Effects of Compound Centella on Oxidative Stress and Keap1‐Nrf2‐ARE Pathway Expression in Diabetic Kidney Disease Rats

Abstract

The formula of Compound Centella mainly contains 3 traditional Chinese herbs: Centella asiatica (L.) Urb. (JiXueCao), Astragalus Membranaceus Fish. (HuangQi), and Tripterygium wilfordii Hook. f. (LeiGongTeng). Though this formula is effective for treating diabetic kidney disease (DKD) in clinic, the exact mechanism is still unclear. This study aims to investigate the effect and antioxidant mechanism of Compound Centella on DKD rats. High-performance liquid chromatography (HPLC) was applied to analyse 3 herbs in Compound Centella. Sprague-Dawley rats were divided into the normal group (NG), DKD group (DKDG), Compound Centella group (CCG), and losartan group (LG), with 8 rats in each group. On the first day of the experiment, rats in the NG were fed with ordinary –feed, while the other groups were fed with high-fat and high-sugar feed. On the 29th day, except the NG, the other 3 groups received a single intraperitoneal injection of streptozocin (STZ, 35 mg/kg). Fasting blood glucose (FBG) was measured on the 1st day, 32nd day, 46th day, 56th day, 84th day, and 112th day. Total protein/creatinine ratio of urine was determined by the phenol red assay on the 1st day and 112th day. Serum creatinine (Scr) was determined by an automatic biochemical analyser on the 112th day. Kidneys were collected on the 112th day for analysis and evaluation. Periodic acid-Schiff (PAS) staining, hematoxylin-eosin (HE) staining, and transmission electron microscopy were used to observe kidney pathological changes. The mRNA and protein expressions of Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor-erythroid 2-related factor 2 (Nrf2) in renal tissues were detected by RT-qPCR, Western blot, and immunohistochemistry. Oxidative stress was evaluated by detecting the levels of malondialdehyde (MDA) and heme oxidase-1 (HO-1). The results showed that the content of asiaticoside, astragaloside, and triptolide in the herb was 5960, 809, and 2.42 μg/g and in the Compound Centella was 340, 64, and 0.1403 μg/mL by HPLC. Compound Centella reduced the urine protein/creatinine ratio and improved renal pathology in the kidneys of DKD rats. In addition, the mRNA and protein expressions of Keap1 and Nrf2 in kidneys were upregulated by Compound Centella. The expressions of MDA were downregulated but HO-1 were upregulated by Compound Centella. Therefore, the protective effect of Compound Centella in the kidney of DKD rats may be related to regulating the Keap1-Nrf2-ARE pathway under oxidative stress, suggesting Compound Centella as a promising treatment against DKD.

Ethanolic Extract of Centella asiatica Treatment in the Early Stage of Hyperglycemia Condition Inhibits Glomerular Injury and Vascular Remodeling in Diabetic Rat Model

“…Then, it attenuates blood glucose level and lipid profile serum followed by diminished polyphagia, polydipsia, and polyuria [ 38 , 42 ]. A previous study mentioned that CeA has several potent active compounds such as asiatic acid, asiatocoside, madecassic acid, madecassoside, astragaloside, and triptolide [ 33 , 44 , 45 ] that cause a reduction in proteinuria and glomerulosclerosis. In addition, the administration of the asiatocoside and asiatic acid significantly reduced urinary protein excretion and blood glucose level in DM rat models [ 33 , 45 ].…”

The effects of compound centella formula on OxInflammation and silent information regulator 1 in a high‑fat diet/streptozotocin‑induced diabetic kidney disease rat model

“…As a classic drug for the treatment of diabetic nephropathy, LST was used as the positive control drug for centella formula in this experiment. Plasma fasting blood glucose (FBG) was measured from the tail vein, and FBG levels >16.7 mmol/l (72 h after injection) were considered diabetic rats (14). Subsequently, the drug intervention was carried out from the 32nd to the 112th day.…”

“…In a previous study (14), the concentration of representative components in CCF was measured. The representative chemical components in CCF were detected by high-performance liquid chromatography (Table II).…”

“…At present, the use of medicinal plants and their natural components as future drugs for the treatment of diabetes and its complications has received considerable interest from researchers worldwide. The Chinese decoction compound centella formula (CCF) was designed by a famous contemporary doctor of traditional Chinese medicine, Professor Yongjun Wang (14). The composition and daily dose for adults of this decoction are as follows: Centella asiatica (L.) Urb.…”

Antioxidant Effects and Potential Molecular Mechanism of Action of Limonium aureum Extract Based on Systematic Network Pharmacology

“…Many environmental stimuli, including UV, ionizing radiation, chemotherapeutics, heavy metals, and environmental toxins, can trigger the high levels production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), resulting in random oxidative damage of cellular proteins, DNA, and lipids, finally leading to cell death ( 2 , 3 ). Repeated exposure to oxidative stress accelerates the development of a variety of diseases that include diabetes ( 4 ), cancer ( 5 ), cardiovascular diseases ( 6 ), autoimmune diseases ( 7 ), and neurodegenerative disorders ( 8 ). Therefore, the balance between ROS production and antioxidant defense helps maintain the normal physiological processes of organisms.…”