Diabetic nephropathy (DN) is a serious complication of diabetes mellitus, and its prevalence has been increasing all over the world, which is also the leading cause of end-stage renal failure. Hydroxysafflor yellow A (HSYA) is the main active chemical component of Carthamus tinctorius L., and it is commonly used in patients with cardiovascular and cerebrovascular diseases in China. The aim of this study was to investigate the renal protective effects and molecular mechanisms of HSYA on high-fat diet (HFD) and streptozotocin- (STZ-) induced DN in rats. The DN rats were treated with HSYA for eight weeks. We assessed creatinine (CR), urea nitrogen (UN), glomerular volume, podocyte number, renal inflammation, oxidative stress, and cells apoptosis markers after HSYA treatment. The number of apoptotic cells was measured by the TUNEL assay, and apoptosis-related proteins BAX, caspase-3, and BCL-2 in the renal tissue were analyzed by western blot. The treatment with HSYA significantly decreased fasting blood glucose, CR, UN, and blood lipid profile, including triglyceride and total and low-density lipoprotein cholesterol, even though it did not change the rats’ body weights. The western blot results indicated that HSYA reversed the upregulation of BAX and caspase-3 and significantly increased BCL-2 in renal tissue. Moreover, the levels of TNF-α and the inflammatory products, including free fatty acids (FFA) and lactic dehydrogenase (LDH) in the HSYA group, were significantly decreased. For the oxidative stress marker, the superoxide dismutase (SOD) markedly increased in the HSYA treatment group, while the malondialdehyde (MDA) in the serum and kidney tissue evidently decreased. In conclusion, HSYA treatment preserved kidney function in diabetic nephropathy in the HFD- and STZ-induced rats. The potential mechanism of renal protective effect of HSYA might be through inhibiting oxidative stress, reducing inflammatory reaction, and attenuating renal cell apoptosis. Our studies present a promising use for Hydroxysafflor yellow A in the treatment of type 2 diabetes mellitus.

Background and Aim: Type 2 diabetes mellitus (T2DM), a complex metabolic disease, has become a major public health issue around the world. Hydroxysafflor yellow A (HSYA) is the major active chemical ingredient of Carthamus tinctorius L. (safflower), which is widely used in patients with cardiovascular and cerebrovascular diseases in China. The aim of this study was to investigate the anti-diabetic effect and potential mechanism of HSYA on the high-fat diet (HFD) and streptozotocin (STZ-)-induced T2DM rats. Materials and Methods: T2DM rats were induced by feeding HFD (60% fat) for four weeks followed by intraperitoneal injection of a low dose of streptozocin (35mg/kg). The T2DM rats were treated with HSYA (120mg/kg) or metformin (90mg/kg) for eight weeks. Biochemical analysis, histological analysis and Western blot analysis were conducted after 8 weeks of intervention. Results: The treatment with HSYA evidently reduced fasting-blood glucose and insulin resistance in T2DM rats, indicated by results from fasting-blood glucose, oral glucose tolerance test, fasting insulin levels and histology of pancreas islets. The Western blot results revealed that HSYA reversed the down-regulation of PI3K and AKT in liver. The TUNEL assay analysis of pancreatic tissue showed that HSYA could inhibit the apoptosis of pancreatic β-cells to a certain extent. Moreover, HSYA-treatment increased the levels of glycogen synthase and hepatic glycogen and improved lipid metabolism by reducing the triglyceride, total and low-density lipoprotein cholesterol levels, even though it did not change the rats’ body weights. Conclusion: The results of this study suggested that HSYA could promote PI3K/Akt activation and inhibit the apoptosis of pancreatic β-cells directly or indirectly, which might be the underlying mechanisms in HSYA to improve insulin resistance and regulate glycolipid metabolism in T2DM rats.

Purpose: The purpose of this systematic review was to assess potential gender differences in prevalence and clinical relevance of insulin-related lipohypertrophy (LH). Patients and Methods: Five electronic databases (PubMed, Embase, CNKI, Wanfang and VIP) were systematically searched for studies, from inception to 1st Sep 2022, on the prevalence of insulin-related LH. The eligibility of articles was independently screened, and the included studies were evaluated using standardized quality assessment tools. Results: A total of 22 studies mentioned the LH prevalence in different genders, of which two are about gestational diabetes; therefore, 20 studies were eventually included, providing data on 6238 patients. The prevalence of LH varied from 30.26% to 72.54%. Ten studies (4392 patients) were conducted with the adult diabetes patients of different genders over the age of 18, the total prevalence rate of LH was 51.73%, the LH prevalence in male gender was from 41.94% to 68.57% and the rate of the total population was 54.89% (2046 patients); The LH prevalence in female gender was from 33.18% to 70% and the rate of the total population was 48.98% (2346 patients), and the prevalence of LH was significantly different between male and female gender (P< 0.001). Interestingly, only one study (n=1227) showed that there were dramatic differences between different genders (P< 0.001), the subjects were T2DM patients, the LH prevalence rate of male vs female was 70.52% (299/424) VS 52.18% (419/803), while the other studies either only include T1DM or both T1DM and T2DM. Conclusion: The evidence shows that the results of gender differences in the LH prevalence are inconsistent with different types of DM. Probably, there is no gender differences in the LH prevalence in adult patients with T1DM, but it has a gender difference between male and female in T2DM. More strictly designed clinical studies are needed to further verify and reveal the underlying mechanisms.

Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes mellitus. The most common type is distal symmetric polyneuropathy, and lesions frequently lead to disabling neuropathic pain and even amputation, increasing the risk of death. At present, the pathogenesis of DPN has not been clarified, and its insidious onset and lack of obvious symptoms in most patients in the early stages often lead to delayed diagnosis, which is unfavourable for prevention and treatment. This article provides an overview of the existing research progress on early diagnostic markers of DPN, especially oxidative stress-related markers, neural tissue damage markers, inflammation-related markers, neurovascular damage markers, and gene-related markers, in the hope that it can provide a reference for early diagnosis and treatment of DPN, and slow down the occurrence and development of DPN.

Introduction: A traditional Chinese herbal decoction, Huoxue-Jiangtang decoction (HXJT), has been clinically prescribed to patients with type 2 diabetes mellitus (T2DM) to improve hyperglycemia and hyperlipidemia for many years. However, the potential mechanisms underlying its anti-diabetic effects remain unclear.Methods: The aim of this study was to explore the anti-diabetic effects and underlying molecular mechanisms of HXJT in T2DM rats, which were fed with a high-fat diet (HFD) and subsequently induced with streptozotocin (STZ). HPLC-MS analysis was performed to characterize the chemical composition of HXJT and serve as a quality control measure. The T2DM rats were treated with metformin or HXJT for 8 weeks.Results and discussion: Treatment with HXJT significantly reduced hyperglycemia and improved insulin resistance in T2DM rats, as revealed by multiple assessments, including fasting blood glucose (FBG), glucose tolerance, fasting insulin levels, homeostasis model assessment of insulin resistance, insulin sensitivity index analysis, and histological examination of pancreas islets. HXJT treatment decreased blood lipid profile, including total cholesterol, low-density lipoprotein cholesterol, and triglycerides, although it did not change the rats’ body weight. The Western blot results indicated that HXJT reversed the downregulation of AKT and PI3K and markedly increased glucose transporter type 4 (GLUT4) in skeletal muscles. Moreover, the levels of glycogen synthetase (GS), hexokinase, superoxide dismutase (SOD), glycogen, and muscle glycogen in the HXJT group significantly increased relative to those in untreated T2DM group, while TNF-α levels decreased observably. In conclusion, HXJT improves insulin resistance, enhances insulin sensitivity, and helps preserve glucose homeostasis. The potential molecular mechanisms are related to the activation of PI3K/AKT and GLUT4 in skeletal muscles, either directly or indirectly.

Background and Purpose: Diabetic retinopathy (DR) is one of the common and serious microvascular complications of diabetes mellitus (DM), DR carries a high risk of blindness and significantly impairs patients’ quality of life. This study aims to systematically evaluate the efficacy and safety of Chinese Medicine Eye Nebulization (CMEN) therapy for DR and further explore its mechanisms of action. Patients and Methods: As a single-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial, this study will enroll 80 patients with non-proliferative diabetic retinopathy (NPDR) at stage II, characterized by the TCM syndrome of Qi-Yin deficiency with blood stasis. Participants will be randomized in a 1:1 ratio to receive either CMEN therapy (n=40) or placebo aerosol therapy (n=40). The intervention will be administered continuously for 2 weeks. The primary outcome measures include the improvement of clinical symptoms (blurred vision, dry eyes) and quality of life, assessed using the “Xiaoke Eye Disease Primary Symptom Score Scale”, the Ocular Surface Disease Index (OSDI) Dry Eye Score Scale, and the Diabetes Mellitus Quality of Life Scale (DMQLS) Chinese Version for type 2 diabetes. Secondary outcomes encompass changes in visual acuity, fall risk assessment, levels of inflammatory and oxidative stress biomarkers (VEGFA, TNF-α, IL-6, IL-8, CCL2, MDA, SOD, GSH), and the progression of fundus lesions evaluated by optical coherence tomography (OCT). Assessments will be conducted at baseline, the end of the 2-week treatment period, and the end of the 4-week follow-up period. Multivariate analysis of variance (MANOVA) will be employed to examine the associations between different groups, time points, and group-time interactions. Discussion: This study represents the pioneering application of CMEN therapy in the treatment of DR, with a specific focus on its effects on core clinical symptoms (blurred vision and dry eyes), quality of life, as well as inflammatory and oxidative stress biomarkers in DR patients.