Exploring the Underlying Mechanism of Alpinia officinarum Hance Ameliorating Diabetic Gastroparesis through Combining Network Pharmacology, Molecular Docking, and in Vivo Experimental Verification.

BACKGROUND: Alpinia officinarum Hance (AOH) has a long history in China as a Chinese medicine and exerts the pharmacological effects of antidiabetic and gastrointestinal protection. In traditional Chinese medicine theory, AOH is often combined with other Chinese medicines for the treatment of diabetic gastroparesis (DGP). However, the molecular mechanisms, potential targets, and bioactive ingredients of AOH that act against DGP are yet to be elucidated. In this study, network pharmacology, molecular docking, and experimental study were used to predict the therapeutic effects and the potential molecular mechanism of AOH in DGP. METHODS: Network pharmacology analysis was performed to acquire information on the active chemical ingredients, DGP-related target proteins in AOH, and potential signaling pathway. In addition, molecular docking approach was used to simulate the binding of drugs and targets. Finally, DGP-mice model was used for experimental verification in vivo. Results: Through the network pharmacological research, AKT1 was found to be the core protein in AOH for the treatment of DGP and was mainly involved in the PI3K-AKT signaling pathway. Additionally, the interactions between bioactive compounds and target proteins (PIK3CA and AKT1) were analyzed using molecular docking, which verified the results of network pharmacology. Further in vivo studies indicated that AOH could reduce fasting blood glucose levels, improve gastric emptying rate, and ameliorate biochemical indicators in DGP mice. Moreover, AOH could increase the expressions and phosphorylation levels of PI3K and AKT in the stomach to regulate oxidative stress. CONCLUSIONS: The study has shown that AOH may play a protective role on DGP through mediation of the PI3K-AKT signaling pathway to regulate oxidative stress.

A diarylheptanoid compound from Alpinia officinarum Hance ameliorates high glucose-induced insulin resistance by regulating PI3K/AKT-Nrf2-GSK3ß signaling pathways in HepG2 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Alpinia officinarum Hance, a perennial natural medicine-food herb, has been traditionally used to treat colds, stomachache, and diabetes for thousands of years. 1,7-Diphenyl-4E-en-3-heptanone (DPH5), a diarylheptanoid isolated from the rhizome of A. officinarum has been reported to be safe and to have antioxidant and hypoglycemic effects, suggesting its potential in the treatment of insulin resistance (IR). AIM OF THE STUDY: Aim of to investigate the protective effect of DPH5 on IR and elucidate its underlying mechanism of action. MATERIALS AND METHODS: HepG2 cells were used as the research objects. Glucose uptake and reactive oxygen species (ROS) levels in high glucose-induced insulin-resistant HepG2 cells were assessed using flow cytometry. Glucose consumption and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed using the corresponding assay kits. The expression of mRNA and proteins related to insulin signaling, glucose metabolism, and antioxidant factor, including insulin receptor substrate-1 (IRS1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), translocation of glucose transporter-4, glycogen synthase kinase-3ß (GSK3ß), glucokinase (GCK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), nuclear factor-erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NADPH quinoneoxidoreductase (NQO1), and glutathione peroxidase (GSH-Px) was determined using real-time quantitative polymerase chain reaction and western blotting. Furthermore, molecular docking was performed to determine the spatial mechanism of DPH5 on the key targets PI3K, AKT, Nrf2, and GSK3ß. RESULTS: DPH5 could improve IR that manifested as increased glucose uptake and glucose consumption in insulin-resistant HepG2 cells. Moreover, DPH5 could enhance antioxidant capacity by activating Nrf2/HO-1 elements, including increasing Nrf2, HO-1, SOD, NQO1, and GSH-Px expression and reducing MDA, ROS, and JNK levels, thereby improving oxidative stress and ultimately alleviating IR. Additionally, DPH5 could promote the expression of IRS1, PI3K, AKT, GSK3ß, GCK, and PK, and downregulate the expression of PEPCK and G6pase, thereby accelerating glucose utilization and enhancing insulin sensitivity. The mechanism underlying the effect of DPH5 in alleviating IR was related to the PI3K/AKT- and Nrf2/HO-1-mediated regulation of the GSK3ß signaling pathway, and the results were further confirmed using the specific inhibitors LY294002 and ML385. Results from molecular docking indicated that there were different regulatory sites and interacting forces between DPH5 and PI3K, AKT, Nrf2, and GSK3ß; however, the binding force was relatively strong. CONCLUSIONS: DPH5 improved oxidative stress and glucose metabolism via modulating the PI3K/AKT-Nrf2-GSK3ß pathway, thereby ameliorating IR. Overall, our findings suggest the potential of DPH5 as a natural medicine to treat type-2 diabetes mellitus.

Effectiveness of acupuncture combined mecobalamin in the treatment of elderly diabetic peripheral neuropathy: A protocol of systematic review and meta-analysis.

BACKGROUND: Although previous studies have reported the effectiveness of acupuncture combined mecobalamin (AM) in the treatment of elderly diabetic peripheral neuropathy (EDPN), no systematic study has assessed its effectiveness and safety. Thus, this study will evaluate the effectiveness and safety of AM for the treatment of patients with EDPN. METHODS: Bibliographic electronic databases will be searched as follows: Cochrane Library, PUBMED, EMBASE, CINAHL, PsycINFO, WANGFANG, and China National Knowledge Infrastructure. All of them will be searched from each database initial to March 1, 2020 without language restrictions. All study selection, information extracted, and study quality evaluation will be performed by 2 independent authors. Any disagreements between 2 authors will be resolved by a third author via discussion. RevMan 5.3 software will be used for data pooling and meta-analysis performance if it is possible. RESULTS: This study will provide synthesis of current evidence of AM for patients with EDPN through primary outcome of glycemic profile, and secondary of neuropathic pain intensity, plantar tactile sensitivity, sensory nerve conduction velocity and motor nerve conduction velocity, health-related quality of life, and adverse events. CONCLUSION: This study will provide helpful reference for the efficacy and safety of AM for the treatment of patients with EDPN to the clinicians and further studies.Study registration number: INPLASY202040094.

Exploring the Protective Effect of ShenQi Compound on Skeletal Muscle in Diabetic Macrovasculopathy Mice.

OBJECTIVE: ShenQi compound (SQC) is a traditional herbal formula, which has been used to treat Type 2 diabetes mellitus (T2DM) and complications for years. The aim of this study was to explore the preventive and protective effects of SQC recipe on the skeletal muscle of diabetic macrovasculopathy mice, which provides a theoretical basis for the clinical use of this formula. METHODS: We evaluated the effect of SQC in a diabetic vasculopathy mouse model by detecting a series of blood indicators (blood glucose, lipids and insulin) and performing histological observations. Meanwhile, we explored the molecular mechanism of SQC treatment on skeletal muscle by genome expression profiles. RESULTS: The results indicated that SQC could effectively improve blood glucose, serum lipids (total cholesterol (TC), Triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)) and insulin (INS) levels in diabetic vasculopathy mice, as well as alleviating skeletal muscle tissue damage for diabetic macrovasculopathy. Meanwhile, compared with rosiglitazone, SQC showed a better effect on blood glucose fluctuation. Moreover, the gene microarray analysis indicated that SQC might improve T2DM by affecting biological functions related to cell death and cell adhesion. Moreover, 7 genes (Celsr2, Rilpl1, Dlx6as, 2010004M13Rik, Anapc13, Gm6097, Ddx39b) might be potential therapeutic targets of SQC. CONCLUSION: All these results indicate that SQC is an effective preventive and protective drug for skeletal muscle in diabetic macrovasculopathy, and could alleviate skeletal muscle tissue damage through affecting biological functions related to cell death and cell adhesion.