Fasudil combined with methylcobalamin or lipoic acid can improve the nerve conduction velocity in patients with diabetic peripheral neuropathy

Jiang, De-Qi; Xu, Lan-Cheng; Jiang, Li-Lin; Li, Mingxing; Wang, Yong

doi:10.1097/md.0000000000011390

“…Fasudil toxicity includes subcutaneous hemorrhage, subarachnoid hemorrhage, nausea, pyrexia, kidney failure and hypotension, and it has not been used chronically for any condition. [18][19][20][21][22] In contrast, atorvastatin is commonly used in clinical practice. Human statin dose varies between approximately 0.1-1 mg/kg bodyweight, while most studies in rodents have used doses of 1-100 (or up to 500) mg/kg.…”

Section: Discussionmentioning

confidence: 99%

Rho Kinase Inhibition Blunts Lesion Development and Hemorrhage in Murine Models of Aggressive Pdcd10/Ccm3 Disease

Shenkar

¹

,

Peiper

²

,

Pardo

³

et al. 2019

Stroke

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Background and Purpose— Previously, murine models Krit1 +/− Msh2 −/ − and Ccm2 +/ − Trp53 −/ − showed a reduction or no effect on cerebral cavernous malformation (CCM) burden and favorable effects on lesional hemorrhage by the robust Rock (Rho-associated protein kinase) inhibitor fasudil and by simvastatin (a weak pleiotropic inhibitor of Rock). Herein, we concurrently investigated treatment of the more aggressive Pdcd10/Ccm3 model with fasudil, simvastatin, and higher dose atorvastatin to determined effectiveness of Rock inhibition. Methods— The murine models, Pdcd10 +/ − Trp53 −/ − and Pdcd10 +/ − Msh2 −/ − , were contemporaneously treated from weaning to 5 months of age with fasudil (100 mg/kg per day in drinking water, n=9), simvastatin (40 mg/kg per day in chow, n=11), atorvastatin (80 mg/kg per day in chow, n=10), or with placebo (n=16). We assessed CCM volume in mouse brains by microcomputed tomography. Lesion burden was calculated as lesion volume normalized to total brain volume. We analyzed chronic hemorrhage in CCM lesions by quantitative intensity of Perls staining in brain sections. Results— The Pdcd10 +/ − Trp53 −/ − /Msh2 −/ − models showed a mean CCM lesion burden per mouse reduction from 0.0091 in placebos to 0.0042 ( P =0.027) by fasudil, and to 0.0047 ( P =0.025) by atorvastatin treatment, but was not changed significantly by simvastatin. Hemorrhage intensity per brain was commensurately decreased by Rock inhibition. Conclusions— These results support the exploration of proof of concept effect of high-dose atorvastatin on human CCM disease for potential therapeutic testing.

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“…We found no solid evidence to propose the exclusive use of ALA. Finally, the review by Jiang 2018 [32] proposed that the administration of ALA combined with epalrestat is an effective option for patients with PN associated with DM. Jiang performed an exhaustive meta-analysis measuring different outcomes resulting from the combination of ALA with another drug.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of alpha-lipoic acid in patients with neuropathic pain associated with type I and type II diabetes mellitus: A systematic review and meta-analysis

Orellana-Donoso,

López-Chaparro,

Barahona-Vásquez

et al. 2023

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Background: This systematic review explores the most current evidence regarding the mechanisms of neuropathic pain in patients with different types of diabetes and how this pain affects different functional and structural components of the neuroanatomical pain pathways. The review also seeks to provide guidelines for the best approach and treatment for patients experiencing this type of pain. The objective is to determine the effectiveness of alpha-lipoic acid (ALA) in improving functional and symptomatic outcomes in patients with diabetes mellitus type I and type II. Objective: To determine the effectiveness of alpha-lipoic acid (ALA) in improving functional and symptomatic outcomes in patients with diabetes mellitus type I and type II. Methods: We systematically search MEDLINE (via PubMed), EMBASE, SCOPUS, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature, and Web of Science databases. Results: The findings of this review show that different forms of ALA do not present statistically significant changes for any of the scales included, including total symptom score (standardized mean difference [SMD] = −3.59, confidence interval [CI] = −4.16 to −3.02, and P < .00001), neuropathy impairment score (SMD = −1.42, CI = −3.68 to 0.84, and P = .22), and neuropathy symptom checklist (SMD = −0.09, CI = −0.15 to −0.02, and P = .01). Conclusion: In comparison to the use of a placebo, the findings suggest that ALA does not exhibit significant differences in terms of pain reduction and different functional scales. Moreover, no specific dosages are identified to support the use of ALA for the reduction of neuropathic pain.

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“…The results of the risk of bias assessment are shown in Figures 2 and 3. Three studies grouped patients according to drug regimens [37,45,60] and two studies grouped patients according to order of admission [49,50], all of whom were rated as high risk. 25 studies explicitly stated that patients were grouped according to rolling dice or random number table methods, all of which were rated as low risk.…”

Section: Methodological Qualitymentioning

confidence: 99%

Mudan Granules for Diabetic Peripheral Neuropathy: A Systematic Review of Preclinical and Clinical Evidence

Zhou,

Zhu,

Li

2023

Preprint

0

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Background Mudan granules has been used in China to treat diabetic peripheral neuropathy (DPN), but there is a lack of systematic review of reports in this area. The aim of this systematic review was to evaluate the efficacy and safety of Mudan granules in the treatment of diabetic peripheral neuropathy. Methods Initial studies were searched from PubMed, Embase, Cochrane, China National Knowledge Infrastructure (CNKI), VIP database, Wanfang electronic databases. The Cochrane Risk of Bias tool was used to evaluate the risk of bias. The meta-analysis was performed by Stata 16.0 software. For dichotomous and continuous outcomes, the relative risk (RR) and standardized mean difference (SMD) with 95% confidence interval (CI) were conducted, respectively. Results 51 randomized controlled trials (RCTs) involving 5,416 patients were included. In the meta-analysis, compared with routine treatment (RT) alone, Mudan granules plus RT reduced Toronto clinical scoring system (TCSS) score (SMD, -0.52; 95% CI, -0.66 to -0.38; P < 0.01), total symptoms score (TSS) (SMD, -1.44; 95% CI, -2.88 to -0.00; P = 0.05), serum homocysteine (Hcy) levels (SMD, -3.84; 95% CI, -5.99 to -1.70; P < 0.01), serum high sensitive C-reactive protein (hs-CRP) levels (SMD, -1.68; 95% CI, -3.29 to -0.08; P = 0.04), and improved total clinical efficacy (RR, 1.23; 95% CI, 1.19 to 1.27; P < 0.01) and serum superoxide dismutase (SOD) levels (SMD, 1.54; 95% CI, 1.13 to 1.95; P < 0.01). Besides, Mudan granules presented an adjuvant efficacy on median motor nerve conduction velocity (SMD, 1.61; 95% CI, 1.16 to 2.07), median sensory nerve conduction velocity (SMD, 1.73; 95% CI, 1.26 to 2.20), common peroneal motor nerve conduction velocity (SMD, 1.48; 95% CI, 1.10 to 1.86), common peroneal sensory nerve conduction velocity ( SMD, 1.57; 95% CI, 1.23 to 1.92), tibial motor nerve conduction velocity (SMD, 1.34; 95% CI, 0.82 to 1.87), and tibial sensory nerve conduction velocity (SMD, 1.03; 95% CI, 0.86 to 1.20). In terms of adverse events, there was no statistically significant difference between the trial group and the control group (P=0.87). Five preclinical studies were also retrieved for the study. Animal studies have shown that Mudan granules have anti-oxidative stress effects and could reduce the inflammatory response. It may improve peripheral nerve injury in diabetic rats by modulating the TLR4/MyD88/NF-κB pathway, TLR4/p38 MAPK pathway and PI3K/AKT pathway. Conclusions Mudan granules presented an adjuvant efficacy on patients with DPN and could improve the oxidative stress and inflammatory levels in preclinical models. However, high-quality original studies are needed to further prove the evidence. Systematic review registration: PEROPERO (CRD42022373113)

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Fasudil combined with methylcobalamin or lipoic acid can improve the nerve conduction velocity in patients with diabetic peripheral neuropathy

Cited by 10 publications

References 34 publications

Rho Kinase Inhibition Blunts Lesion Development and Hemorrhage in Murine Models of Aggressive Pdcd10/Ccm3 Disease

Rho Kinase Inhibition Blunts Lesion Development and Hemorrhage in Murine Models of Aggressive Pdcd10/Ccm3 Disease

Effectiveness of alpha-lipoic acid in patients with neuropathic pain associated with type I and type II diabetes mellitus: A systematic review and meta-analysis

Mudan Granules for Diabetic Peripheral Neuropathy: A Systematic Review of Preclinical and Clinical Evidence

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