Diabetes, especially type 2, has been rapidly increasing all over the world. Although many drugs have been developed and used to treat diabetes, side effects and long-term efficacy are of great challenge. Therefore, natural health product and dietary supplements have been of increasing interest alternatively. In this regard, Chinese herbs and herbal products have been considered a rich resource of product development. Although increasing evidence has been produced from various scientific studies, the mechanisms of action are lacking. Here, we have proposed that many herbal monomers and formulae improve glucose homeostasis and diabetes through the BMID axis; B represents gut microbiota, M means mucosal immunity, I represents inflammation, and D represents diabetes. Chinese herbs have been traditionally used to treat diabetes, with minimal side and toxic effects. Here, we reviewed monomers such as berberine, ginsenoside, M. charantia extract, and curcumin and herbal formulae such as Gegen Qinlian Decoction, Danggui Liuhuang Decoction, and Huanglian Wendan Decoction. This review was intended to provide new perspectives and strategies for future diabetes research and product.

Background: Panax notoginseng, a Chinese herbal medicine, has been widely used to treat vascular diseases. Diabetic retinopathy (DR) is one of the complications of diabetic microangiopathy. According to recent studies, the application of Panax notoginseng extract and related Chinese patent medicine preparations can significantly improve DR. However, the pharmacological mechanisms remain unclear. Therefore, the purpose of this study was to decipher the potential mechanism of Panax notoginseng treatment of DR using network pharmacology. Methods: We evaluated and screened the active compounds of Panax notoginseng using the Traditional Chinese Medicine Systems Pharmacology database and collected potential targets of the compounds by target fishing. A multi-source database was also used to organize targets of DR. The potential targets as the treatment of DR with Panax notoginseng were then obtained by matching the compound targets with the DR targets. Using protein-protein interaction networks and topological analysis, interactions between potential targets were identified. In addition, we also performed gene ontology-biological process and pathway enrichment analysis for the potential targets by using the Biological Information Annotation Database. Results: Eight active ingredients of Panax notoginseng and 31 potential targets for the treatment of DR were identified. The screening and enrichment analysis revealed that the treatment of DR using Panax notoginseng primarily involved 28 biological processes and 10 related pathways. Further analyses indicated that angiogenesis, inflammatory reactions, and apoptosis may be the main processes involved in the treatment of DR with Panax notoginseng. In addition, we determined that the mechanism of intervention of Panax notoginseng in treating DR may involve five core targets, VEGFA, MMP-9, MMP-2, FGF2, and COX-2. Conclusion: Panax notoginseng may treat diabetic retinopathy through the mechanism of network pharmacological analysis. The underlying molecular mechanisms were closely related to the intervention of angiogenesis, inflammation, and apoptosis with VEGFA, MMP-9, MMP-2, FGF2, and COX-2 being possible targets.

Background Sciatic nerve injury (SNI), which frequently occurs under the traumatic hip and hip fracture dislocation, induces serious complications such as motor and sensory loss, muscle atrophy, or even disabling. The present work aimed to determine the regulating factors and gene network related to the SNI pathology. Methods Sciatic nerve injury dataset GSE18803 with 24 samples was divided into adult group and neonate group. Weighted gene co-expression network analysis (WGCNA) was carried out to identify modules associated with SNI in the two groups. Moreover, differentially expressed genes (DEGs) were determined from every group, separately. Subsequently, co-expression network and protein–protein interaction (PPI) network were overlapped to identify hub genes, while functional enrichment and Reactome analysis were used for a comprehensive analysis of potential pathways. GSE30165 was used as the test set for investigating the hub gene involvement within SNI. Gene set enrichment analysis (GSEA) was performed separately using difference between samples and gene expression level as phenotype label to further prove SNI-related signaling pathways. In addition, immune infiltration analysis was accomplished by CIBERSORT. Finally, Drug–Gene Interaction database (DGIdb) was employed for predicting the possible therapeutic agents. Results 14 SNI status modules and 97 DEGs were identified in adult group, while 15 modules and 21 DEGs in neonate group. A total of 12 hub genes was overlapping from co-expression and PPI network. After the results from both test and training sets were overlapped, we verified that the ten real hub genes showed remarkably up-regulation within SNI. According to functional enrichment of hub genes, the above genes participated in the immune effector process, inflammatory responses, the antigen processing and presentation, and the phagocytosis. GSEA also supported that gene sets with the highest significance were mostly related to the cytokine–cytokine receptor interaction. Analysis of hub genes possible related signaling pathways using gene expression level as phenotype label revealed an enrichment involved in Lysosome, Chemokine signaling pathway, and Neurotrophin signaling pathway. Immune infiltration analysis showed that Macrophages M2 and Regulatory T cells may participate in the development of SNI. At last, 25 drugs were screened from DGIdb to improve SNI treatment. Conclusions The gene expression network is determined in the present work based on the related regulating factors within SNI, which sheds more light on SNI pathology and offers the possible biomarkers and therapeutic targets in subsequent research.

Introduction: Diabetic lower extremity arteriosclerosis obstruction (DLASO) is a common macrovascular complication in type 2 diabetic mellitus (T2DM), which can cause amputations and a higher risk of cardiovascular events. However, there are few effective treatments for DLASO currently. To evaluate the safety and efficacy of Jiedu Tongluo Tiaogan Formula (JTTF) in type 2 diabetic lower extremity arteriosclerosis obliterans and looking for a mechanism of action, we designed a clinical trial and mechanism exploration based on metabolomics technology. Methods and Analysis: This study is designed as a randomized controlled clinical trial. A total of 80 participants will be recruited and randomized to a TCM group (JTTF + essential treatments) and a control group (essential treatments) in a ratio of 1:1. The treatment duration is 12 weeks. Changes in clinical symptom scores, color ultrasound Doppler hemodynamics of lower extremity arteries, and Ankle-Brachial Ratio (ABI) will be the primary outcomes. Changes in TCM symptoms scores, other indicators related to arteriosclerosis, blood glucose, lipids, and body mass will be the secondary outcomes. The primary and secondary outcomes will be evaluated at baseline and week 12. Safety outcomes and adverse events will also be properly assessed. After treatment completion, blood and urine samples from subjects will be tested for metabolomics. Discussion: This study aims to verify the efficacy and safety of JTTF in type 2 diabetic lower extremity arteriosclerosis obliterans and obtain the key action pathway. It helps to provide scientific evidence for TCM treatment of diabetic vascular complications. Ethics and Dissemination: This trial has been approved by the Ethics Committee (GZYLL(KY)-2021-024). Results of this trial will be published in journals and presented at scientific conferences. We share raw data in the ResMan network platform. All the authors declare that they have no conflicts of interest. Trial registration: Chinese Clinical Trials Register, ChiCTR2100051337. Registered on 20 September 2021.