In Vitro and In Vivo Evaluation of the Antidiabetic Activity of Solidago virgaurea Extracts

Abstract

Background: Solidago virgaurea (Asteraceae) has been used for more than 700 years for treating cystitis, chronic nephritis, urolithiasis, rheumatism, and inflammatory diseases. However, the antidiabetic activity of Solidago virgaurea has been rarely studied.

Methods: Three extracts of Solidago virgaurea were prepared, and their antidiabetic potentials were evaluated by various cell-free, cell-based, and in vivo studies.

Results: We found that the Solidago virgaurea contained multiple bioactive phytochemicals based on the GC-MS analysis. The Solidago virgaurea extracts effectively inhibited the functions of the carbohydrate digestive enzyme (α-glucosidase) and protein tyrosine phosphatase 1B (PTP1B), as well as decreased the amount of advanced glycation end products (AGEs). In the L6 myotubes, the Solidago virgaurea methanolic extract remarkably enhanced the glucose uptake via the upregulation of glucose transporter type 4 (GLUT4). The extract also significantly downregulated the expression of PTP1B. In the streptozotocin-nicotinamide induced diabetic mice, the daily intraperitoneal injection of 100 mg/kg Solidago virgaurea methanolic extract for 24 days, substantially lowered the postprandial blood glucose level with no obvious toxicity. The extract's anti-hyperglycemic effect was comparable to that of the glibenclamide treatment.

Conclusion: Our findings suggested that the Solidago virgaurea extract might have great potential in the prevention and treatment of diabetes.

Keywords: GC-MS; Solidago virgaurea; advanced glycation end products; glucose transporter; protein tyrosine phosphatase 1B; α-glucosidase.

Fig. 1.

Antidiabetic activities of the Solidago virgaurea extracts determined by the cell-free assays. (A) α-glucosidase inhibitory activities of the Solidago virgaurea extracts. Acarbose was used as a positive control. (B) Inhibition of AGEs by the Solidago virgaurea extracts. Rutin was used as a positive control. (C) Inhibition of PTP1B by the Solidago virgaurea extracts. (D) Dose response (PTP1B inhibition) curve of the methanolic extract.

Fig. 2.

Cytotoxicity and glucose uptake study of the Solidago virgaurea methanolic extract in L6 myoblasts. (A) Cell viability in the presence of the Solidago virgaurea methanolic extract determined by the MTT assay. Cell incubation time: 48 hours. (B) Effect of the Solidago virgaurea methanolic extract on glucose uptake. Data were presented as mean ± S.D. (n=3). ** P <0.01, *** P <0.001, **** P <0.0001.

Fig. 3.

Relative mRNA levels of (A) GLUT4 and (B) PTP1B. Cell incubation time: 12 hours. Data were presented as mean ± S.D. (n=3). **** P <0.0001.

Fig. 4.

Western blot of (A) GLUT4 and (B) PTP1B proteins. Cell incubation time: 12 hours. Densitometric analysis was carried out by ImageJ software. The data was expressed as the mean ± S.D. (n= 3). * P <0.05, *** P <0.001.

Fig. 5.

Antidiabetic activity of the Solidago virgaurea methanolic extract in the STZ-NA induced diabetic mice. (A) Mouse blood glucose levels. The postprandial blood glucose was measured by the OneTouch^® glucometer. (B) Mouse body weights at the beginning and end of the experiment. Glibenclamide was used as a positive control. Data were presented as Means ± S.D. (n=5). **** p<0.0001.

Fig. 6.

H&E staining. At the end of the in vivo experiment, liver, kidney, and pancreas were collected and sectioned, followed by H&E staining (scale bar: 100 μm). The arrows refer to the necrotic/apoptotic tissues (cells).

Fig. 7.

GC chromatogram of the Solidago virgaurea methanolic extract. The major phytochemicals were identified with the help of the mass spectral library of NIST (Table 1).