Potential role of selenium in alleviating obesity-related iron dyshomeostasis.

Obesity is a serious health problem in modern life and increases the risk of many comorbidities including iron dyshomeostasis. In contrast to malnourished anemia, obesity-related iron dyshomeostasis is mainly caused by excessive fat accumulation, inflammation, and disordered gut microbiota. In obesity, iron dyshomeostasis also induces disorders associated with gut microbiota, neurodegenerative injury, oxidative damage, and fat accumulation in the liver. Selenium deficiency is often accompanied by obesity or iron deficiency, and selenium supplementation has been shown to alleviate obesity and overcome iron deficiency. Selenium inhibits fat accumulation and exhibits anti-inflammatory activity. It regulates gut microbiota, prevents neurodegenerative injury, alleviates oxidative damage to the body, and ameliorates hepatic fat accumulation. These effects theoretically meet the requirements for the inhibition of factors underlying obesity-related iron dyshomeostasis. Selenium supplementation may have a potential role in the alleviation of obesity-related iron dyshomeostasis. This review verifies this hypothesis in theory. All the currently reported causes and results of obesity-related iron dyshomeostasis are reviewed comprehensively, together with the effects of selenium. The challenges and strategies of selenium supplementation are also discussed. The findings demonstrate the possibility of selenium-containing drugs or functional foods in alleviating obesity-related iron dyshomeostasis.

Exploration of the mechanisms underlying the beneficial effect of Luo Tong formula on retinal function in diabetic rats via the "gut microbiota-inflammation-retina" axis.

BACKGROUND: Diabetic retinopathy (DR) is a common microvascular complication of diabetes. Luo Tong formula (LTF), a classical traditional Chinese medicine (TCM) prescription, consists of four plants that have been widely and effectively used to treat DR. Previous work in our laboratory has confirmed that LTF can effectively ameliorate DR. However, the potential mechanism underlying the therapeutic effect of LTF on DR has not been fully elucidated. To explore the potential mechanism of action through which LTF prevents and alleviates DR from an inflammation and gut microbiota perspective. MATERIALS AND METHODS: Metabolite profiling of LTF was performed using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). Type 1 diabetes was induced in male Sprague Dawley (SD) rats via tail vein injection of 45 mg/kg streptozotocin. Next, 100 SD rats were randomly divided into four groups, normal control; diabetic control; diabetic + insulin + calcium dobesilate; and diabetic + insulin + LTF. After 12 weeks of treatment, glucose metabolism, fundus oculi, blood-retinal barrier permeability, retinal thickness, microvascular damage, as well as cell junction expression in retinas were measured and the changes observed in different groups were compared. Finally, the alteration in gut microbiota and inflammatory cytokine expression in serum and tissues were monitored, and their correlation was analyzed. RESULTS: A total of 1024 valid peaks were obtained for LTF using GC-MS. The HbA1c and fasting blood glucose (FBG) levels in the LTF group were slightly decreased. LTF exerted protective effects on fundus oculi and the retina structure to different degrees. LTF attenuated systemic and local retinal inflammation by significantly decreasing the levels of seven pro-inflammatory cytokines, including ICAM-1, IL-6, IL-8, MCP-1, VCAM-1, VEGF, and IL-1ß. LTF restored the intestinal microbiota of diabetic rats to levels that were similar to those of normal rats. Further analysis revealed that Enterobacteriales, Prevotellaceae, Enterobacteriaceae, Bacteroides, and Klebsiella were significantly and positively correlated with the inflammatory factors in DR after LTF treatment. CONCLUSIONS: Our results revealed the mechanisms underlying the preventive effects of LTF on DR development and progression. LTF inhibited pathological changes in retinal histopathology, cell composition, and cell junction proteins while effectively ameliorating systemic and local retinal inflammation via regulating pivotal gut microbiota.

Potentials of orally supplemented selenium-enriched Lacticaseibacillus rhamnosus to mitigate the lead induced liver and intestinal tract injury.

Lead is a metal that exists naturally in the Earth's crust and is a ubiquitous environmental contaminant. The alleviation of lead toxicity is important to keep human health under lead exposure. Biosynthesized selenium nanoparticle (SeNPs) and selenium-enriched Lactobacillus rhamnosus SHA113 (Se-LRS) were developed in this study, and their potentials in alleviating lead-induced injury to the liver and intestinal tract were evaluated in mice by oral administration for 4 weeks. As results, oral intake of lead acetate (150 mg/kg body weight per day) caused more than 50 times and 100 times lead accumulation in blood and the liver, respectively. Liver function was seriously damaged by the lead exposure, which is indicated as the significantly increased lipid accumulation in the liver, enhanced markers of liver function injury in serum, and occurrence of oxidative stress in liver tissues. Serious injury in intestinal tract was also found under lead exposure, as shown by the decrease of intestinal microbiota diversity and occurrence of oxidative stress. Except the lead content in blood and the liver were lowered by 52% and 58%, respectively, oral administration of Se-LRS protected all the other lead-induced injury markers to the normal level. By the comparison with the effects of normal L. rhamnosus SHA113 and the SeNPs isolated from Se-LRS, high protective effects of Se-LRS can be explained as the extremely high efficiency to promote lead excretion via feces by forming insoluble mixture. These findings illustrate the developed selenium-enriched L. rhamnosus can efficiently protect the liver and intestinal tract from injury by lead.

Yiqi Tongluo Fang could preventive and delayed development and formation of diabetic retinopathy through antioxidant and anti-inflammatory effects.

BACKGROUND: Yiqi Tongluo Fang (YQTLF) is an effective prescription for the treatment of diabetic retinopathy (DR), but its mechanism of action remains unclear. METHOD: The content of YQTLF was determined using liquid and gas chromatography-mass spectrometry (LC-MS and GC-MS, respectively). Twenty-five Sprague Dawley (SD) rats were randomly selected as the normal control group. One hundred SD streptozotocin-induced diabetes (type 1) rats were randomly divided into diabetic control, diabetic+insulin+ calcium dobesilate (CaD), and diabetic+insulin+ YQTLF groups, with 25 rats in each group. Bodyweight level was measured every 2 weeks. After 12 weeks of gavage, the glucose levels, lipids, oxidative stress, inflammation, retinal histopathology, and the blood-retinal barrier were assessed in each group. The p38 MAPK pathway was changed to explore its internal mechanism. The measurement data were expressed as mean ± standard deviation, and different statistical methods were used according to a normal distribution, square error, or not. RESULTS: A total of 1024 valid peaks were identified in YQTLF using GC-MS. YQTLF significantly lowered the fasting blood glucose levels in diabetic rats. YQTLF early inhibited changes in retinal histology, capillaries, cells, and tight junction proteins (such as ZO-1, occludin, claudin-5, and VE-cadherin) before the formation and development of DR. These findings correlated with the alleviation of glucolipid metabolism, inflammation, and oxidative stress. The lncRNA MALAT1 and the PRC 2/p38 MAPK-related pathway, such as the expression of EZH2, SUZ12, EED, p38 MAPK, MMP-9, and VEGFR, were also correlated. CONCLUSION: We have demonstrated the molecular and cellular mechanisms underlying the preventive and delayed development and formation of DR. YQTLF prevents changes in dyslipidemia, retinal histology, capillaries, cells, and tight junction proteins. These protective effects appear to be linked to its antioxidant and anti-inflammatory effects, which prevent the activation of intracellular signaling pathways, such as the lncRNA MALAT1 and PRC 2/p38 MAPK-related pathway.

Vitamin A supplementation ameliorates ulcerative colitis in gut microbiota-dependent manner.

Ulcerative colitis (UC), is a chronic relapsing inflammatory condition of the gastrointestinal track. The purpose of this study is to explore whether Vitamin A (VA) can treat UC and its mechanisms. A mouse model of UC was established using 3.0% (w/v) dextran sodium sulfate (DSS). VA was used to treat UC by intragastric administration of 5000 international unit (IU) retinyl acetate. Fecal microbiota transplantation (FMT) was also used to treat the UC model mice to verify the effect of influenced gut microbiota. The content of short-chain fatty acids (SCFAs) in cecal contents was quantitatively detected by gas chromatography and mass spectrometry. VA supplementation significantly ameliorated UC. 16S rRNA sequencing indicated that VA-treated mice exhibited much more abundant gut microbial diversity and flora composition. Targeted metabolomics analysis manifested the increased production of SCFAs in VA-treated mice. Gut microbiota depletion and FMT results confirmed the gut microbiota-dependent mechanism as that VA relieved UC via regulating gut microbiota: increase in SCFA-producing genera and decrease in UC-related genera. The restore of intestinal barrier and the inhibition of inflammation were also found to contribute to the amelioration of UC by VA. It was concluded that a VA supplement was enough to cause a significant change in gut microbiota and amelioration of UC.

Effectiveness of Herbal Medicine for Leukopenia/Neutropenia Induced by Chemotherapy in Adults with Colorectal Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the effectiveness of Chinese Herbal Medicine (CHM) on leukopenia/neutropenia induced by chemotherapy in adults with colorectal cancer (CRC). METHODS: Eight electronic databases were searched from their inception to June 2020. Randomized controlled trials with clarified sequence generation were qualified. Two reviewers independently conducted the screening and data extraction. Methodological quality was assessed using the Risk of Bias tool. RevMan 5.4 was applied to the meta-analysis. RESULTS: Twenty-seven studies involving 1867 participants were qualified, of which 26 were included in the quantitative synthesis. Meta-analysis showed that CHM significantly reduced the incidence of leukopenia induced by chemotherapy (RR = 0.69; 95% CI 0.59-0.82), as well as the grade 3/4 leukopenia (RR = 0.71; 95% CI 0.55-0.90). Meanwhile,CHM decreased the occurrence of neutropenia (RR = 0.52, 95% CI 0.35-0.77), especially for the grades 3/4 neutropenia (RR = 0.42, 95% CI 0.27-0.64). Twenty-six of the included studies focused on the adverse events related to CHM. CONCLUSION: CHM may relieve neutropenia/leukopenia induced by chemotherapy in adults with colorectal cancer.

Prevention of Diabetes in Overweight/Obese Adults through Traditional Chinese Patent Medicine: Study Protocol for a Prospective Cohort Study.

Background. Early intervention in prediabetes can prevent or delay the incidence of type 2 diabetes mellitus (T2DM). Traditional Chinese patent medicine (TCPM) is widely used in China to prevent T2DM. This study aims to evaluate the efficacy and safety of TCPMs for preventing T2DM. Method/Design. This study is a multicenter, cohort study with two arms. A total of 600 participants will be recruited. The participants will be divided into either intervention or control groups according to their own desire, and the exposure factor is the application of TCPMs. All participants will be encouraged to lead a healthy lifestyle, and the intervention group also used TCPMs based on syndrome differentiation. Incident diabetes and normalization of blood glucose are indexes of end point. Safety assessments and adverse event monitoring will also be conducted. The treatment duration is set for 24 weeks, and we will follow-up for another 2 years. Discussion. This trial may provide initial evidence regarding the efficacy and safety of TCPMs plus lifestyle intervention (LI) compared to LI alone for preventing T2DM and provide a comprehensive intervention plans that choose suitable TCPMs for diabetes prevention according to syndrome differentiation. Trial Registration Number. Chinese Clinical Trial Registry ID: ChiCTR1900023541, registered on 1 Jun 2019. The version identifier is 2018121702.

Moxibustion for the treatment of diabetic peripheral neuropathy: A systematic review and meta-analysis following PRISMA guidelines.

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.

Interactions Between Gut Microbiota, Host, and Herbal Medicines: A Review of New Insights Into the Pathogenesis and Treatment of Type 2 Diabetes.

Herbal medicines (HMs) are a major subset of complementary and alternative medicine. They have been employed for the efficient clinical management of type 2 diabetes mellitus (T2DM) for centuries. However, the related underlying mechanisms still remain to be elucidated. It has been found out that microbiota is implicated in the pathogenesis and treatment of T2DM. An interplay between gut microbiota and host occurs mainly at the gastrointestinal mucosal barrier. The host movements influence the composition and abundance of gut microbiota, whereas gut microbiota in turn modulate the metabolic and immunological activities of the host. Intestinal dysbiosis, endotoxin-induced metabolic inflammation, immune response disorder, bacterial components and metabolites, and decreased production of short-chain fatty acids are considered significant pathogenic mechanisms underlying T2DM. The interaction between gut microbiota and HMs during T2DM treatment has been investigated in human, animal, and in vitro studies. HMs regulate the composition of beneficial and harmful bacteria and decrease the inflammation caused by gut microbiota. Furthermore, the metabolism of gut microbiota modulates HM biotransformation. In this review, we have summarized such research findings, with the aim to improve our understanding of the pathogenesis and potential therapeutic mechanisms of HMs in T2DM and to provide new insights into specific targeted HM-based therapies and drug discovery.

Prebiotic properties of different polysaccharide fractions from Artemisia sphaerocephala Krasch seeds evaluated by simulated digestion and in vitro fermentation by human fecal microbiota.

Artemisia sphaerocephala Krasch polysaccharide (ASKP) and its two fractions-60P (branched xylan) and 60S (branched glucomannan), were subjected to simulated gastrointestinal digestion and in vitro fermentation by human fecal microbiota. The results showed that all polysaccharide fractions could transit through gastrointestinal tract without dramatic degradation and be utilized by gut microbiota. ASKP exhibited the highest depletion rate and highest capability to decrease the pH than its fractions. Meanwhile, 60S showed the stronger capability to increase the production of propionic acid and reduce the ratio of acetic acid to propionic acid. At the phylum level, all polysaccharides efficiently reduced the Firmicutes/Bacteroidetes ratio and relative abundance of Proteobacteria, with ASKP being the most capable to suppress the proliferation of Proteobacteria. At the genus level, ASKP and 60P markedly promoted the growth of Bacteroidetes, and 60S promoted the growth of Parabacteroides and Collinsella. Prediction on metabolic function revealed that polysaccharide administration could dramatically change the metabolic profile of bacteria compared with fructooligosaccharides. Besides, all the polysaccharides dramatically promoted the bile acid metabolism. Compared with 60S, ASKP and 60P showed stronger ability to suppress the metabolisms on carbohydrate and amino acid. In summary, both ASKP and its two fractions showed the prebiotic potentials.

Banxia Xiexin Decoction Ameliorates t-BHP-Induced Apoptosis in Pancreatic Beta Cells by Activating the PI3K/AKT/FOXO1 Signaling Pathway.

BACKGROUND: Banxia Xiexin Decoction (BXXD) reportedly regulates glycolipid metabolism and inhibits pancreatic ß-cell apoptosis. This study is aimed at investigating the protective effect of BXXD on tert-butyl hydroperoxide- (t-BHP-) induced apoptosis in MIN6 cells and the underlying mechanisms. METHODS: MIN6 cells were preincubated with BXXD or liraglutide (Li) with or without PI3K inhibitor LY294002 (LY) for 12 h, following which t-BHP was added to induce MIN6 cell apoptosis. The protective effects of BXXD on MIN6 cells were evaluated by detecting cell viability and proliferation and glucose-stimulated insulin secretion (GSIS). The antiapoptotic effects were evaluated by Hoechst 33342 staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL). Malondialdehyde and glutathione peroxidase content and superoxide dismutase activity were measured using commercial kits. The expression of PI3K/AKT/FOXO1 signaling pathway-related signal molecules, and that of apoptotic indicators Bax, P27, and Caspase-3, was quantified using western blotting. RESULTS: Preincubation with BXXD significantly improved t-BHP-induced proliferation inhibition and apoptosis and enhanced GSIS. t-BHP induced the generation of reactive oxygen species and inhibited the activities of antioxidant enzymes, which could be neutralized by pretreatment with BXXD. BXXD promoted the phosphorylation of AKT and FOXO1 in t-BHP-induced MIN6 cells. Moreover, BXXD attenuated the expression of related apoptotic indicators Bax, P27, and Caspase-3. LY abolished these effects of BXXD. CONCLUSION: BXXD protected MIN6 cells against t-BHP-induced apoptosis and improved insulin secretory function through modulation of the PI3K/AKT pathway and the downstream FOXO1, thus suggesting a novel therapeutic approach for type 2 diabetes mellitus (T2DM).

Traditional chinese medicine for diabetic retinopathy: A systematic review and meta-analysis.

BACKGROUND: Traditional Chinese medicine (TCM) has been used to treat diabetic complications including diabetic retinopathy for many years. OBJECTIVES: This review was performed to systematically assess the efficacy and safety of TCM for treating non- proliferative diabetic retinopathy (NPDR). METHODS: Retrieval from 7 electronic databases was conducted to determine eligible trials published until March 1, 2018. Randomized controlled trials of NPDR that comparing compound Chinese medicine containing the therapeutic method of activating blood and remove stasis versus controls were included for analysis. Primary outcomes were progression of retinopathy. Secondary outcomes included visual acuity, mean defect of visual field, micro-aneurysms, hemorrhage areas, exudates, capillary nonperfusion areas, hemorheological indicators, oscillatory potentials (Ops), glycated haemoglobin (HbA1c), and adverse events. Data extraction and quality assessment were performed. Results expressing as risk ratios (RRs) or mean differences (MD) were analyzed with a fixed- or random- effect model. I statistics were used to assess heterogeneity. RESULTS: A total of 33 trials and 3373 participants were included. Findings revealed that no included studies reported the progression of retinopathy. Compared with conventional medicine, TCM was significantly better at improving visual acuity (MD, -0.10; 95% confidence interval [CI] -0.16 to -0.05) and Ops (MD, -4.68, 95% CI -8.51 to -0.85), and reducing the mean defect of visual field (MD, -1.43; 95%CI, -2.17 to -0.68), micro-aneurysms (MD, -4.51; 95% CI, -6.23 to -2.79), hemorrhage areas (MD, -0.62; 95% CI, -1.06 to -0.19), plasma viscosity (MD, -0.10; 95% CI, -0.20 to 0.00), and HbA1c (MD, -0.22; 95% CI, -0.42 to -0.03). Compared with placebo, TCM was also associated with a decline in the number of microaneurysms (MD, -4.35; 95% CI, -6.25 to -2.45), exudates (MD, -0.17; 95% CI -0.31 to -0.03), capillary nonperfusion areas (MD, -0.18; 95% CI, -0.31 to -0.04), and HbA1c (MD, -0.88; 95% CI, -1.44 to -0.32). Compared with blank groups, TCM was superior at decreasing the mean defect of visual field (MD, -0.87; 95% CI -0.95 to -0.79) and the numbers of micro-aneurysms (MD, -3.35; 95% CI, -4.73 to -1.97). Adverse events were also assessed. CONCLUSION: Activating blood compound Chinese herbal medicine could help to improve visual acuity, micro-aneurysms and HbA1c. Further trials are needed to provide more reliable evidence.

Metabolomics Reveals the Response of the Phenylpropanoid Biosynthesis Pathway to Starvation Treatment in the Grape Endophyte Alternaria sp. MG1.

Phenylpropanoid (PPPN) compounds are widely used in agriculture, medical, food, and cosmetic industries because of their multiple bioactivities. Alternaria sp. MG1, an endophytic fungus isolated from grape, is a new natural source of PPPNs. However, the PPPN biosynthesis pathway in MG1 tends to be suppressed under normal growth conditions. Starvation has been reported to stimulate the PPPN pathway in plants, but this phenomenon has not been well studied in endophytic fungi. Here, metabolomics analysis was used to examine the profile of PPPN compounds, and quantitative reverse transcription-polymerase chain reaction was used to detect the expression of key genes in the PPPN biosynthesis pathway under starvation conditions. Starvation treatment significantly increased the accumulation of shikimate and PPPN compounds and upregulated the expression of key genes in their biosynthesis pathways. In addition to previously reported PPPNs, sinapate, 4-hydroxystyrene, piceatannol, and taxifolin were also detected under starvation treatment. These findings suggest that starvation treatment provides an effective way to optimize the production of PPPN compounds and may permit the investigation of compounds that are undetectable under normal conditions. Moreover, the diversity of its PPPNs makes strain MG1 a rich repository of valuable compounds and an extensive genetic resource for future studies.

Artemisia sphaerocephala Krasch polysaccharide mediates lipid metabolism and metabolic endotoxaemia in associated with the modulation of gut microbiota in diet-induced obese mice.

Artemisia sphaerocephala Krasch polysaccharide (ASKP) has been proved to have many bioactivities. To determine the underlying mechanisms on anti-obesogenic effect of ASKP in mice, parameters related to obesity, gut microbiota composition, and the correlation between the parameters and specific bacterial taxa were investigated. The results showed that ASKP significantly alleviated high-fat-diet-induced obesity in mice with the amelioration of dyslipidemia, and metabolic endotoxaemia. Relative expression analyses of genes indicated that ASKP administration modulated hepatic lipid metabolism with the downregulation of related genes, including ACC-1, FAS, SREBP-1c, and PPARγ. 16S rRNA analysis showed that ASKP mediated the gut dysbiosis induced by high-fat diet, such as the reduction of Proteobacteria, AF12, and Helicobacter. Spearman's correlation showed that some specific genera, such as Odoribacter, AF12, and Rikenella, were strongly associated with obesity-related parameters. Our results demonstrated that ASKP could serve as a potential prebiotic agent in the prevention of diet-induced obesity.

[Application of classical formula in treatment of diabetes].

The application of classical formula in the treatment of diabetes has a long history. Zhang Zhongjing set up a special chapter on consumptive thirst in Synopsis of the Golden Chamber,listing Baihu Jia Renshen Decoction for exuberant heat in the lung and stomach,dual deficiency of Qi and Yin syndrome,and Shenqi Pills for kidney Qi deficiency syndrome. However,the clinical application is not limited to them. In this study,formulas of Huanglian,Dahuang,Chaihu,Gualougen,Lingzhu,Huangqi and Dihuang are listed as the main therapeutic methods for diabetes mellitus,with effects in clearing heat,dredging the bowels and purging turbid,clearing depression and dispersing knots,nourishing Yin and quenching thirst,invigorating spleen and draining dampness,supplementing Qi and tonifying deficiency,nourishing Yin and tonifying kidney,which have the advantages for the treatment of diabetes and its complications. Based on accurate differentiation of symptoms and signs,consideration shall be given to both " of diseases and syndromes",while emphasis shall be given to the " main symptoms",so as to flexibly apply classical formula and expand the scope of application.

Sheng Mai San protects H9C2 cells against hyperglycemia-induced apoptosis.

BACKGROUND: Sheng Mai San (SMS) has been proven to exhibit cardio-protective effects. This study aimed to explore the molecular mechanisms of SMS on hyperglycaemia (HG)-induced apoptosis in H9C2 cells. METHODS: HG-induced H9C2 cells were established as the experimental model, and then treated with SMS at 25, 50, and 100 µg/mL. H9C2 cell viability and apoptosis were quantified using MTT and Annexin V-FITC assays, respectively. Furthermore, Bcl-2/Bax signalling pathway protein expression and Fas and FasL gene expression levels were quantified using western blotting and RT-PCR, respectively. RESULTS: SMS treatments at 25, 50, 100 µg/mL significantly improved H9C2 cell viability and inhibited H9C2 cell apoptosis (p < 0.05). Compared to the HG group, SMS treatment at 25, 50, and 100 µg/mL significantly downregulated p53 and Bax expression and upregulated Bcl-2 expression (p < 0.05). Moreover, SMS treatment at 100 µg/mL significantly downregulated Fas and FasL expression level (p < 0.05) when compared to the HG group. CONCLUSION: SMS protects H9C2 cells from HG-induced apoptosis probably by downregulating p53 expression and upregulating the Bcl-2/Bax ratio. It may also be associated with the inhibition of the Fas/FasL signalling pathway.

Efficacy of Chinese Herbal Medicine in the Treatment of Moderate-Severe Painful Diabetic Peripheral Neuropathy: A Retrospective Study.

Painful diabetic peripheral neuropathy (pDPN) is a debilitating complication of diabetes. The aim of this retrospective study was to investigate the effectiveness of a Chinese herbal medicine regimen-the modified Huangqi Guizhi Wuwu Decoction (HGWD)-in the treatment of moderate-severe pDPN. The primary objective was to estimate the improvement in neuropathic pain severity. The secondary objective was to assess the response of common symptoms to the treatment. The change in patients' blood glucose level during the whole treatment was also evaluated. By searching through our medical records of all the diabetic patients from January 2006 to January 2012, we identified and enrolled 30 moderate and severe pDPN patients in the study, for whom the treatment of neuropathic pain by regular pharmacotherapies had failed. The modified HGWD treatment was administered orally twice a day for 6 months. The numerical rating scale (NRS) level at month 6 was 2.57 ± 2.30, significantly improved compared with the baseline level of 6.03 ± 1.83 (P < 0.05). The amelioration of 3 common symptoms, namely, limb pain, limb numbness, and insomnia, was evident, and the major response of common symptoms at month 6 including limb pain, insomnia, and limb coldness was significantly increased compared with the results at month 3 (P < 0.05). Moreover, 2-hour postprandial blood glucose (2hPG) level decreased from 10.77 ± 1.29 mmol/L at baseline to 9.66 ± 0.60 mmol/L at month 6 (P < 0.05). No serious adverse events occurred throughout the treatment period. The modified HGWD was effective in the treatment of moderate and severe pDPN and can thus be offered as a new alternative treatment option for pDPN patients who failed to respond to regular pharmaceutical therapies.

Structural Alteration of Gut Microbiota during the Amelioration of Human Type 2 Diabetes with Hyperlipidemia by Metformin and a Traditional Chinese Herbal Formula: a Multicenter, Randomized, Open Label Clinical Trial.

Accumulating evidence implicates gut microbiota as promising targets for the treatment of type 2 diabetes mellitus (T2DM). With a randomized clinical trial, we tested the hypothesis that alteration of gut microbiota may be involved in the alleviation of T2DM with hyperlipidemia by metformin and a specifically designed herbal formula (AMC). Four hundred fifty patients with T2DM and hyperlipidemia were randomly assigned to either the metformin- or AMC-treated group. After 12 weeks of treatment, 100 patients were randomly selected from each group and assessed for clinical improvement. The effects of the two drugs on the intestinal microbiota were evaluated by analyzing the V3 and V4 regions of the 16S rRNA gene by Illumina sequencing and multivariate statistical methods. Both metformin and AMC significantly alleviated hyperglycemia and hyperlipidemia and shifted gut microbiota structure in diabetic patients. They significantly increased a coabundant group represented by Blautia spp., which significantly correlated with the improvements in glucose and lipid homeostasis. However, AMC showed better efficacies in improving homeostasis model assessment of insulin resistance (HOMA-IR) and plasma triglyceride and also exerted a larger effect on gut microbiota. Furthermore, only AMC increased the coabundant group represented by Faecalibacterium spp., which was previously reported to be associated with the alleviation of T2DM in a randomized clinical trial. Metformin and the Chinese herbal formula may ameliorate type 2 diabetes with hyperlipidemia via enriching beneficial bacteria, such as Blautia and Faecalibacterium spp.IMPORTANCE Metabolic diseases such as T2DM and obesity have become a worldwide public health threat. Accumulating evidence indicates that gut microbiota can causatively arouse metabolic diseases, and thus the gut microbiota serves as a promising target for disease control. In this study, we evaluated the role of gut microbiota during improvements in hyperglycemia and hyperlipidemia by two drugs: metformin and a specifically designed Chinese herbal formula (AMC) for diabetic patients with hyperlipidemia. Both drugs significantly ameliorated blood glucose and lipid levels and shifted the gut microbiota. Blautia spp. were identified as being associated with improvements in glucose and lipid homeostasis for both drugs. AMC exerted larger effects on the gut microbiota together with better efficacies in improving HOMA-IR and plasma triglyceride levels, which were associated with the enrichment of Faecalibacterium spp. In brief, these data suggest that gut microbiota might be involved in the alleviation of diabetes with hyperlipidemia by metformin and the AMC herbal formula.

The Efficacy and Safety of the Chinese Herbal Formula, JTTZ, for the Treatment of Type 2 Diabetes with Obesity and Hyperlipidemia: A Multicenter Randomized, Positive-Controlled, Open-Label Clinical Trial.

BACKGROUND AND AIM: Studies have shown an increasing number of type 2 diabetes (T2D) patients with concomitant obesity and hyperlipidemia syndromes, resulting from relevant metabolic disorders. However, there are few medications and therapies, which can thoroughly address these issues. Therefore, the current study evaluated the efficacy and safety of using JTTZ, a Chinese herbal formula, to treat T2D with obesity and hyperlipidemia. METHODS: A total of 450 participants with T2D (HbA1c ≥ 7.0%; waist circumference ≥ 90 cm and 80 cm in males and females, resp.; and triglycerides (TG) ≥ 1.7 mmol/L) were randomly assigned, in equal proportions, to two groups in this multicenter randomized, positive-controlled, open-label trial. One group received JTTZ formula, and the other received metformin (MET) for 12 consecutive weeks. The primary efficacy outcomes were changes in HbA1c, TG, weight, and waist circumference. Adverse reactions and hypoglycemia were monitored. RESULTS: HbA1c decreased by 0.75 ± 1.32% and 0.71 ± 1.2% in the JTTZ and MET groups, respectively, after 12 weeks of treatment. TG levels in the JTTZ and MET groups were reduced by 0.64 ± 2.37 mmol/L and 0.37 ± 2.18 mmol/L, respectively. Weight was decreased by 2.47 ± 2.71 kg in the JTTZ group and by 2.03 ± 2.36 kg in the MET group. JTTZ also appeared to alleviate insulin resistance and increase HOMA-ß. In addition, symptoms were significantly relieved in participants in the JTTZ group compared to those in the MET group. One case of hypoglycemia was reported in the MET group. No severe adverse events were reported in either group. CONCLUSIONS: The JTTZ formula led to safe and significant improvements in the blood glucose, blood lipids, and weight levels; relieved symptoms; and enhanced ß cell function for T2D patients with obesity and hyperlipidemia. The JTTZ formula has shown that it could potentially be developed as an alternative medicine for patients with T2D, particularly those who cannot tolerate metformin or other hypoglycemic drugs. This trial was registered with Clinicaltrials.gov NCT01471275.

Traditional Chinese Patent Medicine for Treating Impaired Glucose Tolerance: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION/AIM: To assess the effectiveness and safety of Traditional Chinese patent medicines (TCPMs) for managing impaired glucose tolerance (IGT). METHODS: Seven databases were searched to identify eligible trials published from incepting to May 1, 2016. Randomized controlled trials (RCTs) involving TCPM for IGT with a minimum follow-up duration of 6 months were included for analysis. Data extraction and quality assessment were performed by two reviewers independently. Data synthesis was analyzed using Review Manager 5.3 software. Subgroup analysis was carried out to assess the robustness of results of meta-analysis. RESULTS: Eighteen trials with a total of 3172 participants met the inclusion criteria. The methodological quality of the RCTs was variable. Comparing with receiving lifestyle modification (LM) alone, TCPM plus LM was significantly better at reducing the incidence of diabetes (risk ratio [RR] 0.45; 95% confidence interval [CI] 0.36-0.57, p < 0.00001) and normalizing the blood glucose (RR 0.72; 95% CI 0.64-0.82, p < 0.00001). TCPM plus LM was superior in decreasing the levels of 2hPG, body mass index (BMI), fasting insulin, and 2 h insulin compared with LM alone (2hPG: mean difference [MD] -1.13; 95% CI -1.68 to -0.58, p < 0.0001; BMI: MD -0.42; 95% CI -0.71 to -0.14, p = 0.004; fasting insulin: MD -2.44; 95% CI -3.79 to -1.09, p = 0.0004; and 2 h insulin: MD -8.26; 95% CI -8.47 to -8.05, p < 0.00001). Compared with placebo plus LM, TCPM plus LM was superior in reducing diabetes (RR 0.54; 95% CI 0.42-0.69, p < 0.00001) and normalizing blood glucose (RR 0.55; 95% CI 0.41-0.73, p < 0.00001; the interventions were also associated with a decline in the two-hour postprandial blood glucose (2hPG) levels (MD -1.45; 95% CI -2.11 to -0.79, p < 0.0001) and BMI levels (MD -1.12; 95% CI -2.00 to -0.24, p < 0.0001). There were no significant differences in adverse events between two groups. Subgroup analysis found no significant difference in overall effects among all study characteristics, indicating that the overall effects were stable. CONCLUSIONS: The study indicated that TCPM combined with moderate lifestyle modification had significant effect on IGT. Further studies are needed to provide more reliable evidence. The PROSPERO registration is No. CRD42016039312.