Preparati

……………..

BILJNI PREPARATI MAKLURE:

TINKTURA – MAKLURA HSS, tečni hidroetanolni ekstrakt svežeg lista,  DER 1:1,

MATIČNA TINKTURA – MAKLURA TM, tečni hidroetanolni ekstrakt svežeg ploda, DER 1:1.

Maklurae tinctura

Maclurae fructus recentis extractum ethanolicum liquidum

preparati namenjeni kod kožnih tegoba.

 ATC:

 MeSH Tree:

 U skladu sa:

 French Pharmacopoeia 2005 (Pharmacopée française 2005):

 EMA/HMPC/  od   : Community herbal monograph on

 USP:

 Biljni preparati u tečnom obliku (nerazblaženi ili razblaženi) za oralnu i lokalnu upotrebu.

a) Maclura pomifera L., fructus (fresh fruit).

b) Maclura pomifera L., folium (fresh leaf).

Sastav:

 a) tečni ekstrakt (DER 1:1), ekstrakcioni rastvarač etanol 51% v/v,

 Maclura pomifera L., sadrži 154 istraženih hemijskih jedinjenja koja ispoljavaju 435 dejstava ( *podaci ažurirani septembra 2016.). Maclura pomifera contains an agglutinin, a lectin, that is highly specific toward the T-antigen.

 Sadržaj:

a) minimalno 0,05% m/m osađžina (osajin) (MF: C₂₅H₂₄O₅  MW: 404,45506 g/mol−1),

b) u većoj koncentraciji sadrži pektin (pectin) 46.04%, resin (16.64%), alkaloie, glukozide, kiseline i vitamin C.

c) više od svih biljaka sadrži flavonol morin, jedinjenja slična triterpenima – amirin (9ppt antitumorik alfa-amyrin, beta-amyrin), kaempferol (10ppt), osajin (64ppt) i pomiferin (20ppt), flavonoidne pigmente.

d) svež plod sadrži do 80% vode.

 The milky sap can cause dermatitis in some people. An extract and the juice of the fruit is toxic, though a 10% aqueous infusion and extract diluted 1:1 are not toxic.
Mlečni sok može izazvati dermatitis kod nekih ljudi. Ekstrakt i sok od voća su toksični, iako 10% vodena infuzija i ekstrakt razblažen 1:1 nisu toksični.

Indikacije:

biljni preparati su namenjeni poboljšanju opšteg stanja organizma kroz razna naučno dokazana dejstva.

Upotreba kod kožnih tegoba, za regeneraciju tkiva. 

– ima jako dejstvo kod: 

– delotvoran kod: 

– u narodnoj medicini kod: A tea made from the roots has been used as a wash for sore eyes. The inedible fruits contain antioxidant and fungicidal compounds. A 10% aqueous infusion and an extract diluted 1:1 have cardiovascular potentialities.

– spoljašnja primena kod: 

– upotrebljava se kao: Activity: Pesticide, Antioxidant,
Cancer-Preventive, Antiinflammatory, Antibacterial, Antitumor, Antimutagenic, Gypocholesterolemic, Aldose-Reductase-Inhibitor,
Antiulcer, Hepatoprotective, Antiseptic, Antiherpetic, Antiaggregant, Antileukemic, Antispasmodic, Apoptotic, Antihepatotoxic, Fungicide, ….

Stitt, P. A. Why George Should Eat Broccoli. Dougherty Co, Milwaukee, WI, 1990, 399 pp.AntiviralAmoros, M., Simoes, C.M.O., Girre, L., et al. Synergistic Effect Of Flavones And Flavonols Against Herpes Simplex Virus Type 1 In Cell Culture. Comparison With The Antiviral Activity Of Propolis. J. of Natural Products 55(12)_1732-1740, 1992_
Phenolic Compounds in Food and Their Effects on Health. Antioxidants & Cancer Prevention. Huang, M.T., Ho, C.T. and Lee, C.Y. eds. 1992. ACS Symposium Series 507.ACS, Washington 402 pp.
Vlietinck, A.J. and Dommisse, R.A. eds. 1985. Advances in Medicinal Plant Research. Wiss. Verlag. Stuttgart.
Challem, J., Berkson, Burt, and Smith, Melissa Dianne. 2000. Syndrome X – The complete nutritional program to prevent and reservse insulin resistance. John Wiley & Sons, New York. 272 pp. $24.95
Life Sciences 55: 1061.
Williamson, E. M. and Evans, F. J., Potter’s New Cyclopaedia of Botanical Drugs and Preparations, Revised Ed., Saffron Walden, the C. W. Daniel Co., Ltd., Essex UK, 362 pp, 1988, reprint 1989.
Keeler, R.F. and Tu, A.T. eds. 1991. Toxicology of Plant and Fungal Compounds. (Handbook of Natural Toxins Vol. 6) Marcel Dekker, Inc. NY. 665 pp.

jak

Monografija nemačke E komisije (Commission E Monographs), terapijski vodič za biljne lekove, preporučuje kkk u tretmanu tegoba hhh.

Doziranje i način primene:

2 mL (80 kapi) podeljeno u 2 do 4 doze.

Biljni preparati MAKLURA HSS i TM:

pojedinačna doza: 0,5-1 mL,

preporučena dnevna doza (PDD): 2 mL.

Oralna (sat vremena pre obroka) sa malo tečnosti i lokalna primena.

Upotreba na koži: aplicirati na obolelo mesto u tankom sloju ili obliku impregniranog zavoja.

Napraviti pauzu posle 4 nedelje neprekidne upotrebe.

Po preporukama, preparat postiže najbolje efekte pri upotrebi od 8 do 12 nedelja, duža upotreba je bezbedna uz pauze.

Potrebna je pažljiva upotreba kod pacijenata sa ++++

Isoflavones within osage orange may cause stomach irritation.

Kontraindikacije: preosetljivost na aktivne supstance,

preosetljivost na biljke porodice (genus Maclura, family Moraceae). 

Čuvanje: na tamnom, suvom i hladnom mestu do 20˚C, van domašaja dece i izlaganja EM zračenju, u dobro zatvorenoj originalnoj ambalaži. 

Rok upotrebe: 5 godina, posle prvog otvaranja 6 meseci. Uz adekvatno čuvanje, rok trajanja je neograničen. 

Pakovanje: 50 mL i 100 mL, standardne farmaceutske braon bočice, 250 mL, 500 mL, 1000 mL i 5000 mL na zahtev. 

Nutritivne informacije:

MAKLURA HSS i TM

energetska vrednost u 100 mL: 1504 kJ/ 360 kcal,

u preporučenoj dnevnoj dozi (PDD) 2 mL: 30 kJ/ 7,17 kcal,

suve materije (DR) više od 1,0% (Ph.Fr.),

etanola (2.9.10): 50 % V/V do 60 % V/V (Fr. Ph.), 65% v/v HAB.

Maclura pomifera (Moraceae)

Common names: Hedge Apple; Osage-Orange  How used Medicinal

Activities: 435   Chemicals w/Activities: 65   Chemicals: 154

Redosled po količini jedinjenja

WATER, PECTIN, FAT, LIGNIN, PROTEIN, RESIN, SUGAR, FAT, FIBER, PROTEIN, TANNIN, ASH,

OSAJIN, MACLURAXANTHONE, NITROGEN, POMIFERIN, FAT, ALVAXANTHONE, 2-3-4′-5-TETRAHYDROXYSTILBENE, KAEMPFEROL, PROTEIN, AMYRIN, DL-EUCHRESTAFLAVANONE-C, OXYRESVERATROL, 8-PRENYL-TOXYLOXANTHONE-C, DL-EUCHRESTAFLAVANONE-B,

ASH, ASTRAGALIN, LURENOL, LUPEOL, DIHYDROMORIN, GLUCOSIDES, QUERCETIN, MORIN, 1,3,6,7-TETRAHYDROXYXANTHONE, AROMADENDRIN, 2-3-4′-5-TETRAHYDROXYSTILBENE, OSAJAXANTHONE, ALKALOIDS, QUERCETIN, 19-ALPHA-H-LUPEOL, BUTYROSPERMOL, ASCORBIC-ACID, BETA-SITOSTEROL, 6-DEOXYJAKAREUBIN, BUTYROSPERMOL-ACETATE, KAEMPFEROL, LUP-20(29)-EN-3(R)-HYDROXY-HEXADECANOIC-ACID, LUPANE-3-BETA-20-DIOL, RESORCINOL, 2′,4′,5,7-TETRAHYDROXY-6-(3-METHYL-BUT-3-ENYL)-FLAVONE, AROMADENDRIN-7-O-BETA-D-GLUCOSIDE, LUPENOL-ACETATE, QUERCETIN, POPULNIN, 2“,3′,4′,5-TETRAHYDROXY-6-(3“-METHYL-3“-BUTENYL)-ISOFLAVONE, 4′,5,7-TRIHYDROXY-6-(3-METHYL-BUT-3-ENYL)-FLAVONE, TOVOXANTHONE, APIGENIN

Reference:

Stitt, P. A. Why George Should Eat Broccoli. Dougherty Co, Milwaukee, WI, 1990, 399 pp.

Phenolic Compounds in Food and Their Effects on Health. Antioxidants & Cancer Prevention. Huang, M.T., Ho, C.T. and Lee, C.Y. eds. 1992. ACS Symposium Series 507.ACS, Washington 402 pp.

Okada,Y,et al.1995.Search for Naturally Occurring Substances to Prevent the Complications of Diabetes.II.Inhibitory Effect of Coumarin and Flavonoid Derivatives on Bovine Lens Aldose Reductase and Rabbit Platelet Aggregation.Chem Pharm Bull43(8):1385-1387

Amoros, M., Simoes, C.M.O., Girre, L., et al. Synergistic Effect Of Flavones And Flavonols Against Herpes Simplex Virus Type 1 In Cell Culture. Comparison With The Antiviral Activity Of Propolis. J. of Natural Products 55(12):1732-1740, 1992.

Chemical Constituents of Oriental Herbs (3 diff. books)

Williamson, E. M. and Evans, F. J., Potter’s New Cyclopaedia of Botanical Drugs and Preparations, Revised Ed., Saffron Walden, the C. W. Daniel Co., Ltd., Essex UK, 362 pp, 1988, reprint 1989.

Constantinou, A., Mehta, R., Runyan, C., Rao, K., Vaughan, A., Moon, R. 1995. Flavonoids as DNA Topoisomerase Antagonists and Poisons: Structure-Activity Relationships. J Natural Products, 58: 217-225.

Oszmianski, J. and Lee, C.Y. 1990. Inhibitory Effect of Phenolics on Carotene Bleaching in Vegetables. J. Agric. Food Chem. 38: 688-690.

Yasukawa, K., Takido, M., Takeuchi, M., Sato, Y., Nitta, K., and Nakagawa, S. 1989. Inhibitory Effects of Flavonol Glycosides on 12-O-Tetradecanoylphorbol-13-acetate-Induced Tumor Promotion. Chem. Pharm. Bull. 38(3): 774-776, 1990.

Economic & Medicinal Plant Research, 6: 189.

Matsukawa, Y., et al. The Effect of Quercetin and Other Flavonoids on Cell Cycle Progresssion and Growth of Human Gastric Cancer Cells. Planta Medica, 56(6): 677, 1990.

Medicinal and Poisonous Plants of the Tropics. Leeuwenberg, A.J.M., ed. Pudoc, Wageningen. 1987.

Pizzorno, J.E. and Murray, M.T. 1985. A Textbook of Natural Medicine. John Bastyr College Publications, Seattle, Washington (Looseleaf).

Leung, A. Y. and Foster, S. 1995. Encyclopedia of Common Natural Ingredients 2nd Ed. John Wiley & Sons, New York. 649 pp.

Khalid, S.A., Farouk, A., Geary**, T.G., and Jensen, J.B. 1985. Potential Antimalarial Candidates From African Plants: An In Vitro Approach Using Plasmodium falciparum*. Journal of Ethnopharmacology, 15: 201-209, 1986.

Ivorra, M.D., Paya, M., and Villar, A. 1989. A Review of Natural Products and Plants as Potential Antidiabetic Drugs. Journal of Ethnopharmacology, 27: 243-275, 1989.

Malini, T. and Vanithakumari, G. 1989. Rat Toxicity Studies With B-Sitosterol. Journal of Ethnopharmacology, 28: 221-234, 1990.

Lydon, J. & Duke, S., The potential of pesticides from plants, pp. 1-41 in Craker, L. & Simon, J., eds, Herbs, Spices & Medicinal Plants: Recent Advances in Botany, Horticulture, & Pharmacology, v. 4, Oryx Press, Phoenix, 1989, 267pp.

Jeffery B. Harborne and H. Baxter, eds. 1983. Phytochemical Dictionary. A Handbook of Bioactive Compounds from Plants. Taylor & Frost, London. 791 pp.

Planta Medica, 57: A110, 1991.

Science News, 146: 421.

Huang, K. C. 1993. The Pharmacology of Chinese Herbs. CRC Press, Boca Raton, FL 388 pp.

Nigg, H.N. and Seigler, D.S., eds. 1992. Phytochemical Resources for Medicine and Agriculture. Plenum Press, New York. 445 pp.

Journal of Medicinal Food 2: 227.1999.

Joseph, J., Nadeau, D. and Underwood, A. 2001. The Color Code. Hyperion, NY.

Spiller, G. A. 1996 (Spiller, G. A. Ed. 1996. CRC Handbook of Lipids in Human Nutrition. CRC Press. Boca Raton, FL. 233 pp.)

Jung, J.H., Pummangura, S., Chaichantipyuth, c., Patarapanich, C., and McLaughlin, J.L. 1989. Bioactive Constituents of Melodorum fruticosum. Phytochemistry. 29(5): 1667-1670. 1990.

Jacobson, M., Glossary of Plant-Derived Insect Deterrents, CRC Press, Inc., Boca Raton, FL, 213 p, 1990.

Martindale’s 29th

Maclura pomifera (Moraceae)

Common names: Hedge Apple; Osage-Orange  How used Medicinal

Activities: 435   Chemicals w/Activities: 65   Chemicals: 154

Redosled aktivnosti po broju bioaktivnih jedinjenja

Pesticide, Antioxidant, Cancer-Preventive, antiinflammatory, Antibacterial, Antiviral, Antimutagenic, Antitumor, Hypocholesterolemic, Aldose-Reductase-Inhibitor,
Antiulcer, Hepatoprotective, Antiherpetic, Antiaggregant,
Antispasmodic, Apoptotic, Fungicide, Antileukemic, Hypotensive, Antihepatotoxic, Antiradicular, Estrogenic, Antiseptic, Anticancer, Antihistaminic, Cyclooxygenase-Inhibitor, Topoisomerase-II-Inhibitor, Lipoxygenase-Inhibitor, Antiedemic, Antidiabetic, Antitumor-Promoter, Vasodilator, Antihypertensive, AntiHIV, Topoisomerase-I-Inhibitor, Cytotoxic,
Antiallergic, Antitumor (Breast), Antiaflatoxin, Antiproliferant, Antifeedant, Antialopecic, 11B-HSD-Inhibitor, cAMP-Phosphodiesterase-Inhibitor, Diuretic, TNF-alpha-Inhibitor, Quinone-Reductase-Inducer, COX-2-Inhibitor, Mutagenic, Antiperoxidant, Carcinogenic, Antiaflatoxin, Antitumor (Breast), Antiproliferant, Ornithine-Decarboxylase-Inhibitor, Antiangiogenic, Choleretic, Hypoglycemic, Antimetastatic, Antimalarial, Allelochemic, Antiperistaltic, Antitumor (Skin), Candidicide, Antiaging, Laxative, Anticataract, NF-kB-Inhibitor, Antinociceptive, ntiatherosclerotic, Antidiarrheic, iNOS-Inhibitor, Aromatase-Inhibitor, MAO-Inhibitor, 5-Lipoxygenase-Inhibitor, Sweetener, Antiprostatitic, Antiophidic, Antieczemic, Myorelaxant,

Reference

Stitt, P. A. Why George Should Eat Broccoli. Dougherty Co, Milwaukee, WI, 1990, 399 pp.

Jeffery B. Harborne and H. Baxter, eds. 1983. Phytochemical Dictionary. A Handbook of Bioactive Compounds from Plants. Taylor & Frost, London. 791 pp.

Martindale’s 28th

Martindale’s 29th

Mao, X. M., Zhang, J. Q. 1993. Inhibition of Aldose Reductase by Extracts of Chinese Herbal Medicine. Zhongguo Zhongyao Zazhi , 18(10): 623-624.

Planta Medica, 56(6): 695, 1990.

Planta Medica, 57: A110, 1991.

Economic & Medicinal Plant Research, 5: 225.

Economic & Medicinal Plant Research, 5: 333.

Economic & Medicinal Plant Research, 5: 363.

Leung, A. Y. and Foster, S. 1995. Encyclopedia of Common Natural Ingredients 2nd Ed. John Wiley & Sons, New York. 649 pp.

Joyeux, M., Rolland, A., Fleurentin, J., Mortier, F., and Dorfman, P. 1989. Tert-Butyl Hydroperoxide-Induced Injury in Isolated Rat Hepatocytes: A Model for Studying Anti-Hepatotoxic Crude Drugs. Planta Medica 56(2): 171-173, 1990.

Jin, G-Z., Yamagata, Y., and Tomita, K.-i. 1989. Structure of Rutin Pentamethanol. Chem. Pharm. Bull. 38(2): 297-300, 1990.

Huang, K. C. 1993. The Pharmacology of Chinese Herbs. CRC Press, Boca Raton, FL 388 pp.

Jacobson, M., Glossary of Plant-Derived Insect Deterrents, CRC Press, Inc., Boca Raton, FL, 213 p, 1990.

Pizzorno, J.E. and Murray, M.T. 1985. A Textbook of Natural Medicine. John Bastyr College Publications, Seattle, Washington (Looseleaf).

Hutchings, A, Scott, AH, Lewis, G, and Cunningham, A. 1996. Zulu Medicinal Plants. An inventory. University of Natal Press, Pietermaritzburg. 450 pp.

Ivorra, M.D., Paya, M., and Villar, A. 1989. A Review of Natural Products and Plants as Potential Antidiabetic Drugs. Journal of Ethnopharmacology, 27: 243-275, 1989.

Medicinal and Poisonous Plants of the Tropics. Leeuwenberg, A.J.M., ed. Pudoc, Wageningen. 1987.

Lydon, J. & Duke, S., The potential of pesticides from plants, pp. 1-41 in Craker, L. & Simon, J., eds, Herbs, Spices & Medicinal Plants: Recent Advances in Botany, Horticulture, & Pharmacology, v. 4, Oryx Press, Phoenix, 1989, 267pp.

Journal of Medicinal Food 2: 235.1999.

=ICMR(Indian Council of Medical Research).1976.Medicinal Plants of India.Vol.1.Indian Council of Med. Res.Cambridge Printing Works, New Delhi.487 pp;ICMR.1987.Medicinal Plants of India.Vol.2.Indian Council of Med. Res.Cambr. Printing Works,New Delhi.600pp

Izvor: dr Duke, James A.

Podaci  ažurirani septembra 2016.

Osage Orange 

OSAGE APPLE TINCTURE

X X X X X

Antioxidant isoflavones in Osage orange, Maclura pomifera (Raf.) Schneid.

Tsao R, Yang R, Young JC.

Abstract

Recent findings that many human chronic diseases are associated with oxidative stresses have instigated the search for dietary antioxidants. Many phytochemicals, particularly phenolic compounds, have been found to possess strong antioxidant activity and reduce the risks of those diseases. Isoflavones, a special phenolic group found in soybean, have been found to act as antioxidants in some model systems. This study investigated the isoflavone content in a unique nonedible tree fruit, Osage orange [Maclura pomifera (Raf.) Schneid], and methods for the extraction, identification, and quantification of the two major isoflavones, osajin and pomiferin, were developed. The ethyl acetate extract contained 25.7% osajin and 36.2% pomiferin, and the two isoflavones were at 9.5 g kg(-1) of fresh Osage orange. Two model systems, FRAP and beta-CLAMS, were used to measure the antioxidant activity of these two isoflavones. Pomiferin was found to be a strong antioxidant in both systems, comparable to the antioxidant vitamins C and E and the synthetic antioxidant BHT. Osajin and the two soybean isoflavones (genistein and daidzein) showed no antioxidant activity. Although the Osage orange fruit is not a food source, it is considered to be safe and, therefore, a potentially good source of an antioxidant nutraceutical and functional food ingredient.

 X X X X X

The fruits of Maclura pomifera extracts inhibits glioma stem-like cell growth and invasion.

Zhao D, Yao C, Chen X, Xia H, Zhang L, Liu H, Jiang X, Dai Y, Liu J.

Abstract

Glioma is the most common primary intracranial tumour. Recently, growing evidence showed that glioma possesses stem-like cells, which are thought to be chemo- and radio-resistant and believed to contribute to the poor clinical outcomes of these tumours. In this study, we found that stem-like glioma cells (CD133+) were significantly increased in neurosphere cells, which are highly invasive and resistant to multiple chemotherapeutic agents. From our natural products library, we screened 48 natural products and found one compound, Pomiferin, which was of particular interest. Our results showed that Pomiferin could inhibit cell viability, CD133+ cell population, sphere formation, and invasion ability of glioma neurosphere cells. We also found that multiple stemness-associated genes (BIM1, Nestin, and Nanog) were down-regulated by Pomiferin treatment of glioma neurosphere cells. Taken together, our results suggest that Pomiferin could kill the cancer stem-like cells in glioma and may serve as a potential therapeutic agent in the future.

X X X X X

Antiproliferative activity of pomiferin in normal (MCF-10A) and transformed (MCF-7) breast epithelial cells.

Yang R, Hanwell H, Zhang J, Tsao R, Meckling KA.

Abstract

Pomiferin and osajin are prenylated isoflavones from Osage orange fruit that both have potent antioxidant activity in a variety of assays. Pomiferin, in particular, has strong activity against the superoxide anion in a photochemiluminescence (PCL) assay system. In vitro, pomiferin, but not osajin, demonstrated selective antiproliferative activity against the tumorigenic breast epithelial cell line MCF-7 (IC(50) = 5.2 μM) with limited toxicity toward nontumorigenic breast epithelial cells (MCF-10A). The differential sensitivity of normal and tumorigenic cells to the antiproliferative action of pomiferin was examined further by using cDNA microarrays. With a stringent cutoff of p < 0.01, a total of 94 genes were significantly differentially expressed between MCF-7 and MCF-10A cells; 80 up-regulated and 14 down-regulated when cells were exposed to 5 μM pomiferin for 24 h. Fold changes by microarray analysis were confirmed using RT-qPCR, and the most significant changes were found with genes related to antioxidant enzymes. Genes involved in mitotic inhibition and apoptotic regulations were also found to be up-regulated. Pomiferin is therefore a good anticancer candidate agent that may be useful either alone or in combination with other therapeutic agents and, because of its selectivity toward tumor cells, likely to have fewer side effects that classic chemotherapy drugs

X X X X X 

Esterifikovani fitosteroli iz maklure (Maclura pomifera)
Filip Snežana, Čanadi Janoš J., Djarmati Zoltan, Jankov Ratko M.

Sažetak
Plod maklure kao izvor triglicerida, fosfolipida, triterpena i izoflavonoida, predstavlja dragocenu sirovinu za kozmetičku i farmaceutsku industriju. U ovom radu iz ploda maklure ekstrahovani su lipidi ekstrakcijom pomoću ugljen dioksida povećanog pritiska (210 i 350 bara). Glavne komponente dobijenih ekstrakata sačinjavali su esterifikovani lupeol i butirospermol. Hromatografskim razdvajanjem na stubu silika-gela izdvojeni su lupeol-heksadekanoat i butirospermol-heksadekanoat. Strukturne karakteristike ovih supstanci određene su na osnovu hemijskih transformacija i upotrebom savremenih instrumentalnih metoda 1H i 13C NMR spektroskopije i masene spektometrije.

Biljka se često koristi za jačanje imunosistema, kao i u lečenju ginekoloških problema, uključujući i ciste. U narodnoj medicini koristi se kod terapije tumora dojke, raka debelog creva, želuca, materice, kancera grla, pluća i prostate jer je bogata antioksidansima. Tinktura mora precizno da se pripremi jer se uzima jako dugo, nekada i duže od godinu dana, jer samo dugotrajna upotreba daje efekte, tvrde narodni lekari.

Koristi se i kod čišćenja organizma od toksina, ublažava umor, ubija viruse i jača nervni i kardiovaskularni sistem. Mlečni sok biljke koristi se u lečenju različitih kožnih bolesti. Ima značajan terapeutski efekat u lečenju išijasa, reume, artritisa, gihta, opekotina, rana i čireva.

Koristi se i kao sredstvo protiv insekata, a sok iz ploda (razređen sa vodom u jednakoj razmeri) za tretiranje biljaka i sprečavanje razvoja gljivica.