Efficacy and mechanism of Shenqi Compound in inhibiting diabetic vascular calcification.

BACKGROUND: Shenqi Compound (SQC) has been used in clinic for several decades in the prevention and treatment of diabetes and its complications. But this is merely a heritage of experience. The primary aim of this study is to scientifically validate the therapeutic effects of SQC on diabetic vascular calcification (DVC) in an animal model and, simultaneously, uncover its potential underlying mechanisms. METHOD: Spontaneous diabetic rat- Goto Kakizaki (GK) rats were selected for rat modeling. We meticulously designed three distinct groups: a control group, a model group, and an SQC treatment group to rigorously evaluate the influence of SQC. Utilizing a comprehensive approach that encompassed methods such as pathological staining, western blot analysis, qRT-PCR, and RNA sequencing, we thoroughly investigated the therapeutic advantages and the underlying mechanistic pathways associated with SQC in the treatment of DVC. RESULT: The findings from this investigation have unveiled the extraordinary efficacy of SQC treatment in significantly mitigating DVC. The underlying mechanisms driving this effect encompass multifaceted facets, including the restoration of aberrant glucose and lipid metabolism, the prevention of phenotypic transformation of vascular smooth muscle cells (VSMCs) into osteogenic-like states, the subsequent inhibition of cell apoptosis, the modulation of inflammation responses, the remodeling of the extracellular matrix (ECM), and the activation of the Hippo-YAP signaling pathway. Collectively, these mechanisms lead to the dissolution of deposited calcium salts, ultimately achieving the desired inhibition of DVC. CONCLUSION: Our study has provided compelling and robust evidence of the remarkable efficacy of SQC treatment in significantly reducing DVC. This reduction is attributed to a multifaceted interplay of mechanisms, each playing a crucial role in the observed therapeutic effects. Notably, our findings illuminate prospective directions for further research and potential clinical applications in the field of cardiovascular health.

Modular characteristics and mechanism of action of herbs for type 2 diabetes treatment in Chinese medicine.

Type 2 diabetes (T2D) has emerged as a global epidemic, and conventional treatment approaches often face limitations in achieving long-term glycemic control and preventing complications. Traditional Chinese Medicine (TCM) offers a valuable alternative for managing T2D, with a long history of effectively using herbal formulations in clinical practice. However, the modular characteristics of these herbs and their specific mechanisms of action remain poorly understood. To comprehensively investigate the modular characteristics and mechanisms of Chinese herbs in treating T2D, as well as explore the synergistic interactions among different herbs and their modular components, we employed data mining, systematic pharmacology, and molecular docking. Our aim was to gain a comprehensive understanding of the potential therapeutic targets and pathways involved in herbal T2D treatment. In this study, a total of 1114 studies investigating the effects of TCM interventions in the treatment of T2D in adults were included. The analysis revealed 170 distinct types of Chinese herbs, 118 active components, and 238 common targets shared between the medicine and T2D. Additionally, this study identified six hub proteins (TNF, MMP2, PTGS, CASP3, CASP8, and CASP9) and two key chemicals (Diosgenin and Formononetin) found in TCM-mediated T2D suppression. It was observed that these proteins could bind with the ingredients. The MMP2-Diosgenin interaction exhibited the lowest binding free energy (-13.05 kJ/mol) and was primarily driven by hydrogen bonds with ALA-165. TNF-Diosgenin (-10.5 kcal/mol) showed three hydrogen bonds with LEU-37, ARG-82, and ASN-30. PTGS2 and Diosgenin (-8.71 kJ/mol) demonstrated a hydrogen bond with HIS-214. Furthermore, CASP9-Formononetin (-6.53 kcal/mol) exhibited the lowest binding free energy and hydrogen bonds with GLU-261 and SER-339 as the primary forces involved. CASP3-Formononetin (-6.07 kcal/mol) displayed three hydrogen bonds with ASN-342, TRP-348, and GLU-379. Lastly, CASP8 and Formononetin (-6.06 kJ/mol) formed a hydrogen bond with THR-390, TYR-392, and TYR-334. Moreover, critical therapeutic pathways, such as the immune inflammatory response, AGE-RAGE, and IL-17 signaling pathway, were found to be associated with T2D Chinese herb therapy. In conclusion, this study sheded light on the modular characteristics and mechanism of action of herbs used in Chinese Medicine for the treatment of T2D, which provided valuable insights for both researchers and practitioners in the field of Chinese Medicine, offering potential avenues for improved treatment strategies and personalized approaches to address the complex nature of T2D.

The protective role of shenqi compound in type 2 diabetes: A comprehensive investigation of pancreatic ß-cell function and mass.

Type 2 diabetes (T2D) is a prevalent metabolic disorder characterized by impaired insulin secretion and insulin resistance, resulting in elevated blood glucose levels. The dysfunction and loss of pancreatic ß-cells, responsible for producing insulin, contribute to the development of T2D. Traditional Chinese medicine (TCM) has emerged as a potential source of innovative therapeutic interventions. However, limited research exists on Chinese herbal formulations specifically targeting the protection of pancreatic ß-cell function and mass. One such formulation is the Shenqi compound (SQC), widely used in China and consisting of Panax Ginseng, Astragali Radix, Rhizoma Dioscoreae, Corni Fructus, Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma, Radix Trichosanthis, and Rhei Radix et Rhizoma. Understanding the mechanisms underlying the therapeutic effects of SQC is crucial for developing novel treatment strategies for T2D. This study aims to comprehensively investigate the scientific evidence supporting the role of SQC in alleviating T2D by targeting the protection of pancreatic ß-cell function and mass. Spontaneously diabetic GK rats were used as the animal model, receiving SQC (14.4 g/kg/d) for 8 weeks. The results demonstrate multiple beneficial effects of SQC, including significant control of blood glucose levels (P < 0.05), inhibition of insulin resistance (measured by Western Blot), reduction of hyperinsulinemia (P < 0.05), attenuation of oxidative stress (P < 0.05), suppression of inflammation (P < 0.05), protection against islet hypertrophy and beta cell proliferation (evaluated through pathological staining), and inhibition of ß-cell apoptosis and senescence (also assessed through pathological staining). These findings indicate the promotion of ß-cell survival and function. In vitro experiments using isolated islets further support these results, revealing improvements in insulin secretion (P < 0.05) and ß-cell function following SQC therapy (P < 0.05). This represents a significant breakthrough in addressing ß-cell dysfunction and preserving mass within the context of TCM. Overall, SQC shows promise as a natural therapeutic approach for T2D, with potential benefits in preserving pancreatic ß-cell function and mass. This enhances the practical applicability and significance of the research by bridging the gap between experimental findings and clinical practice, thereby providing important clinical value in TCM treatment of T2D. Further research is necessary to elucidate its precise mechanisms of action and optimize its clinical application.

Inhibiting apoptosis of Schwann cell under the high-glucose condition: A promising approach to treat diabetic peripheral neuropathy using Chinese herbal medicine.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes. Glycemic control and lifestyle alterations cannot prevent the development of DPN; therefore, investigating effective treatments for DPN is crucial. Schwann cells (SCs) maintain the physiological function of peripheral nerves and promote the repair and regeneration of injured nerves. Inhibiting the apoptosis of SCs through various pathological pathways in a high-glucose environment plays an important role in developing DPN. Therefore, inhibiting the apoptosis of SCs can be a novel treatment strategy for DPN. Previous studies have indicated the potential of Chinese herbal medicine (CHM) in treating DPN. In this study, we have reviewed the effects of CHM (both monomers and extracts) on the apoptosis of SCs by interfering with the production of advanced glycation end products, oxidative stress, and endoplasmic reticulum stress pathological pathways. This review will demonstrate the potentialities of CHM in inhibiting apoptosis in SCs, providing new insights and perspectives for treating DPN.

[Experimental research progress in traditional Chinese medicine prevention and treatment of diabetic peripheral neuropathy based on autophagy].

Diabetic peripheral neuropathy(DPN) is a chronic complication resulted from peripheral nerve injury in the late stage of diabetes. It involves a variety of pathological changes such as oxidative stress, endoplasmic reticulum stress, neuroinflammation, and apoptosis of Schwann cells(SCs). DPN is the main factor leading to lower limb disability or amputation in diabetic patients, with high incidence, long disease course, and poor prognosis. The modern medicine treatment of DPN mainly focuses on controlling blood glucose and improving microcirculation and nerve nutrition, which can only mitigate the clinical symptoms and not fundamentally reverse the pathological changes of peripheral nerves. Autophagy is a self-clearing mechanism that maintains cellular homeostasis by removing excess metabolites. Traditional Chinese medicine(TCM), featuring the holistic concept and syndrome differentiation, can treat chronic diseases in a multi-target, multi-pathway, and wide-range manner. Modern studies have shown that the occurrence and development of DPN are related to a variety of pathological changes, and autophagy is a key mechanism associated with DPN. The environment with persistent high glucose can lead to the inhibition or over-activation of peripheral nerve cells, which causes irreversible damage of nerve cells and the occurrence and development of DPN. Therefore, restoring autophagy balance and reducing nerve damage is one of the key ways to treat DPN. The recent studies have confirmed that some active ingredients in traditional Chinese medicines and TCM compound prescriptions can inhibit the oxidative stress, endoplasmic reticulum stress, mitochondrial damage, inflammation, and apoptosis of SCs in DPN by regulating the autophagy pathway, thus playing a role in the prevention and treatment of DPN. However, the systematic induction in this field remains to be carried out. This paper reviewed the relevant literature, explained the mechanism of TCM in the prevention and treatment of DPN by regulating autophagy, and summarized the potential targets of TCM in the treatment of DPN, with a view to providing new ideas for clinical research and drug development.

[Protection and mechanism of shenqi compound for diabetic angiopathy model rats].

OBJECTIVE: To investigate the protective effect and mechanism of Shenqi Compound on diabetic angiopathy modeled rats. METHODS: Totally 18 SD rats were randomized into 3 groups, i.e., the normal control group, the diabetic mellitus (DM) group, and Shenqi Compound group, 6 in each group. The DM rat model was established by feeding high-fat diet (to induce hyperlipidemia) +intraperitoneal injection of small dose streptozotocin (STZ). Shenqi Compound was given to rats in the Shenqi Compound group at the daily dose of 2 g/kg. Equal volume of normal saline was given to rats in the model group and the normal control group by gastrogavage. All treatment was lasted for 12 weeks. Then 2-D and ultrasonic integrated backscatter technique were used to evaluate structural and functional changes of abdominal aorta in the progression of diabetic macroangiopathy. The fibrosis degree of the aorta vessel and myocardium capillaries were observed by using HE and Masson trichrome staining. The tension of the aortic vascular ring was determined. The transforming growth factor beta (TGF-beta) mRNA expression was detected by real time PCR (RT-PCR). The protein expression of TGF-beta, collagen I, collagen III, connective tissue growth factor (CTGF), and phosphorylation P38 MAPK were detected by Western blot. RESULTS: Compared with the normal control group, abdominal aortic systolic inner diameter, diastolic inner diameter, Peterson elastic modulus, stiffness index, and backscatter integral significantly increased; the rangeability of integral backscatter and the extension coefficient of cross section significantly decreased in the DM group (all P < 0.05). After 12 weeks aforesaid indices were obviously improved in the Shenqi Compound group (P < 0.05). Results of HE and Masson staining showed that the fibrosis degree of the aorta vessel and myocardium capillaries was obviously alleviated in rats of the Shenqi Compound group (P < 0.05). Results of the aortic vascular ring tension showed that acetylcholine induced vasodilatation and maximum diastolic percent were obviously elevated in the Shenqi Compound group (P < 0.05). Compared with the normal control group, the mRNA expression of TGF-beta, and the protein expression of TGF-beta, collagen I, and collagen III, and phosphorylation of P38 MAPK all significantly increased in the DM group (P < 0.05). Compared with the DM group, the mRNA expression of TGF-beta, and the protein expression of TGF-beta, collagen I, and collagen III, and phosphorylation of P38 MAPK all decreased (P < 0.05). CONCLUSIONS: Shenqi Compound could effectively improve the arterial function in diabetic marcoangiopathy and microvascular dysfunction. The mechanism might be due to the down-regulating the expression of TGF-beta, and further suppressing the phosphorylation of P38 MAPK, reducing the synthesis of collagen I and collagen III, therefore, ameliorating arterial and myocardial interstitial fibrosis.