Phytochemistry Reviews (2005) 4: 177190 DOI 10.

1007/s11101-005-1234-5

Springer 2005

Saponins and phenolics of Yucca schidigera Roezl: Chemistry and bioactivity

Sonia Piacente1,*, Cosimo Pizza1 & Wieslaw Oleszek2
Dipartimento di Scienze Farmaceutiche, Universita` degli Studi di Salerno, via Ponte Don Melillo, 84084, Fisciano (Salerno), Italy; 2Department of Biochemistry, Institute of Soil Science and Plant Cultivation, ul. Czartoryskich 8, 24100, Pulawy, Poland; *Author for correspondence (Tel: +39-089-962616; Fax: +39-089962828; E-mail: piacente@unisa.it)
1

Key words: animal nutrition, antioxidant activity, anti-yeast activity, foaming agent, furostanol saponins, NO production inhibition, platelet aggregation inhibition, resveratrol, spirostanol saponins, yuccaols AE

Abstract Yucca schidigera (Agavaceae) is one of the major commercial source of steroidal saponins. Two products of yucca are available on the market. These include dried and nely powdered logs (yucca powder) or mechanically pressed and thermally condensed juice (yucca extract). These products possess the GRAS label which allows their use as foaming agent in soft drink (root beer), pharmaceutical, cosmetic, food, and feeding-stus industries. The main application of yucca products is in animal nutrition, in particular as a feed additive to reduce ammonia and fecal odors in animal excreta. The positive eects of dietary supplementation with yucca products on the growth rates, feed eciency, and health of livestock seem to be due not only to the saponin constituents but also to other constituents. These observations prompted us to investigate the phenolic constituents of Y. schidigera. This study led to the isolation of resveratrol, trans3,3,5,5-tetrahydroxy-4-methoxystilbene, the sprirobiavonoid larixinol along with novel phenolic derivatives with very unusual spirostructures, named yuccaols AE and yuccaone A. Taking into account the multifunctional activities of resveratrol and the novelty of yuccaols AE, structurally related to resveratrol, a program aimed to evaluate for yucca phenolics some of the activities exerted by resveratrol has been carried out. This review describes the chemistry of yucca saponins and phenolics, summarizes the biological activities of yucca products and constituents and gives an account on the actual and potential applications of yucca products. Introduction Yucca schidigera, known as yucca, is a plant belonging to the Agavaceae family, native to the South-Western United States and Mexico. Indians recognized Yucca as one of the nicest desert plants, a tree of life with health promoting activity. Its extracts have been used for centuries in folk medicine to treat a wide variety of inammatory disorders, especially headaches, gonorrhea, arthritis, and rheumatism (Cheeke, 1998). Two products obtained from the trunk of Y. schidigera are available on the market: yucca powder which is dried and nely powdered logs and yucca extract which is obtained by subjecting the powdered material to mechanical squeezing in a press, producing a juice which is concentrated by evaporation. These products possess GRAS label (Generally Recognized As Safe) given by FDA which allows their human dietary use. An important application of yucca extract is as foaming agent in soft drink, pharmaceutical, cosmetic, food, and feeding-stu industries. The foaming activity of Yucca extract is due to the very high saponin content (about 10% of dried material) (Oleszek et al., 2001a). Y. schidigera is one of

178 the two major commercial sources of saponins, the other one being Quillaia saponaria (Cheeke, 2000). The main application of yucca products is in animal nutrition, in particular as a feed additive to reduce ammonia and fecal odors in animal excreta (Cheeke, 2000). Dietary supplementation with yucca products is reported to produce positive eects on the growth rates (Mader and Brumm, 1987; Anthony et al., 1994; Cline et al., 1996), feed eciency (Mader and Brumm, 1987) and health of livestock (Anthony et al., 1994; Balog et al., 1994). These eects have been historically attributed to the saponin constituents but investigations performed on rat metabolism to determine if the biological eects of yucca were due exclusively to its saponin fraction or also to non-saponin compounds, indicated that the active constituents are present in both fractions (Duy et al., 2001). Taking into account these results we have undertaken a systematic investigation of the phenolic fraction of yucca which led to the isolation of resveratrol, trans-3,3,5,5-tetrahydroxy-4-methoxystilbene, the spirobiavonoid larixinol along with novel phenolic derivatives with very unusual spirostructures, named yuccaols AE and yuccaone A (Oleszek et al, 2001b; Piacente et al. 2002, 2004). Resveratrol is the natural phytoalexin found in considerable amounts in the skin of grapes (Calderon et al., 1993; Jeandet et al., 1995), mulberries and peanuts (Langcake and Price, 1976) and in some medicinal plants (Jayatilake et al., 1993; Kimura et al., 1995; Orsini et al., 1997). In the last 15 years this compound has received a lot of attention because of its biological activities, as antimutagenic (Uenobe et al., 1997), antiviral (Docherty et al., 1999), antiinammatory (Tsai et al., 1999) and cancer preventing (Jang et al., 1997; Surh et al., 1999). In particular, it is believed that because of its antioxidant properties, resveratrol is responsible for the reduced risk of cardiovascular disease associated with a moderate consumption of red wine (Siemann and Creasy, 1992; Pendurthi et al., 1999). The multifunctional activities of resveratrol together with the novelty of yuccaols AE (Oleszek et al., 2001b; Piacente et al. 2004), structurally related to resveratrol, prompted us to carry out a program aimed to evaluate for yucca phenolics some of the activities exerted by resveratrol (Olas et al., 2002, 2003; Czeczot et al., 2003; Marzocco et al., 2004; Piacente et al. 2004). The results obtained show that new opportunities could be explored which could increase the commercial value of yucca.

Chemistry of yucca saponins Yucca saponins are steroidal saponins possessing spirostanol (Figure 1) and furostanol (Figure 2) aglycones (Tanaka et al., 1996; Miyakoshi et al., 2000; Oleszek et al., 2001a). The main spirostanol aglycones are smilagenin and sarsapogenin which are characterized by a cis junction between ring A and B and a b-OH group at position 3 which is the glycosidation site. These two aglycones dier only for stereochemistry at C-25, being sarsapogenin the 25S isomer and smilagenin its 25R epimer. Generally the separation of a mixture of C-25 epimeric saponins into each C-25 epimer is very dicult, thus structures are often elucidated as C-25 epimeric mixtures. Other aglycones occurring in Y. schidigera are markogenin which diers from sarsapogenin only for the occurrence of a further b-hydroxy group at C-2 and its C-25 epimer samogenin. Gloriogenin and its 25S epimer characterized by a keto group at C-12 are also present. There are also aglycones characterized by a double bond between C-25 and C-27. Also in this case, we can nd only one hydroxyl group at C-3, a further hydroxyl group at C-2 or a keto group at C-12. A further aglycone, known as convallamarogenin, characterized by a b-OH group at position C-1 was also reported (Miyakoshi et al., 2000). Our study aimed to isolate and characterize the main saponins of yucca trunk showed that Y. schidigera saponin mixture contain predominantly spirostanol saponins but also furostanol saponins, which make up 67% of the total saponin mixture (Oleszek et al., 2001a). The furostane aglycones of Y. schidigera saponins isolated until now are (25R)-3b,26-dihydroxy-5b-furost-20(22)en-12-one and (25R)-5b-furostan-3b,22a,26-triol (Figure 2). Sugar chains of Y. schidigera saponins contain two or three sugars. They have glucose or galactose linked to the aglycone and this rst sugar links at position 2 another glucose. Only in one case, compound 24, there is galactose linked at position 2 of the rst sugar glucose. In the case of trisaccharide chains, at position 3 of the rst sugar we can nd xylose or glucose (Figure 3).

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Figure 1. Spirostane aglycones of Y. schidigera saponins.

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Figure 2. Furostane saponins of Y. schidigera.

Biological activities of Yucca products A study of Japanese researchers showed that a saponin fraction of Y. schidigera logs exhibited potent growth-inhibitory activity with MIC ranging from 31.3 to 125 lg/ml against certain food-deteriorating yeasts (Candida albicans), lm-forming yeasts (Debaryomyces hansenii, Pichia nakazawae, Zygosaccharomyces rouxii), dermatophytic yeasts (Candida famata, Hansenula anomala, Pichia carsonii), and against brewers yeast (Saccharomyces cerevisiae) (Miyakoshi et al., 2000). Some structure activity relationships were deduced. Saponins having a trisaccharide chain without any oxygen functionalities at C-2 and/or C-12 of the aglycone exhibited potent activity, while saponins with 2b-OH or 12-keto groups showed very weak or no activity. Low activity was observed for saponins with a disaccharide chain and no activity was observed for the aglycones obtained after acid hydrolysis. It is known that the deterioration of cooked foods is mainly caused by infections with yeasts. Thus the extract of yucca and its saponin fraction are now on sale in Japan as an

anti-deteriorating agent for extending the shelf-life of food products containing cooked rice, beans, pickled vegetables, processed sh meat, and fermented seasonings. The main use of Yucca extract is in animal nutrition to reduce ammonia concentration and fecal odors (Cheeke, 2000). Since Y. schidigera extract has become commercially available, a number of investigations into its eects on a wide range of animals have been carried out (Hussain et al., 1996; Hristov et al., 1999; Killeen et al., 1998a; Colina et al., 2001; Duy et al., 2001; Flaoyen et al., 2002; Kaya et al., 2003). These studies have shown that the extract has many benets on growth and performance of livestock (Mader and Brumm, 1987; Anthony et al., 1994; Balog et al., 1994; Cline et al., 1996) in particular it reduces gastrointestinal and fecal ammonia levels (Cheeke, 2000). Eects of Yucca extracts on nitrogen metabolism include reduction in serum urea and ammonia. Yucca extract components may alter kidney function increasing the rate of urea clearance, lowering blood urea and ammonia

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Figure 3. Saponins of Y. schidigera.

182 concentrations (Wallace et al., 1994; Hristov et al., 1999). Reduction in serum urea concentration in cattle may have some practical implications. Milk production and conception rates of dairy cattle can be adversely aected by high blood urea levels. Thus the assumption of Yucca extract can result in an improvement of milk production and conception rates (Hussain and Cheeke, 1995; Cheeke, 2000). Despite the data on the positive eects of dietary supplementation with yucca, the mechanism of action of Y. schidigera products remains unclear and the compounds responsible for the biological activity have not been conclusively identied. The eects of Y. schidigera have been historically attributed to its saponin constituents but experiments performed on rat metabolism to evaluate the eects of dietary supplementation with the butanol extractable fraction (saponin fraction) and non-butanol extractable fraction (non-saponin fraction) of Y. schidigera extract on a number of serum, excretory, and hepatic variables with particular regard to measurements relating to nitrogen metabolism, showed that both fractions displayed eects, indicating that the active constituents are present in both fractions (Duy et al., 2001). Regarding the mode of action of Y. schidigera extract, several mechanisms have been proposed but none has been conclusively proven. Firstly, Y. schidigera extract was thought to be a potent in vitro inhibitor of the enzyme urease (Asplund, 1991) and its in vivo properties were attributed to inhibition of gastrointestinal urease (Anthony et al., 1994; Balog et al., 1994) but further studies have questioned this hypothesis (Killeen et al., 1994, 1998b). Other proposed mechanisms of action include modulation of microbial populations in vivo (Peestok, 1979), direct binding to ammonia (Headon et al., 1991), inhibition of selected gut microorganisms (Hussain and Cheeke, 1995; Killeen et al., 1998b), in particular rumen protozoa (Wallace et al., 1994). Saponins seem to be involved in the reduction of ruminal ammonia when Yucca extract is administered to ruminants. The major source of ruminal ammonia is proteolysis of bacterial proteins due to ingestion of ruminal bacteria by protozoa (Wallace et al., 1994; Cheeke, 2000). Saponins have antiprotozoal activity due to their ability to complex with cholesterol of protozoal cell membranes causing cell lysis and death. Thus reduction of ruminal ammonia has been attributed to the antiprotozoal activity exerted by saponins (Wallace et al. 1994; Makkar et al., 1998). Antiprotozoal activity against ruminal protozoa raises the question of whether saponins would be eective against protozoal diseases that aict humans, livestock, and poultry. Those protozoal diseases in which part of the life cycle occurs in the gastrointestinal tract would be expected to be responsive to antiprotozoal activity of saponins (Cheeke, 2000). An example is the disease giardiasis, caused by the protozoan Giardia lamblia, also known as Giardia duodenalis. G. lamblia is one of the most common intestinal pathogens of humans (Adam, 1991) and livestock (Olson et al., 1997) and is widely recognized as a principal cause of waterborne disease in North America and Europe. Giardiosis is contracted when infective cysts are ingested with waters, food or from contaminated surroundings. The trophozoites excysts within the duodenum multiply and cause histological and enzymatic changes in the small intestine (Buret et al., 1990). These changes in intestinal morphology and function have been related to diarrhea and malabsorption in humans (Farthing, 1994) and livestock (OHandley et al., 1999). In livestock, Giardia-mediated diarrhea and malabsorption reduce growth rate, feed eciency and the protability of livestock production (Olson et al., 1995). Because of the suspected zoonotic potential of G. lamblia, and its negative impact on livestock production, there is great interest in identifying chemicals able to control G. lamblia. A butanol extract of Y. schidigera powder resulted to be eective for killing G. lamblia tropozoites in vitro. Oral administration of butanol extract to gerbils reduced but did not eliminate trophozoite populations in the small intestine. Including yucca powder in diets for gerbils or lambs did not aect the course of experimentally induced giardiosis, but reduced the excretion of cysts (McAllister et al., 2001). Saponins form insoluble complexes with cholesterol, other sterols and bile acids. It is generally believed that the principal action of saponins on blood cholesterol is by sequestration of cholesterol and bile acids in the intestine, preventing their absorption. Another possibility could be that increased rate of exfoliation of intestinal cells caused by the membranolytic action of saponins could result in an increased loss of cell membrane cholesterol contained in the exfoliated cells

183 (Cheeke, 1999). Cholesterol lowering properties of saponins in humans are of obvious interest. Being Y. schidigera along with Q. saponaria the worldwide two major commercial sources of saponins, a study to evaluate the hypocholesterolemic properties of a preparation based on Y. schidigera and Quillaia saponaria saponins in human blood has been performed. The results of this study show that this preparation reduced signicantly total cholesterol and LDL levels in blood plasma of hypercholesterolemic patients without signicant changes in HDL levels (Kim et al., 2003). intermediate in the oxidative avanoneavanol conversion and subsequent rearrangement of the intermediate. The dierent stereochemistry of yuccaols at C-3 is in good agreement with the involvement of the C-3 carbocationic intermediate in the proposed biogenetic pathway (Figure 5). Yuccaone A is a novel phenolic constituent based on a spirobenzopyran-4-cyclopentan-3-one system.

Biological activities of yucca phenolics The multifunctional activities of resveratrol together with the novelty of yuccaols AE, structurally related to resveratrol, prompted us to carry out a program aimed to evaluate for yucca phenolics some of the activities exerted by resveratrol. First of all the antioxidant activity of the MeOH extract, its phenolic fraction and the single phenolic constituents of Y. schidigera bark was assayed also with a view to the potential use of Y. schidigera, which already possesses GRAS label, as an antioxidant in food stus. The antioxidant activity was evaluated by radical scavenging activity in the Trolox Equivalent Antioxidant Capacity (TEAC) assay and in the coupled oxidation of b-carotene and linoleic acid (Piacente et al., 2004). The TEAC assay (Pietta et al., 1998; Re et al., 1999) measures the relative ability of antioxidant substances to scavenge the radical cation 2,2-azinobis-(3-ethylbenzothiozoline-6-sulfonate) (ABTS+) as compared to a standard amount of the synthetic antioxidant Trolox (6-hydroxy2,5,7,8-tetramethylcroman-2-carboxylic acid), a water soluble vitamin E analogue. The activity of the tested samples was expressed as TEAC values; TEAC value is dened as the concentration of standard Trolox with the same antioxidant capacity as a 1 mM concentration of the antioxidant investigated sample. All the tested samples exhibited good free radical scavenging activity (Table 1). The phenolic extract showed the highest activity, which was also higher than that of quercetin, the reference antioxidant compound. Trans-3,3,5,5-tetrahydroxy-4-methoxystilbene was more active than resveratrol; this was in good agreement with the higher activity exhibited by yuccaols CE, which possess as stilbenic portion,

Chemistry of yucca phenolics The eects of Y. schidigera products seem to be due not only to their saponin content but also to other constituents. Considering that, we have performed an investigation aimed to dene the phenolic prole of Y. schidigera bark. It is noteworthy that phenolics occur in the external part of the trunk, not inside. Investigation of the phenolic fraction of Y. schidigera bark resulted in the isolation of the stilbenic derivatives trans-3,3,5,5-tetrahydroxy4-methoxystilbene and trans-3,4,5,-trihydroxystilbene well known as resveratrol, along with larixinol, a spirobiavonoid previously isolated from Larix gmelini which is made up of two C15 units of avonoid origin (Shen et al., 1986). Furthermore, the novel yuccaols AE (Oleszek et al., 2001b; Piacente et al., 2004) and yuccaone A were isolated (Piacente et al., 2002) (Figure 4). Yuccaols AE are characterized by unusual spiro structures made up of a C15 unit, probably derived from a avonoid skeleton, and a stilbenic portion linked via a c-lactone ring. They dier for the stilbenic portion which is resveratrol in yuccaols A and B and trans-3,3,5,5-tetrahydroxy-4-methoxystilbene in yuccaols C, D, E; for the stilbenic position involved in the linkage with the C15 unit which is position 2 of the dioxygenated ring in yuccaols A D and position 2 of the trioxygenated ring in yuccaol E; for the stereochemistry at C-3. To our knowledge, yuccaols AE represent the unique example in nature of spirostructures including C15 and C14 units condensed to form a c-lactone ring. They probably derive from the attachment of the stilbenic derivative to the carbocationic

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Figure 4. Phenolics of Y. schidigera bark.

trans-3,3,5,5-tetrahydroxy-4-methoxystilbene. Membrane lipids are rich in unsaturated fatty acids, that are susceptible to oxidative processes, linoleic acid being especially the target of lipid peroxidation (Pratt, 1992; Igile et al., 1994). The antioxidative eect of the MeOH extract of Y. schidigera, its phenolic fraction and the isolated compounds on the autooxidation of linoleic acid was also determined. The values of antioxidant activity (AA) measured at t=60 and 120 min, employing bleaching of b-carotene as a model

system are reported in Table 1. The data show that all the tested samples, except trans-3,3,5,5-tetrahydroxy-4-methoxystilbene, exhibited signicant activity in this test. In particular, all the yuccaols showed activity higher than that of the standard phenolic antioxidant 2,6-di-tert-butyl-4-methoxyphenol (BHT) (at t=120 min). Many in vitro studies have shown that resveratrol possesses antiplatelet activity which comprises the decreased reactivity and function of platelets and the diminished platelet activation

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Figure 5. Biogenetic pathway hypothesized for yuccaols AE.

186
Table 1. Antioxidant activities of MeOH extract, phenolic fraction and single phenolic constituents in the TEAC and autooxidation assays.a TEAC assay (mM) SDb) Autooxidation assay t=60 min MeOH extract Phenolic fraction Resveratrol Trans-3,3,5,5-tetrahydroxy-4-methoxystilbene Yuccaol A Yuccaol B Yuccaol C Yuccaol D Yuccaol E Yuccaone A Larixinol Quercetin BHTc
a b c

t=120 min 55.7 45.7 45.9 2.9 72.1 72.1 71.7 66.2 79.3 43.4 51.0 61.2

1.787 3.301 1.896 2.252 0.960 1.093 1.598 1.422 1.852 1.037 1.788 2.600

0.02 0.01 0.09 0.12 0.04 0.08 0.01 0.02 0.13 0.04 0.01 0.02

34.3 26.4 24.9 3.1 52.6 76.3 59.5 66.4 74.3 40.6 24.4 71.8

For protocols used, see Piacente et al. (2004). n = 3. BHT, 2,6-di-tert-butyl- 4-methoxyphenol, standard control substance.

induced by agonists (Zbikowska et al., 1999; Olas et al., 2001). On the basis of these reports, the effects of trans-3,3,5,5-tetrahydroxy-4-methoxystilbene, yuccaols A and C on platelet aggregation induced by thrombin and ADP have been evaluated (Olas et al., 2002). Pretreatment of platelets with resveratrol or other tested phenolics (125 lg/ml) slightly reduced platelet aggregation stimulated by 5 lM ADP or 10 lM ADP. The comparison of the inhibitory eects of tested compounds in thrombin-induced platelet aggregation revealed that phenolics showed even stronger antiplatelet activity than resveratrol. These compounds also had an inhibitory eect on the thrombin-induced enzymatic platelet lipid peroxidation determined as the level of thiobarbituric acid active substances. On the basis of these results, the comparative eects of resveratrol,trans-3,3,5,5-tetrahydroxy4-methoxystilbene, and yuccaols A and C on oxidative stress in resting blood platelets and blood platelets activated by dierent agonists (thrombin or thrombin receptor activating peptide, TRAP) have been evaluated (Olas et al., 2003). Phenolics, tested at a concentration range of 125 lg/ml, reduced to dierent degrees the level of reactive oxygen species measured by the luminol-dependent chemiluminescence and changed

the production of O2) measured by the reduction of cytochrome c in resting blood platelets. They also inhibited the generation of free radicals in blood platelets activated by thrombin (p<0.05) or thrombin receptor activating peptide (p<0.05). Comparative studies using in vitro tests showed that all the phenolics from Yucca bark exerted an antioxidant eect on dierent ROS produced in resting blood platelets and blood platelets activated by thrombin or TRAP. Trans-3,3,5,5-tetrahydroxy4-methoxystilbene showed the highest ability, also higher than that of resveratrol, to inhibit the production of O2) and chemiluminescence. This compound showed also a stronger antiplatelet action than resveratrol. Thus this compound may be a promising candidate for future evaluations of its pharmacological activity associated with antiplatelet action. Blood platelet activation plays a crucial role in hemostasis and pathomechanisms of several arterial disorders, including artherosclerosis, strokes, and myocardial infarction (Kroll and Schafer, 1995; Levy-Toledano, 1999). Blood platelets also participate in tumor progression, allergic inammation, and non-allergic responses (Blockmans et al., 1995; Kroll and Schafer, 1995; LevyToledano, 1999). Phenolics of Y. schidigera bark, in particular trans-3,3,5,5-tetrahydroxy-4-methoxystilbene, reduce the deleterious eects of oxidative

187 stress on blood platelets and, with other antioxidant in diet, may exhibit stronger protective activity against oxidative stress in blood platelet in vivo (Olas et al., 2003). The above results show the potential use of Y. schidigera as a source of antioxidant principles. This is interesting if we consider that Y. schidigera products possess GRAS label which allows application of its extract and powder in pharmaceutical, cosmetic, food and feeding-stu industries (Wallace et al., 1994; Tanaka et al., 1996). Resveratrol was found strongly to inhibit nitrogen oxide generation in activated macrophages and to reduce the expression of the inducible isoform of nitrogen oxide synthase (iNOS) (Tsai et al., 1999). NO produced by iNOS is a key mediator in inammatory processes and its production is a crucial step in both the immunoresponsive cells activation and in the mechanism of NO-mediated cytotoxicity (Nathan, 1997). Thus the eects of yuccaols AC on NO production have been examined, incubating macrophages with dierent concentrations of yuccaols AC 1 h before stimulation with Escherichia coli lipopolysaccharide (LPS) (Marzocco et al., 2004). As shown in Figure 6 yuccaol C, added 1 h before LPS induction, inhibited signicantly and in a doserelated manner NO release, yuccaol A had a signicant eect on NO release only at the highest concentration of 100 lM, no signicant activity was observed for yuccaol B. To determine if the inhibitory eect of yuccaol C was related to a modulation of iNOS induction, iNOS expression by Western blot analysis was evaluated. A significant and concentration-related inhibition of iNOS expression could be observed (Figure 7). Deletion and mutational analyses have demonstrated that the transcription factor NF-jB is involved in the activation of iNOS by LPS (Ruetten and Thiemermann, 1997). To examine whether yuccaol C selectively inhibited activation of NF-jB, analysis of NF-jB binding activity by gel mobility shift assay was performed. Under control conditions activation of J774.A1 cells with LPS resulted in a

Figure 6. Eect of yuccaol C (0.0110 lM) on NO release by LPS-stimulated J774.A1 macrophages.

Figure 7. Concentration-dependent eect of yuccaol C (0.0110 lM) on LPS-induced iNOS expression in J774.A1 macrophages. Representative blot of iNOS expression.

188 time-dependent increase in NF-jB expression which peaked between 1 and 2 h and approached baseline values after 24 h. The induction of specic NF-jB binding activity by LPS was reduced signicantly by yuccaol C (0.1100 lM) added to cells 1 h before LPS challenge (Marzocco et al., 2004). Our results are strongly supported by other studies indicating the capability of resveratrol in suppressing nitric oxide synthase and down-regulating NF-jB activation in cultured macrophages RAW 264.7 (Tsai et al., 1999). The above reported data are in good agreement with the anti-inammatory activity attributed to Y. schidigera in folk medicine. References
Adam RD (1991) The biology of Giardia spp Microbiol. Rev. 55: 706732. Anthony NB, Balog JM, Staudinger FB, Wall CV, Walker RD & Hu WE (1994) Eect of urease inhibitor and ceiling fans on ascites in broilers. 1. Environmental variability and incidence of ascites. Poult. Sci. 73: 801809. Asplund RO (1991) Urease inhibition by extracts and extract fractions from species of the plant genus Yucca J. Anim. Sci. 69:((Suppl. 1): 113. Balog JM, Anthony NB, Wall CV, Walker RD, Rath NC & Hu WE (1994) Eect of urease inhibitor and ceiling fans on ascites in broilers. 2. Blood variables, ascites scores and body and organ weights. Poult. Sci. 73: 810816. Blockmans D, Deckmyn H & Vermylen J (1995) Platelet activation. Blood Rev. 9: 143. Buret A, Gall DG & Olson ME (1990) Eects of murine giardiasis on growth, intestinal morphology, and disaccharidase activity. J. Parasitol. 76: 403409. Calderon AA, Zapata JM, Munoz R, Pedreno MA & Ros Barcelo A (1993) Resveratrol production as a part of the hypertensive-like response of grapevine cells to an elicitor from Trichoderma viride. New Phytol. 124: 455463. Cheeke PR (1998) Saponins: Surprising benets of desert plants. In: The Linus Pauling Institute Newsletter (pp. 45). Oregon State University, Corvallis, OR. Cheeke PR (2000) Actual and potential applications of Yucca schidigera and Quillaja saponaria saponins in human and animal nutrition. Proceedings of the Phytochemical Society of Europe 45: 241254. Cline JL, Fischer BA, Trottier NL, Walker RD & Easter RA. (1996) Eect of feeding Micro-Aid on stillbirths, preweaning mortality, blood oxygen values of piglets and blood urea nitrogen in sows. J. Anim. Sci. 74(Suppl. 1): 189. Colina JJ, Lewis AJ, Miller PS & Fischer RL (2001) Dietary manipulation to reduce aerial ammonia concentrations in nursery pig facilities. J. Anim. Sci. 79: 30963103. Czeczot H, Podsiad M, Skrzycki M, Stochmal A & Oleszek W (2003) Evaluation of the mutagenic activity of phenolics from the bark of Yucca schidigera Roezl. Acta Polon. Pharm. 60: 357362. Docherty JJ, Fu MM, Stier BS, Limperos RJ, Pokabla CM & De Lucia AL (1999) Resveratrol inhibition of herpes simplex virus replication. Antiviral Res. 43: 145155. Duy CF, Killeen GF, Connolly CA & Power RF (2001) Eects of dietary supplementation with Yucca schidigera Roezl ex Ortgies and its saponin and non-saponin fractions on rat metabolism. J. Agric. Food Chem. 49: 34083413. Farthing MJG (1994): Giardiasis as a disease, Giardia: From Molecules to Disease. In: Thompson RCA, Reynoldson JA & Lymbery AJ (eds), Giardia: From Molecules to Disease (pp. 1537). University Press, Cambridge, UK. Flaoyen A, Wilkins AL & Sandvik M (2002) Ruminal metabolism in sheep of saponins from Yucca schidigera. Veter. Res. Commun. 26: 159169. Headon DR, Buggle KA, Nelson AB & Killeen GF (1991): Glycofractions of the Yucca plant and their role in ammonia control, Biotechnology in the Feed Industry. In: Lyons TP (eds), Biotechnology in the Feed Industry (pp. 95108). Alltech Technical Publications, Nicholasville, KY. Hristov AN, McAllistar TA, Van Herk FH, Cheng KJ, Newbold CJ & Cheeke PR (1999) Eect of Yucca schidigera

Conclusions This review gives an account on the chemistry and biological activities of Y. schidigera. In particular, it is the rst report which summarizes the results gathered so far on the two metabolite classes occurring in the polar fraction of Y. schidigera trunk: saponins and phenolics. Biological activities of Y. schidigera have been traditionally attributed to its saponin constituents, thus more attention has been given to the isolation and structure elucidation of this class of compounds. More recently our investigations aimed to identify other metabolites eventually co-responsible for the biological activities of yucca products, led to the isolation of very unusual stilbenic derivatives occurring only in this plant. Their similarity to the well-known resveratrol prompted us to carry out a program aimed to evaluate for yucca phenolics some of the activities exerted by resveratrol. As a consequence of such eorts, interesting antioxidant-, platelet activation inhibiting-, iNOS expression-inhibiting activities have been highlighted. Thus the case of Y. schidigera indicate that even extensively studied plants may be the source of exciting and unexpected discoveries, such as novel bioactivities of considerable promise. The results obtained show that new opportunities could be explored which could increase the commercial value of yucca. In particular, the possible application of Y. schidigera products, which already possess GRAS label, as food supplements with antioxidant properties has to be evaluated.

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