Treatment Of Diabetic Peripheral Neuropathy Research Articles

Bibliometric and visualized analysis of 2014–2024 publications on therapy for diabetic peripheral neuropathy

BackgroundThis research aimed to examine the global developing patterns in the treatment of diabetic peripheral neuropathy (DPN) using a bibliometric analysis of published literature.MethodsWe extracted publication data from papers published between 2014 and 2024 using a specific topic search in the “Web of Science Core Collection” (WoSCC) database. Various metrics, such as the number of papers, citations, authors, countries, institutions, and references, were collected for analysis. To further explore the data, CiteSpace was employed to examine co-citation patterns among authors, identify collaborative efforts between countries and institutions, and uncover emerging trends using burst keywords and reference analysis.ResultsThe study encompassed 2,488 publications that exhibited an increasing trend in annual output. Notably, the journal PAIN, the United States, the Pfizer institution, and the author Feldman, EvaL emerged as the most prolific contributors to this research domain. The term “placebo-controlled trial” was the most prominent burst keyword from 2014 to 2017, whereas “spinal cord stimulation” held this distinction in the recent 5-year span. Furthermore, the publication titled “Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis-2015” demonstrated the highest burst in terms of references.ConclusionThis study is the first to objectively reveal the current hotspots and trends in DPN treatment. The results indicate that drug therapy remains the primary first-line treatment for DPN and that future research on DPN treatment will likely focus on “spinal cord stimulation” and “pain management.” These findings provide valuable insights into DPN treatment.

Therapeutic effects of Mudan granules on diabetic retinopathy: Mitigating fibrogenesis caused by FBN2 deficiency and inflammation associated with TNF-α elevation

Ethnopharmacological relevanceMudan granules (MuD), a time-honored traditional Chinese patent medicine (TCPM), are widely utilized in the clinical treatment of diabetic peripheral neuropathy (DPN). In the field of biomedical diagnostics, both diabetic retinopathy (DR) and DPN are recognized as critical microvascular complications associated with diabetes. According to the principles of traditional Chinese medicine (TCM), these conditions are primarily attributed to a deficiency in Qi and the obstruction of collaterals. Despite this, the protective effects of MuD on DR and the underlying mechanisms remain to be comprehensively elucidated. Aims of the studyThe purpose of this study was to investigate the effect of MuD on DR and to further explore the promising therapeutic targets. MethodsA diabetic mouse model was established by administering 60 mg/kg of streptozotocin (STZ) via intraperitoneal injection for five consecutive days. The therapeutic efficacy of MuD was evaluated using a comprehensive approach, which included electroretinogram (ERG) analysis, histopathological examination, and assessment of serum biochemical markers. Then, the pharmacodynamic mechanisms of MuD were systematically analyzed using Tandem Mass Tags-based proteomics. Meanwhile, the candidate compounds of MuD were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and molecular docking was applied to estimate the affinity of the active ingredient to their potential key targets. In addition, the functional mechanisms identified through bioinformatics analysis were confirmed by molecular biological methods. ResultsWe demonstrated that MuD provided significant protection to retinal function and effectively mitigated the reduction in retinal thickness observed in the animal model. Through proteomic analysis, we identified a substantial regulation by MuD of 70 biomarkers associated with diabetic retinal damage. These proteins were notably enriched in the tumor necrosis factor (TNF) signaling pathway, a critical mediator in inflammatory processes. A particularly intriguing finding was the significant downregulation of fibrillin-2 (FBN2) in the diabetic retina compared to the control group (0.36 times the level), and its most pronounced upregulation (3.26 times) in the MuD treatment group. This suggests that FBN2 may play a pivotal role in the protective effects of MuD. Molecular docking analyses have unveiled a robust interplay between the components of MuD and TNF-α. Further corroboration was provided by molecular biological methods, which confirmed that MuD could suppress TNF-mediated inflammation and prevent retinal neovascularization and fibrogenesis. ConclusionMuD have the potential to alleviate diabetic retinal dysfunction by effectively curbing the fibrogenesis-associated neoangiogenesis and mitigating the inflammatory response, thereby restoring retinal health and function.

Melittin promotes the proliferation of Schwann cells in hyperglycemic environment by up‑regulating the Crabp2/Wnt/β‑catenin signaling pathway.

The present study aimed to explore the effect of melittin (MLT) on the growth of Schwann cells (SCs) in high glucose conditions and to understand the mechanisms involved. The goal was to provide a theoretical basis for using MLT in the treatment of diabetic peripheral neuropathy (DPN). The CCK‑8 assay was used to measure cell activity at different concentrations of glucose and MLT. Flow cytometry was employed to analyze the effect of MLT on cell cycle phases and apoptosis in SCs under high glucose conditions. To identify differentially expressed proteins, 4D label‑free quantitative proteomics with liquid chromatography‑mass spectrometry was used, followed by biological analysis to explore potential mechanisms. PCR, western blotting and immunofluorescence were conducted to confirm these mechanisms. Melittin (0.2 µg/ml) increased the proliferation of SCs in a high glucose environment. Flow cytometry showed that after MLT treatment, the proportion of cells in the G2/M+S phase increased and the combined ratio of early and late apoptosis decreased under high glucose conditions. Proteomics identified 1,784 proteins with significant changes in expression; 725 were upregulated, and 1,059 were downregulated. Kyoto Encyclopedia of Genes and Genomes analysis indicated that the differentially expressed proteins were mainly involved in metabolic pathways and neurodegenerative disease pathways. PCR, western blotting and immunofluorescence confirmed the increase in Crabp2, Wnt3a, C‑Jun, CDK4, CyclinD1 and proliferating cell nuclear antigen. In high glucose conditions, MLT protects SCs from glucose toxicity by upregulating the Crabp2/Wnt/β‑catenin signaling pathway, potentially providing a new treatment for DPN.

Unveiling the Role of Schwann Cell Plasticity in the Pathogenesis of Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy (DPN) is a prevalent complication of diabetes that affects a significant proportion of diabetic patients worldwide. Although the pathogenesis of DPN involves axonal atrophy and demyelination, the exact mechanisms remain elusive. Current research has predominantly focused on neuronal damage, overlooking the potential contributions of Schwann cells, which are the predominant glial cells in the peripheral nervous system. Schwann cells play a critical role in neurodevelopment, neurophysiology, and nerve regeneration. This review highlights the emerging understanding of the involvement of Schwann cells in DPN pathogenesis. This review explores the potential role of Schwann cell plasticity as an underlying cellular and molecular mechanism in the development of DPN. Understanding the interplay between Schwann cell plasticity and diabetes could reveal novel strategies for the treatment and management of DPN.

Acupuncture treatment of diabetic peripheral neuropathy: an overview of systematic reviews based on evidence mapping.

The study attempted to evaluate the meta-analyses (MAs) of the acupuncture treatment of diabetic peripheral neuropathy (DPN) to provide a basis for clinical decision-making. Eight databases, such as PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang Data, CQVIP, and CBM, were searched from database creation to December 22, 2023. The MAs of DPN treatment using acupuncture or acupuncture combined with conventional Western medicine were included. AMSTAR-2 and PRISMA 2020 helped evaluate the methodological and reporting quality of the included studies. The GRADE methodology helped assess the evidence quality of outcome indicators. Evidence mapping was performed to display evaluation results. A total of 18 MAs involving 23,240 DPN patients were included. Based on the methodological quality evaluation, four MAs were of "moderate" quality, seven had a quality grade of "low," and another seven were of "critically low" quality. The evidence quality evaluation showed that among studies of acupuncture vs. conventional Western medicine, four had an evidence quality of "moderate," 18 had an evidence quality of "low," and 17 had an evidence quality of "critically low" and that among studies of acupuncture + conventional Western medicine vs. conventional Western medicine, 12 had an evidence quality of "moderate," 29 had an evidence quality of "low," and 33 had an evidence quality of "critically low." Compared with conventional Western medicine, simple acupuncture and acupuncture + conventional Western medicine significantly improved total effective rate (TER) and nerve conduction velocity (NCV). Acupuncture treatment of DPN significantly improves TER and NCV with proven safety. However, the MAs of the acupuncture treatment of DPN must strictly refer to relevant standards and specifications regarding methodological and reporting quality, along with the design, execution, and reporting of primary randomized controlled trials (RCTs).

Natural Product Interventions in Peripheral Diabetic Neuropathy: A Multi-Target Approach

Peripheral diabetic neuropathy (PDN) is a well-known impediment of diabetes mellitus. That is one of the common kinds of neuropathy, categorized by reduced neuronal function in the minor limbs including excruciating neurological pain. A medical examination is used to subclassify asymmetric and symmetric neuropathy. Diabetes is associated with several pathways, one of which is the activation of the polyol route, the production of oxidative stress, poly ADP-ribose polymerase, the formation of advanced glycation outputs, and the pathways of hexosamine. Although there are a few symptomatic and supportive treatments in use, like antiarrhythmics, tricyclic medications, aldose reductase, opioid analgesics, protein kinase C inhibitors, and incretin the results are unimpressive. To bridge this space, herbal product-based treatment can be a very successful replacement. This narrative review tries to understand the research currently accessible on the function of different biological entities in the treatment of PDN. These chemicals are essential for lowering aldose reductase activity, oxidative-nitrosative stress, and neuronal death. They improve axonal regeneration, nerve transmission velocity, as well as antioxidant molecules while controlling glucose and HbA1c%. (Malondialdehyde, catalase, superoxide dismutase). They are renowned for their ability to reduce heat and mechanical hyperalgesia as well as tactile allodynia. Thus, these substances need to have their animal study and clinical efficiency assessed. Natural compounds may be auspicious participants in the fight against PDN that provide a glimpse of optimism to those in need.

Diabetic peripheral neuropathy and neuromodulation techniques: a systematic review of progress and prospects.

Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this condition. Diabetic peripheral neuropathy, a common complication of diabetes, is characterized by nerve damage due to high blood sugar levels that lead to symptoms, such as pain, tingling, and numbness, primarily in the hands and feet. The aim of this systematic review was to evaluate the efficacy of neuromodulatory techniques as potential therapeutic interventions for patients with diabetic peripheral neuropathy, while also examining recent developments in this domain. The investigation encompassed an array of neuromodulation methods, including frequency rhythmic electrical modulated systems, dorsal root ganglion stimulation, and spinal cord stimulation. This systematic review suggests that neuromodulatory techniques may be useful in the treatment of diabetic peripheral neuropathy. Understanding the advantages of these treatments will enable physicians and other healthcare providers to offer additional options for patients with symptoms refractory to standard pharmacologic treatments. Through these efforts, we may improve quality of life and increase functional capacity in patients suffering from complications related to diabetic neuropathy.

"Effect Of Electroacupuncture On Sensory Peripheral Nerve Function In Diabetic Peripheral Neuropathy: A Randomized Controlled Trial Protocol."

Background: Diabetes, a chronic metabolic disorder, affects millions globally, with Type 2 diabetes being the most prevalent. Diabetic Peripheral Neuropathy (DPN) is a common complication, characterized by symptoms such as pain, tingling, and numbness due to peripheral nerve damage. The global burden of diabetes has been rising, particularly in low- and middle-income countries. In India, the number of diabetes cases is projected to reach over 134 million by 2045. Traditional treatments for DPN often have limited efficacy and adverse longterm effects, highlighting the need for alternative therapies. Objective: This study aims to investigate the efficacy of electroacupuncture in improving sensory nerve functions in patients with DPN. Specific acupuncture points will be targeted to assess their impact on vibration perception, hot and cold perception, touch sensitivity, and skin temperature. Methods: A randomized controlled trial will be conducted with 80 participants divided equally into an interventional group and a control group. The interventional group will receive electroacupuncture at specific points (ST44, ST36, ST43, K2, K3, BL60, SP9, and GB41) three times a week for 8 weeks. The control group will continue their usual routine and receive the treatment post-study. Primary outcomes will be measured using the NEURO TOUCH instrument to assess sensory thresholds and skin temperature. Secondary outcomes will include pain assessment using the Visual Analog Scale (VAS). Data will be analyzed using SPSS version 16. Results: The study will evaluate the degree of sensory improvement in peripheral nerves and the effectiveness of electroacupuncture in reducing neuropathic pain. This research seeks to bridge the gap in understanding the mechanisms and efficacy of electroacupuncture in DPN treatment. Conclusion: This study will provide significant insights into the potential benefits of electroacupuncture for DPN, offering an alternative approach to improve the management of this debilitating condition. The findings could inform future clinical practices and guidelines for DPN treatment

"Effect Of Electroacupuncture On Sensory Peripheral Nerve Function In Diabetic Peripheral Neuropathy: A Randomized Controlled Trial Protocol."

Background: Diabetes, a chronic metabolic disorder, affects millions globally, with Type 2 diabetes being the most prevalent. Diabetic Peripheral Neuropathy (DPN) is a common complication, characterized by symptoms such as pain, tingling, and numbness due to peripheral nerve damage. The global burden of diabetes has been rising, particularly in low- and middle-income countries. In India, the number of diabetes cases is projected to reach over 134 million by 2045. Traditional treatments for DPN often have limited efficacy and adverse longterm effects, highlighting the need for alternative therapies. Objective: This study aims to investigate the efficacy of electroacupuncture in improving sensory nerve functions in patients with DPN. Specific acupuncture points will be targeted to assess their impact on vibration perception, hot and cold perception, touch sensitivity, and skin temperature. Methods: A randomized controlled trial will be conducted with 80 participants divided equally into an interventional group and a control group. The interventional group will receive electroacupuncture at specific points (ST44, ST36, ST43, K2, K3, BL60, SP9, and GB41) three times a week for 8 weeks. The control group will continue their usual routine and receive the treatment post-study. Primary outcomes will be measured using the NEURO TOUCH instrument to assess sensory thresholds and skin temperature. Secondary outcomes will include pain assessment using the Visual Analog Scale (VAS). Data will be analyzed using SPSS version 16. Results: The study will evaluate the degree of sensory improvement in peripheral nerves and the effectiveness of electroacupuncture in reducing neuropathic pain. This research seeks to bridge the gap in understanding the mechanisms and efficacy of electroacupuncture in DPN treatment. Conclusion: This study will provide significant insights into the potential benefits of electroacupuncture for DPN, offering an alternative approach to improve the management of this debilitating condition. The findings could inform future clinical practices and guidelines for DPN treatment.

Maltol Improves Peripheral Nerve Function by Inhibiting Schwann Cell Apoptosis via the PERK/eIF2α/CHOP Pathway and MME Upregulation in Diabetic Peripheral Neuropathy.

Diabetic peripheral neuropathy (DPN) is the most prevalent chronic complication among diabetic patients and a primary risk factor contributing to the deterioration of diabetic foot conditions. The pathogenesis of DPN remains complex and not fully understood, and there are hardly any effective treatment drugs. Maltol (3-hydroxy-2-methyl-4-pyranone) has demonstrated antioxidant and anti-inflammatory properties. However, the potential role of maltol in the treatment of DPN remains unclear. This study aimed to assess maltol's effects on DPN rats and high glucose (HG)/palmitic acid (PA)-induced rat Schwann cells (RSC96). The results indicated maltol's capacity to enhance peripheral nerve function in DPN rats. In RSC96 cells stimulated with high HG and PA, maltol treatment reduced DPN markers and apoptosis-related proteins. Functional enrichment analysis of differentially expressed genes revealed that endoplasmic reticulum (ER) stress pathways were involved in this process. Western blot results demonstrated the activation of ER stress pathway in HG/PA-induced RSC96 cells, with maltol attenuating ER stress-related protein expression. Furthermore, the knockdown of Membrane metallo-endopeptidase (MME) reversed maltol's effects on apoptosis-related protein expression, suggesting a potential therapeutic role for maltol via MME in treating DPN. These findings indicate that maltol may hold promise as a therapeutic agent for DPN treatment.

The Landscape of Products for Diabetic Peripheral Neuropathy: A Scientific and Patent Systematic Review.

Diabetic peripheral neuropathy (DPN) is a complication of diabetes that occurs in 40 - 60 million individuals worldwide and is associated with other chronic diseases. However, there are no review studies that present the state-of- the- art and technologies developed to circumvent this important health problem. This review was conducted based on scientific papers and patents. The papers were retrieved from Lilacs, PubMed, and Web of Science databases, and the patents from INPI, ESPACENET, WIPO, and GOOGLE PATENTS. Thus, a sample consisting of 14 scientific articles and 667 patents was analyzed. From the analysis of the data, we drew an overview of the development of biomedical technologies for DPN and detected the pioneering spirit of China, the USA, and Japan in the area, with a focus on the treatment of DPN. Based on this, we carried out a SWOT analysis to help direct future efforts in the area, which should focus primarily on developing technologies for prevention, early diagnosis, and, above all, cure of the disease to reduce the important impact of this disease in various sectors of society. This study finds a concentration of diabetic peripheral neuropathy products, especially therapeutic drugs, in high-income countries. It highlights the need for global collaboration and strategic focus on therapeutic adherence and preventive strategies to effectively manage DPN.

Effectiveness and safety of photobiomodulation therapy in diabetic peripheral neuropathy: Protocol for a systematic review and meta-analysis.

Diabetic peripheral neuropathy (DPN), a widely prevalent complication in patients with type 2 diabetes, exerts a significant influence on patients' overall health and financial circumstances. Photobiomodulation therapy is one of the means of physical therapy for DPN. Although preliminary findings suggest the efficacy of photobiomodulation therapy in alleviating peripheral neuropathy, the existing literature lacks substantial evidence regarding its safety and effectiveness specifically in the context of diabetes-related peripheral neuropathy. Therefore, we plan to arrive at more distinct findings through systematic evaluation and meta-analysis. We will conduct a comprehensive search for studies published from the beginning until October 1, 2023, using various databases including Web of Science, Embase, Cochrane Library, PubMed, AMED, Wanfang database, VIP database, China National Knowledge Infrastructure, and the Chinese Biomedical Literature database. Simultaneously, we will also search for the WHO International Clinical Trial Registration Platform, China Clinical Trial Registration Platform, and Clinical Trials.gov. Gray literature will be retrieved using Google Scholar and opengrey.edu. Only randomized controlled trials in Chinese and English were included, with no restrictions on publication status. The primary outcomes will include change of symptom scores, change of nerve conduction velocity. Additional outcomes will encompass quality of life, change in pain, blood glucose levels after fasting and 2 hours after eating, levels of glycosylated hemoglobin, and any adverse events associated with photobiomodulation therapy. Reman V.5.4 and R language will be used for the meta-analysis. Assessment of potential bias will be conducted through Cochrane risk of bias 2 tool (RoB 2.0) and Physiotherapy Evidence Database (PEDro) scale. Registration: PROSPERO (registration number: CRD42023466586). This meta-analysis aims to assess the efficacy and safety of photobiomodulation therapy as a potential treatment for diabetic peripheral neuropathy (DPN), and providing a straightforward and convenient therapeutic for patients. Additionally, it expands the range of treatment alternatives available to healthcare professionals managing DPN.

Bioinformatics and validation reveal the potential target of curcumin in the treatment of diabetic peripheral neuropathy

Diabetic peripheral neuropathy (DPN) is a common nerve-damaging complication of diabetes mellitus. Effective treatments are needed to alleviate and reverse diabetes-associated damage to the peripheral nerves. Curcumin is an effective neuroprotectant that plays a protective role in DPN promoted by Schwann cells (SCs) lesions. However, the potential molecular mechanism of curcumin remains unclear. Therefore, our aim is to study the detailed molecular mechanism of curcumin-mediated SCs repair in order to improve the efficacy of curcumin in the clinical treatment of DPN. First, candidate target genes of curcumin in rat SC line RSC96 cells stimulated by high glucose were identified by RNA sequencing and bioinformatic analyses. Enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was carried out by Metascape, followed by 8 algorithms on Cytoscape to determine 4 hub genes, namly Hmox1, Pten, Vegfa and Myc. Next, gene set enrichment analysis (GSEA) and Pearson function showed that Hmox1 was significantly correlated with apoptosis. Subsequently, qRT-PCR, MTT assay, flow cytometry, caspase-3 activity detection and westernblot showed that curcumin treatment increased RSC96 cell viability, reduced cell apoptosis, increased Hmox1, Pten, Vegfa and Myc expression, and up-regulated Akt phosphorylation level under high glucose environment. Finally, molecular docking predicted the binding site of curcumin to Hmox1. These results suggest that curcumin can reduce the apoptosis of SCs induced by high glucose, and Hmox1 is a potential target for curcumin. Our findings provide new insights about the mechanism of action of curcumin on SC as a potential treatment in DPN.

Injectable, reversibly thermoresponsive captopril-laden hydrogel for the local treatment of sensory loss in diabetic neuropathy

A major and irreversible complication of diabetes is diabetic peripheral neuropathy (DPN), which can lead to significant disability and decreased quality of life. Prior work demonstrates the peptide hormone Angiotensin II (Ang II) is released locally in neuropathy and drives inflammation and impaired endoneurial blood flow. Therefore, we proposed that by utilizing a local thermoresponsive hydrogel injection, we could deliver inhibitors of angiotensin-converting enzyme (ACE) to suppress Ang II production and reduce nerve dysfunction in DPN through local drug release. The ACE inhibitor captopril was encapsulated into a micelle, which was then embedded into a reversibly thermoresponsive pluronics-based hydrogel matrix. Drug-free and captopril-loaded hydrogels demonstrated excellent product stability and sterility. Rheology testing confirmed sol properties with low viscosity at ambient temperature and increased viscosity and gelation at 37 °C. Captopril-loaded hydrogels significantly inhibited Ang II production in comparison to drug-free hydrogels. DPN mice treated with captopril-loaded hydrogels displayed normalized mechanical sensitivity and reduced inflammation, without side-effects associated with systemic exposure. Our data demonstrate the feasibility of repurposing ACE inhibitors as locally delivered anti-inflammatories for the treatment of sensory deficits in DPN. To the best of our knowledge, this is the first example of a locally delivered ACE inhibitor for the treatment of DPN.

Advances in the treatment of diabetic peripheral neuropathy by modulating gut microbiota with traditional Chinese medicine.

Diabetic peripheral neuropathy (DPN) is one of the strongest risk factors for diabetic foot ulcers (neuropathic ulcerations) and the existing ulcers may further deteriorate due to the damage to sensory neurons. Moreover, the resulting numbness in the limbs causes difficulty in discovering these ulcerations in a short time. DPN is associated with gut microbiota dysbiosis. Traditional Chinese medicine (TCM) compounds such as Shenqi Dihuang Decoction, Huangkui Capsules and Qidi Tangshen Granules can reduce the clinical symptoms of diabetic nephropathy by modulating gut microbiota. The current review discusses whether TCM compounds can reduce the risk of DPN by improving gut mic-robiota.

Exploration of the Mechanisms of Bu-Yang-Huan-Wu Decoction in the Treatment of Diabetic Peripheral Neuropathy by Integrating of Serum Pharmacochemistry and Network Pharmacology.

Diabetic peripheral neuropathy (DPN) is a significant and frequent complication of diabetes. Bu-Yang-Huan-Wu Decoction (BHD) is a classic traditional Chinese herbal prescription that is commonly used in modern clinical practice for the effective treatment of DPN, but the underlying mechanism is not yet clearly defined. The chemical constituents of BHD were characterized by UPLC-Q-Orbitrap HR MS/MS, and a total of 101 chemical components were identified, including 30 components absorbed into blood. An interaction network of "compound-target-disease" interactions was constructed based on the compounds detected absorbed in blood and their corresponding targets of diabetic neuropathy acquired from disease gene databases, and the possible biological targets and potential signalling pathways of BHD were predicted via network pharmacology analysis. Subsequently, methylglyoxal-induced (MGO-induced) Schwann cells (SCs) were used to identify the active ingredients in blood components of BHD and verify the molecular mechanisms of BHD. Through network topological analysis, 30 shared targets strongly implicated in the anti-DPN effects of BHD were identifed. Combined network pharmacology and in vitro cellular analysis, we found that the active ingredient of BHD may treat DPN by modulating the AGEs/RAGE pathway. This study provides valuable evidence for future mechanistic studies and potential therapeutic applications for patients with DPN.

Xiaoke Bitong capsule alleviates inflammatory impairment via inhibition of the TNF signaling pathway to against diabetic peripheral neuropathy

BackgroundXiaoke Bitong capsule (XBC) is a crude herbal compound believed to tonify qi, improve blood circulation, and alleviate blood stasis. It has been used as an herbal formula for the prevention and treatment of diabetic peripheral neuropathy (DPN) under the guidance of traditional Chinese medicine (TCM). However, the pharmacological mechanisms by which XBC ameliorates DPN remain poorly understood. The interaction between pro-inflammatory factors and the activation of tumor necrosis factor (TNF) plays a critical role in the underlying mechanisms of DPN. XBC may protect against DPN through the regulation of the TNF pathway. PurposeMany studies show the association between DPN and nerve dysfunction, however, treatment options are limited. To identify specific therapeutic targets and active components of XBC that contribute to its anti-DPN effects, our study aimed to investigate the potential mechanism of action of XBC during the progression of DPN using a system pharmacology approach. MethodsAn approach involving UPLC-Q-TOF/MS and network pharmacology was used to analyze the compositions, potential targets, and active pathways of XBC. Further, models of streptozocin (STZ) induced mouse and glucose induced RSC96 cells were established to explore the therapeutic effects of XBC. High glucose induced RSC96 cells were pretreated with small interfering RNA (siRNA) to identify potential therapeutic targets of DPN. ResultsSeventy-one active compositions of XBC and five potential targets, including mitogen-activated protein kinase 8 (MAPK), interleukin-6 (IL-6), poly-ADP-ribose polymerase-1 (PARP1), vascular endothelial growth factor A (VEGFA), and transcription factor p65 (NF-κB), were considered as the potential regulators of DPN. In addition, the results revealed that the TNF signaling pathway was closely related to DPN. Moreover, DPN contributed to the decreased expressions of PI3K and AKT, increased TNF-α and IL-1β in RSC96 cells, which were both reversed by XBC or TNF-α siRNA. ConclusionXBC could protect against DPN by inhibiting the release of pro-inflammatory cytokines and regulating the activation of the TNF signaling pathway, further accelerating neurogenesis, and alleviating peripheral nerve lesions. Therefore, this study highlights the therapeutic value of XBC for DPN.

Combination therapy is it in the future for successfully treating peripheral diabetic neuropathy?

In 2022, the Center for Disease Control and Prevention reported that 11.3% of the United States population, 37.3 million people, had diabetes and 38% of the population had prediabetes. A large American study conducted in 2021 and supported by many other studies, concluded that about 47% of diabetes patients have peripheral neuropathy and that diabetic neuropathy was present in 7.5% of patients at the time of diabetes diagnosis. In subjects deemed to be pre-diabetes and impaired glucose tolerance there was a wide range of prevalence estimates (interquartile range (IQR): 6%-34%), but most studies (72%) reported a prevalence of peripheral neuropathy ≥10%. There is no recognized treatment for diabetic peripheral neuropathy (DPN) other than good blood glucose control. Good glycemic control slows progression of DPN in patients with type 1 diabetes but for patients with type 2 diabetes it is less effective. With obesity and type 2 diabetes at epidemic levels the need of a treatment for DPN could not be more important. In this article I will first present background information on the "primary" mechanisms shown from pre-clinical studies to contribute to DPN and then discuss mono- and combination therapies that have demonstrated efficacy in animal studies and may have success when translated to human subjects. I like to compare the challenge of finding an effective treatment for DPN to the ongoing work being done to treat hypertension. Combination therapy is the recognized approach used to normalize blood pressure often requiring two, three or more drugs in addition to lifestyle modification to achieve the desired outcome. Hypertension, like DPN, is a progressive disease caused by multiple mechanisms. Therefore, it seems likely as well as logical that combination therapy combined with lifestyle adjustments will be required to successfully treat DPN.

Evaluation of tricyclic antidepressant deprescribing in the treatment of diabetic peripheral neuropathy within federally qualified health centers

BackgroundTricyclic antidepressants (TCAs) are a treatment option for diabetic peripheral neuropathy (DPN). Existing evidence demonstrates the prolonged use of TCA therapy increases the risk of cognitive decline and dementia, likely due to the anticholinergic effects of these medications. Anticholinergic activity is thought to contribute significantly to the observed increase in cognitive decline and dementia risks associated with long-term TCA use. There is little information available to describe the usage patterns of TCAs in DPN, particularly within underserved populations who receive care at federally qualified health centers. ObjectivesThe objective of this study was to characterize (1) prescribing patterns of TCAs as a treatment for DPN and (2) evidence of deprescribing attempts in an FQHC population. MethodsA retrospective chart review of electronic medical record data for patients at 2 different FQHCs was performed. A convenience sample of 100 adults ≥ 18 years of age was stratified into 2 age groups, 18-55 years and 55+ years. All patients had a diagnosis of type 1 or type 2 diabetes mellitus and had been prescribed TCAs in the previous 4 years and had a visit with a primary care provider in the past 12 months. ResultsThe study population was comprised of 100 individuals. Seventy-four of 100 were persistent users of TCAs at the time of data collection, and the mean duration of utilization was 54.8 months. In total, 104 TCAs were prescribed across 100 individual patients. Of all 104 prescribed TCAs, 66 (63%) were prescribed at a rate that exceeded thresholds associated with a higher risk of dementia. Black older adults prescribed TCAs were more likely to exceed this dose threshold. ConclusionSixty-five percent of patients used TCAs with a strength, frequency, and duration that exceeded risk thresholds for dementia in an older adult population. Interventions preventing use of or deprescribing TCAs in patients with DPN should be conducted for the potential benefits of preventing or delaying cognitive impairment and promoting equitable care.

The efficacy and safety of electroacupuncture for diabetic peripheral neuropathy: A protocol for a systematic review and meta-analysis.

Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes mellitus, which is the most common neuropathy worldwide. Owing to the inadequacies of existing treatment methods, managing DPN remains a significant challenge. Studies suggest that electroacupuncture (EA) could potentially serve as a beneficial alternative treatment for this condition. Nevertheless, there is still inadequate proof of its therapeutic effectiveness and safety. As a result, the goal of this protocol is to methodically compile the data pertaining to the effectiveness and security of EA in the management of DPN. To find appropriate randomized controlled trials (RCTs), nine reliable databases in the English and Chinese languages will be examined. RevMan5.3 will be used to combine the retrieved data and perform meta-analyses. The methodological quality of the included RCTs will be evaluated using the Cochrane Risk of Bias Assessment 2.0 tool. The Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) system will be utilized to evaluate the degree of strength and certainty of the evidence. We will also perform publication bias, sensitivity and subgroup analyses. This protocol describes the intended scope and approach for a forthcoming systematic review and meta-analysis that will inform therapeutic decision-making by offering current information on the efficacy and safety of EA in the treatment of DPN. The results of the study will help standardize strategies for EA in the treatment of DPN.