 min (protokatecho rūgštis), 11,30 min (chlorogeno rūgštis), 12,26 min (vanilinė rūgštis), 12,93 min (kavos rūgštis), 13,80 min (vanilinas), 16,97 min (kumaro rūgštis), 17,95 min (ferulo rūgštis), 22,29 min (rozmarino rūgštis) ir 26,30 min (cinamono rūgštis). Aptikimo riba ir nustatymo riba buvo atitinkamai tarp 0,004–0,021 ir 0,0... [toliau žr. visą tekstą] / The phenolic acids and phenylpropanoids have an important biological activity and are therapeutic agents of crude drugs. Development of validated analysis techniques of these phytotherapeutic agents (fingerprinting and assay procedures) is an important practice for efficacy, safety and quality control of herbal drug preparations. 18 samples of propolis were collected from different districts of Lithuania. The aim of the present work was to study chemical composition of collected samples and estimate analytical capabilities of the evaluation of selected phenolic acids and phenylpropanoids: caffeic acid, chlorogenic acid, cinnamic acid, coumaric acid, ferulic acid, gallic acid, protocatechuic (3,4-dihydroxybenzoic) acid, rosmarinic acid, vanillic acid and vanillin. Optimization and validation procedures of rapid and simple method of reversed phase high performance liquid chromatography were carried out. The mobile phase of the optimized chromatographic method consisted of methanol and 0.5 per cent acetic acid solvent in water. Under the optimal separation conditions (described in Methods), analysis was done in 27 min, with the retention times 4.04 min (gallic acid), 6.93 min (protocatechuic acid), 11.30 min (chlorogenic acid), 12.26 min (vanillic acid), 12.93 min (caffeic acid), 13.80 min (vanillin), 16.97 min (coumaric acid), 17.95 min (ferulic acid), 22.29 min (rosmarinic acid) and 26.30 min (cinnamic acid). The limits of detection and the limits of quantitation were between... [to full text]

<p>The incidence of cardiovascular diseases, including hypertension, is on the increase worldwide. Medicinal plants played an important role in the treatment of hypertension for centuries. Very few scientific studies have, however, been done to validate the use of these phytotherapies. O africana is on of the many phytotherapies that has been use indigenously for years to treat hypertension. The objectives of this study were to determine the most effective does of O africana aqueous extract which will reduce blood pressure / to determine whether chronic administration of O africana can be used to prevent and treat hypertension / to determine whether O africana exert its effects by modulation of the renin-angiotensin system.</p>

Bioactive compounds from plant origin have the potential to subside the biochemical imbalances induced by various toxins associated with mutagenesis and carcinogensis. Therefore new strategy are interested in finding a potent phytotherapeutic agent with non toxic properties. The goal of the present study to evaluate the potential of Doash- leaves water extracts Origanum majorana (2% w/v) as antimutagenic and anticarcinogenic effects against known• .. .mutagens classes (heterocyclic amines, polycyclic aromatic hydrocarbons, nitrosoamines and direct acting carcinogens) in vivo and in vitro. The antimutagenic activity was determined by Ames test using different strains of Salmonella Typhimurium. Results obtained showed that, Doash extract possesses powerful antimutagenic against different mutagene. In vivo study revealed that treatment of rats with Doash extracts for one day or 30 days caused a decrease in hepatic cytochrome P450 enzymes such as CYP2B, CYP2El and CYPIA, the latter P450 subfamily being closely associated with the inhibition of chemical carcinogens inactivation. Aqueous Doash tea extract diminishes the excretion of indirect acting mutagens in rats treated with ( 2-Amino-3-methylimidiazol-[4,50-f]quinoiine) IQ or (2- hydroxyamino-3-methyl-3H-imidazo[ 4,5,f] quinoline )PhIP; the antimutagenic effect associated with elevation of hepatic CYPIA2 expression which is involved in the metabolism of carcinogens (IQ and PhIP). HPLC/MS analysis of Doash extract showed that a highest peak related to high terpens contents. Based on these records, it appears that Doash tea extract can in vivo affect the mutagenicity of various structurally diverse promutagens including many food-borne carcinogen, by decreasing cytochrome P450-mediated activation. It was concluded that, daily intake of Doash tea may protect against the conversion of promutagene to mutagene and scavenging carcinogen from environmental contact. More study is needed to examine the mechanistic action of active ingredients of Doash extract fractions on cellular and molecular level.