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Riparoside B and timosaponin J, two steroidal glycosides from Smilax riparia, resist to hyperuricemia based on URAT1 in hyperuricemic mice.

ABSTRACT

The roots and rhizomes of Smilax riparia (SR), called "Niu-Wei-Cai" in traditional Chinese medicine (TCM), are believed to be effective in treating gout symptoms. However, it is not clear if the active constituents and uricosuric mechanisms of S. riparia support its therapeutic activities. In this study, we isolated two steroidal glycosides named riparoside B and timosaponin J from the total saponins of S. riparia. We then examined if these two compounds were effective in reducing serum uric acid levels in a hyperuricemic mouse model induced by potassium oxonate. We found that the two steroidal glycosides possess potent uricosuric effect in hyperuricemic mice through decreasing renal mURAT1 mainly and inhibiting XOD activity in a certain extent, which contribute to the enhancement of uric acid excretion and attenuate hyperuricemia-induced renal dysfunction. Riparoside B and timosaponin J may have a clinical utility in treating gout and other medical conditions caused by hyperuricemia.

Keywords:

Steroidal glycosides

Smilax riparia

Riparoside B

Timosaponin J

Hyperuricemia

URAT1

Introduction

Hyperuricemia is one of the most extensive metabolic diseases. It is characterized by high uric acid level in the blood, causing deposition of urate crystals in the joints and kidneys, and is well known as important risk factor for gout, hyperlipidemia, hypertension and diabetes (Boffetta et al., 2009; Tong et al., 2012). Underexcretion of urate has been proved to result in hyperuricemia (Boffetta et al., 2009). Urate transporter in kidney such as URAT1, GLUT9 and OAT1 may have important roles in the impaired urate excretion and hyperuricemia (Enomoto and Endou 2005; Eraly et al., 2008; Habu et al., 2003; Preitner et al., 2009) and they constitutes an important target for drugs to treat hyperuricemia. Anti-hyperuricemic drugs, such as allopurinol and probenecid are demonstrated to produce adverse effects such as hypersensitivity and agranulocytosis (Bardin 2004; Harris et al., 1999). Therefore, it underlines much impetus for urgent need of safer and more effective antihyperuricemic agents, especially herbal medicine (Ahmad et al., 2008; An et al., 2010).

Smilax riparia A. DC. (SR) which belongs to genus Smilax and family Liliaceae, is distributed in the south and midland of China. The roots and rhizomes of S. riparia in traditional Chinese medicine (TCM) are a source of Chinese folk drug "Niu-Wei-Cai", and are supposed to be effective as gout, hyperuricemia diuretic, anti-inflammatory, and antitumor agents in folklore medicine (Zhang and Han 2012), and as edible wild herbs in some regions of China (Wang et al., 2000). Some constituents, such as phenylpropanoid glycosides, steroidal saponins and aromatic compounds, have been isolated from the roots and rhizomes of S. riparia in the past (Li et al., 2006; Sashida et al., 1992; Sun et al., 2012). However, it is not clear that the active constituents and their pharmacological mechanisms of S. riparia support for its therapeutic action such as gout and hyperuricemia diuretics.

In the past, we had isolated two steroidal glycosides named smilaxchinoside A and smilaxchinoside C from total saponins of S. riparia (SR) and found they had significant anti-hyperuricemia activities. As continue to research on this herbal, in this study, we have isolated other two steroidal glycosides named riparoside B and timosaponin J, we then examined them in reducing serum uric acid levels in mice model of hyperuricemia induced by potassium oxonate. We found that the two steroidal glycosides possesses potent uricosuric effect in hyperuricemic mice through decreasing renal mURAT1 mainly and inhibiting XOD activity in a certain extent, which are attributable to the enhancement of uric acid excretion and attenuate hyperuricemia-induced renal dysfunction.

Materials and methods

Plant material

The roots and rhizomes of S. riparia were collected from Tieling, Liaoning Province of China, in September 2011, and were authenticated by Prof. Ye Zhou, Tianjin Medical University, China. A voucher specimen (SR-2011-12) was deposited at School of Pharmacy, Tianjin Medical University, Tianjin, People's Republic of China.

Extraction and isolation

The 90% EtOH extracts of roots and rhizomes of S. riparia were suspended in water and extracted with petroleum ether, chloroform, EtOAc and BuOH respectively. The BuOH fraction was passed through a D101 macropore resin eluted successively with 30% EtOH, 50% EtOH, 70% EtOH and 90% EtOH, respectively. And the total saponins of S. riparia were obtained from the 70% EtOH fraction. Then the total saponin fraction was subjected to silica gel and Sephadex LH-20 column chromatography and finally purified by semi-preparative scale HPLC to afford two steroidal glycosides 1 and 2 (Fig. 1).

Characterization of compound 1

An amorphous power, [[a].sub.D] -52.5[degrees] (MeOH), had a molecular formula of [C.sub.51][H.sub.84][O.sub.22] determined by high resolution HR-FAB-MS (m/z 1071.3802 [[M+Na].sup.+]) as well as its [sup.13]C and [sup.1]H NMR data. By UV, IR, MS and extensive [sup.1]H and [sup.13]C NMR spectra analysis and comparison with literature data (Li et al., 2006), the structure of compound 1 was identified as 3-0-[alpha]-L-rhamnopyranosyl-(1 [right arrow] 2)-[[alpha]-L-rhamnopyranosyl-( 1 [right arrow] 6)]-[beta]-D-glucopyranosyl 3[beta],20[alpha]-dihydroxy-5[alpha]-furost-22(23)-ene 26-O-[beta]-D-glucopyranoside, and named riparoside B.

Characterization of compound 2

Compound 2 was obtained as a white amorphous powder. The molecular formula of 2 was determined as [C.sub.45][H.sub.74][O.sub.20] from the [[M+Na].sup.+] ion at m/z 957.4663 in the positive ion mode HR-ESI-MS and [[M+H].sup.+] ion at m/z 935.4 in FAB-MS. On the basis of the analysis methods such as UV, 1R, MS and extensive [sup.1]H and [sup.13]C NMR spectra analysis and comparison with literature data (Kang et al., 2012), compound 2 was characterized as (3[beta],5[beta],25S)-26-O-[beta]-D-glucopyranosyl-3-hydroxyl-20,22-secofurostane-20,22-dione 3-O-[beta]-D-glucopyranosyl-(1 [right arrow] 2)-[beta]-D-galactopyranoside, and named timosaponin J.

Preparation of hyperuricemia model and drug administration

Male Kunming mice (20 [+ or -] 2g) were purchased from the China BK Experimental Animal Center (Beijing, China). They were kept in metabolic cages in a normally controlled breeding room with standard laboratory food and water for one week prior to the experiments. Experiments reported in this study were carried out in accordance with local guidelines for the care of laboratory animals of Tianjin Medical University, and were approved by the ethics committee for research on laboratory animal use of the institution.

The uricase inhibitor potassium oxonate was used to induce hyperuricemia in mice according to previous reports (Li et al., 2011; Wang et al., 2010). Except the normal control mice (NC), others were orally administered by 250 mg/kg potassium oxonate once daily for 7 consecutive days to induce hyperuricemia. The test compounds (riparoside B, timosaponin J and allopurinol) were dispersed in water and were orally administered once daily from day 1 to day 7, while the NC mice was treated with a similar vehicle to the treatment group. After 7 days of treatment, diets were removed from the cages 12 h before the animals were sacrificed. The blood was allowed to clot for approximately 1 h at room temperature and centrifuged at 3000 rpm for 10 min to obtain serum. The serum and urine were stored at -20[degrees]C until assayed. The levels of XOD activities, uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN) in liver and kidney were determined by colorimetric method using commercially available kits (purchased from Beijing Aoboseng Bioengineering Institute, China) according to the manufacturers' instructions. FEUA stands for Fractional Excretion of Uric Acid, and the index of FEUA was calculated as follows (Kong et al., 2004):

FEUA = [S.sub.Cr] x [U.sub.UA]/[U.sub.Cr] x [S.sub.UA] x 100

* [S.sub.Cr]: serum creatinine, SUA: serum uric acid

* [U.sub.UA]: urine uric acid, [U.sub.Cr]: urine creatinine

Simultaneously the kidney cortex was rapidly and carefully separated on ice-plate and stored at -80 [degrees]C for protein assays of mURAT1, mGLUT9 and mOAT1, and partly fixed in 10% formalin and processed in paraffin for subsequent histological assessment.

Western blotting analysis of mURAT1, mGLUT9 and mOAT1 in kidney tissues

Mice renal cortical brush-border membrane vesicles for analysis of mURAT1, mGLUT9, mOAT1 and m[Na.sup.+]-[K.sup.+] ATPase were prepared by a modified procedure (Hosoyamada et al., 2004). Immunoblotting was assayed using anti-URAT1 (1:200), mGLUT9 (1:200), mOAT1 (1:200) as well as mGAPDH (1:400) antibodies (Santa Cruz Biotech, USA). The contents of target proteins were analyzed via densitometry using Molecular Analyst software (Bio-Rad Laboratories, Hercules, CA) and normalized by the respective blotting from mNaMC ATPase or mGAPDH.

Renal histological analyses

Mice's kidneys were fixed for 24 h at room temperature in fixing agent (ethyl alcohol:chloroform:acetic acid = 6:3:1) and preserved in 75% ethanol. Renal biopsies were dehydrated with series graded concentration of alcohol and embedded in paraffin. Samples were cut in 3 [micro]m thick sections on a rotary microtome and stained with Periodic acid-Schiff reagent for histopathologic evaluation. Renal sections were observed under the light microscope at a 200 x magnification.

Statistical analysis

All data were expressed as the mean [+ or -] standard error of the mean (S.E.M.) and statistical analysis was performed using a one-way analysis of variance (ANOVA) to determine the level of significance. A value of p < 0.05 was considered statistically significant. Figures were obtained by the Statistical Analysis System (GraphPad Prism 4, GraphPad Software, Inc., San Diego, CA).

Results and discussion

Riparoside B and timosaponin J affect levels of UA, [S.sub.cr] and BUN in hyperuricemic mice

As shown in the Table 1 and Fig. 2, after orally administered 7 times with potassium oxonate, the level of serum uric acid ([S.sub.UA]) in model group were significantly higher than those in normal control group (p<0.01), which indicated that the model was successful for inducing hyperuricemia in mice. Compared with model group, the levels of [S.sub.UA] were suppressed significantly by riparoside B and timosaponin J treated at the dose of 0.01 g/kg (p<0.01 and p < 0.05, respectively), while the levels of [U.sub.UA] were increased significantly (both p <0.05). Although some effects have been described in limited reports using these two steroidal glucosides (Li et al., 2006; Kang et al., 2012), for the first time, we observed the effects on the activities using hyperuricemic mice.

[S.sub.Cr] and BUN levels can be associated with renal dysfunction. Renal damage can be accompanied by an increase in [S.sub.Cr] and BUN indicating reduced urea and creatinine clearance (Hoffmann et al., 2010). Compared with the model group, the levels of [S.sub.Cr] and BUN were suppressed significantly (both p<0.05) by riparoside B and timosaponin J, These results are in accordance with histological analyses as in the following. Moreover, riparoside B and timosaponinj treated at the dose of 0.01 g/kg could significantly increase the renal UA handling parameter FEUA(both p < 0.05) and enhances the UA excretion. Our data of [S.sub.Cr] and BUN in general supports the effects of the two compounds on the levels of serum uric acid.

Riparoside B and timosaponin J from total saponins affect the XOD activities

As showed in Fig. 3 riparoside B and timosaponin J also had significant effects on serum and liver XOD activities in hyperuricemic mice (both p < 0.05). However, allopurinol as the positive control at the dose of 10 mg/kg significantly (p < 0.01) suppressed hepatic XOD activity of hyperuricemic mice, even to be lower than that of normal control mice. It indicated that XOD inhibitory activity might be one of anti-hyperuricemiame chanisms of riparoside B and timosaponinj, but not the main. Although the XOD activities of the compounds were not as strong as allopurinol, we believe that they would not have the same adverse event profile as allopurinol, which needs to be confirmed in future studies.

Riparoside B and timosaponin J affect protein levels of mURAT1, mCLUT9 and mOTA1 in hyperuricemic mice

The effects of riparoside B, timosaponin J and allopurinol (positive control) on renal protein levels of mURAT1, mGLUT9 and mOTA1 in hyperuricemic were shown in Fig. 4. Potassium oxonate-induced hyperuricemic mice developed the elevated levels of renal mURAT1 and mGLUT9 protein and depressed mOTA1 protein levels (all p<0.01) compared with normal-vehicle mice (Fig. 4 B-D). Allopurinol, riparosides B and timosaponin J at the dose of 0.01 g/kg could down-regulated the expression levels of renal mURAT1 protein in hyperuricemic mice (p < 0.01, p < 0.01, and p < 0.05 respectively) compared with model control group as showed in Fig. 4B. However, as shown in Fig. 4 C and D riparoside B and timosaponin J showed almost no effects on protein levels of mGLUT9 and mOTA1. There results may demonstrate that riparoside B and timosaponin J possess potent uricosuric effect in hyperuricemic mice only through decreasing renal mURAT1, but not mGLUT9 and mOTA1, which are attributable to the enhancement of uric acid excretion. It has been reported that protein levels of mURAT1, mGLUT9 and mOTA1 are associated with renal uric acid excretion (Enomoto and Endou 2005; Eraly et al., 2008; Habu et al., 2003; Preitner et al., 2009). Data from these observations provide future mechanistic information of riparoside B and timosaponinj.

Effect of riparoside B and timosaponin J on improving renal dysfunction

As results above, levels of [S.sub.Cr], [U.sub.Cr] and BUN could be restored by 0.01 g/kg doses of riparoside B and timosaponinj in hyperuricemic mice. Besides, compared with control rats (Fig. 5A), histological analyses displayed that brush border of epithelial cells was remarkably disappeared and renal tubules were shrank in fructose-fed rats (Fig. 5B). These pathological states were ameliorated in some degree by treating with allopurinol and 10mg/kg doses of riparoside B and timosaponin J (Fig. 5C-E). Our histological data support the observations of uric acid level changes after treatment, and is consistent with the [S.sub.Cr], [U.sub.Cr] and BUN observations in our hyperuricemic mice model.

Conclusion

In conclusion, we isolated two steroidals glycosides, riparoside B and timosaponin J from total saponins of S. riparia extract. The present study demonstrates that, for the first time, riparoside B and timosaponin J possesses potent uricosuric effect in hyperuricemic mice through decreasing renal mURAT1 mainly and inhibiting XOD activity in a certain extent, which are attributable to the enhancement of uric acid excretion and attenuate hyperuricemia-induced renal dysfunction. Since S. riparia is an edible botanical (Wang et al., 2000), we expected that the studied compounds riparoside B and timosaponinj, which are isolated from this plant, would be safe for humans. We believe that they would not have the same adverse event profile as allopurinol, although the safety of the two compounds needs to be confirmed in future studies. Future studies are needed to evaluate the potential clinical utility of these two compounds in the uric acid excretion and renal dysfunction reduction.

Conflict of interest

The authors have no conflict of interest to report.

ARTICLE INFO

Article history:

Received 27 November 2013

Received in revised form 7 February 2014

Accepted 23 March 2014

Acknowledgments

Supported in part by the National Natural Science Foundation of China (No. 81202895) and the Post-doctoral Program Foundation from Ministry of Education of the People's Republic of China (No. 2013M530882).

References

Ahmad, N.S., Farman, M., Najmi, M.H., Mian, K.B., Hasan, A., 2008. Pharmacological basis for use of Pistacia integerrima leaves inhyperuricemia and gout. J. Ethnopharmacol. 117, 478-482.

An, J., Yang, H.J., Park, K., Lee, J., Kim, B.W., 2010. Reparatory and preventive effects of oriental herb extract mixture (OHEM) on hyperuricemia and gout. Food Sci. Biotechnol. 19, 517-524.

Bardin, T., 2004. Current management of gout in patients unresponsive or allergic to allopurinol. Joint Bone Spine 71, 481-485.

Boffetta, P., Nordenvall, C., Nyren, O., Ye, W., 2009. A prospective study of gout and cancer. Eur. J. Cancer. Prev. 18, 127-132.

Enomoto, A., Endou, H., 2005. Roles of organic anion transporters (OATs) and a urate transporter (URAT1) in the pathophysiology of human disease. Clin. Exp. Nephrol. 9, 195-205.

Eraly, S.A., Vallon, V., Rieg, T., Gangoiti, J.A., Wikoff, W.R., Siuzdak, G., Barshop, B.A., Nigam, S.K., 2008. Multiple organic anion transporters contribute to net renal excretion of uric acid. Physiol. Genomics 33, 180-192.

Habu, Y., Yano, I., Takeuchi, A., Saito, H., Okuda, M., Fukatsu, A., Inui, K., 2003. Decreased activity of basolateral organic ion transports in hyperuricemic rat kidney: roles of organic ion transporters, rOAT1, rOAT3 and rOCT2. Biochem. Pharmacol. 66, 1107-1114.

Harris, M.D., Siegel, L.B., Alloway, J.A., 1999. Gout and hyperuricemia. Am. Fam. Physician 59, 925-934.

Hoffmann, D., Fuchs, T.C., Henzler, T., Matheis, K.A., Herget, T., Dekant, W., Hewitt, P., Mally, A., 2010. Evaluation of a urinary kidney biomarker panel in rat models of acute and subchronic nephrotoxicity. Toxicology 277, 49-58.

Hosoyamada, M., Ichida, K., Enomoto, A., Hosoya, T., Endou, H., 2004. Function and localization of urate transporter 1 in mouse kidney. J. Am. Soc. Nephrol. 15, 261-268.

Kang, LP., Zhang, J., Cong, Y., Li, B., Xiong, C.Q., Zhao, Y., Tan, D.W., Yu, H.S., Yu, Z.Y., Cong, Y.W., Liu, C., Ma, B.P., 2012. Steroidal glycosides from the rhizomes of Anemarrhena asphodeloides and their antiplatelet aggregation activity. Planta Med. 78 (6), 611-616.

Kong, L.D., Yang, C., Ge, F., Wang, H.D., Guo, Y.S., 2004. A Chinese herbal medicine Ermiao wan reduces serum uric acid level and inhibits liver xanthine dehydrogenase and xanthine oxidase in mice. J. Ethnopharmacol. 93, 325-330.

Li, J., Bi, X.L., Zheng, G.H., Hitoshi, Y., Ikeda, T., Nohara, T., 2006. Steroidal glycosides and aromatic compounds from Smilax riparia. Chem. Pharm. Bull. 54, 1451-1454.

Li, J.M., Zhang, X., Wang, X., Xie, Y.C., Kong, L.D., 2011. Protective effects of cortex fraxini coumarines against oxonate-induced-hyperuricemia and renal dysfunction in mice. Eur. J. Pharmacol. 666, 196-204.

Preitner, F., Bonny, O., Laverriere, A., Rotman, S., Firsov, D., Da Costa, A., Metref, S., Thorens, B., 2009. Glut9 is a major regulator of urate homeostasis and its genetic inactivation induces hyperuricosuria and urate nephropathy. Proc. Natl. Acad. Sci. U.S.A. 106, 11501-11506.

Sashida, Y., Kubo, S., Mimaki, Y., Nikaido, T., Ohmoto, T., 1992. Steroidal saponins from Smilax riparia and S. china. Phytochemistry 31, 2439-2443.

Sun, T.T., Zhang, D.W., Han, Y., Dong, F.Y., Wang, W., 2012. Smilasides M and N, two new phenylpropanoid glycosides from Smilax riparia. J. Asian Nat. Prod. Res. 14, 165-170.

Tong, X.L., Dong, L., Chen, L, Zhen, Z., 2012. Treatment of diabetes using raditional Chinese medicine: past, present and future. Am. J. Chin. Med. 40 (5), 877-886.

Wang, W.H., Shao, M.N., Han, Y.G., 2000. The nutrition composition analysis of Smilax riparia A.DC. Spec. Wild Econ. Anim. Plant Res. 3, 46-47.

Wang, X., Wang, C.P., Hu, Q.H., Lv, Y.Z., Zhang, X., Ouyang, Z., Kong, L.D., 2010. The dual actions of Sanmiao wan as a hypouricemic agent: down-regulation of hepatic XOD and renal mURAT1 in hyperuricemic mice. J. Ethnopharmacol. 128, 107-115.

Zhang, S.L., Han, Z.H., 2012. Textural research of categories and functions on Nian-Yu-Xu recorded in Cai-Yao-Lu from Ben-Cao-Gang-Mu-Shi-Yi. J. Zhejiang Univ. TCM 36, 484-486.

Abbreviations: mURAT1, mouse Urate Transporter 1; mGLUT9, mouse Glucose Transporter 9: mOAT1, mouse Organic Anion Transporter 1; mGAPDH, gIyceraldehyde-3-phosphate dehydrogenase; EtOH, ethyl alcohol; BuOH, n-butyl alcohol; HR-ES1-MS, high-resolution mass spectrometer; NMR, nuclear magnetic resonance; XOD, xanthine oxidase; UA, uric acid; Cr, creatinine; BUN, blood urea nitrogen; FEUA, fraction excretion of uric acid; NC, normal control.

Xiao-Hui Wu (a,b), *, Jun Zhang (a), Shu-Qing Wang (a), Victor C. Yang (a), Samantha Anderson (b), Yan-Wen Zhang (a) **

(a) Tianjin Key Laboratory on Technologies Enabling Development of Clinical, Therapeutics and Diagnostics, College of Pharmacy, Tianjin Medical University, Tianjin 300070, China

(b) Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA

* Corresponding author at: Tianjin Key Laboratory on Technologies Enabling Development of Clinical, Therapeutics and Diagnostics, College of Pharmacy, Tianjin Medical University, Tianjin 300070, China. Tel.: +86 22 60357206; fax: +86 22 60357208.

** Corresponding author. Tel.: +86 22 60357206; fax: +86 22 60357208.

E-mail addresses: xwu@dacc.uchicago.edu, longhui804@163.com (X.-H. Wu), zhangyanwen@tijmu.edu.cn (Y.-W. Zhang).

http://dx.doi.org/ 10.1016/j.phymed.2014.03.009

Table 1
Effects of riparoside B, timosaponin J and allopurinol on serum and
urinary levels of UA and Cr, as well as BUN and urine volumes in
hyperuricemic mice.

Group   Dose(g/kg)   [S.sub.UA] (mg/l)    [U.sub.UA] (mg/l)

NC      --           3.20 [+ or -] 0.31   41.12 [+ or -] 4.05
MC      --           6.41 [+ or -] 0.62   17.05 [+ or -] 1.83
AP      0.01         3.76 [+ or -] 0.37   35.01 [+ or -] 3.47
C1      0.01         4.03 [+ or -] 0.51   28.01 [+ or -] 2.96
C2      0.01         5.01 [+ or -] 0.47   29.38 [+ or -] 3.09

Group   [S.sub.Cr] ([micro]mol/l)   [U.sub.Cr] (mmol/l)

NC      0.61 [+ or -] 0.06          35.91 [+ or -] 3.89
MC      0.95 [+ or -] 0.09          18.53 [+ or -] 1.81
AP      0.67 [+ or -] 0.07          29.99 [+ or -] 3.01
C1      0.76 [+ or -] 0.08          31.42 [+ or -] 3.09
C2      0.80 [+ or -] 0.08          28.09 [+ or -] 2.90

Group   BUN (mmol/l)           FEUA (%)

NC       9.21 [+ or -] 1.03   21.83 [+ or -] 2.74
MC      16.28 [+ or -] 1.64   13.63 [+ or -] 1.58
AP      11.21 [+ or -] 1.18   20.80 [+ or -] 2.35
C1      12.89 [+ or -] 1.29   16.81 [+ or -] 1.79
C2      13.53 [+ or -] 1.35   16.70 [+ or -] 1.63

N = 8 per group. NC, normal control; MC, model group with potassium
oxonate; AP, allopurinol (10 mg/kg); C1 or C2, riparoside B 10 mg/kg
or timosaponin J 10 mg/kg.

** p < 0.01 compare with NC; ** p < 0.01, * p < 0.05 compare with MC.
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Author:Wu, Xiao-Hui; Zhang, Jun; Wang, Shu-Qing; Yang, Victor C.; Anderson, Samantha; Zhang, Yan-Wen
Publication:Phytomedicine: International Journal of Phytotherapy & Phytopharmacology
Article Type:Report
Date:Sep 15, 2014
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