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Real-time PCR of the sciatic nerve from N (normal control, n = 20), DPN (model, n = 23), M1 (moxibustion for 15 min/day, n = 19), and M2 (moxibustion for 30 min/day, n = 21) groups (Δp < 0.05 versus the normal control group, *p < 0.05 versus the model group).
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Moxibustion is the main alternative medicine treatment that has been beneficial to diabetic peripheral neuropathy (DPN), a common complication secondary to diabetic microvascular injury. However, the underlying protective mechanism of moxibustion against neuroinflammation remains unclear. We hypothesized that moxibustion treats DPN by regulating th...
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Context 1
... groups compared with the model group (n = 19 in Group M1 while n = 21 in group M2, p < 0.05). By contrast, the mRNA expression of Nrf2 was decreased in the DPN group compared with the normal control group but relatively increased in the moxibustion-treated groups. However, no significant difference was observed between M1 and M2 groups (Fig. ...
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Background
The prevalence of knee osteoarthritis (KOA) is increasing, and it has emerged as a major health issue. Studies have been reported that moxibustion is effective for treating KOA, but conventional moxibustion is difficult to control the intensity of stimulation and causes smoke, harmful gases, or odors. An electrical moxibustion (EM) devic...
Citations
... In addition, NF-κB has the ability to inhibit the expression of Nrf2, which worsens inflammation and oxidative damage. By concurrently modulating the expression of NF-κB (lowering) and Nrf2 (increasing), the effects of alleviating DN, reducing neuroinflammation, and decreasing the levels of IL-1β, IL-6, and IL-8 are improved [55]. A notable feature is that NF-κB can function as a regulatory factor upstream of Nrf2 in DN. ...
... As previously stated, both NF-κB and Nrf2 have a role in DN. Therefore, drugs that affect both of these routes have the potential to provide improved alleviation from DN. Moxibustion reduces the expression of NF-κB and increases the expression of Nrf2, which disrupts neuroinflammation and lowers the levels of IL-1β, IL-6, and IL-8 in the blood serum [55]. This suggests that NF-κB is a crucial objective for medications, and therapeutic substances can impact not only the expression of NF-κB but also its subsequent and related pathways [68]. ...
Diabetes mellitus (DM) is a metabolic illness defined by elevated blood glucose levels, mediating various tissue alterations, including the dysfunction of vital organs. Diabetes mellitus (DM) can lead to many consequences that specifically affect the brain, heart, and kidneys. These issues are known as neuropathy, cardiomyopathy, and nephropathy, respectively. Inflammation is acknowledged as a pivotal biological mechanism that contributes to the development of various diabetes consequences. NF-κB modulates inflammation and the immune system at the cellular level. Its abnormal regulation has been identified in several clinical situations, including cancer, inflammatory bowel illnesses, cardiovascular diseases, and Diabetes Mellitus (DM). The purpose of this review is to evaluate the potential impact of NF-κB on complications associated with DM. Enhanced NF-κB activity promotes inflammation, resulting in cellular harm and compromised organ performance. Phytochemicals, which are therapeutic molecules, can potentially decline the NF-κB level, therefore alleviating inflammation and the progression of problems correlated with DM. More importantly, the regulation of NF-κB can be influenced by various factors, such as TLR4 in DM. Highlighting these factors can facilitate the development of novel therapies in the future.
... Traditional Chinese medicine external treatment includes acupuncture, massage, fumigation, acupoint application, foot therapy, ear acupoint therapy, and many other methods [4]. At present, more and more RCT studies have confrmed that TCM external treatments play a key role in the treatment of DPN [9][10][11][12]. Although much research has been carried out on all kinds of TCM external treatment to evaluate the therapeutic efect of DPN, the results of the research outcome indicators difer and RCT studies are of mixed quality. ...
Background:
Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes. Traditional Chinese medicine (TCM) external treatment has been widely used in China as adjunctive treatment, and some small sample clinical studies have proved its effectiveness. However, due to the limited number of studies, we used network meta-analysis to compare the effectiveness of 5 commonly used external treatment methods of traditional Chinese medicine in the treatment of diabetic peripheral neuropathy.
Methods:
We searched PubMed, EMBASE, The Cochrane Library, Web of Science, CNKI, CBM, WanFang Knowledge Service Platform, and VIP databases and collected and screened randomised controlled trials on the external treatment of traditional Chinese medicine combined with mecobalamin in the treatment of DPN according to the inclusion and exclusion criteria. The search period was from 2011 to May 2021. The quality of included studies was assessed using the revised Cochrane risk-of-bias tool for randomized trials. The outcome indicators are Toronto score, median nerve sensory conduction velocity, and median nerve motor conduction velocity.
Results:
A total of 22 publications were included in the study. The results of the network meta-analysis showed that acupuncture combined with mecobalamin was superior to other TCM external treatments combined with mecobalamin in terms of decreasing the Toronto score (MD = -2.8, 95% CI: -5.2∼-0.49), improving median nerve sensory conduction velocity (MD = 3.6, 95% CI: 2.4∼4.9), and median nerve motor conduction velocity (MD = 4.5, 95% CI: 2.6∼6.5). The SUCRA value and probability ranking chart showed that among the three outcome indicators, acupuncture combined with mecobalamin was the best, followed by acupoint injection combined with mecobalamin.
Conclusion:
In this network meta-analysis, acupuncture combined with mecobalamin shows the best results in the treatment of DPN, followed by acupoint injection combined with mecobalamin.
... [5,6] Moxibustion, on the other hand, was showed in some studies to be able to raise serum superoxide dismutase level, [7] lower free-radical production, protect nerve tissues from damage due to free-radical build-up, and relieve neuroinflammation, potentially through inhibition of NF-kB and activation of Nrf2. [8] Liu et al [9] found out that moxibustion with methylcobalamin is more effective than using methylcobalamin only, also Li [10] showed that treatment using methylcobalamin and alpha lipoic acid can be more effective when combined with moxibustion therapy. Lan et al [3] study showed that moxibustion can help reduce the Toronto clinical neuropathy score and simple pain scale score (VAS) of DPN patients. ...
Background:
Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus. The main clinical manifestations of DPN include pain, numbness, paraesthesia, and weakness of the lower limbs which often leads to diabetic foot ulceration, eventually resulting in amputation. Based on Traditional Chinese Medicine theory, moxibustion has a great effect on treating and preventing DPN. However, randomized clinical trials done to evaluate the efficacy of this treatment are still lacking. Hence, this study is carried out to evaluate the effectiveness and safety of moxibustion therapy on diabetic peripheral neuropathy.
Methods:
This study will be a pilot, interventional, randomized, 2-armed, parallel, singled-masked, controlled trial. A total of 40 diabetes mellitus patients with peripheral neuropathy will be recruited and assigned randomly into 2 groups (moxibustion group and waiting group) at a 1:1 ratio. This trial consists of an 8-week intervention period and a 4-week follow-up period. During the intervention period, the moxibustion group will take 3 moxibustion sessions per week, whereas no intervention will be done on the waiting group to act as the control group. The outcome will be assessed by an outcome assessor who is unaware of the group assignment. The primary outcome will be pain assessment measured with algometry, Leeds Assessment of Neuropathic Symptoms and Signs pain scale, visual analogue scale, and neuropathy pain scale. The secondary outcome will be an evaluation of functional performance capacity with 6 minutes walking test, evaluation of the Foot and Ankle Ability Measure, and serum HbA1c and albumin levels.
Discussion:
We hope that this trial will provide valuable insights on the efficacy of moxibustion in the management of diabetic peripheral neuropathy.
Trial registration:
ClinicalTrials.gov Registry No.: NCT04894461 (URL: https://clinicaltrials.gov/ct2/show/NCT04894461?term=NCT04894461&draw=2&rank=1) Registered on May 20, 2021.
... Recent studies showed that moxibustion can increase serum superoxide dismutase concentration, [8] reduce free-radical production, prevent impairments of nerve tissues resulting from free-radical accumulation, and alleviate neuroinflammation possibly by inhibiting NF-kB and activating Nrf2. [9] The efficacy of moxibustion therapy has been claimed by many studies but there is still a lack of objective evaluation of its benefits in treating DPN. Therefore, the effectiveness of moxibustion therapy in DPN remains controversial and its application is limited. ...
... Other therapeutic approaches to control DPN including those evaluated in clinical trials have shown limited efficacy especially on painless symptoms. [9,26] According to the theory of TCM, DPN belongs to the "bi syndrome" of TCM and is related to the blockage of meridians. Moxibustion can warm Yang, eliminate cold, and dredge meridians, and is a representative external treatment in TCM. ...
... A study demonstrated that moxibustion could improve DPN-related neuroinflammation by restoring the balance between NF-kB and Nrf2 in rats and may thus be complementary to the current treatment of DPN. [9] Our study evaluated the efficacy and safety of moxibustion in treating DPN. ...
Background:
At present, the effect of western-medicine (WM) therapy to treat diabetic peripheral neuropathy (DPN) is limited. Moxibustion is a representative external treatment in traditional Chinese medicine that has been beneficial to DPN. We aim to systematically assess the efficacy and safety of moxibustion in treating DPN, following PRISMA guidelines.
Methods:
Eight electronic databases were searched to acquire information on eligible trials published from inception to June 1, 2019. We included randomized controlled trials (RCTs) applying moxibustion therapy with a minimum of 14-days treatment duration for DPN patients compared with placebo, no intervention, or conventional WM interventions. The primary outcomes in our study include the sensory-nerve conduction velocity (SNCV) and motor-nerve conduction velocity (MNCV). We used the Cochrane Collaboration Risk of Bias tool to assess the methodological quality of eligible RCTs. Statistical analyses were conducted using Review Manager 5.3. Risk ratios (RR) and mean differences (MD) were calculated with a 95% confidence interval (CI). The χ test was applied to assess the heterogeneity.
Results:
In total, 11 RCTs were included that involved 927 DPN patients. Compared with the control group, there was an increase in median MNCV (MD = 6.26, 95% CI 2.64-9.89, Z = 3.39, P = .0007) and peroneal MNCV (MD = 6.45, 95% CI 5.30-7.61, P < .00001). There was also an increase in median SNCV (MD = 6.64, 95% CI 3.25-10.03, P = .0001) and peroneal SNCV (MD = 3. 57, 95% CI 2.06-5.09, Z = 4.63, P < .00001) in the treatment groups. The treatment groups receiving moxibustion therapy indicated a more significant improvement in total effectiveness rate (RR = 0.25, 95% CI 0.18-0.37, Z = 7.16, P < .00001). Toronto Clinical Scoring System indicated a significant decrease in the treatment groups (MD = -2.12, 95% CI -2.82 to 1.43, P < .00001). Only 1 study reported that treatment groups experienced no adverse reactions. The other 10 studies did not mention adverse events.
Conclusions:
Moxibustion therapy may be an effective and safe option for DPN patients but needs to be verified in further rigorous studies.
... Diabetic peripheral neuropathy (DPN) is a common chronic complication of diabetes and potentially affects the distal sensory, motor, and autonomic nerves. Clinically, DPN is characterized by pain, numbness, and dysfunction of the autonomic nervous system, which seriously impairs individual quality of life [1]. Tang-luo-ning (TLN) is a traditional Chinese herbal recipe that is comprised of Astragalus root, Fructuscorni, and Salvia miltiorrhiza. ...
Tang-luo-ning (TLN) is a traditional Chinese herbal recipe that has been used to treat diabetic peripheral neuropathy (DPN); nevertheless, the underlying mechanism remains unclear. This study was aimed to investigate the microRNA (miRNA) expression profile in diabetic rats treated with TLN, and the target genes were predicted. Male Sprague-Dawley rats were randomly divided into control, diabetes, and TLN-treated diabetes groups. Diabetes was induced with streptozotocin, and TLN (5 g/kg/day) was orally given for eight weeks. Then, the sciatic nerves were harvested for miRNA microarray analyses. The differentially expressed miRNAs and their target genes were analyzed. Compared with the control rats, 24 miRNAs were significantly upregulated, and 59 were downregulated in the sciatic nerves of the diabetic rats by more than two folds (all P < 0.05). In TLN-treated diabetes rats, 26 miRNAs were upregulated, and 14 were downregulated compared with diabetic rats without TLN treatment (all P < 0.05). DPN-induced alterations of the miRNA profile were reversed by the TLN treatment. A total of 1402 target genes were screened. In GO analysis, genes in localization, cytoplasm, and protein binding processes were enriched, and the most significantly enriched pathways included the neurotrophin, Fc epsilon RI, and Wnt signaling pathways. Further analyses revealed that DVL1 and NTF3 genes were involved in these pathways. Our findings indicate that TLN may affect the Wnt and neurotrophin pathways by acting on DVL1 and NTF3 genes.
This study investigated the protective effect of Shenfu injection (SI) on septic acute kidney injury (AKI) induced by lipopolysaccharide (LPS) and its underlying mechanism. A mouse model of septic AKI was established, and various dosages of SI (2 mL/kg, 4 mL/kg, and 8 mL/kg) were administered as treatment. HE staining and TUNEL assay were conducted for pathological analysis. The content of ATP was detected by the biochemical kit. The mitochondrial membrane potential (MMP) was detected by flow cytometry. Western blotting was used for the detecting expression of apoptosis and inflammation related proteins. To explore the molecular mechanism, septic mice were treated by SI (8 mL/kg) combined with ML385 (30 mg/kg). The number and morphology of mitochondria were observed by the transmission electron microscope (TEM). The increased renal volume, paler renal cortex, and necrotic renal tubules observed in septic AKI mice were significantly alleviated by treatment with either 4 mL/kg or 8 mL/kg of SI. Furthermore, signally declined ATP content and increased MMP value in septic AKI mice were markedly reversed by 8 mL/kg SI. Additionally, the increased IL-6, p-p65, cle-caspase-3, and Bax levels, as well as the decreased Bcl-2 level, observed in septic AKI mice were notably rescued by 8 mL/kg SI. The protective function of SI on pathological changes and mitochondria in septic AKI mice was abolished by ML385. These findings suggested that SI alleviated LPS-induced septic AKI by regulating the Nrf2/NF- κ B axis.
The incidence of diabetes mellitus (DM) is steadily increasing all over the world, and at the same time there is an increase in its complications, which are the main causes of early disability and premature death. The pathogenesis of DM is based on a steady decrease in pancreatic β-cells. A decrease in β-cell mass leads to a decrease in insulin production and the development of hyperglycemia and associated severe complications. Therefore, the need to prevent the death of β-cells and stimulate their regeneration is obvious. In recent literature, much attention has been paid to the role of GABA in the regulation of the function of α- and β-cells of the pancreas and carbohydrate metabolism, which is the subject of this review. Gamma-aminobutyric acid (GABA) in β-cells and pancreatic islets is determined in quantities comparable to those in the brain. It also contains a high amount of glutamadecarboxylase, an enzyme that synthesizes GABA. In DM, the level of GABA in pancreatic β-cells decreases and this correlates with the severity of DM. GABA plays an important role in the paracrine regulation of α- and β-cell functions and carbohydrate homeostasis. The potential possibility of using GABA to achieve a decrease in apoptosis and, at the same time, an increase in the regeneration of β-cells, an increase in the β-cell mass of the pancreas has been proven. It has been proven that the positive effect of GABA on the structure and functions of pancreatic β-cells in DM can be significantly higher when combined with antidiabetic agents: GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2 inhibitors, and others. The antidiabetic properties of GABA are explained by its interaction with various signaling proteins (Kloto protein, SIRT, PI3K/Akt, CREB-IRS2, NF-kB, Nrf2 and many others), through which these effects are realized. Data on the pancreatic protective effect of GABA and its derivatives can form the basis for the development of a new pharmacotherapeutic strategy for the treatment of DM and associated complications.
Oligoasthenoteratozoospermia (OAT) decreases male fertility, seriously affecting the production of offspring. This study clarified the preventive impact of different moxibustion frequencies on OAT and selected the optimal frequency to elucidate the underlying mechanism. An OAT rat model was constructed by gavage of tripterygium glycosides (TGS) suspension. Daily moxibustion (DM) or alternate-day moxibustion (ADM) was administered on the day of TGS suspension administration. Finally, we selected DM for further study based on sperm quality and DNA fragmentation index, testicular and epididymal morphology, and reproductive hormone level results. Subsequently, the oxidative stress (OS) status was evaluated by observing the OS indices levels; malondialdehyde (MDA), 8-hydroxy-deoxyguanosine (8-OHdG), total antioxidant capacity (T-AOC), and total superoxide dismutase (T-SOD) in testicular tissue using colorimetry and enzyme-linked immunosorbent assay. Furthermore, heme oxygenase 1 (HO-1) and nuclear factor erythropoietin-2-related factor 2 (Nrf2) were evaluated using Western blotting. Immunohistochemistry was employed to locate and assess the expression of HO-1 and Nrf2 protein, while quantitative real-time polymerase chain reaction was utilized to detect their mRNA expression. MDA and 8-OHdG levels decreased following DM treatment, while T-SOD and T-AOC increased, suggesting that DM may prevent TGS-induced OAT in rats by decreasing OS in the testis. Furthermore, protein and mRNA expression of Nrf2 and HO-1 in the testis were elevated, indicating that DM may reduce OS by activating the signaling pathway of Nrf2/HO-1. Therefore, DM could prevent OAT in rats via the Nrf2/HO-1 pathway, thereby presenting a promising therapeutic approach against OAT.
