Therapeutic Effects of Compound Herba Houttuyniae in Type 2 Diabetic Rats
Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by insulin resistance (IR) and β-cell dysfunction. If not well managed, it can lead to the development of microvascular complications, such as nephropathy and retinopathy, as well as macrovascular complications. Diabetic nephropathy (DN), a form of chronic kidney disease caused by diabetes, is particularly concerning. In China, the incidence of chronic kidney disease among patients with T2DM is steadily increasing. The early stages of DN are marked by elevated urine albumin concentration and renal hyperfiltration.
In traditional Chinese medicine (TCM), diabetes mellitus falls under the category of “wasting-thirst.” Houttuynia cordata Thunb, a TCM herb known for its heat-clearing and detoxifying properties, has been considered a potential treatment for the glucotoxicity and oxidative stress associated with diabetes. Fructus arctii, another TCM herb, is traditionally used to disperse wind-heat. Modern pharmacological studies have shown that Fructus arctii can prevent and treat DN. However, there has been limited research on the therapeutic effects of compound herba Houttuyniae (CHH), which is a combination of H. cordata Thunb and F. arctii, in animal models of T2DM.
This study aimed to investigate the therapeutic effects of CHH in rats with T2DM induced by a high-fat, high-sugar diet and low-dose streptozotocin (STZ) administration. The researchers prepared volatile oil, aqueous, and ethanolic extracts from H. cordata Thunb and F. arctii, which were then combined to form CHH. The effects of CHH were evaluated based on fasting blood glucose levels, markers of early renal injury, serum concentrations of glucagon-like peptide-1 (GLP-1) and fasting insulin (FINS), and the homeostasis model of assessment-insulin resistance (HOMA-IR). The goal was to provide a scientific basis for the development of a novel treatment for T2DM and DN.
The study was conducted on 50 rats, 45 of which were fed a high-fat, high-sugar diet for four weeks. After fasting for 12 hours, these rats were injected with 1% STZ (30 mg/kg) to induce T2DM. To prevent hypoglycemia, the rats were provided with a sugar solution. Three days later, their fasting blood glucose (FBG) levels were measured using a portable blood glucose meter. Rats with FBG levels significantly higher than normal (≥11.1 mmol/L) and exhibiting symptoms such as polydipsia, polyphagia, and polyuria were confirmed to have T2DM. These rats were then divided into four groups: a vehicle group (n = 10), a resveratrol (Res) group (n = 10), a rosiglitazone (Rsg) group (n = 10), and a CHH group (n = 15). The remaining five rats were fed a standard chow diet and served as the non-diabetic group.
CHH was prepared by mixing H. cordata Thunb and F. arctii in a 1:1 ratio. Five volumes of water and 0.004 volumes of ethyl acetate were added to the mixture, which was then left to stand for one hour. The essential oils were extracted using an essential oil extractor. An aqueous extract was prepared by immersing the mixture in cold water in a round-bottomed flask, while an alcoholic extract was obtained by refluxing the mixture in 50% ethanol. The aqueous and ethanolic extracts were dried into powder forms through vacuum evaporation, concentration, and drying. The volatile oils, aqueous extract, and alcoholic extract were then combined to yield CHH. Based on human and mouse doses, an appropriate daily oral dose for rats was calculated to be 4.5 g/kg.
Blood samples were collected and centrifuged at 12,000 g for 15 minutes to obtain serum. The serum was used to measure FBG, creatinine, blood urea nitrogen (BUN), aspartate transaminase (AST), alanine transaminase (ALT), and uric acid (UA) concentrations using an automated biochemical analyzer. Commercial kits were used to measure FINS, GLP-1, glycated serum protein (GSP), and glutathione concentrations. Additionally, 24-hour urine samples were collected to measure total protein (TP), albumin (ALB), and creatinine concentrations.
Statistical analysis was performed using SPSS version 21.0. Data were presented as means ± standard deviations. Each dataset was tested for similar variance, and one-way analysis of variance (ANOVA), paired-samples t-tests, and the least significant difference method were used to compare the groups. A p-value of less than 0.05 (two-sided) was considered statistically significant.
The study found that all treatments administered, including CHH, Res, and Rsg, ameliorated the effects of T2DM on body mass, food intake, and water intake in the rats. CHH significantly reduced the activities of AST, ALT, BUN, and serum concentrations of UA and GSP in diabetic rats. Resveratrol, an activator of silent information regulator 1 (SIRT1), was found to increase the expression of catalase and exert antioxidant effects. The glutathione concentration was significantly higher in the Res group compared to the non-diabetic group, suggesting that Res could reduce cellular damage caused by oxidative stress. The molecular mechanisms involved in these effects will be further investigated in future studies, focusing on pathways such as SIRT1/Forkhead box class O1 and SIRT1/peroxisome proliferator-activated receptor gamma coactivator 1a.
Insulin resistance is a major characteristic of T2DM, and HOMA-IR is commonly used to assess IR in diabetes studies. GLP-1, which circulates at lower concentrations in T2DM, stimulates post-prandial insulin secretion. Rosiglitazone activates peroxisome proliferator-activated receptor gamma, increasing the sensitivity of peripheral tissues to insulin and enhancing glucose uptake and utilization, thereby improving defective glucose metabolism in T2DM. The study found that Res, Rsg, and CHH all had similar beneficial effects on IR, as they all reduced HOMA-IR. Additionally, CHH increased the concentrations of FINS and GLP-1 in diabetic rats.
Glomerular filtration rate (GFR) is a critical indicator of glomerular function, and 24-hour endogenous creatinine clearance (Ccr) is widely used clinically to assess GFR. The study found that CHH significantly reduced the concentrations of TP and ALB in 24-hour urine samples, as well as 24-hour Ccr and the renal index. Pathological changes such as enlarged glomeruli, mesangial proliferation, and inflammatory cell infiltration into the renal interstitium were observed in the vehicle-treated group. These early pathological changes were ameliorated by all treatments, including CHH.
In conclusion, the study demonstrated that a high-sugar, high-fat diet combined with low-dose STZ administration induces early renal injury and metabolic disorders in rats with T2DM. The administration of CHH, as well as Res and Rsg, was found to prevent and/or treat these conditions. CHH, in particular, showed promising therapeutic effects by reducing IR, improving renal function, and mitigating oxidative stress. These findings provide a scientific basis for the potential use of CHH as a novel treatment for T2DM and DN.
doi.org/10.1097/CM9.0000000000000701
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