Effects of Huangqi Liuyi Decoction in the Treatment of Diabetic Nephropathy and Tissue Distribution Difference of its Six Active Constituents Between Normal and Diabetic Nephropathy Mouse Models

Abstract

The purpose of this study was to investigate the effects of Huangqi Liuyi decoction extract (HQD) on diabetic nephropathy (DN), and the tissue distribution difference of six main active ingredients of HQD between normal and DN mouse models. DN mice were administered HQD for 12 weeks to investigate its efficacy in the treatment of DN. Liquid chromatography-tandem mass-spectrometry (HPLC-MS/MS) was used to analyze the tissue distribution of the six active ingredients of HQD in normal and DN mice, including astragaloside IV, calycosin-7-O-β-D-glucoside, calycosin glucuronide, ononin, formononetin, and glycyrrhizic acid. DN mice treated with HQD showed significantly decreased fasting blood glucose (FBG), 24-h urinary protein (24 h U-Alb), blood urea nitrogen (BUN), serum creatinine (Scr), and triglyceride levels (TG) (p < 0.05). Moreover, there were no significant differences in pharmacodynamics between HQD and Huangqi Liuyi decoction. Treated mice also had decreased expression of collagen I, ɑ–smooth muscle actin (ɑ-SMA), and vimentin; and upregulated expression of E-cadherin in their kidneys. Compared to normal mice, distributions of the six ingredients in the liver, heart, spleen, lungs, kidneys, stomach, small intestine, brain, and muscle of DN mice were different. The results indicated that the HQD could be used for the treatment of DN and to improve renal function. The pathological state of diabetic nephropathy may affect tissue distribution of HQD active ingredients in mice.

Study on the liver Drug’s dominant metabolic enzymes for six effective components of the Huang qi Liuyi decoction

“…Ten-week-old db/db male mice (45 ± 5 g) and db/m mice (20 ± 2 g) were purchased from the Model Animal Research Center of Nanjing University and MOE Key Laboratory of Model Animal for Disease Study (SCXK [Su]2021-0016) and housed in polypropylene cages at a relative humidity of 60% ± 5%, constant temperature (25 °C ± 1 °C) and under a 12 h light/12 h dark cycle, mice were given free access to water and food. Twelve-week-old db/db mice developed nephropathy (Ponchiardi et al, 2013;Wang et al, 2022b). The animal studies were approved by the Animal Ethical Committee of Guizhou University of Traditional Chinese Medicine (the approval number is NO1702060).…”

“…Previously, our team discovered that the combination of four components extracted from Huangqi Liuyi Decoction, namely, astragalus saponin, glycyrrhizic acid, astragalus flavone, and astragalus polysaccharide (AKA HQD), improved renal fibrosis and slowed the progression of diabetic nephropathy in db/db mice (Wang et al, 2022). The study also discovered no statistical difference between the efficacy of Huangqi Liuyi decoction and HQD in mice with diabetic nephropathy (Wang et al, 2022b). According to pharmacokinetic studies, mice with diabetic nephropathy exhibited greater absorption and delayed elimination of the six effective components (astragaloside IV, glycyrrhizic acid, calycosin-glucuronide, formononetin, ononin, calycosin-7-O-β-D-glucoside) following oral administration HQD (Wang et al, 2022c).…”