Beneficial Effect of 7-O-Galloyl-D-sedoheptulose, a Polyphenol Isolated from Corni Fructus, against Diabetes-Induced Alterations in Kidney and Adipose Tissue of Type 2 Diabetic db/db Mice

Abstract

Traditional medicines are being focused on as possible treatments for diabetes and its complications because of their negligible toxic and/or side effects. In line with this, our group has reported that Corni Fructus, a traditional medicine considered exhibiting beneficial effects on liver and kidney functions, possessed an antidiabetic effect via ameliorating glucose-mediated metabolic disorders. To add to these findings, we screened the iridoid glycoside fraction containing morroniside and loganin, and low molecular weight polyphenol fraction containing 7-O-galloyl-d-sedoheptulose (GS) from Corni Fructus. To our knowledge, GS is a compound only detected in Corni Fructus, and its biological activity has been poorly understood until now. For these reasons, we examined whether GS has an ameliorative effect on diabetic changes using type 2 diabetic db/db mice. Our findings suggest that GS has a beneficial effect on the pathological state of the serum, kidney, and adipose tissue related to diabetic damage.

Figure 1

Fractionation of Corni Fructus, HPLC profile of GS, and its structure. (a) Fractionation of Corni Fructus was performed as described in Biological & Pharmaceutical Bulletin, vol. 30, no. 7, pp. 1289–1296, 2007. (b) HPLC profile. The large peak shown by the arrow is the structure of GS, as described in (c), and the other peaks represent its four isomers, as described in (d).

Figure 2

ROS (a), TBARS (b), GSH (c), GSSG (d), and GSH/GSSG (e) levels in the kidney. m/m, Misty; Veh, vehicle-treated db/db mice; GS20, GS 20 mg/kg body weight-treated db/db mice; GS100, GS 100 mg/kg body weight-treated db/db mice. The results are presented as the means ± S.E.M. ^a P < 0.05, ^b P < 0.01 versus vehicle-treated db/db mouse values.

Figure 3

Nox-4 (a) and p22^phox (b) protein expressions in the kidney. m/m, Misty; Veh, vehicle-treated db/db mice; GS20, GS 20 mg/kg body weight-treated db/db mice; GS100, GS 100 mg/kg body weight-treated db/db mice. The results are presented as the means ± S.E.M. ^a P < 0.05, ^b P < 0.01 versus vehicle-treated db/db mouse values.

Figure 4

Bax (a), Bcl-2 (b), and cytochrome c (c) protein expressions in the kidney. m/m, Misty; Veh, vehicle-treated db/db mice; GS20, GS 20 mg/kg body weight-treated db/db mice; GS100, GS 100 mg/kg body weight-treated db/db mice. The results are presented as the means ± S.E.M. ^a P < 0.05, ^b P < 0.01 versus vehicle-treated db/db mouse values.

Figure 5

NF-κBp65 (a), COX-2 (b), and iNOS (c) protein expressions in the kidney. m/m, Misty; Veh, vehicle-treated db/db mice; GS20, GS 20 mg/kg body weight-treated db/db mice; GS100, GS 100 mg/kg body weight-treated db/db mice. The results are presented as the means ± S.E.M.   ^a P < 0.05, ^b P < 0.01 versus vehicle-treated db/db mouse values.

Figure 6

HE staining of the kidney. (a) Misty, (b) vehicle-treated db/db mice, (c) GS 20 mg/kg body weight-treated db/db mice, and (d) GS 100 mg/kg body weight-treated db/db mice. ×200.

Figure 7

Triglycerides (a), total cholesterol (b), and NEFA (c) contents in the adipose tissue. m/m, Misty; Veh, vehicle-treated db/db mice; GS20, GS 20 mg/kg body weight-treated db/db mice; GS100, GS 100 mg/kg body weight-treated db/db mice. The results are presented as the means ± S.E.M.  ^a P < 0.05, ^b P < 0.01, ^c P < 0.001 versus vehicle-treated db/db mouse values.

Figure 8

ROS (a) and TBARS (b) levels in the adipose tissue. m/m, Misty; Veh, vehicle-treated db/db mice; GS20, GS 20 mg/kg body weight-treated db/db mice; GS100, GS 100 mg/kg body weight-treated db/db mice. The results are presented as the means ± S.E.M. ^a P < 0.05, ^b P < 0.01, ^c P < 0.001 versus vehicle-treated db/db mouse values.

Figure 9

PPARα (a), PPARγ (b), SREBP-1 (c), and SREBP-2 (d) protein expressions in the adipose tissue. m/m, Misty; Veh, vehicle-treated db/db mice; GS20, GS 20 mg/kg body weight-treated db/db mice; GS100, GS 100 mg/kg body weight-treated db/db mice. The results are presented as the means ± S.E.M. ^a P < 0.05, ^b P < 0.01, ^c P < 0.001 versus vehicle-treated db/db mouse values.

Figure 10

NF-κBp65 (a), COX-2 (b), and iNOS (c) protein expressions in the adipose tissue. m/m, Misty; Veh, vehicle-treated db/db mice; GS20, GS 20 mg/kg body weight-treated db/db mice; GS100, GS 100 mg/kg body weight-treated db/db mice. The results are presented as the means ± S.E.M. ^a P < 0.05, ^b P < 0.01, ^c P < 0.001 versus vehicle-treated db/db mouse values.

Figure 11

JNK (a), p-JNK (b), AP-1 (c), and TGF-β ₁ (d) protein expressions in the adipose tissue. m/m, Misty; Veh, vehicle-treated db/db mice; GS20, GS 20 mg/kg body weight-treated db/db mice; GS100, GS 100 mg/kg body weight-treated db/db mice. The results are presented as the means ± S.E.M. ^a P < 0.05, ^b P < 0.01, ^c P < 0.001 versus vehicle-treated db/db mouse values.