Common mechanisms underlying diabetic vascular complications: focus on the interaction of metabolic disorders, immuno-inflammation, and endothelial dysfunction.

Diabetic vascular complications (DVCs), including macro- and micro- angiopathy, account for a high percentage of mortality in patients with diabetes mellitus (DM). Endothelial dysfunction is the initial and role step for the pathogenesis of DVCs. Hyperglycemia and lipid metabolism disorders contribute to endothelial dysfunction via direct injury of metabolism products, crosstalk between immunity and inflammation, as well as related interaction network. Although physiological and phenotypic differences support their specified changes in different targeted organs, there are still several common mechanisms underlying DVCs. Also, inhibitors of these common mechanisms may decrease the incidence of DVCs effectively. Thus, this review may provide new insights into the possible measures for the secondary prevention of DM. And we discussed the current limitations of those present preventive measures in DVCs research. Video Abstract.

Timely treatment and higher compliance to traditional Chinese medicine: New influencing factors for reducing severe COVID-19 based on retrospective cohorts in 2020 and 2021.

OBJECTIVE: From the beginning of 2020, our study team formulated a traditional Chinese medicine (TCM) prescription named Sanhanhuashi formula (SHHS) to treat COVID-19 patients. Then we conducted several studies to explore the effectiveness of SHHS formula and other influencing factors on prognosis of disease. The purpose of this study was to describe the trends of patients' characters from 2020 to 2021 based on two separate cohorts, and to explore the influencing factors on incidence of severe COVID-19 conditions, especially the contributions of timely treatment and higher compliance to SHHS formula. METHODS: A retrospective cohort study was conducted in Wuhan, Hubei province and Tonghua, Jilin province. Participants were hospitalized mild to moderate COVID-19 consecutive enrolled patients in Wuhan hospital of traditional Chinese and western medicine (from Feb 13, 2020 to March 8, 2020) and Tonghua central hospital (from Jan 17, 2021 to Feb 5, 2021). Age, sex, time waiting to be hospitalized, medical history, initial symptoms, concomitant medication, and severity of disease were collected. Univariate and multivariate logistic regression were used to explore the associations between various exposures and the outcome, ie. the proportion of patients who were converted to severe status. E-values and its lower control limit (LCL) were calculated for sensitivity analysis. RESULTS: Totally, 176 COVID-19 patients in two hospitals were enrolled. 81 patients were from Wuhan hospital of traditional Chinese and western medicine and 95 from Tonghua central hospital. 42 patients used SHHS formula arrival or exceed 7 days, and 2 (4.8%) progressed to severe condition. Among 134 patients who were exposed SHHS less than 7 days, 18 (13.4%) were converted to severe situation. Compared with those diagnosed in 2020, cases in 2021 were characterized as lower rates of initial symptoms (88.9% vs 35.8%, P < 0.001) and concomitant medications ever widely used, eg. antiviral medicine (71.6% vs 43.2%, P < 0.001), antibiotics (61.7% vs 13.7%, P < 0.001) and Chinese patent medicine (76.5% vs 44.2%, P < 0.001). They also waited less time for hospitalization (median: 12 vs 2 days, P < 0.001). The final multivariate logistic regression model showed that age (> 60 yrs) (OR: 3.943; 95% CI: 1.402-11.086; P = 0.009; E-value = 7.35, LCL:2.15), diagnosis year (OR: 0.165; 95% CI: 0.050-0.551; P = 0.003; E-value=11.6, LCL: 3.03) and SHHS exposure (OR: 0.118; 95% CI: 0.014-0.992; P = 0.049; E-value = 16.43, LCL:1.1) were independent risk factors for predicting severe status. CONCLUSIONS: The profile of COVID-19 patients has changed after one year. In addition to age, diagnosis year and SHHS exposure are two new factors to predict the prognosis of disease. The patients diagnosed in 2021 were mainly benefited from timely treatment. Subsequently, adhere to use SHHS formula a quite longer time reduced the number of severe cases. Therefore, both the current epidemic prevention and control measures and increasing compliance to traditional Chinese medicine are effective ways to reducing severe cases and improving public health.

Hanshiyi Formula, a medicine for Sars-CoV2 infection in China, reduced the proportion of mild and moderate COVID-19 patients turning to severe status: A cohort study.

We formulated a traditional Chinese medicine (TCM) prescription, Hanshiyi Formula (HSYF), which was approved and promoted by the Wuhan Municipal Health Commission for treating mild and moderate coronavirus disease 2019 (COVID-19). We aimed to evaluate the effect of HSYF on the progression to severe disease in mild and moderate COVID-19 patients. We conducted a retrospective cohort study of patients with mild and moderate COVID-19 in a quarantine station in Wuchang District, Wuhan. Using the real-time Internet information collection application and Centers for Disease Control for the Wuchang District, patient data were collected through patient self-reports and follow-ups. HSYF intervention was defined as the exposure. The primary outcome was the proportion of patients who progressed to a severe disease status, and a stratification analysis was performed. Univariate and multivariate regression analyses were performed to identify influencing factors that may affect the outcome. Further, we used propensity score matching (PSM) to assess the effect of HSYF intervention on the conversion of mild and moderate to a severe disease status. Totally, 721 mild and moderate COVID-19 patients were enrolled, including 430 HSYF users (exposed group) and 291 non-users (control group). No cases in the exposed group and 19 (6.5 %, P < 0.001) cases in the control group progressed to severe disease, and the difference between the two groups (exposed group-control group) was -6.5 % [95 % confidence interval (CI): (-8.87 %, -4.13 %)]. Univariate regression analysis revealed sex (male), age, fever, cough, and fatigue as risk factors for progression to severe disease. After PSM, none of the HSYF users and 7 (4.7 %, P = 0.022) non-users transitioned to severe disease, and the difference between the two groups (exposed group-control group) was -4.7 % [95 % CI: (-8.2 %, -1.2 %)]. Multivariate regression analysis revealed that sex (male) [OR: 3.145; 95 % CI: 1.036-9.545; P = 0.043] and age (> 48 years) [odds ratio (OR): 1.044; 95 % CI: 1.001-1.088; P = 0.044] were independent risk factors for conversion to severe disease. Therefore, HSYF can significantly reduce the progression to severe disease in patients with mild and moderate COVID-19, which may effectively prevent and treat the disease. However, further larger clinical studies are required to verify our results.

Evidence and potential mechanisms of traditional Chinese medicine for the treatment of type 2 diabetes: A systematic review and meta-analysis.

Traditional Chinese medicine (TCM) has recorded knowledge of diabetes for over 2000 years. Because a considerable number of TCM studies exhibit design defects, such as limited intervention duration, small sample sizes and inconsistent efficacy evaluations, the role of TCM in the treatment of diabetes cannot be fully elucidated. In this review, we evaluate randomized controlled trials of prediabetes, diabetes and diabetic complications published in the past decade. We found that TCM could significantly improve glucose control and clinical indices in patients with diabetes and effectively delay the progression of diabetes. We also summarize potential pharmacological mechanisms underlying the efficacy of TCM medication/herbs and their active ingredients for treating diabetes. More rigorously designed experiments and long-term evaluation of TCM for diabetes will allow for more effective diabetes management.

Innate Lymphoid Cells: A Link between the Nervous System and Microbiota in Intestinal Networks.

Innate lymphoid cells (ILCs) are a novel family of innate immune cells that act as key coordinators of intestinal mucosal surface immune defense and are essential for maintaining intestinal homeostasis and barrier integrity by responding to locally produced effector cytokines or direct recognition of exogenous or endogenous danger patterns. ILCs are also involved in the pathogenesis of inflammatory bowel disease (IBD). Many studies have demonstrated the occurrence of crosstalk between ILCs and intestinal microbiota, and ILCs have recently been shown to be connected to the enteric nervous system (ENS). Thus, ILCs may act as a key link between the nervous system and microbiota in intestinal networks. In this review, we briefly summarize the role of the ILCs in the intestinal tract (particularly in the context of IBD) and discuss the relationship between ILCs and the microbiota/ENS.

Intestinal Immunomodulatory Cells (T Lymphocytes): A Bridge between Gut Microbiota and Diabetes.

Diabetes mellitus (DM) is one of the most familiar chronic diseases threatening human health. Recent studies have shown that the development of diabetes is closely related to an imbalance of the gut microbiota. Accordingly, there is increasing interest in how changes in the gut microbiota affect diabetes and its underlying mechanisms. Immunomodulatory cells play important roles in maintaining the normal functioning of the human immune system and in maintaining homeostasis. Intestinal immunomodulatory cells (IICs) are located in the intestinal mucosa and are regarded as an intermediary by which the gut microbiota affects physiological and pathological properties. Diabetes can be regulated by IICs, which act as a bridge linking the gut microbiota and DM. Understanding this bridge role of IICs may clarify the mechanisms by which the gut microbiota contributes to DM. Based on recent research, we summarize this process, thereby providing a basis for further studies of diabetes and other similar immune-related diseases.

Investigation on Phenomics of Traditional Chinese Medicine from the Diabetes.

With thousands of years of application history, traditional Chinese medicine (TCM) has unique advantages in the prevention of various chronic diseases, and in recent years, the development of TCM has presented a situation where opportunities and challenges coexist. Phenomics is an emerging area of life science research, which has numerous similarities to the cognitive perspective of TCM. Thus, how to carry out the interdisciplinary research between TCM and phenomics deserves in-depth discussion. Diabetes is one of the most common chronic non-communicable diseases around the world, and TCM plays an important role in all stages of diabetes treatment, but the molecular mechanisms are difficult to elucidate. Phenomics research can not only reveal the hidden scientific connotations of TCM, but also provide a bridge for the confluence and complementary between TCM and Western medicine. Facing the challenges of the TCM phenomics research, we suggest applying the State-target theory (STT) to overall plan relevant researches, namely, focusing on the disease development, change trends, and core targets of each stage, and to deepen the understanding of TCM disease phenotypes and the therapeutic mechanisms of herbal medicine. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00146-6.

Multiomics Analyses With Stool-Type Stratification in Patient Cohorts and Blautia Identification as a Potential Bacterial Modulator in Type 2 Diabetes Mellitus.

Heterogeneity in host and gut microbiota hampers microbial precision intervention of type 2 diabetes mellitus (T2DM). Here, we investigated novel features for patient stratification and bacterial modulators for intervention, using cross-sectional patient cohorts and animal experiments. We collected stool, blood, and urine samples from 103 patients with recent-onset T2DM and 25 healthy control subjects (HCs), performed gut microbial composition and metabolite profiling, and combined it with host transcriptome, metabolome, cytokine, and clinical data. Stool type (dry or loose stool), a feature of the stool microenvironment recently explored in microbiome studies, was used for stratification of patients with T2DM as it explained most of the variation in the multiomics data set among all clinical parameters in our covariate analysis. T2DM with dry stool (DM-DS) and loose stool (DM-LS) were clearly differentiated from HC and each other by LightGBM models, optimal among multiple machine learning models. Compared with DM-DS, DM-LS exhibited discordant gut microbial taxonomic and functional profiles, severe host metabolic disorder, and excessive insulin secretion. Further cross-measurement association analysis linked the differential microbial profiles, in particular Blautia abundances, to T2DM phenotypes in our stratified multiomics data set. Notably, oral supplementation of Blautia to T2DM mice induced inhibitory effects on lipid accumulation, weight gain, and blood glucose elevation with simultaneous modulation of gut bacterial composition, revealing the therapeutic potential of Blautia. Our study highlights the clinical implications of stool microenvironment stratification and Blautia supplementation in T2DM, offering promising prospects for microbial precision treatment of metabolic diseases.

Double-blinded, randomized clinical trial of Gegen Qinlian decoction pinpoints Faecalibacterium as key gut bacteria in alleviating hyperglycemia.

Background: Accumulating evidence suggests that metabolic disorders, including type 2 diabetes mellitus (T2DM), can be treated with traditional Chinese medicine formulas, such as the Gegen Qinlian decoction (GQD). This study elucidates the mechanisms by which gut microbes mediate the anti-diabetic effects of GQD. Methods: We conducted a double-blind randomized clinical trial involving 120 untreated participants with T2DM. During the 12-week intervention, anthropometric measurements and diabetic traits were recorded every 4 weeks. Fecal microbiota and serum metabolites were measured before and after the intervention using 16S rDNA sequencing, liquid chromatography-mass spectrometry, and Bio-Plex panels. Results: Anti-diabetic effects were observed in the GQD group in the human trial. Specifically, glycated hemoglobin, fasting plasma glucose, and two-hour postprandial blood glucose levels were significantly lower in the GQD group than in the placebo group. Additionally, Faecalibacterium was significantly enriched in the GQD group, and the short-chain fatty acid levels were higher and the serum inflammation-associated marker levels were lower in the GQD group compared to the placebo group. Moreover, Faecalibacterium abundance negatively correlated with the levels of serum hemoglobin, fasting plasma glucose, and pro-inflammatory cytokines. Finally, the diabetes-alleviating effect of Faecalibacterium was confirmed by oral administration of Faecalibacterium prausnitzii (DSMZ 17677) in T2DM mouse model. Conclusions: GQD improved type 2 diabetes primarily by modulating the abundance of Faecalibacterium in the gut microbiota, alleviating metabolic disorders and the inflammatory state. Trial registration: Registry No. ChiCTR-IOR-15006626.

Efficacy and safety assessment of traditional Chinese medicine for erectile dysfunction: A meta-analysis and trial sequential analysis.

BACKGROUND: Several patients with erectile dysfunction do not accept or benefit from conventional therapy with phosphodiesterase type 5 inhibitors; thus, alternative and complementary therapies are in need. Traditional Chinese medicine has been treating erectile dysfunction in China, but its clinical value is inconclusive. OBJECTIVE: To systematically evaluate the efficacy and safety of traditional Chinese medicine in treating erectile dysfunction. METHODS: Randomized controlled trials were retrieved from a comprehensive search in the literature published in the past decade from the Web of Science, PubMed, Embase, Cochrane Library, SinoMed, China National Knowledge Internet, WanFang, and VIP. We performed a meta-analysis of the International Index of Erectile Function 5 questionnaire scores, clinical recovery rates, and testosterone levels using Review Manager 5.4 software. The trial sequential analysis was conducted to check the results. RESULTS: A total of 45 trials with 5016 patients were included. Meta-analysis results showed that traditional Chinese medicine effectively improved the International Index of Erectile Function 5 questionnaire scores (weighted mean difference = 3.78, 95% confidence interval: 3.12, 4.44; p < 0.001), clinical recovery rates (risk ratio = 1.57, 95% confidence interval: 1.38, 1.79; p < 0.001), testosterone levels (weighted mean difference = 2.42, 95% confidence interval: 1.59, 3.25; p < 0.001) compared with the controls. The single and add-on applications of traditional Chinese medicine could improve the International Index of Erectile Function 5 questionnaire score (p < 0.001). The trial sequential analysis confirmed the robustness of the analysis of the International Index of Erectile Function 5 questionnaire scores. A significant difference in the incidence of adverse effects between the treatment and control groups was not observed (risk ratio = 0.82, 95% confidence interval: 0.65, 1.05; p = 0.12). CONCLUSION: Traditional Chinese medicine can gain better responses in improving the International Index of Erectile Function 5 questionnaire scores, clinical recovery rates, and testosterone levels as an alternative and complementary treatment, with no increase in side effects. However, more standardized, long-term, traditional Chinese medicine and integrative therapy clinical trials are needed to support the clinical application of traditional Chinese medicine.

The mechanism of berberine alleviating metabolic disorder based on gut microbiome.

With socioeconomic advances and improved living standards, metabolic syndrome has increasingly come into the attention. In recent decades, a growing number of studies have shown that the gut microbiome and its metabolites are closely related to the occurrence and development of many metabolic diseases, and play an important role that cannot be ignored, for instance, obesity, type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), cardiovascular disease and others. The correlation between gut microbiota and metabolic disorder has been widely recognized. Metabolic disorder could cause imbalance in gut microbiota, and disturbance of gut microbiota could aggravate metabolic disorder as well. Berberine (BBR), as a natural ingredient, plays an important role in the treatment of metabolic disorder. Studies have shown that BBR can alleviate the pathological conditions of metabolic disorders, and the mechanism is related to the regulation of gut microbiota: gut microbiota could regulate the absorption and utilization of berberine in the body; meanwhile, the structure and function of gut microbiota also changed after intervention by berberine. Therefore, we summarize relevant mechanism research, including the expressions of nitroreductases-producing bacteria to promote the absorption and utilization of berberine, strengthening intestinal barrier function, ameliorating inflammation regulating bile acid signal pathway and axis of bacteria-gut-brain. The aim of our study is to clarify the therapeutic characteristics of berberine further and provide the theoretical basis for the regulation of metabolic disorder from the perspective of gut microbiota.

Research status and trends of the diabetic cardiomyopathy in the past 10 years (2012-2021): A bibliometric analysis.

Background: Diabetic cardiomyopathy is one of the most life-threatening diabetic complications. However, the previous studies only discuss a particular aspect or characteristic of DCM, the current state and trends were explored by limited research. We aimed to perform a systemically bibliometric study of DCM research progress status in the past decade, visualize the internal conceptual structure and potential associations, and further explore the prospective study trends. Methods: Articles related to DCM published from January 2012 to December 2021 were collected in the Web of Science core collection (WoSCC) database on June 24, 2022. We exported all bibliographic records, including titles, abstracts, keywords, authorship, institutions, addresses, publishing sources, references, citation times, and year of publication. In addition, the journal Impact Factor and Hirsch index were obtained from the Journal Citation Report. We conducted the data screening, statistical analysis, and visualization via the Bibliometrix R package. VOS viewer software was employed to generate the collaboration network map among countries and institutions for better performance in visualization. Results: In total, 1,887 original research articles from 2012 to 2021 were identified. The number of annual publications rapidly increased from 107 to 278, and a drastic increase in citation times was observed in 2017-2019. As for global contributions, the United States was the most influential country with the highest international collaboration, while China was the most productive country. Professor Cai Lu was the most prolific author. Shandong University published the most articles. Cardiovascular Diabetology journal released the most DCM-related articles. "Metabolic Stress-induced Activation of FoxO1 Triggers Diabetic Cardiomyopathy in Mice" Battiprolu PK et al., J Clin Invest, 2012. was the most top-cited article regarding local citations. The top three keywords in terms of frequency were apoptosis, oxidative stress, and fibrosis. The analysis of future topic trends indicated that "Forkhead box protein O1," "Heart failure with preserved ejection fraction," "Dapagliflozin," "Thioredoxin," "Mitochondria dysfunction," "Glucose," "Pyroptosis," "Cardiac fibroblast" and "Long non-coding RNA" could be promising hotspots. Conclusion: This study provides meaningful insights into DCM, which is expected to assist cardiologists and endocrinologists in exploring frontiers and future research directions in the domain through a refined and concise summary.

Inflammation-Related Epigenetic Modification: The Bridge Between Immune and Metabolism in Type 2 Diabetes.

T2DM, as a typical metabolic inflammatory disease, is under the joint regulation of environmental factors and genetics, combining with a variety of epigenetic changes. Apart from epigenetic changes of islet ß cells and glycometabolic tissues or organs, the inflammation-related epigenetics is also the core pathomechanism leading to ß-cell dysfunction and insulin resistance. In this review, we focus on the epigenetic modification of immune cells' proliferation, recruitment, differentiation and function, providing an overview of the key genes which regulated by DNA methylation, histone modifications, and non-coding RNA in the respect of T2DM. Meanwhile, we further summarize the present situation of T2DM epigenetic research and elucidate its prospect in T2DM clinical diagnosis and treatment.

Effect of natural polyphenols in Chinese herbal medicine on obesity and diabetes: Interactions among gut microbiota, metabolism, and immunity.

With global prevalence, metabolic diseases, represented by obesity and type 2 diabetes mellitus (T2DM), have a huge burden on human health and medical expenses. It is estimated that obese population has doubled in recent 40 years, and population with diabetes will increase 1.5 times in next 25 years, which has inspired the pursuit of economical and effective prevention and treatment methods. Natural polyphenols are emerging as a class of natural bioactive compounds with potential beneficial effects on the alleviation of obesity and T2DM. In this review, we investigated the network interaction mechanism of "gut microbial disturbance, metabolic disorder, and immune imbalance" in both obesity and T2DM and systemically summarized their multiple targets in the treatment of obesity and T2DM, including enrichment of the beneficial gut microbiota (genera Bifidobacterium, Akkermansia, and Lactobacillus) and upregulation of the levels of gut microbiota-derived metabolites [short-chain fatty acids (SCFAs)] and bile acids (BAs). Moreover, we explored their effect on host glucolipid metabolism, the AMPK pathway, and immune modulation via the inhibition of pro-inflammatory immune cells (M1-like Mϕs, Th1, and Th17 cells); proliferation, recruitment, differentiation, and function; and related cytokines (TNF-α, IL-1ß, IL-6, IL-17, and MCP-1). We hope to provide evidence to promote the clinical application of natural polyphenols in the management of obesity and T2DM.

Effectiveness and safety analysis of SanHanHuaShi granules for the treatment of coronavirus disease 2019: Study protocol and statistical analysis plan for a randomized, parallel-controlled, open-label clinical trial.

Background: Coronavirus disease 2019 (COVID-19) was declared a global pandemic in March 2020 by the World Health Organization (WHO). As of July 2, 2022, COVID-19 has caused more than 545 million infections and 6.3 million deaths worldwide, posing a significant threat to human health. Currently, there is still a lack of effective prevention and control strategies for the variation and transmission of SARS-CoV-2. Traditional Chinese medicine (TCM), which has a unique theoretical system, has treated various conditions for thousands of years. Importantly, recent studies have revealed that TCM contributed significantly to COVID-19. SanHanHuaShi (SHHS) granules, a Chinese herbal medicine, which has been included in Protocol for the Diagnosis and Treatment of Novel Coronavirus Disease 2019 (6th to 9th editions) issued by the National Health Commission of China and used to prevent and treat COVID-19 disease. A previous retrospective cohort study showed that SHHS could significantly reduce the severity of mild and moderate COVID-19. However, there is an absence of high-quality randomized controlled clinical studies to confirm the clinical effectiveness of SHHS. Therefore, a clinical study protocol and a statistical analysis plan were designed to investigate the efficacy and safety of SHHS for the prevention and treatment of COVID-19. This study will increase the integrity and data transparency of the clinical research process, which is of great significance for improving the practical application of SHHS granules in the future. Methods and analysis: The study was designed as a 7-day, randomized, parallel controlled, open-label, noninferiority clinical trial of positive drugs. A total of 240 patients with mild and moderate COVID-19 will be enrolled and randomly assigned to receive SanHanHuaShi granules or LianHuaQingWen granules treatment in a 1:1 ratio. Disease classification, vital signs, SARS-CoV-2 nucleic acid testing, symptoms, medications, adverse events, and safety evaluations will be recorded at each visit. The primary outcome will be the clinical symptom recovery rate. Secondary outcomes will include the recovery time of clinical symptoms, negative conversion time of SARS-CoV-2 nucleic acid test negative conversion rate, hospitalization time, antipyretic time, rate of conversion to severe patients, and time and rate of single symptom recovery. Adverse incidents and safety assessments will be documented. All data will be analyzed using a predetermined statistical analysis plan, including our method for imputation of missing data, primary and secondary outcome analyses, and safety outcomes. Discussion: The results of this study will provide robust evidence to confirm the effectiveness and safety of SHHS in the treatment of COVID-19. Clinical Trial Registration: http://www.chictr.org.cn. Trial number: ChiCTR2200058080. Registered on 29 March 2022.

State-target strategy: a bridge for the integration of Chinese and Western Medicine.

The methods ofTraditional Chinese Medicine(TCM)'s diagnosis and treatment have undergone several changes. It is crucial to build a proper model which is capable to modernize TCM into a both standardized and individualized treatment. Tong xiao-lin proposed the state-target strategy to build a bridge for the integration of Chinese and Western medicine. It is a model based on modern medical disease concepts and using the method of TCM to balance the pathological states and adopting the achievements of pharmacology of Chinese medicine to focus on the disease targets, symptom targets, and biochemical indicator targets. The reconstruction of TCM diagnosis and treatment system for diabetes is a good example to demonstrate this theory. It could improve the clinical efficacy, support the scientific research, and reinforce the standardization of TCM.

Alleviation Effects of GQD, a Traditional Chinese Medicine Formula, on Diabetes Rats Linked to Modulation of the Gut Microbiome.

Gegen Qinlian Decoction (GQD) is a Chinese herbal medicine that has been reported to significantly decrease blood glucose levels, which is suggested to be related to interactions with the gut microbiota. However, the protective effect of GQD on intestinal barrier function with regard to its influence on the gut microbiota has not been explored to date. In this study, we investigated the role of the gut microbiota in mediating the hypoglycemic mechanism of GQD in type 2 diabetes mellitus (T2DM) rats induced by a single intraperitoneal injection of streptozotocin after 4 weeks of high-fat diet feeding. The T2DM rats were randomly allocated to receive GQD, metformin (Met), or saline for 12 consecutive weeks, and changes in metabolic parameters, intestinal barrier function, and inflammation were investigated. Gut microbiota was analyzed using 16S rRNA gene sequencing from fecal samples, and statistical analyses were performed to correlate microbiota composition with phenotypes of the T2DM rats. GQD administration decreased the levels of blood glucose and inflammatory cytokines, and increased the levels of tight junction proteins. Besides, GQD had a protective effect on islet function, restoring intestinal permeability, and inhibiting inflammation, as evidenced by increases in the levels of serum C-peptide, occludin, and claudin-1 in the colon, and also improved the expression of serum inflammatory factors. In addition, GQD regulated the structure of the gut microbiota by increasing the proportions of short-chain fatty acids-producing and anti-inflammatory bacteria, and decreasing the proportions of conditioned pathogenic bacteria associated with the diabetic phenotype. Overall, these findings suggest that GQD could ameliorate hyperglycemia and protect islet function by regulating the structure of the gut microbiota, thereby restoring intestinal permeability and inhibiting inflammation in T2DM rats. Our study thus suggests that the hypoglycemic mechanism of GQD is mediated by its modulation of the gut microbiota.

Potential Role of Natural Plant Medicine Cyclocarya paliurus in the Treatment of Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disease that has become increasingly prevalent worldwide. It poses a serious threat to human health and places a considerable burden on global social medical work. To meet the increasing demand for T2DM treatment, research on hypoglycemic drugs is rapidly developing. Cyclocarya paliurus (Batal.) Iljinskaja is a medicinal plant that grows in China. The leaves of C. paliurus contain polysaccharides, triterpenoids, and other chemical components, which have numerous health benefits. Therefore, the use of this plant has attracted extensive attention in the medical community. Over the past few decades, contemporary pharmacological studies on C. paliurus extracts have revealed that it has abundant biological activities. Multiple in vitro and in vivo experiments have shown that C. paliurus extracts are safe and can play a therapeutic role in T2DM through anti-inflammatory and antioxidation activities, and intestinal flora regulation. Its efficacy is closely related to many factors, such as extraction, separation, purification, and modification. Based on summarizing the existing extraction methods, this article further reviews the potential mechanism of C. paliurus extracts in T2DM treatment, and we aimed to provide a reference for future research on natural plant medicine for the prevention and treatment of T2DM and its related complications.

In silico network pharmacology and in vivo analysis of berberine-related mechanisms against type 2 diabetes mellitus and its complications.

ETHNOPHARMACOLOGICAL RELEVANCE: Berberine (BBR), extracted from the traditional medicinal plant Coptis chinensis Franch., has been widely used for the treatment of type 2 diabetes mellitus (T2DM) and its complications. AIM OF THE STUDY: To determine the potential pharmacological mechanisms underlying BBR therapeutic effect on T2DM and its complications by in silico network pharmacology and experimental in vivo validation. MATERIALS AND METHODS: A predictive network depicting the relationship between BBR and T2DM was designed based on information collected from several databases, namely STITCH, CHEMBL, PharmMapper, TTD, Drugbank, and PharmGKB. Identified overlapping targets related to both BBR and T2DM were crossed with information on biological processes (BPs) and molecular/signaling pathways using the DAVID platform and Cytoscape software. Three candidate targets identified with the BBR-T2DM network (RXRA, KCNQ1 and NR3C1) were evaluated in the C57BL/6J mouse model of T2DM. The mice were treated with BBR or metformin for 10 weeks. Weight, fasting blood glucose (FBG), oral glucose tolerance, and expression levels of the three targets were evaluated. RESULTS: A total of 31 targets of BBR that were also related to T2DM were identified, of which 14 had already been reported in previous studies. Furthermore, these 31 overlapping targets were enriched in 21 related BPs and 18 pathways involved in T2DM treatment. The identified BP-target-pathway network revealed the underlying mechanisms of BBR antidiabetic activity were mediated by core targets such as RXRA, KCNQ1, and NR3C1. In vivo experiments further confirmed that treatment with BBR significantly reduced weight and FBG and alleviated insulin resistance in T2DM mice. Moreover, BBR treatment promoted RXRA expression, whereas it reduced KCNQ1 and NR3C1 expression in the liver. CONCLUSION: Using network pharmacology and a T2DM mouse model, this study revealed that BBR can effectively prevent T2DM symptoms through vital targets and multiple signaling pathways. Network pharmacology provides an efficient, time-saving approach for therapeutic research and the development of new drugs.

Network Pharmacology and Experimental Assessment to Explore the Pharmacological Mechanism of Qimai Feiluoping Decoction Against Pulmonary Fibrosis.

Pulmonary fibrosis (PF) is one of the pathologic changes in COVID-19 patients in convalescence, and it is also a potential long-term sequela in severe COVID-19 patients. Qimai Feiluoping decoction (QM) is a traditional Chinese medicine formula recommended in the Chinese national medical program for COVID-19 convalescent patients, and PF is one of its indications. Through clinical observation, QM was found to improve the clinical symptoms and pulmonary function and reduce the degree of PF of COVID-19 convalescent patients. To further explore the pharmacological mechanisms and possible active components of QM in anti-PF effect, UHPLC/Q-TOF-MS was used to analyze the composition of the QM extract and the active components that can be absorbed into the blood, leading to the identification of 56 chemical compounds and 10 active components. Then, network pharmacology was used to predict the potential mechanisms and targets of QM; it predicted that QM exerts its anti-PF effects via the regulation of the epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) degradation, and TGF-ß signaling pathway. Finally, TGF-ß1-induced A549 cells were used to verify and explore the pharmacological effects of QM and found that QM could inhibit the proliferation of TGF-ß1-induced A549 cells, attenuate EMT, and promote ECM degradation by inhibiting the TGF-ß/Smad3 pathway.