Determination of the regulatory properties of Yucca schidigera extracts on the biochemical parameters and plasma hormone levels associated with obesity

ABSTRACT

Yucca schidigera Ortgies, Asparagaceae, is a herbaceous plant. Due to the high saponin content the powdered branches and leaves are used as natural food additive for human and animal. The aim of this study was to investigate the effects of Y. schidigera extracts on plasma leptin, ghrelin, adiponectin, insulin, thyroid hormones and some biochemical parameters in mice fed a high-fat diet. Male Swiss Albino mice were divided into seven equal groups. Group I (negative control group) was given standard diet; Group II was given high-fat diet; Group III was given high-fat diet with carboxymethylcellulose; Groups IV–VII were given hexane, petroleum ether, ethyl acetate, and methanol extracts of Y. schidigera and high-fat diet via gastric gavage for 60 days. High-fat diet significantly increased plasma leptin, insulin, free T₃ hormone, glucose, cholesterol, low-density lipoprotein, triacylglyceride, aspartate aminotransferase and alanine aminotransferase levels, and significantly decreased plasma ghrelin, adiponectin and free T₄ hormone levels. On the other hand, hormone levels, lipid profile and biochemical parameters were improved by the administration of the PE extract. Y. schidigera extracts could be used as preventive medicine in nutritional disorders via regulating energy metabolism and hormonal functions.

Keywords:
Adiponectin; Ghrelin; Insulin; Leptin; Obesity; Mice

Introduction

Yucca schidigera Ortgies is a herbaceous plant from the family Asparagaceae, native to the deserts of the south-western United States and northern Mexico. Due to the antiprotozoal and antifungal properties and hormone-stimulating effects it has been used safely to enhance performance as feed material for livestock as well as food material for humans (Narutoshi, 1992). Moreover, in recent researches, Y. schidigera has shown to possess antioxidant, anti-hypercholesterolemic, anticarcinogenic, antiarthritic, anti-inflammatory, antiprotozoal, antifungal and antihypertensive properties. The plant was shown to have secondary metabolites such as eugenol, caffeic acid, rosmarinic acid and α-tocopherol. Moreover, the dried and powdered plant material also contains approximately 10% steroidal saponins and is used commercially as a saponin source (Francis et al., 2002; Piacente et al., 2004; Enginar et al., 2006; Kucukkurt and Dündar, 2013).

Saponins are a class of secondary metabolites found in several plant species. More specifically, they produce soap-like foaming when shaken in aqueous solutions, and, in terms of structure, one or more hydrophilic glycoside moieties combined with a lipophilic triterpene or steroidal aglycone. These compounds are used in phytotherapy and in the cosmetic industry for their cytotoxic, hemolytic, molluscicidal, anti-inflammatory, antifungal, antiyeast, antibacterial and antiviral activities (Leung et al., 1997; Sen et al., 1998; Bachran et al., 2006) as well as in the pharmaceutical industry for the semi-synthesis of steroidal drugs (Chwalek et al., 2006). Moreover, saponins stimulate luteinizing hormone release leading to abortifacient properties (Francis et al., 2002), have immunomodulatory potential (Sun et al., 2009), cytostatic and cytotoxic effects (Bachran et al., 2008) and adjuvant properties for vaccines (Sjolander et al., 1998). Due to their physiological properties, saponins are now expected to serve as functional components in food. They have been reported to decrease plasma cholesterol in rats when added to their diets (Oakenfull, 1981; Sidhu and Oakenfull, 1986).

Fatty diet, as well as imbalance between the food intake and energy expenditure are the factors affecting the prevalence of obesity (Altunkaynak, 2005; Milagro et al., 2006). Obesity and overweight pose a major risk for serious diet-related chronic diseases, including type-II diabetes, cardiovascular diseases, hypertension, stroke and certain forms of cancer. Leptin, insulin and T₃ are among the most important hormones to provide this balance (Otukonyong et al., 2005). Leptin, an adipose tissue hormone, regulates body fat mass and body weight by decreasing the appetite and increasing energy expenditure (Zabrocka et al., 2006).

The present study was planned to determine the effects of the extracts obtained from Y. schidigera, which was reported to be rich in saponins in the previous studies, on leptin, ghrelin, insulin and thyroid hormones and some biochemical parameters in mice fed a high-fat diet.

Materials and methods

Plant material

Yucca schidigera Ortgies, Asparagaceae, standard powder (Sarsaponin 30^® contains more than 8% steroidal saponin) was purchased from Desert King International (San Diego, CA, USA).

Preparation of the extracts

Y. schidigera powder (500 g) was successively extracted with 5 l of hexane (HE), petroleum ether (PE), ethyl acetate (EA) and methanol (ME) by percolation method at room temperature. After completion of extraction the extracts were filtered and the solvent was removed by distillation under reduced pressure and low temperature (40–50 ºC) on a rotary evaporator to give crude extracts. Extracts were weighed and yield percentages were calculated as 17.93% for HE, 26.42% for PE, 11.02% for EA and 9.27% for ME.

Animals

Male Swiss Albino mice (25–35 g) were purchased from the animal breeding laboratories of Afyon Kocatepe University Experimental Animal Research and Application Center (Afyon, Turkey). The animals were allowed to acclimatize to the animal facility for at least 7 day before experiment started. The room conditions were maintained in a 12 h light/12 h dark cycle at room temperature (25 ± 3 ºC), with rodent standard diet and water provided ad libitum. A minimum of ten animals was used in each group. The study was permitted by the Institutional Animal Ethics Committee (Ankara University Ethical Council Study Number: 2009/34) and was performed according to the international rules considering the animal experiments and biodiversity right.

Experimental protocol

Two different control groups were employed in the study. The negative control group was maintained on standard pellet diet and water ad libitum without administering any plant extract (negative control group). The high-fat diet (HFD) group received special diet containing 40% beef tallow for eight weeks (HFD group-positive control). The vehicle control group received 0.5% CMC suspension in distilled water and was maintained on HFD (CMC group). On the other hand, the experimental group animals received hexane (HE), petroleum ether (PE), ethyl acetate (EA), and methanol (ME) extracts obtained from Y. schidigera along with HFD. Extracts were administered orally after suspending in distilled water and 0.5% sodium carboxymethyl cellulose (CMC) by using a gastric gavage at 100 mg/kg doses daily for eight weeks. This dose was determined according to a previous preliminary study (Avci et al., 2006). Blood samples were taken from the heart into tubes with heparin and plasma was obtained at the end of the experimental period, then centrifugation performed at 1500 × g (+4 ºC) for 10 min and kept at −30 ºC in advance of assays.

Biochemical analysis

Plasma leptin (Biovendor, Czech Republic, Cat No. RD291001200R), insulin (Millipore, USA, Cat No. EZRMI-13K), ghrelin (Millipore, USA, Cat No. EZRGRT-91K), total adinopectin (Biovendor, Czech Republic, Cat No. RD293023100R), total tri-iodothyronine (T₃) (DRG International Inc., USA, Cat No. EIA-4569), total tetra-iodothyronine (T₄) (DRG International Inc., USA, Cat No. EIA 4568), free tri-iodothyronine (FT3) (DRG International Inc., USA, Cat No. EIA-2385) and free tetra-iodothyronine (FT4) (DRG. International Inc., USA, Cat No. EIA 2386) were measured using an enzyme-linked immunosorbent assay (ELISA).

Liver damage was assessed by the estimation of serum levels of alanine aminotransferase (ALT), and aspartate aminotransferase (AST) by using commercial kits Teco Diagnostics assay kit (Teco Diagnostics, CA, USA). Serum levels of total protein (Tp), urea, total cholesterol (Tc), glucose, low density lipoprotein-cholesterol (LDL-c), high density lipoprotein-cholesterol (HDL-c) and triacylglyceride (Tg) were determined using COBAS test kits (Roche Diagnostics Systems, Istanbul, Turkey) according to the manufacturers' instructions in Laboratory of Biochemistry, Faculty of Veterinary Medicine, University of Afyon Kocatepe (Turkey).

Statistical analysis of data

The data obtained from the animal experiments was expressed as mean and standard error (±SEM). The statistical differences among the experimental groups were evaluated by one-way ANOVA and Duncan post hoc tests using the SPSS computer software program. A difference of p < 0.05 in the mean values was considered significant.

Results

Body weights of the mice are shown in Table 1. Supplementation of HFD to the animals during eight weeks significantly increased the body weight compared to the control group (p < 0.05). On the other hand, during the experimental period PE extract prevented the weight gain of mice compared to the other groups.

Table 1
The effects of Yucca shidigera extracts on body weight in mice (n: 15; mean ± SEM).

Groups	0 day	15 day	30 day	45 day	60 day	p value
Control	25.43 ± 0.75	25.57 ± 0.67	25.17 ± 0.69	25.61 ± 0.87	26.00 ± 0.99	0.966
HFD	26.44 ± 0.79c	29.44 ± 1.02b	32.27 ± 1.20b	35.40 ± 1.06a	36.90 ± 1.18a	0.000
HFD + CMC	26.19 ± 0.82c	29.61 ± 1.21b	31.86 ± 1.28b	36.16 ± 0.93a	36.63 ± 1.21a	0.000
HE extract	25.86 ± 1.06b	30.85 ± 0.98a	29.47 ± 1.44a	30.01 ± 1.10a	30.08 ± 0.98a	0.038
PE extract	26.93 ± 1.36	30.31 ± 1.77	30.20 ± 0.89	30.81 ± 0.88	30.68 ± 1.04	0.083
EA extract	27.87 ± 1.49b	31.60 ± 1.42a	31.76 ± 1.26a	33.86 ± 1.08a	34.19 ± 1.08a	0.012
ME extract	26.17 ± 0.87b	33.31 ± 0.74a	33.27 ± 0.77a	33.90 ± 0.72a	34.64 ± 0.72a	0.000

• ^a,b,c
  Values with different letters within a column are significantly different by Duncan's multiple range test.
• HE, hexane; PE, petroleum ether; EA, ethyl acetate; ME, methanol.

Plasma glucose, TC, LDL, HDL, TG, AST, and ALP were found to be high in HFD and CMC + HFD groups compared to the control group (p < 0.05) as shown in Table 2. On the other hand, administration of 100 mg/kg Y. schidigera extracts, especially HE and PE, decreased the levels of these parameters (p < 0.05). These results suggest that Y. schidigera extracts have capacity to alleviate the biochemical status caused by HFD.

Table 2
The effects of Yucca schidigera extracts on blood biochemical parameters in mice (n: 15; mean ± SEM).

Groups	Glucose (mg/dl)	Tc (mg/dl)	LDL-c (mg/dl)	HDL-c (mg/dl)	Tg (mg/dl)	Tp (g/dl)	AST (U/L)	ALT (U/L)
Control	103.6 ± 2.50cd	88.71 ± 2.69c	22.30 ± 2.59c	85.66 ± 2.45c	64.37 ± 3.16bc	4.30 ± 0.08	39.34 ± 4.09b	164.1 ± 11.3b
HFD	163.7 ± 9.28a *	189.1 ± 8.45a *	66.7 ± 6.47a *	116.8 ± 2.71b *	99.85 ± 4.25a *	4.34 ± 0.15	76.19 ± 4.48a *	235.5 ± 23.8a *
HFD + CMC	179.5 ± 7.47a	197.6 ± 14.31a	70.6 ± 3.13a	118.2 ± 4.37b	102.9 ± 5.14a	4.37 ± 0.12	71.68 ± 5.02a	241.7 ± 20.1a
HE extract	91.03 ± 3.01d	137.7 ± 8.65b	49.32 ± 1.99b	139.1 ± 6.09a	76.00 ± 4.55b	4.83 ± 0.12	36.28 ± 2.93b	173.1 ± 13.1b
PE extract	118.2 ± 7.35c	129.3 ± 5.29b	42.97 ± 1.48b	111.3 ± 3.96b	66.71 ± 3.74bc	4.77 ± 0.12	46.26 ± 2.42b	179.3 ± 12.1b
EA extract	124.1 ± 7.17c	128.2 ± 3.06b	62.64 ± 4.94a	108.6 ± 3.61b	57.01 ± 5.01c	4.50 ± 0.18	36.80 ± 2.97b	173.9 ± 14.6b
ME extract	148.4 ± 13.2b	148.5 ± 6.81b	65.0 ± 3.97a	124.4 ± 9.03b	66.43 ± 6.82bc	4.31 ± 0.23	44.09 ± 2.99b	180.1 ± 10.8b
p value	0.000	0.000	0.000	0.000	0.000	0.067	0.000	0.003

• ^*
  HFD group is statistically different compared to the control group (p < 0.05)
• ^a,b,c
  Values with different letters within a column are significantly different by Duncan's multiple range test (p < 0.05).
• HE, hexane; PE, petroleum ether; EA, ethyl acetate; ME, methanol.

Supplementation of HFD increased leptin, insulin, and FT3 whereas decreased ghrelin, adiponectin, and FT4 (p < 0.05). In addition, TT4 and TT3 levels were not changed in all groups (Table 3). On the other hand, administration of 100 mg/kg Y. schidigera extracts especially PE resulted in reversal of HFD-induced hormone levels (p < 0.05). These results suggest that Y. schidigera extracts affected hormone status.

Table 3
The effects of Yucca schidigera extracts on some hormones in mice (n: 15; mean ± SEM).

Groups	Leptin (ng/ml)	Ghrelin (mg/dl)	Adiponectin (mg/dl)	Insulin (ng/ml)	TT4 (µg/dl)	ST4 (ng/ml)	TT3 (µg/dl)	ST3 (pg/ml)
Control	28.14 ± 1.75b	1.21 ± 0.05a	1.41 ± 0.13a	0.44 ± 0.05c	34.45 ± 3.45	0.36 ± 0.04a	18.33 ± 0.15	1.91 ± 0.05b
HFD	57.41 ± 4.13a *	0.79 ± 0.06b *	0.79 ± 0.09b *	2.07 ± 0.24a *	41.39 ± 1.22	0.14 ± 0.02b *	18.58 ± 0.14	3.52 ± 0.33a *
HFD + CMC	54.24 ± 4.81a	0.73 ± 0.04b	0.81 ± 0.11b	2.21 ± 0.15a	42.44 ± 2.47	0.15 ± 0.02b	18.90 ± 0.26	3.03 ± 0.31a
HE extract	36.55 ± 2.04b	0.81 ± 0.04b	1.49 ± 0.12a	0.56 ± 0.11bc	36.89 ± 1.53	0.42 ± 0.04a	18.41 ± 0.04	3.25 ± 0.17a
PE extract	36.05 ± 3.13b	1.38 ± 0.07a	1.52 ± 0.08a	0.80 ± 0.04bc	43.54 ± 2.57	0.49 ± 0.05a	18.44 ± 0.03	3.26 ± 0.09a
EA extract	37.81 ± 5.72b	0.77 ± 0.07b	1.21 ± 0.11a	0.84 ± 0.04b	43.70 ± 3.37	0.50 ± 0.04a	18.47 ± 0.09	3.16 ± 0.18a
ME extract	35.39 ± 2.27b	0.75 ± 0.09b	1.46 ± 0.10a	0.79 ± 0.12bc	40.02 ± 2.88	0.44 ± 0.07a	18.45 ± 0.05	3.19 ± 0.07a
p value	0.000	0.000	0.000	0.000	0.126	0.000	0.098	0.000

• ^*
  HFD group is statistically different compared to the control group (p < 0.05).
• ^a,b,c
  Values with different letters within a column are significantly different by Duncan's multiple range test (p < 0.05).
• HE, hexane; PE, petroleum ether; EA, ethyl acetate; ME, methanol.

Discussion

Although in some studies it was shown that HFD does not affect weight gain (Gao et al., 2002), in our study it was observed that mice given fat exhibited weight gain as in the long term studies carried out with HFD (Cha et al., 2000). Compared to the control group, the increase in 15 days live weight was found to be statistically significant in all groups but the PE and HE groups. The other measurements were also supported these data.

Although body fat index and body mass index are the major determinants of leptin levels, insulin, glucocorticoids and prolactin stimulate leptin synthesis while NPL, thyroid hormones, GH, somatostatin, free fatty acids and long exposure to cold inhibit it (Kucukkurt, 2015). In a previous study by İşbilen et al. (2007) HFD fed rats during five weeks, the plasma, aort and liver leptin levels increased. Similarly, in our study, plasma leptin levels increased in the high-fat diet and CMC groups. In Y. schidigera extract groups, however, leptin levels decreased significantly although mice were fed a high-fat diet. The decrease of leptin levels in the extract groups and increase in high-fat diet groups were parallel with the changes in the live-weight as shown in Table 1. Indeed, Kim et al. (2005) fed the rats with high-fat diet for eight weeks and then refined the steroidal saponins in Red Korean Ginseng, which is considered as a steroidal saponin source like Y. schidigera, and administered it intraperitoneally for three weeks at a dose of 200 mg/kg/day. At the end of the study, it was noted that plasma leptin levels decreased significantly in the animals that were given saponin, and the researchers suggested that this could be due to the fact that saponin resulted in decrease in live-weight and body fat mass. In another study by the same researchers, protopanaxadiol and protopanaxatriol-type saponins from Red Ginseng were administered to the rats fed a HFD at 50 mg/kg/day dose. It was reported that the decrease in plasma leptin levels could be attributed to thermogenesis properties of the saponins (Kim et al., 2009). The mentioned researches on the activity of the saponins on the leptin levels, supported our results which reveal a decrease in body fat mass in mice with the administration of Y. schidigera extracts.

Consistent with these findings, in our study, both ghrelin and adinopectin levels decreased significantly in the mice fed a HFD compared to the control group. Ghrelin levels increased in the PE and HE groups while they did not change in the other extract groups. This increase in the PE and HE groups is consistent with the decrease in leptin levels and live-weight. In the other extract groups, no change was seen in ghrelin hormone levels compared to the HFD group and in these groups live-weight decrease was not similar to that in the PE and HE groups. In our study, insulin hormone increased statistically, particularly in the HFD and CMC groups. Increase in insulin reflects that blood glucose was stored as glycogen in the liver and as fatty acids in the adipose tissue (Bayşu Sözbilir and Bayşu, 2008). Increase in adipose tissue also increases leptin hormone levels in the blood (Patel et al., 1998). Srinivasan et al. (2005) reported that body weight increases in rats fed a HFD, which leads to increase in plasma glucose, triacylglyceride, total cholesterol and insulin levels compared to the control group. Besides, Winzell and Ahren (2004) studied the effect of HFD and reported that insulin levels increase in mice parallel to feeding on a HFD. In the present study, the same situation was seen in the HFD group, however, insulin levels decreased in the Y. schidigera extract administered-groups suggesting that active ingredients found in extracts may probably play a role in this action. A review by Margetic et al. revealed that many studies conducted in humans and rats suggest that hyperinsulinemic conditions increase plasma leptin levels. Patel et al. (1998) reported that plasma leptin levels decrease in diabetic rats, but administration of insulin acts by increasing plasma leptin levels. Our findings are found to be in accord with those previous data.

Considering thyroid hormone measurements, although in our study there was not any difference between the total T₄ and T₃ and free T₃ levels increased, free T₄ hormone decreased in the Y. schidigera extract groups compared to the HFD and CMC groups and we did not note any change compared to control group. Our previous study shows that escin which contains saponin effects serum T₃ and T₄ levels in HFD fed mice (Avci et al., 2010). Although we did not spot any study in literature that focus especially on saponins and thyroid hormones, there are data suggesting that short- and long-term use of natural and synthetic flavanoids cause decrease in plasma T₃ and T₄ levels (Van der Heidi et al., 2003). Fain et al. (1997) found that administration of T₃ to hypothyroid rats decreased leptin mRNA levels by 40% at the 8th hour; therefore, they suggested high thyroid hormone levels can diminish leptin levels. Zabrocka et al. (2006) showed that serum leptin levels and white adipose tissue mRNA levels that are considered as indicators of leptin synthesis decrease in rats, to which they had given various amounts of T_3. In some studies, however, no correlation was reported between thyroid hormones and leptin (Friedman and Halaas, 1998).

Studies show that HFD increases ALT and AST levels in the blood (Friedman et al., 1996). In this study, it was also observed that plasma AST and ALT levels increased and this increase was less in the Y. schidigera plant extract groups. The plant Y. schidigera contains mainly steroidal saponins as well as vegetal chemicals such as phenolic substances, fiber, resveratrol and stilbens in its dry matter and these saponins are widely used in industry and stockbreeding (Kucukkurt and Dündar, 2013). It was showed in several studies that plants containing saponin act by reducing the absorption of nutritions in the digestive tract and can alter metabolism by this route. Y. schidigera lowers lipid metabolism and blood glucose levels. It is thought that these effects of saponins are revealed when taken in small amounts and they particularly alter normal absorption of lipids and glucose in the digestive tract (Kucukkurt and Dündar, 2013). Y. schidigera acts on lipid metabolism and lowers cholesterol, LDL and triacylglyceride levels (Kim et al., 2003; Kucukkurt et al., 2011). When the extract groups were taken into account, the lowest value that decreased glucose levels of all the groups was the HE-administered group. While a decrease in cholesterol and triacylglyceride levels was noted in all the extract groups, LDL levels decreased only in the HE and PE groups. Findings in this study indicate the effect of Y. schidigera on lipid metabolism and similar results were also obtained in the other studies (Ince et al., 2013; Kucukkurt and Dündar, 2013). Here, Y. schidigera generated a regulatory effect on the lipid profile and lipid metabolism by regulating hepatic functions. As a conclusion, extracts obtained from Y. schidigera can be used for the prevention of the diseases caused by HDF and regulation of the energy metabolism and hormonal functions. Petroleum ether and hexane extracts exert the most significant effect, yet, further studies should be conducted to reveal the active secondary metabolites.

Acknowledgement

This study was supported by Afyon Kocatepe University Scientific Research Projects Commission with the Project number of 09.VF.11.

References

• Altunkaynak, Z., 2005. Effects of high fat diet induced obesity on female rat livers. Eur. J. Gen. Med. 2, 100-109.
• Avci, G., Kupeli, E., Eryavuz, A., Yesilada, E., Kucukkurt, I., 2006. Antihypercholesterolaemic and antioxidant activity assessment of some plants used as remedy in Turkish Folk Medicine. J. Ethnopharmacol. 107, 418-423.
• Avci, G., Kucukkurt, I., Akkol, E.K., Yeşilada, E., 2010. Effects of escin mixture from the seeds of Aesculus hippocastanum on obesity in mice fed on high-fat diet. Pharm. Biol. 48, 247-252.
• Bachran, C., Sutherland, M., Heisler, I., Hebestreit, P., Melzig, M.F., Fuchs, H., 2006. The saponin-mediated enhanced uptake of targeted saporin-based drugs is strongly dependent on the saponin structure. Exp. Biol. Med. 231, 412-420.
• Bachran, C., Bachran, S., Sutherland, M., Bachran, D., Fuchs, H., 2008. Saponins in tumor therapy. Mini Rev. Med. Chem. 8, 575-584.
• Bay şu Sözbilir, N., Bay şu, N., 2008. Biyokimya, Güne ş Tıp Kitapevleri, 1. Baskı, Ankara.
• Cha, M.C., Chou, C.J., Boozer, C.N., 2000. High-fat diet feeding reduces the diurnal variation of plasma leptin concentration in rats. Metabolism 49, 503-507.
• Chwalek, M., Lalun, N., Bobichon, H., Pĺe, K., Voutquenne-Nazabadioko, L., 2006. Structure–activity relationships of some hederagenin diglycosides: haemolysis, cytotoxicity and apoptosis induction. Biochim. Biophys. Acta 1760, 1418-1427.
• Enginar, H., Avcı, G., Eryavuz, A., Kaya, E., Kucukkurt, İ., Fidan, A.F., 2006. Effect of Y. schidigera extract on lipid peroxidation and antioxidant activity in rabbits expose gamma radiation. Revue Méd. Vét. 157, 415-419.
• Fain, J.N., Coronel, E.C., Beauchamp, M.J.B.S., 1997. Expression of leptin and β₂-adrenerjic receptors in rat adipoze tissue in altered thyroid states. Biochem. J. 322, 145-150.
• Francis, G., Kerem, Z., Makkar, H.P.S., Becker, K., 2002. The biological action of saponins in animal systems. Br. J. Nutr. 88, 587-605.
• Friedman, L.S., Martin, P., Munoz, S.J., 1996. Liver function tests and the objective evaluation of the patient with liver disease. In: Zakin, D., Boyer, T.D. (Eds.), Hepatolog: A Textbook of Liver Disease., 3rd ed. WB Saunders, Philadelphia, pp. 791–833.
• Friedman, J.M., Halaas, J.L., 1998. Leptin and the regulation of body weight in mammals. Nature 395, 763-770.
• Gao, J., Ghibaudi, L., van Heek, M., Hwa, J.J., 2002. Characterization of diet-induced obese rats that develop persistent obesity after 6 months of high-fat followed by 1 month of low-fat diet. Brain Res. 936, 87-90.
• Ince, S., Kucukkurt, I., Turkmen, R., Demirel, H.H., Sever, E., 2013. Dietary Yucca schidigera supplementation reduces arsenic induced oxidative stress in Swiss albino mice. Toxicol. Ind. Health 29, 904-914.
• İşbilen, B., Arı, Z., Var, A., Onur, E., Uyanık, B.S., 2007. Yüksek Yağ İçeren Diyet İle Beslenen Ratlarda DHEAS’ın Leptin, Lipid Profili Ve Endotel Fonksiyonu Üzerine Etkileri. F.Ü. Sağ. Bil. Derg. 21, 109-116.
• Kim, J.H., Hahm, D.H., Yang, D.C., Kim, J.H., Lee, H.J., Shim, I., 2005. Effect of crude saponin of Korean red ginseng on high-fat diet-induced obesity in the rat. J. Pharmacol. Sci. 97, 124-131.
• Kim, J.H., Kang, S.A., Han, S.M., Shim, I., 2009. Comparison of the antiobesity effects of the protopanaxadiol- and protopanaxatriol-type saponins of red ginseng. Phytother. Res. 23, 78-85.
• Kim, S.W., Park, S.K., Kang, S.I., Kang, H.C., Oh, H.J., Bae, C.Y., Bae, D.H., 2003. Hypocholesterolemic property of Yucca schidigera and Quillaja saponaria extracts in human body. Arch. Pharm. Res. 26, 1042-1046.
• Kucukkurt, I., Ince, S., Enginar, H., Eryavuz, A., Fidan, A.F., Kargıoglu, M., 2011. Protective effects of Agrostemma githago L. and Saponaria officinalis L. extracts against ionizing radiation-induced oxidative damage in rats. Revue Méd. Vét. 162, 289-296.
• Kucukkurt, I., Dündar, Y., 2013. Effects of dietary Yucca schidigera supplementation on plasma leptin, insulin, iodated thyroid hormones and some biochemical parameters in rats. Revue Méd. Vét. 164, 362-367.
• Kucukkurt, I., 2015. The effects of leptin on other hormones. Kocatepe Vet. J. 8, 75-83.
• Leung, Y.M., Ou, Y.J., Kwan, C.Y., Loh, T.T., 1997. Specific interaction between tetrandrine and Quillaja saponins in promoting permeabilization of plasma membrane in human leukemic HL-60 cells. Biochim. Biophys. Acta 1325, 318-328.
• Milagro, F.I., Campion, J., Martinez, J.A., 2006. Weight gain induced by high-fat feeding involves increased liver oxidative stress. Obesity 14, 1118-1123.
• Narutoshi, H., 1992. Composite for curing intestinal disorders. Japanese Patent, 4-16163.
• Oakenfull, D., 1981. Saponins in foods. A review. Food Chem. 6, 19-40.
• Otukonyong, E.E., Dube, M.G., Torto, R., Karla, P.S., Kalra, S.P., 2005. Highfat diet-induced ultradian leptin and insulin hypersecretion are absent in obesity-resistant rats. Obes. Res. 13, 991-999.
• Patel, B.K., Koenig, J.I., Kaplan, L.M., Hooi, S.C., 1998. Increase in plasma leptin and Lep mRNA concentrations by food intake is dependent on insulin. Metabolism 47, 603-607.
• Piacente, S., Montoro, P., Oleszek, W., Pizza, C., 2004. Yucca schidigera Bark: phenolic constituents and antioxidant activity. J. Nat. Prod. 67, 882-885.
• Sen, S., Makkar, H.P.S., Muetzel, S., Becker, K., 1998. Effect of Quillaja saponaria saponins and Yucca schidigera plant extract on growth of Escherichia coli . Lett. App. Microbiol. 27, 35-38.
• Sidhu, G.S., Oakenfull, D.G., 1986. A mechanism for the hypocholerterolaemic activity of saponins. Br. J. Nutr. 55, 643-649.
• Sjolander, A., Cox, J.C., Barr, I.G., 1998. ISCOMs: an adjuvant with multiple functions. J. Leukoc. Biol. 64, 713-723.
• Srinivasan, K., Viswanad, B., Asrat, L., Kaul, C.L., Ramarao, P., 2005. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacol. Res. 52, 313-320.
• Sun, H.X., Xie, Y., Ye, Y.P., 2009. Advances in saponin-based adjuvants. Vaccine 27, 1787-1796.
• Van der Heidi, D., Kastelijn, J., Schröder-van der Elst, J.P., 2003. Flavonoids and thyroid disease. Biofactors 19, 113-119.
• Winzell, M.S., Ahren, B., 2004. The high-fat diet-fed mouse: a model for studying mechanisms and treatment of impaired glucose tolerance and type 2 diabetes. Diabetes 53, 215-219.
• Zabrocka, L., Klimek, J., Swierczynski, J., 2006. Evidence that triiodothyronine decreases rat serum leptin concentration by down-regulation of leptin gene expression in white adipose tissue. Life Sci. 79, 1114-1120.

Publication Dates

• Publication in this collection
  Mar-Apr 2016

History

• Received
  11 Sept 2015
• Accepted
  06 Dec 2015