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Effect of Cydonia oblonga Mill. fruit and leaf extracts on blood pressure and blood rheology in renal hypertensive rats
Journal of Ethnopharmacology 152 (2014) 464–469
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Effect of Cydonia oblonga Mill. fruit and leaf extracts on blood pressure and blood rheology in renal hypertensive rats Wenting Zhou a,1, Elzira Abdusalam a,1, Parida Abliz b, Nadira Reyim c, Shuge Tian d, Qimangul Aji a, Mehray Issak a, Guldiyar Iskandar a, Nicholas Moore a,e,n, Anwar Umar a,e,nn a
Department of Pharmacology, Xinjiang Medical University, 393 Xinyi Road, 830011 Urumqi, Xinjiang, People's Republic of China Department of Pharmacognosy, Faculty of Pharmacy, Xinjiang Medical University, 393 Xinyi Road, 830011 Urumqi, Xinjiang, People's Republic of China c Department of Cardiovascular Internal Medicine, the Second Affiliated Hospital of Xinjiang Medical University, 38 Nanhu Road, Urumqi City, Shuimogou District, 830063 Urumqi, Xinjiang, People's Republic of China d Faculty of traditional Chinese Medicine, Xinjiang Medical University, 393 Xinyi Road, 830011 Urumqi, Xinjiang, People's Republic of China e Department of Pharmacology, University Bordeaux Segalen, 33076 Bordeaux, France b
art ic l e i nf o
a b s t r a c t
Article history: Received 8 October 2013 Received in revised form 16 January 2014 Accepted 17 January 2014 Available online 25 January 2014
Ethnopharmacological relevance: Quince, Cydonia oblonga Mill. (COM), is used in traditional Uyghur medicine to treat or prevent cardiovascular diseases. Uyghur people have greater longevity and lower blood pressure than other central Asian populations. We therefore tested COM fruit and leaf extracts on blood pressure and rheology in renal hypertensive rats (RHR). Materials and methods: Two-kidney, one-clip (2K1C) renal hypertensive rats were divided randomly into eleven groups: sham, model, and model treated with daily doses of 80 and 160 mg/kg aqueous or ethanol extracts of COM fruit or leaves, or 25 mg/kg captopril (n ¼10 per group), given orally once daily for 8 weeks. Blood pressure was measured before treatment and every 2 weeks thereafter. Blood rheology was tested after 8 weeks. Results: Model rats had higher blood pressure than sham 8 weeks after the procedure (systolic blood pressure 19377 vs. 1387 8 mmHg, po 0.05). Those treated with captopril had decreased blood pressure within 2 weeks but that did not return to the level found in the sham group at 8 weeks (1677 7, po 0.05 vs. model). With the COM extracts, the effect on blood pressure was notable after 4 weeks. At 8 weeks blood pressure was similar with captopril and with 160 mg ethanol leaf extract (1667 4, p o0.05 vs. model), the most effective of the extracts. Model rats had higher blood viscosity and lower erythrocyte deformability than sham. Captopril had little effect on blood rheology; whereas COM extracts reduced whole blood viscosity and improved erythrocyte deformability to levels approaching those found in sham. Conclusions: COM extracts have antihypertensive activity in renal hypertensive rats. The additional effect on rheology, compared to captopril, may convey added interest. Further studies of these effects in man appear warranted. & 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Cydonia oblonga Mill. extracts Renal hypertension rats Systolic blood pressure Diastolic blood pressure Blood rheology
1. Introduction Cardiovascular diseases including arterial hypertension are one of the main causes of morbidity and mortality. The exploration of traditional medicines may reveal new treatment options to
n Corresponding author at: Department of Pharmacology, University Bordeaux Segalen, 33076 Bordeaux, France. Tel.: þ 33 557571560; fax: þ 33 557574671. nn Corresponding author at: Department of Pharmacology, Xinjiang Medical University, 393 Xinyi road, 830011 Urumqi, Xinjiang, People's Republic of China. Tel./fax: þ 86 9914362421. E-mail addresses: [email protected] (N. Moore), [email protected] (A. Umar). 1 Both are equal contributors to this work.
0378-8741/$ - see front matter & 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jep.2014.01.018
increase the therapeutic arsenal by the discovery of novel medicines and to offer lower-cost alternatives in developing countries that increasingly share the same concerns. The South-western part of Xinjiang, in the People's Republic of China (PRC), around Hotan and Kashgar, is renowned for its large number of centenarians. Uyghur men from the region of Hotan have lower blood pressure that other central Asians (Kawamura et al., 2000, 2003; Wufuer et al., 2004). In traditional Uyghur medicine, the fruit and leaves of Quince (Cydonia oblonga Mill. COM) are used to treat or prevent hypertension and other cardiovascular diseases (Sadik, 1993), in addition to other uses (Aibaidula et al., 2009; Yan et al., 2009; Aslan et al., 2010). These are found also in traditional Turkish medicine, which shares common cultural roots (Kultur, 2007). Quince fruit and
W. Zhou et al. / Journal of Ethnopharmacology 152 (2014) 464–469
leaves contain many components with known antioxidant activity (Silva et al., 2005, 2002, 2004a, 2004b; Xakir and Aikebaier, 2006; Wojdylo et al., 2013), but putative antihypertensive effects have not yet been explored. We therefore sought to investigate the merits of this usage by testing the effects of Quince fruit and leaf extracts in an experimental model of renal hypertension, the Goldblatt 2-kidney, 1-clip rat model, compared to the effects of a standard antihypertensive drug, captopril.
2. Materials and methods 2.1. Medicines Cydonia Oblonga Mill. (COM) fruit and leaves were collected in October 2010 from the Kashgar area in Kargilik County, Xinjiang, PRC, dried and crushed then set aside. Fruit and leaf voucher specimens were left in the herbarium of the Traditional Chinese Medicine Ethnical Herbs Specimen Museum of Xinjiang Medical University under number NO.TCMEHSM2013100; Captopril was used as 25 mg/tablet, lot number 100803, Shanxi Huixing Pharmaceutical Co. Ltd., Shanxi, PRC. 2.2. Reagents and instruments The instruments and reagents used were B-260 type constant temperature water bath (Shanghai Ya Rong Biochemical Instrument Factory, Shanghai, PRC); AA520 type rotary evaporator (Shanghai Ya Rong Biochemical Instrument Factory); SHB-III type Multi-purpose water circulating pump (Shanghai Ya Rong Biochemical Instrument Factory); medical alcohol (75%, Weiye Experimental Material Company, Lot no.: 11030801); penicillin sodium for injection (800,000 unit/vial, Zhongguo Pharmaceutical co. Ltd, Lot no.: 101003017); pentobarbital sodium (Solar Bio, Lot no.: 6900183); BP-6 non-invasive blood pressure measuring device for animals (Chengdu Taimeng Technology Co. Ltd.), U-shaped silver clip (inside diameter: 0.20 mm); U-shaped silver clip (internal diameter 0.20 mm) Shanghai Alcott Biotech Co., Ltd.; LBY-N6C automatic self-cleaning blood flow metre; LBY-XC-40 automatic dynamic ESR Tester (Beijing Precil Instrument Co., Ltd.) 2.3. Animals One hundred and ten male Wistar rats were provided by the Experimental Animal Centre of Xinjiang Medical University, bodyweight 200 720 g, Licence no. SCXK (Xin): 2003-0001. They were fed daily with normal pellet chow and provided clean running water. All animals were treated according to the current standard
465
for experimental research in China, and the protocols were approved by the University of Xinjiang Ethics Committee for Animal Research.
2.4. Preparation of the test samples Shade-dried COM fruit and sun-dried leaves were crushed and sieved. The appropriate amount of the resulting powder was weighed, and diluted into 20 times its volume of 65% alcohol for 1 hour followed by 3 reverse extractions. Filtrates were combined, concentrated under reduced pressure and recovered. These were cleaned to remove chlorophyll and other impurities, after which the lower layer was concentrated and lyophilized, resulting in freeze-dried COM fruit and leaf aqueous and ethanol extracts. Extraction yield was about 1 g extract for 1.6 g leaves or fruit.
2.5. Establishment of 2K1C renal hypertensive rat model (Xian and Huang, 2007; Yan et al., 2009; Chelko et al., 2012; Najafipour et al., 2012) To induce hypertension according to the Goldblatt 2K1C model, (Goldblatt, 1958, 1964; Barger, 1979; Pinto et al., 1998; Xian and Huang, 2007; Reinhold et al., 2009; Umar et al., 2010) 200 720 g male Wistar rats were anesthetized with sodium pentobarbital (50 mg/kg intraperitoneally). The left renal artery was exposed by retroperitoneal flank incision and dissected free of the renal vein and connective tissue. A silver clip with a lumen of 0.22 mm was placed around the artery for partial occlusion; in sham operations, the artery was not clipped. The animals were kept under constant temperature (207 1 1C) and illumination (12-h light, 12-h dark cycle) until the day of experiment, with free access to food and water. After 6 weeks the systolic blood pressure (SBP) was measured using the tail-cuff method in conscious rats. Only hypertensive rats (SBP above 150 mmHg) were used in the experiments. When hypertension was established, the 2K1C rats were divided into groups of 10 rats:, an untreated renal hypertensive model group, a 2K1C group treated with captopril 25 mg/kg, and eight 2K1C groups treated with low (80 mg/kg) or high (160 mg/kg) doses of aqueous or ethanol COM fruit and leaf extracts. Doses of COM were chosen in reference to doses used in previous experiments (Abliz et al., 2014). In addition a group of 10 untreated shamoperated rats was used as control. Rats received the indicated preparations or identical quantities of physiological saline, in control and model groups, orally by daily gavage for 8 weeks. All rats were weighed and treatment adjusted to bodyweight once a week.
Table 1 Effects of Cydonia Oblonga Mill. fruit and leaf extracts on systolic blood pressure (mmHg 7 SD) of renal hypertensive rats (n¼ 10 per group).
Sham Model Captopril COM fruit water extract COM fruit water extract COM fruit ethanol extract COM fruit ethanol extract COM leaf water extract COM-leaf water extract COM leaf ethanol extract COM leaf ethanol extract n
#
po 0.05 vs. sham. p o 0.05 vs. model.
Dose (mg/kg)
Before use
2 Weeks
4 Weeks
6 Weeks
8 Weeks
– – 25 80 160 80 160 80 160 80 160
137.2 74.5 180.5 75.4n 181.8 76.7n 182.1 74.1n 183.6 74.9n 180.4 74.7n 182.7 77.5n 183.2 75.1n 182.3 74.7n 181.9 77.7n 182.5 74.5n
136.7 73.2 186.9 76.8n 172.2 77.8n,# 181.8 75.3n 182.3 75.9n 182.7 75.2n 180.5 75.1n 181.7 76.7n 181.0 76.9n 180.1 77.2n,# 181.2 75.7n
138.6 76.2 189.0 74.4n 169.4 77.1n,# 177.4 74.7n,# 176.8 77.0n,# 177.0 76.7n,# 174.0 75.4n,# 178.2 74.8n,# 174.8 76.5n,# 176.3 78.7n,# 176.6 74.9n,#
139.17 6.5 191.5 7 5.4n 167.4 7 8.7n,# 175.4 7 6.7n,# 173.3 7 3.6n,# 174.3 7 6.7n,# 171.3 7 5.6n,# 176.0 7 3.0n,# 172.9 7 3.2n,# 173.17 5.7n,# 171.0 7 5.5n,#
138.4 7 7.5 193.17 6.6n 167.2 7 6.8n,# 176.8 7 5.4n,# 173.0 7 8.1n,# 172.8 7 8.4n,# 168.97 8.3n,# 174.8 7 7.4n,# 170.37 5.1n,# 170.47 7.4n,# 166.17 4.3n,#
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2.6. Measurement of blood pressure and rheology SBP and DBP were measured by the tail-cuff method (BP-6 non invasive Electro-Sphygmomanometer) in conscious rats. Blood pressure was measured at 2, 4, 6, and 8 weeks of treatment, 1 h after product administration. Each measurement was taken 3 times and averaged. Blood pressure was measured 1 h after last administration. Rats were then anesthetised with 30 mg/kg 1% pentobarbital sodium, and blood was collected from the abdominal aorta. Whole blood viscosity under high, medium and low shear stress, and packed cell volume were measured after anticoagulation with heparin.
captopril group, SBP decreased from the second week of treatment, without reaching the values of the sham controls. In the COM fruit and leaf extract groups blood pressure started decreasing at the fourth week and further diminished thereafter (Table 1 and Fig. 1), reaching the same values as the captopril group at the end of 8-week period for the higher dose (160 mg/kg) of ethanol leaf extracts (Fig. 1). Lower doses had lesser effects (Table 1). 3.2. Diastolic blood pressure (DBP) DBP was significantly higher in the model than in the sham group (Table 2). Captopril reduced DBP from the beginning of treatment, to
2.7. Data processing
110 105 100 95 mmHg
Data was analysed using SPSS17.0 statistics software (IBM, Armonk, USA). All results are given as mean 7standard deviation, Mean from multiple groups were compared with One-Way ANOVA. After testing the homogeneity of variances, heterogeneous groups were tested with the Dunnett's t test and homogeneous groups with the LSD-t method. Significance limit was set at α¼ 0.05.
Sham Model Captopril fruit water extract fruit ethanol extract leaf aqueou sextract leaf ethanol extract
90 85 80 75 70 65
3. Results
60
Before
2
4
6
8
Weeks of treatment
3.1. Systolic blood pressure (SBP) (Table 1) Compared with the sham group, SBP increased significantly during the study period in the model group (po0.05; Table 1). In the
Fig. 2. Diastolic blood pressure in sham operated animals, 2K1C model untreated renal hypertensive rats (RHR), RHR treated with 25 mg/kg captopril, or 160 mg/kg Cydonia oblonga Mill. (COM) fruit or leaf, aqueous and ethanol extracts.
200 190 180 SBP mmHG
170 Sham Model Captopril fruit aqueous extract fruit ethanol extract leaf aqueous extract leaf ethanol extract
160 150 140 130 120 110 100
Before
2
4
6
8
Weeks treatment
Fig. 1. Systolic blood pressure in sham operated animals, in 2K1C model untreated hypertensive rats (RHR), in RHR rats treated with 25 mg/kg captopril, 160 mg/kg Cydonia oblonga Mill. (COM) fruit or leaf, aqueous and ethanol extracts.
Fig. 3. Whole blood viscosity in sham operated animals, 2K1C model untreated renal hypertensive rats (RHR), RHR treated with 25 mg/kg captopril, or 160 mg/kg Cydonia oblonga Mill. (COM) fruit or leaf aqueous and ethanol extracts.
Table 2 Effects of Cydonia oblonga Mill. fruit and leaf extracts on diastolic blood pressure (mmHg 7 SD) of renal hypertensive rats (n¼ 10 per group).
Sham Model Captopril COM fruit aqueous extract COM fruit aqueous extract COM fruit ethanol extract COM fruit ethanol extract COM leaf aqueous extract COM leaf aqueous extract COM leaf ethanol extract COM leaf ethanol extract n
#
p o0.05 vs. sham. p o 0.05 vs. model.
Dose (mg/kg)
Before use
2 Weeks
4 Weeks
6 Weeks
8 Weeks
– – 25 80 160 80 160 80 160 80 160
77.1 7 6.5 100.5 7 4.4n 104.3 7 8.7n 102.3 7 5.7n 102.8 7 5.3n 101.5 7 4.3n 101.2 7 6.5n 103.3 7 5.7n 101.8 7 5.3n 104.5 7 4.3n 100.2 7 6.5n
76.7 74.5 102.9 76.9n 96.2 74.8n,# 100.2 75.4n 100.0 77.2n 99.8 74.9n 99.3 74.8n 101.2 75.4n 98.0 77.2n 101.8 74.9n 98.2 75.6n
78.17 6.2 101.5 7 6.4n 90.8 7 6.1n,# 99.6 7 5.1n 97.5 7 6.8n 96.4 7 4.6n,# 95.5 7 4.6n,# 98.6 7 5.1n 95.5 7 6.8n,# 97.4 7 4.6n 95.8 7 8.5n,#
77.1 76.5 104.5 74.3n 85.9 77.7n,# 96.7 79.7n,# 94.2 76.1n,# 92.3 78.3n,# 90.3 77.8n,# 95.7 79.7n,# 94.2 76.1n,# 94.3 78.3n,# 90.9 75.5n,#
76.5 7 7.5 103.9 7 8.6n 82.6 7 6.8n,# 94.0 7 3.4n,# 92.5 7 5.2n,# 89.2 7 5.7n,# 87.4 7 7.6n,# 92.0 7 3.4n,# 91.5 7 5.2n,# 90.2 7 5.7n,# 88.4 7 7.6n,#
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a value close to that of sham controls (82.676.8 vs. 76.57 7.5 mmHg). Fruit and leaf COM extracts also decreased DBP. Ethanol extracts decreased DBP more than aqueous extracts, but not quite to the same extent as captopril even at the higher dose (Fig. 2). 3.3. Blood rheology After 8 weeks of treatment, whole blood and plasma viscosity was increased in the 2K1C model rats compared to sham controls (Table 3, Fig. 3). Treatment with captopril slightly reduced whole blood viscosity. Treatment with COM fruit and leaf extracts reduced viscosity in a dose-dependent manner, that was more pronounced for the leaf than the fruit extracts and for the ethanol than for the water extracts. The greatest effect was found with 160 mg ethanol leaf extract. Compared to the sham group, 2K1C rats had increased haematocrit, red blood cell rigidity and aggregation, and decreased deformability. Captopril did not significantly change these parameters. COM extracts dose-dependently opposed these changes, in particular rigidity, and this reached significance for the higher dose (Table 4). Ethanol extracts seemed to have more effect than aqueous extracts, for both fruit and leaves (Fig. 4).
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preparations such as Polo (pilaf rice with lamb), or as in Europe added to other fruit in jams because of its high pectin content. Fruits and leaves of quince are also used in traditional Uyghur medicine to treat cardiovascular diseases and for anti-infective and other properties (Sadik, 1993; Aibaidula et al., 2009; Costa et al., 2009; Aslan et al., 2010; Carvalho et al., 2010). Since the Uyghur around Kashgar has among the greatest longevity (Jin et al., 1994), and lower blood pressure than other central Asian people (Kawamura et al., 2000, 2003), we thought it relevant to explore the effects of quince extracts on a classic rat model of hypertension (Goldblatt, 1958).
4. Discussion Quince (Cydonia Oblonga Mill.) is endemic to the region of Kashgar and Kargilik in the South-Western part of Xinjiang, People's Republic of China. The fruit is used for various culinary
Fig. 4. Erythrocyte characteristics in sham operated animals, 2K1C model untreated renal hypertensive rats (RHR), RHR treated with 25 mg/kg captopril, or 160 mg/kg Cydonia oblonga Mill. (COM) fruit or leaf, aqueous and ethanol extracts.
Table 3 Effects of Cydonia oblonga fruit and leaf extracts on whole blood and plasma viscosity of renal hypertensive rats (n ¼10 per group). Dose (mg/kg) Group
– – 25 80 160 80 160 80 160 80 160
Sham Model Captopril COM fruit aqueous extract COM fruit aqueous extract COM fruit ethanol extract COM fruit ethanol extract COM leaf aqueous extract COM leaf aqueous extract COM leaf ethanol extract COM leaf ethanol extract n
#
Whole blood viscosity (mPa s)
Plasma viscosity (mPa s)
Low-cut (10 s 1)
Medium-cut (60 s 1)
High-cut (150 s 1)
9.93 7 1.53 14.187 2.40n 12.52 7 2.71n 13.187 1.84n 11.93 7 2.03n,# 12.667 2.66n 11.75 7 2.07n,# 12.86 7 2.38n 11.43 7 1.56n,# 12.39 7 2.37n 11.03 7 2.52n,#
5.38 70.58 7.60 71.90n 7.03 71.67n 7.31 70.95n 7.0770.81n 7.16 70.77n 6.82 70.92n,# 7.25 71.25n 6.87 70.98n,# 7.39 71.07n 6.3370.86n,#
4.03 7 0.23 5.82 7 0.47n 5.50 7 0.33n 5.75 7 0.66n 5.43 7 0.74n,# 5.63 7 0.39n 5.277 0.58n,# 5.78 7 0.26n 5.497 0.54n,# 5.28 7 0.62n,# 5.03 7 0.51n,#
1.187 0.05 1.38 7 0.13n 1.36 7 0.07n 1.357 0.11n 1.30 7 0.14n 1.337 0.09n 1.29 7 0.12n,# 1.32 7 0.08n 1.29 7 0.11n,# 1.28 7 0.09n,# 1.25 7 0.10n,#
po 0.05 vs. sham. p o 0.05 vs. model.
Table 4 Effects of Cydonia oblonga fruit and leaf extracts on haematocrit, erythrocyte aggregation index, erythrocyte deformation index and erythrocyte rigidity index of renal hypertensive rats (n¼ 10 per group).
Sham Model Captopril COM fruit aqueous extract COM fruit aqueous extract COM fruit ethanol extract COM fruit ethanol extract COM leaf aqueous extract COM leaf aqueous extract COM leaf ethanol extract COM leaf ethanol extract n
#
p o0.05 vs. sham. p o 0.05 vs. model.
Dose (mg/kg)
Haematocrit (%)
Erythrocyte aggregation index
Erythrocyte deformation index
Erythrocyte rigidity index
– – 25 80 160 80 160
42.157 5.23 47.55 7 3.31n 46.077 4.18n 46.87 7 4.72n 44.277 5.60n,# 45.89 7 4.22n 43.50 7 5.05n,# 46.84 7 3.77n 43.737 3.16n,# 46.28 7 4.07n 44.167 3.65n,#
2.29 7 0.25 2.647 0.24n 2.577 0.17n 2.60 7 0.31n 2.38 7 0.19n,# 2.42 7 0.25n 2.447 0.37n 2.46 7 0.23n 2.42 7 0.26n 2.497 0.18n 2.40 7 0.30n,#
0.98 7 0.09 0.767 0.05n 0.85 7 0.08n 0.777 0.06n 0.85 7 0.09n 0.88 7 0.09n,# 0.86 7 0.10n,# 0.79 7 0.04n 0.84 7 0.07n 0.83 7 0.08n 0.88 7 0.06n,#
6.03 76.22 7.65 76.45n 7.03 76.18n,# 7.17 75.15n 6.65 76.80n,# 7.22 75.13n 6.57 76.84n,# 7.3575.12n 6.82 76.82n,# 7.08 75.15n 6.62 76.84n,#
80 160 80 160
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Renal hypertension is a commonly seen secondary hypertension, the main cause of which is renal arterial stenosis. Because of lower blood volume in the kidney, the renin angiotensin system is abnormally activated, which leads to retention of sodium and water, and elevation of blood pressure (Goldblatt, 1964; Reinhold et al., 2009; Najafipour et al., 2012). The Goldblatt 2-kidney, 1-clip model is a classic model of hypertension and is among the more frequently used animal models for the selection of anti-hypertensive drugs. Because it inhibits angiotensin-converting enzyme, captopril is the reference compound in this model. In hypertension and especially in renal hypertension, there are changes in whole blood viscosity at different shear rates (Baskurt and Meiselman, 2012; Reinhart et al., 2013), as well as in red blood cell rigidity, as we found. These changes are also associated with hypertension and negative outcomes in man (Dintenfass and Girolami, 1978; Martinez et al., 1997; Banerjee et al., 2000; Konstantinova et al., 2006). In this model of hypertensive rats, COM fruit and leaf extracts had antihypertensive effects that were greater at the higher dose, and with ethanol extracts rather than aqueous extracts. The most potent extract on blood pressure was the 160 mg/kg ethanol extract of COM leaves, which approached equivalence to captopril 25 mg/kg. This may be related to a flavonoid glycoside compound (Sun et al., 2013). Our results would tend to support the traditional use of this plant to treat hypertension. The doses we used showed dose-response. They correspond to the daily use of 9 to 18 g plant in a 70 kg person. If the rat-to-man ratio were the same as that of captopril (25 mg/kg in rats vs. 0.7 to 1.4 mg/kg in man), the actual amount of COM needed in man would be 1 to 2 g daily, well within reasonable intake. Other plants from the rosaceae family also seem to have some antihypertensive properties (Ahmed et al., 2010; Cassidy et al., 2011, 2013; Asher et al., 2012; Balasuriya and Rupasinghe, 2012; Furuuchi et al., 2012; Larsson et al., 2013) but the present report is, to our knowledge, the first such study concerning quince. The antihypertensive effects of COM seem a little less marked than those of captopril, or more precisely not quite as rapid as this reference drug for renal hypertension. This only concerns the first weeks of treatment, since at the end of the study there was no difference between COM and captopril. COM also had an effect on rheological parameters that was not found to the same extent with captopril. Considering the effect of these rheological factors in cardiovascular risk in hypertensive patients (Dintenfass and Girolami, 1978; Martinez et al., 1997; Banerjee et al., 2000; Konstantinova et al., 2006; Baskurt and Meiselman, 2012), and that these rheological effects are not addressed by the usual anti-hypertensive medications, this might be an added interest for the therapeutic use of COM extracts. Regular use of COM may thus also contribute to the longevity of the local user population.
5. Conclusion We show an effect of Cydonia oblonga Mill. extracts on blood pressure and rheology in renal hypertensive rats. If similar effects exist in man, this might be of therapeutic interest and validate the use of the plant in traditional Uyghur medicine.
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Glossary COM: Cydonia oblonga Mill. (Quince); PRC: People's Republic of China; TUM: traditional Uyghur medicine; 2K1C: two-kidney-one clip Goldblatt hypertensive rat.; SBP: systolic blood pressure; DBP: diastolic blood pressure; ANOVA: analysis of variance.
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Effect of Cydonia oblonga Mill. fruit and leaf extracts on blood pressure and blood rheology in renal hypertensive rats Wenting Zhou a,1, Elzira Abdusalam a,1, Parida Abliz b, Nadira Reyim c, Shuge Tian d, Qimangul Aji a, Mehray Issak a, Guldiyar Iskandar a, Nicholas Moore a,e,n, Anwar Umar a,e,nn a
Department of Pharmacology, Xinjiang Medical University, 393 Xinyi Road, 830011 Urumqi, Xinjiang, People's Republic of China Department of Pharmacognosy, Faculty of Pharmacy, Xinjiang Medical University, 393 Xinyi Road, 830011 Urumqi, Xinjiang, People's Republic of China c Department of Cardiovascular Internal Medicine, the Second Affiliated Hospital of Xinjiang Medical University, 38 Nanhu Road, Urumqi City, Shuimogou District, 830063 Urumqi, Xinjiang, People's Republic of China d Faculty of traditional Chinese Medicine, Xinjiang Medical University, 393 Xinyi Road, 830011 Urumqi, Xinjiang, People's Republic of China e Department of Pharmacology, University Bordeaux Segalen, 33076 Bordeaux, France b
art ic l e i nf o
a b s t r a c t
Article history: Received 8 October 2013 Received in revised form 16 January 2014 Accepted 17 January 2014 Available online 25 January 2014
Ethnopharmacological relevance: Quince, Cydonia oblonga Mill. (COM), is used in traditional Uyghur medicine to treat or prevent cardiovascular diseases. Uyghur people have greater longevity and lower blood pressure than other central Asian populations. We therefore tested COM fruit and leaf extracts on blood pressure and rheology in renal hypertensive rats (RHR). Materials and methods: Two-kidney, one-clip (2K1C) renal hypertensive rats were divided randomly into eleven groups: sham, model, and model treated with daily doses of 80 and 160 mg/kg aqueous or ethanol extracts of COM fruit or leaves, or 25 mg/kg captopril (n ¼10 per group), given orally once daily for 8 weeks. Blood pressure was measured before treatment and every 2 weeks thereafter. Blood rheology was tested after 8 weeks. Results: Model rats had higher blood pressure than sham 8 weeks after the procedure (systolic blood pressure 19377 vs. 1387 8 mmHg, po 0.05). Those treated with captopril had decreased blood pressure within 2 weeks but that did not return to the level found in the sham group at 8 weeks (1677 7, po 0.05 vs. model). With the COM extracts, the effect on blood pressure was notable after 4 weeks. At 8 weeks blood pressure was similar with captopril and with 160 mg ethanol leaf extract (1667 4, p o0.05 vs. model), the most effective of the extracts. Model rats had higher blood viscosity and lower erythrocyte deformability than sham. Captopril had little effect on blood rheology; whereas COM extracts reduced whole blood viscosity and improved erythrocyte deformability to levels approaching those found in sham. Conclusions: COM extracts have antihypertensive activity in renal hypertensive rats. The additional effect on rheology, compared to captopril, may convey added interest. Further studies of these effects in man appear warranted. & 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Cydonia oblonga Mill. extracts Renal hypertension rats Systolic blood pressure Diastolic blood pressure Blood rheology
1. Introduction Cardiovascular diseases including arterial hypertension are one of the main causes of morbidity and mortality. The exploration of traditional medicines may reveal new treatment options to
n Corresponding author at: Department of Pharmacology, University Bordeaux Segalen, 33076 Bordeaux, France. Tel.: þ 33 557571560; fax: þ 33 557574671. nn Corresponding author at: Department of Pharmacology, Xinjiang Medical University, 393 Xinyi road, 830011 Urumqi, Xinjiang, People's Republic of China. Tel./fax: þ 86 9914362421. E-mail addresses: [email protected] (N. Moore), [email protected] (A. Umar). 1 Both are equal contributors to this work.
0378-8741/$ - see front matter & 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jep.2014.01.018
increase the therapeutic arsenal by the discovery of novel medicines and to offer lower-cost alternatives in developing countries that increasingly share the same concerns. The South-western part of Xinjiang, in the People's Republic of China (PRC), around Hotan and Kashgar, is renowned for its large number of centenarians. Uyghur men from the region of Hotan have lower blood pressure that other central Asians (Kawamura et al., 2000, 2003; Wufuer et al., 2004). In traditional Uyghur medicine, the fruit and leaves of Quince (Cydonia oblonga Mill. COM) are used to treat or prevent hypertension and other cardiovascular diseases (Sadik, 1993), in addition to other uses (Aibaidula et al., 2009; Yan et al., 2009; Aslan et al., 2010). These are found also in traditional Turkish medicine, which shares common cultural roots (Kultur, 2007). Quince fruit and
W. Zhou et al. / Journal of Ethnopharmacology 152 (2014) 464–469
leaves contain many components with known antioxidant activity (Silva et al., 2005, 2002, 2004a, 2004b; Xakir and Aikebaier, 2006; Wojdylo et al., 2013), but putative antihypertensive effects have not yet been explored. We therefore sought to investigate the merits of this usage by testing the effects of Quince fruit and leaf extracts in an experimental model of renal hypertension, the Goldblatt 2-kidney, 1-clip rat model, compared to the effects of a standard antihypertensive drug, captopril.
2. Materials and methods 2.1. Medicines Cydonia Oblonga Mill. (COM) fruit and leaves were collected in October 2010 from the Kashgar area in Kargilik County, Xinjiang, PRC, dried and crushed then set aside. Fruit and leaf voucher specimens were left in the herbarium of the Traditional Chinese Medicine Ethnical Herbs Specimen Museum of Xinjiang Medical University under number NO.TCMEHSM2013100; Captopril was used as 25 mg/tablet, lot number 100803, Shanxi Huixing Pharmaceutical Co. Ltd., Shanxi, PRC. 2.2. Reagents and instruments The instruments and reagents used were B-260 type constant temperature water bath (Shanghai Ya Rong Biochemical Instrument Factory, Shanghai, PRC); AA520 type rotary evaporator (Shanghai Ya Rong Biochemical Instrument Factory); SHB-III type Multi-purpose water circulating pump (Shanghai Ya Rong Biochemical Instrument Factory); medical alcohol (75%, Weiye Experimental Material Company, Lot no.: 11030801); penicillin sodium for injection (800,000 unit/vial, Zhongguo Pharmaceutical co. Ltd, Lot no.: 101003017); pentobarbital sodium (Solar Bio, Lot no.: 6900183); BP-6 non-invasive blood pressure measuring device for animals (Chengdu Taimeng Technology Co. Ltd.), U-shaped silver clip (inside diameter: 0.20 mm); U-shaped silver clip (internal diameter 0.20 mm) Shanghai Alcott Biotech Co., Ltd.; LBY-N6C automatic self-cleaning blood flow metre; LBY-XC-40 automatic dynamic ESR Tester (Beijing Precil Instrument Co., Ltd.) 2.3. Animals One hundred and ten male Wistar rats were provided by the Experimental Animal Centre of Xinjiang Medical University, bodyweight 200 720 g, Licence no. SCXK (Xin): 2003-0001. They were fed daily with normal pellet chow and provided clean running water. All animals were treated according to the current standard
465
for experimental research in China, and the protocols were approved by the University of Xinjiang Ethics Committee for Animal Research.
2.4. Preparation of the test samples Shade-dried COM fruit and sun-dried leaves were crushed and sieved. The appropriate amount of the resulting powder was weighed, and diluted into 20 times its volume of 65% alcohol for 1 hour followed by 3 reverse extractions. Filtrates were combined, concentrated under reduced pressure and recovered. These were cleaned to remove chlorophyll and other impurities, after which the lower layer was concentrated and lyophilized, resulting in freeze-dried COM fruit and leaf aqueous and ethanol extracts. Extraction yield was about 1 g extract for 1.6 g leaves or fruit.
2.5. Establishment of 2K1C renal hypertensive rat model (Xian and Huang, 2007; Yan et al., 2009; Chelko et al., 2012; Najafipour et al., 2012) To induce hypertension according to the Goldblatt 2K1C model, (Goldblatt, 1958, 1964; Barger, 1979; Pinto et al., 1998; Xian and Huang, 2007; Reinhold et al., 2009; Umar et al., 2010) 200 720 g male Wistar rats were anesthetized with sodium pentobarbital (50 mg/kg intraperitoneally). The left renal artery was exposed by retroperitoneal flank incision and dissected free of the renal vein and connective tissue. A silver clip with a lumen of 0.22 mm was placed around the artery for partial occlusion; in sham operations, the artery was not clipped. The animals were kept under constant temperature (207 1 1C) and illumination (12-h light, 12-h dark cycle) until the day of experiment, with free access to food and water. After 6 weeks the systolic blood pressure (SBP) was measured using the tail-cuff method in conscious rats. Only hypertensive rats (SBP above 150 mmHg) were used in the experiments. When hypertension was established, the 2K1C rats were divided into groups of 10 rats:, an untreated renal hypertensive model group, a 2K1C group treated with captopril 25 mg/kg, and eight 2K1C groups treated with low (80 mg/kg) or high (160 mg/kg) doses of aqueous or ethanol COM fruit and leaf extracts. Doses of COM were chosen in reference to doses used in previous experiments (Abliz et al., 2014). In addition a group of 10 untreated shamoperated rats was used as control. Rats received the indicated preparations or identical quantities of physiological saline, in control and model groups, orally by daily gavage for 8 weeks. All rats were weighed and treatment adjusted to bodyweight once a week.
Table 1 Effects of Cydonia Oblonga Mill. fruit and leaf extracts on systolic blood pressure (mmHg 7 SD) of renal hypertensive rats (n¼ 10 per group).
Sham Model Captopril COM fruit water extract COM fruit water extract COM fruit ethanol extract COM fruit ethanol extract COM leaf water extract COM-leaf water extract COM leaf ethanol extract COM leaf ethanol extract n
#
po 0.05 vs. sham. p o 0.05 vs. model.
Dose (mg/kg)
Before use
2 Weeks
4 Weeks
6 Weeks
8 Weeks
– – 25 80 160 80 160 80 160 80 160
137.2 74.5 180.5 75.4n 181.8 76.7n 182.1 74.1n 183.6 74.9n 180.4 74.7n 182.7 77.5n 183.2 75.1n 182.3 74.7n 181.9 77.7n 182.5 74.5n
136.7 73.2 186.9 76.8n 172.2 77.8n,# 181.8 75.3n 182.3 75.9n 182.7 75.2n 180.5 75.1n 181.7 76.7n 181.0 76.9n 180.1 77.2n,# 181.2 75.7n
138.6 76.2 189.0 74.4n 169.4 77.1n,# 177.4 74.7n,# 176.8 77.0n,# 177.0 76.7n,# 174.0 75.4n,# 178.2 74.8n,# 174.8 76.5n,# 176.3 78.7n,# 176.6 74.9n,#
139.17 6.5 191.5 7 5.4n 167.4 7 8.7n,# 175.4 7 6.7n,# 173.3 7 3.6n,# 174.3 7 6.7n,# 171.3 7 5.6n,# 176.0 7 3.0n,# 172.9 7 3.2n,# 173.17 5.7n,# 171.0 7 5.5n,#
138.4 7 7.5 193.17 6.6n 167.2 7 6.8n,# 176.8 7 5.4n,# 173.0 7 8.1n,# 172.8 7 8.4n,# 168.97 8.3n,# 174.8 7 7.4n,# 170.37 5.1n,# 170.47 7.4n,# 166.17 4.3n,#
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2.6. Measurement of blood pressure and rheology SBP and DBP were measured by the tail-cuff method (BP-6 non invasive Electro-Sphygmomanometer) in conscious rats. Blood pressure was measured at 2, 4, 6, and 8 weeks of treatment, 1 h after product administration. Each measurement was taken 3 times and averaged. Blood pressure was measured 1 h after last administration. Rats were then anesthetised with 30 mg/kg 1% pentobarbital sodium, and blood was collected from the abdominal aorta. Whole blood viscosity under high, medium and low shear stress, and packed cell volume were measured after anticoagulation with heparin.
captopril group, SBP decreased from the second week of treatment, without reaching the values of the sham controls. In the COM fruit and leaf extract groups blood pressure started decreasing at the fourth week and further diminished thereafter (Table 1 and Fig. 1), reaching the same values as the captopril group at the end of 8-week period for the higher dose (160 mg/kg) of ethanol leaf extracts (Fig. 1). Lower doses had lesser effects (Table 1). 3.2. Diastolic blood pressure (DBP) DBP was significantly higher in the model than in the sham group (Table 2). Captopril reduced DBP from the beginning of treatment, to
2.7. Data processing
110 105 100 95 mmHg
Data was analysed using SPSS17.0 statistics software (IBM, Armonk, USA). All results are given as mean 7standard deviation, Mean from multiple groups were compared with One-Way ANOVA. After testing the homogeneity of variances, heterogeneous groups were tested with the Dunnett's t test and homogeneous groups with the LSD-t method. Significance limit was set at α¼ 0.05.
Sham Model Captopril fruit water extract fruit ethanol extract leaf aqueou sextract leaf ethanol extract
90 85 80 75 70 65
3. Results
60
Before
2
4
6
8
Weeks of treatment
3.1. Systolic blood pressure (SBP) (Table 1) Compared with the sham group, SBP increased significantly during the study period in the model group (po0.05; Table 1). In the
Fig. 2. Diastolic blood pressure in sham operated animals, 2K1C model untreated renal hypertensive rats (RHR), RHR treated with 25 mg/kg captopril, or 160 mg/kg Cydonia oblonga Mill. (COM) fruit or leaf, aqueous and ethanol extracts.
200 190 180 SBP mmHG
170 Sham Model Captopril fruit aqueous extract fruit ethanol extract leaf aqueous extract leaf ethanol extract
160 150 140 130 120 110 100
Before
2
4
6
8
Weeks treatment
Fig. 1. Systolic blood pressure in sham operated animals, in 2K1C model untreated hypertensive rats (RHR), in RHR rats treated with 25 mg/kg captopril, 160 mg/kg Cydonia oblonga Mill. (COM) fruit or leaf, aqueous and ethanol extracts.
Fig. 3. Whole blood viscosity in sham operated animals, 2K1C model untreated renal hypertensive rats (RHR), RHR treated with 25 mg/kg captopril, or 160 mg/kg Cydonia oblonga Mill. (COM) fruit or leaf aqueous and ethanol extracts.
Table 2 Effects of Cydonia oblonga Mill. fruit and leaf extracts on diastolic blood pressure (mmHg 7 SD) of renal hypertensive rats (n¼ 10 per group).
Sham Model Captopril COM fruit aqueous extract COM fruit aqueous extract COM fruit ethanol extract COM fruit ethanol extract COM leaf aqueous extract COM leaf aqueous extract COM leaf ethanol extract COM leaf ethanol extract n
#
p o0.05 vs. sham. p o 0.05 vs. model.
Dose (mg/kg)
Before use
2 Weeks
4 Weeks
6 Weeks
8 Weeks
– – 25 80 160 80 160 80 160 80 160
77.1 7 6.5 100.5 7 4.4n 104.3 7 8.7n 102.3 7 5.7n 102.8 7 5.3n 101.5 7 4.3n 101.2 7 6.5n 103.3 7 5.7n 101.8 7 5.3n 104.5 7 4.3n 100.2 7 6.5n
76.7 74.5 102.9 76.9n 96.2 74.8n,# 100.2 75.4n 100.0 77.2n 99.8 74.9n 99.3 74.8n 101.2 75.4n 98.0 77.2n 101.8 74.9n 98.2 75.6n
78.17 6.2 101.5 7 6.4n 90.8 7 6.1n,# 99.6 7 5.1n 97.5 7 6.8n 96.4 7 4.6n,# 95.5 7 4.6n,# 98.6 7 5.1n 95.5 7 6.8n,# 97.4 7 4.6n 95.8 7 8.5n,#
77.1 76.5 104.5 74.3n 85.9 77.7n,# 96.7 79.7n,# 94.2 76.1n,# 92.3 78.3n,# 90.3 77.8n,# 95.7 79.7n,# 94.2 76.1n,# 94.3 78.3n,# 90.9 75.5n,#
76.5 7 7.5 103.9 7 8.6n 82.6 7 6.8n,# 94.0 7 3.4n,# 92.5 7 5.2n,# 89.2 7 5.7n,# 87.4 7 7.6n,# 92.0 7 3.4n,# 91.5 7 5.2n,# 90.2 7 5.7n,# 88.4 7 7.6n,#
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a value close to that of sham controls (82.676.8 vs. 76.57 7.5 mmHg). Fruit and leaf COM extracts also decreased DBP. Ethanol extracts decreased DBP more than aqueous extracts, but not quite to the same extent as captopril even at the higher dose (Fig. 2). 3.3. Blood rheology After 8 weeks of treatment, whole blood and plasma viscosity was increased in the 2K1C model rats compared to sham controls (Table 3, Fig. 3). Treatment with captopril slightly reduced whole blood viscosity. Treatment with COM fruit and leaf extracts reduced viscosity in a dose-dependent manner, that was more pronounced for the leaf than the fruit extracts and for the ethanol than for the water extracts. The greatest effect was found with 160 mg ethanol leaf extract. Compared to the sham group, 2K1C rats had increased haematocrit, red blood cell rigidity and aggregation, and decreased deformability. Captopril did not significantly change these parameters. COM extracts dose-dependently opposed these changes, in particular rigidity, and this reached significance for the higher dose (Table 4). Ethanol extracts seemed to have more effect than aqueous extracts, for both fruit and leaves (Fig. 4).
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preparations such as Polo (pilaf rice with lamb), or as in Europe added to other fruit in jams because of its high pectin content. Fruits and leaves of quince are also used in traditional Uyghur medicine to treat cardiovascular diseases and for anti-infective and other properties (Sadik, 1993; Aibaidula et al., 2009; Costa et al., 2009; Aslan et al., 2010; Carvalho et al., 2010). Since the Uyghur around Kashgar has among the greatest longevity (Jin et al., 1994), and lower blood pressure than other central Asian people (Kawamura et al., 2000, 2003), we thought it relevant to explore the effects of quince extracts on a classic rat model of hypertension (Goldblatt, 1958).
4. Discussion Quince (Cydonia Oblonga Mill.) is endemic to the region of Kashgar and Kargilik in the South-Western part of Xinjiang, People's Republic of China. The fruit is used for various culinary
Fig. 4. Erythrocyte characteristics in sham operated animals, 2K1C model untreated renal hypertensive rats (RHR), RHR treated with 25 mg/kg captopril, or 160 mg/kg Cydonia oblonga Mill. (COM) fruit or leaf, aqueous and ethanol extracts.
Table 3 Effects of Cydonia oblonga fruit and leaf extracts on whole blood and plasma viscosity of renal hypertensive rats (n ¼10 per group). Dose (mg/kg) Group
– – 25 80 160 80 160 80 160 80 160
Sham Model Captopril COM fruit aqueous extract COM fruit aqueous extract COM fruit ethanol extract COM fruit ethanol extract COM leaf aqueous extract COM leaf aqueous extract COM leaf ethanol extract COM leaf ethanol extract n
#
Whole blood viscosity (mPa s)
Plasma viscosity (mPa s)
Low-cut (10 s 1)
Medium-cut (60 s 1)
High-cut (150 s 1)
9.93 7 1.53 14.187 2.40n 12.52 7 2.71n 13.187 1.84n 11.93 7 2.03n,# 12.667 2.66n 11.75 7 2.07n,# 12.86 7 2.38n 11.43 7 1.56n,# 12.39 7 2.37n 11.03 7 2.52n,#
5.38 70.58 7.60 71.90n 7.03 71.67n 7.31 70.95n 7.0770.81n 7.16 70.77n 6.82 70.92n,# 7.25 71.25n 6.87 70.98n,# 7.39 71.07n 6.3370.86n,#
4.03 7 0.23 5.82 7 0.47n 5.50 7 0.33n 5.75 7 0.66n 5.43 7 0.74n,# 5.63 7 0.39n 5.277 0.58n,# 5.78 7 0.26n 5.497 0.54n,# 5.28 7 0.62n,# 5.03 7 0.51n,#
1.187 0.05 1.38 7 0.13n 1.36 7 0.07n 1.357 0.11n 1.30 7 0.14n 1.337 0.09n 1.29 7 0.12n,# 1.32 7 0.08n 1.29 7 0.11n,# 1.28 7 0.09n,# 1.25 7 0.10n,#
po 0.05 vs. sham. p o 0.05 vs. model.
Table 4 Effects of Cydonia oblonga fruit and leaf extracts on haematocrit, erythrocyte aggregation index, erythrocyte deformation index and erythrocyte rigidity index of renal hypertensive rats (n¼ 10 per group).
Sham Model Captopril COM fruit aqueous extract COM fruit aqueous extract COM fruit ethanol extract COM fruit ethanol extract COM leaf aqueous extract COM leaf aqueous extract COM leaf ethanol extract COM leaf ethanol extract n
#
p o0.05 vs. sham. p o 0.05 vs. model.
Dose (mg/kg)
Haematocrit (%)
Erythrocyte aggregation index
Erythrocyte deformation index
Erythrocyte rigidity index
– – 25 80 160 80 160
42.157 5.23 47.55 7 3.31n 46.077 4.18n 46.87 7 4.72n 44.277 5.60n,# 45.89 7 4.22n 43.50 7 5.05n,# 46.84 7 3.77n 43.737 3.16n,# 46.28 7 4.07n 44.167 3.65n,#
2.29 7 0.25 2.647 0.24n 2.577 0.17n 2.60 7 0.31n 2.38 7 0.19n,# 2.42 7 0.25n 2.447 0.37n 2.46 7 0.23n 2.42 7 0.26n 2.497 0.18n 2.40 7 0.30n,#
0.98 7 0.09 0.767 0.05n 0.85 7 0.08n 0.777 0.06n 0.85 7 0.09n 0.88 7 0.09n,# 0.86 7 0.10n,# 0.79 7 0.04n 0.84 7 0.07n 0.83 7 0.08n 0.88 7 0.06n,#
6.03 76.22 7.65 76.45n 7.03 76.18n,# 7.17 75.15n 6.65 76.80n,# 7.22 75.13n 6.57 76.84n,# 7.3575.12n 6.82 76.82n,# 7.08 75.15n 6.62 76.84n,#
80 160 80 160
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Renal hypertension is a commonly seen secondary hypertension, the main cause of which is renal arterial stenosis. Because of lower blood volume in the kidney, the renin angiotensin system is abnormally activated, which leads to retention of sodium and water, and elevation of blood pressure (Goldblatt, 1964; Reinhold et al., 2009; Najafipour et al., 2012). The Goldblatt 2-kidney, 1-clip model is a classic model of hypertension and is among the more frequently used animal models for the selection of anti-hypertensive drugs. Because it inhibits angiotensin-converting enzyme, captopril is the reference compound in this model. In hypertension and especially in renal hypertension, there are changes in whole blood viscosity at different shear rates (Baskurt and Meiselman, 2012; Reinhart et al., 2013), as well as in red blood cell rigidity, as we found. These changes are also associated with hypertension and negative outcomes in man (Dintenfass and Girolami, 1978; Martinez et al., 1997; Banerjee et al., 2000; Konstantinova et al., 2006). In this model of hypertensive rats, COM fruit and leaf extracts had antihypertensive effects that were greater at the higher dose, and with ethanol extracts rather than aqueous extracts. The most potent extract on blood pressure was the 160 mg/kg ethanol extract of COM leaves, which approached equivalence to captopril 25 mg/kg. This may be related to a flavonoid glycoside compound (Sun et al., 2013). Our results would tend to support the traditional use of this plant to treat hypertension. The doses we used showed dose-response. They correspond to the daily use of 9 to 18 g plant in a 70 kg person. If the rat-to-man ratio were the same as that of captopril (25 mg/kg in rats vs. 0.7 to 1.4 mg/kg in man), the actual amount of COM needed in man would be 1 to 2 g daily, well within reasonable intake. Other plants from the rosaceae family also seem to have some antihypertensive properties (Ahmed et al., 2010; Cassidy et al., 2011, 2013; Asher et al., 2012; Balasuriya and Rupasinghe, 2012; Furuuchi et al., 2012; Larsson et al., 2013) but the present report is, to our knowledge, the first such study concerning quince. The antihypertensive effects of COM seem a little less marked than those of captopril, or more precisely not quite as rapid as this reference drug for renal hypertension. This only concerns the first weeks of treatment, since at the end of the study there was no difference between COM and captopril. COM also had an effect on rheological parameters that was not found to the same extent with captopril. Considering the effect of these rheological factors in cardiovascular risk in hypertensive patients (Dintenfass and Girolami, 1978; Martinez et al., 1997; Banerjee et al., 2000; Konstantinova et al., 2006; Baskurt and Meiselman, 2012), and that these rheological effects are not addressed by the usual anti-hypertensive medications, this might be an added interest for the therapeutic use of COM extracts. Regular use of COM may thus also contribute to the longevity of the local user population.
5. Conclusion We show an effect of Cydonia oblonga Mill. extracts on blood pressure and rheology in renal hypertensive rats. If similar effects exist in man, this might be of therapeutic interest and validate the use of the plant in traditional Uyghur medicine.
Acknowledgements This research work was supported by National Natural Science Foundation of China (No. 81060268). References Abliz, A., Aji, Q., Abdusalam, E., Sun, X., Abdurahman, A., Zhou, W., Moore, N., Umar, A., 2014. Effect of Cydonia oblonga Mill. leaf extract on serum lipids and liver function in a rat model of hyperlipidaemia. J. Ethnopharmacol. 151, 970–974.
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Glossary COM: Cydonia oblonga Mill. (Quince); PRC: People's Republic of China; TUM: traditional Uyghur medicine; 2K1C: two-kidney-one clip Goldblatt hypertensive rat.; SBP: systolic blood pressure; DBP: diastolic blood pressure; ANOVA: analysis of variance.