Efficacy of scalp acupuncture combined with conventional therapy in the intervention of post-stroke depression: A systematic review and meta-analysis.

BACKGROUND: Post-stroke depression (PSD) is a common complication following a stroke, significantly impacting patients' quality of life and mental well-being. Currently, two primary approaches are employed to treat PSD: drug therapy and non-drug therapy. Among these, acupuncture, specifically scalp acupuncture (SA), has gained attention due to its cost-effectiveness and broad social benefits. SA is a precise and direct form of acupuncture that has been utilized in the treatment of PSD. Although several randomized controlled trials (RCTs) have demonstrated the efficacy of SA in treating PSD, there is a lack of comprehensive systematic reviews. Given the limitations of existing evidence, we conducted a systematic evaluation to assess the effectiveness of SA in combination with conventional therapy (CT) for intervening in PSD. METHODS: We systematically searched five databases for articles published up until May 31, 2023, pertaining to SA treatment of PSD. A team of researchers meticulously screened and assessed these articles to identify the final included studies. After extracting relevant information and outcome indicators from the selected articles, we employed RevMan5.3 software to evaluate their quality and perform statistical analysis. Throughout our research, we strictly adhered to the PRISMA 2020 guidelines. RESULTS: A total of 11 articles were included, and a meta-analysis was conducted to evaluate the effectiveness of SA combined with CT for treating PSD. The results revealed that SA combined with CT can effectively improve the treatment's success rate for PSD and reduce the severity of depressive symptoms measured by the Self-Rating Depression Scale. However, SA combined with CT did not show significant reductions in depressive symptoms assessed by the Hamilton Rating Scale for Depression, which may be related to the inclusion of high heterogeneity articles. Importantly, the combination treatment did not lead to an increase in adverse reactions among PSD patients. CONCLUSION: While the effectiveness of SA combined with CT in treating PSD still requires further validation through rigorous randomized double-blind trials, this study provides a comprehensive collection of studies that meet the criteria for SA combined with CT in PSD treatment. It objectively and systematically evaluated the impact of SA combined with CT on PSD. Consequently, the findings of this study hold certain clinical significance.

Huoxue Jiangtang Decoction Alleviates Type 2 Diabetes Mellitus by Regulating the Oral Microbiota and Food Preferences.

Purpose: As a formula of traditional Chinese medicine (TCM), Huoxue Jiangtang Decoction (HJD) has positive effects on diabetes mellitus (DM) through improving of the metabolism of glycolipid and the function of ß-cell. Hence, this research aims to explore the potential therapeutic effects of HJD on diabetes and reveal its underlying mechanisms. Methods: Diabetic rat models induced by high-fat diet (HFD) and streptozotocin (STZ) were included in this study. Following successful modeling, diabetic rats were treated with HJD, and then its therapeutic effects in eight weeks were evaluated. In addition to biochemical indicators, two-bottle preference tests were carried out to examine the rats' preferences for fat and sugar, and 16S rRNA gene sequencing was performed to disclose the differences of oral microbiota among groups. Finally, Pearson correlation coefficient was used to explore the correlation between oral microbiota and the preferences for fat and sugar. Results: It was found that HJD significantly improved the levels of fasting blood glucose (FBG), glucose tolerance, and dyslipidemia. Additionally, HJD contributed to decreasing preferences for fat and sugar in diabetic rats, which plays an important role in food intake. Furthermore, HJD regulated the abundance, distribution, and structure of oral microbiota in diabetic rats, serving as one of the underlying mechanisms of its antidiabetic effects. Conclusion: Taken with other formulas, HJD functions to improve the metabolism of glycolipid and the function of ß-cell by inhibiting preferences for fat and sugar, as well as regulating the oral microbiota of diabetic rats. Furthermore, a potential correlation between the oral micro-environment and preferences for fat and sugar in STZ-induced diabetic rats is likely to exist.

Association between caffeine intake and lumbar spine bone mineral density in adults aged 20-49: A cross-sectional study.

Background: Many epidemiological studies have investigated the connection between coffee intake and bone mineral density (BMD), but the results are controversial. This study aimed to assess the association between caffeine consumption and lumbar BMD in adults aged 20-49. Methods: From a cross-sectional study based on a large sample of the National Health and Nutrition Examination Survey 2011-2018. After controlling for confounders, the weighted multivariate linear regression model was created and stratified by age, gender, and race for subgroup analysis. In addition, we simultaneously stratified analysis by age and sex and divided caffeine intake into quartiles to assess the association between coffee intake and BMD. Results: Caffeine intake was not significantly linked with lumbar BMD in this study of 7041 adults. In subgroup studies stratified by age, there was a significant correlation between lumbar BMD and caffeine consumption in participants aged 30-39 and 40-49. In females, there was a positive correlation between lumbar BMD and coffee consumption stratified by gender. When evaluated by race, the association between lumbar BMD and caffeine intake was independent of race. Consequently, when stratifying for age, sex, and coffee intake quartiles, a significant positive correlation was discovered between the fourth coffee intake quartile and lumbar BMD in females aged 30-39. In addition, a negative correlation was discovered between coffee consumption and lumbar BMD in males aged 40-49. Conclusions: Our research indicates that drinking coffee may benefit 30-39 women's lumbar BMD, but it may adversely affect men aged 40-49.

Observation on clinical effect of Huoxue-Jiangtang decoction formula granules in treating prediabetes: a randomized prospective placebo-controlled double-blind trial protocol.

BACKGROUND: Prediabetes is a hypermetabolic syndrome with blood sugar levels falling between the normal and diabetes. People with prediabetes have a significantly increased chances of developing diabetes, cardiovascular and cerebrovascular diseases, tumors, dementia, and other diseases in the future when compared to the healthy population. However, prediabetes is mainly treated based on lifestyle intervention, currently without targeted drug treatment plan. Traditional Chinese medicine (TCM), which has a longstanding experience, has been shown in clinical studies to be effective for the treatment of diabetes and its related complications. Furthermore, different dosage forms such as decoction and granule have developed gradually in clinical application. Preliminary studies have found that Huoxue-Jangtang Decoction (HJD), with good hypoglycemic and lipid-regulating effects, is potentially one of the complementary and alternative treatments for prediabetes. Therefore, this project intends to perform a prospective clinical study to observe the clinical effectiveness of HJD on prediabetes and the consistency of the efficacy of formula granules and the elixation. METHODS: This is a prospective, randomized, double-blind, and placebo-controlled clinical trial. A total of 183 participants are randomly assigned to HJD Formula Granules plus lifestyle intervention, HJD Elixation plus lifestyle intervention, and placebo plus lifestyle intervention. All subjects undergo 1 day of screening before participating in the study, followed by 84 days of drug intervention and observation. During and after treatment, the main outcome measures include fasting blood glucose and 2-hour postprandial blood glucose. DISCUSSION: This research attempts to verify the clinical efficacy and possible mechanism of HJD in the treatment of prediabetes, and prove the consistency of HJD Formula Granules with HJD Elixation. This study also aims to provide a treatment that is both effective and safe for prediabetic patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: ChiCTR2200060813, Registered 12 June 2022.

Integrated microbiome-metabolomics analysis reveals the potential therapeutic mechanism of Zuo-Jin-Wan in ulcerative colitis.

BACKGROUND: Dysregulation in gut microbiota and host cometabolome contributes to the complicated pathology of ulcerative colitis (UC), while Zuo-Jin-Wan (ZJW), a traditional Chinese medicine has shown therapeutic effects against UC with its underlying mechanism remains elusive. PURPOSE: This study utilized an integrated analysis combining gut microbiome and host cometabolism to disclose the potential therapeutic mechanism of ZJW on dextran sulfate sodium (DSS)-induced UC in rats. METHODS: We first evaluated the therapeutic effects of ZJW treatment in DSS-induced rat model. 16S rRNA sequencing, 1H NMR spectroscopy-based metabolomics and Spearman correlation analysis were conducted to explore the potential therapeutic mechanism during the treatment. RESULTS: Our results showed that UC symptoms in ZJW rats were significantly attenuated. Marked decline in microbial diversity in ZJW group was accompanied by its correspondent function adjustment. Specific enrichment of genus Bacteroides, Sutterella, Akkermansia and Roseburia along with the major varying amino acid metabolism and lipid metabolism were observed meantime. Metabolic data further corroborated that ZJW-related metabolic changes were basically gathered in amino acid metabolism, carbohydrate/energy metabolism and lipid metabolism. Of note, some biochemical parameters were deeply implicated with the discriminative microbial genera and metabolites involved in tricarboxylic acid (TCA) cycle and amino acid metabolism, indicating the microbiome-metabolome association in gut microbiota-metabolite-phenotype axis during UC treatment of ZJW. CONCLUSION: For the first time, integrated microbiome-metabolome analysis depicted that ZJW could alleviate DSS-induced UC in rats via a crosstalk between gut microbiota and host cometabolites.

Effects and Mechanism of Zishen Jiangtang Pill on Diabetic Osteoporosis Rats Based on Proteomic Analysis.

OBJECTIVE: To explore the effect and mechanism of ZJP on DOP rats by proteomic analysis. MATERIALS AND METHODS: After the establishment of diabetes model by Streptozocin (STZ, 60 mg/kg), 40 Wistar rats were equally divided into normal group, model group (diabetic rats), high-dose group (3.0 g/kg/d ZJP), and low-dose group (1.5 g/kg/d ZJP) and received treatment for 3 months. Histological changes in bone and pancreas tissues were observed by hematoxylin and eosin staining, electron microscopy, and immunofluorescence. Proteomic and bioinformatic analyses were performed to identify the differentially expressed proteins. The fingerprint and active ingredients of ZJP were identified via high-performance liquid chromatography (HPLC). RESULTS: Compared with the model group, ZJP could rescue the weight, fasting blood glucose, and fasting insulin of rats in both high-dose and low-dose group. ZJP could also improve the microstructures of pancreatic islet cells, bone mass, and trabecular and marrow cavities in DOP rats. Bioinformatic analysis suggested that ZJP might influence DOP via multiple pathways, mainly including ribosomes, vitamin digestion and absorption, and fat digestion and absorption. The primary active ingredients, including notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, icariin, and ginsenoside Rb1, were detected. CONCLUSION: ZJP could significantly improve the histomorphology and ultrastructure of bone and islets tissues and might serve as an effective alternative medicine for the treatment of DOP.

Exploring the Molecular Mechanism of Liuwei Dihuang Pills for Treating Diabetic Nephropathy by Combined Network Pharmacology and Molecular Docking.

BACKGROUND: Diabetic nephropathy (DN) is a common and serious complication of diabetes, but without a satisfactory treatment strategy till now. Liuwei Dihuang pills (LDP), an effective Chinese medicinal formula, has been used to treat DN for more than 1000 years. However, its underlying mechanism of action is still vague. METHODS: Active compounds and corresponding targets of LDP were predicted from the TCMSP database. DN disease targets were extracted from the OMIM, GeneCards, TTD, DisGeNET, and DrugBank databases. Subsequently, the "herbal-compound-target" network and protein-protein interaction (PPI) network were constructed and analyzed via the STRING web platform and Cytoscape software. GO functional and KEGG pathway enrichment analyses were carried out on the Metascape web platform. Molecular docking utilized AutoDock Vina and PyMOL software. RESULTS: 41 active components and 186 corresponding targets of LDP were screened out. 131 common targets of LDP and DN were acquired. Quercetin, kaempferol, beta-sitosterol, diosgenin, and stigmasterol could be defined as five crucial compounds. JUN, MAPK8, AKT1, EGF, TP53, VEGFA, MMP9, MAPK1, and TNF might be the nine key targets. The enrichment analysis showed that common targets were mainly associated with inflammation reaction, oxidative stress, immune regulation, and cell apoptosis. AGE-RAGE and IL-17 were the suggested two significant signal pathways. Molecular docking revealed that the nine key targets could closely bind to their corresponding active compounds. CONCLUSION: The present study fully reveals the multicompound's and multitarget's characteristics of LDP in DN treatment. Furthermore, this study provides valuable evidence for further scientific research of the pharmacological mechanisms and broader clinical application.

Effects of HuoxueJiangtang decoction alone or in combination with metformin on renal function and renal cortical mRNA expression in diabetic nephropathy rats.

CONTEXT: HuoxueJiangtang decoction (ZY) is a traditional Chinese medicine for the treatment of diabetes. OBJECTIVE: The protective effect of ZY on renal injury in diabetic nephropathy rats was investigated in this study. MATERIALS AND METHODS: Fifty 4-week-old SPF Wistar male rats were selected to construct diabetic nephropathy model rats (DN) group by continuous high-fat feeding for 4 weeks, followed by a tail vein injection of 30 mg/kg streptozotocin for 1 week. The experimental rats were divided into six groups of 10 rats: normal (control), DN, DN + ZY, DN + metformin, DN + metformin + ZY, and DN + metformin + captopril (positive control) groups. Among the groups, 6.25 g/kg ZY, 250 mg/kg metformin, and 17.5 mg/kg captopril were given to the rats by gavage once a day for 16 weeks. Blood glucose, dietary behaviour, biochemical indicators, and gene expression changes were measured in each group. RESULTS: Metformin + ZY treatment significantly lowered blood glucose, water intake, urine total protein, urine albumin, urine volume, serum triglyceride, and serum cholesterol levels in the DN group. The pathological changes of kidney tissue showed that the DN + metformin + ZY group had a protective effect on kidney tissue damage. And ZY and metformin + ZY treatments repaired the expression of genes in the DN group. DISCUSSION AND CONCLUSION: The ZY and metformin combined treatment showed a clear therapeutic effect on kidney damage in DN. This study provides a potential mechanism for the treatment of diabetic nephropathy with ZY combined with metformin.

Shenling Baizhu San improves functional dyspepsia in rats as revealed by 1H-NMR based metabolomics.

Functional dyspepsia (FD), a common gastrointestinal disorder around the world, is driven by multiple factors, making prevention and treatment a major challenge. Shenling Baizhu San (SBS), a classical prescription of traditional Chinese medicine, has been proven to be effective in gastrointestinal disorders. However, studies on SBS improving FD are few. Thus, our study aimed to evaluate the effect of SBS on FD and further to explore the mechanism underlying the interactions between FD and SBS by the metabolomics approach. A FD rat model was induced by multiple forms of mild stimulation, and proton nuclear magnetic resonance (1H-NMR) spectroscopy and multivariate data analysis were used to profile the fecal and urinary metabolome in the FD rats during SBS intervention. Significant dyspeptic symptoms such as weight loss, poor appetite, reduced gastrointestinal motility and decreased absorptive capacity were observed in the FD rats, which were subsequently improved by SBS. Additionally, the levels of citrate, branched chain acids and pyruvate decreased, and the levels of choline, trimethylamine and taurine increased in the FD rats. Furthermore, the metabolic disorders were amended with SBS intervention mainly by modulating the metabolic pathways involved in energy metabolism, amino acid metabolism, and gut microbiota and host co-metabolism. Overall, our study highlighted the effect of SBS on the disturbed metabolic pathways in the FD rats, providing new insight into the mechanism of SBS treatment for FD from the perspective of metabolomics.

Untargeted metabolomics analysis on Cicer arietinium L.-Induced Amelioration in T2D rats by UPLC-Q-TOF-MS/MS.

ETHNOPHARMACOLOGICAL RELEVANCE: Cicer arietinium L., which belongs to Cicer genus, was not only a kind of traditional Chinese medicines (TCM) recorded in Pharmacopoeia of the People's Republic of China (version 2015), but also a kind of Uighur antidiabetic medicines. It has been used as an adjuvant drug or functional food for thousand years in Xinjiang province, China. However, the mechanisms of C. arietinium treatment in T2D have not been fully understood especially on the perspective of metabolomics. AIM OF THE STUDY: To clarify the potential mechanisms of C. arietinium treatment in T2D from the perspective of metabolomics since T2D is indeed a kind of metabolic syndromes. MATERIALS AND METHODS: T2D rat model was built by HFD for 4 weeks, combining with STZ administration. T2D rats were administrated C. arietinium extraction or metformin (positive control) for 4 weeks. UPLC-Q-TOF-MS was applied to screen and identify differential metabolites among groups. RESULTS: After 4 weeks of treatments, IR and inflammation were greatly ameliorated in C. arietinium group. And the therapeutic efficiency of C. arietinium treatment was comparable to metformin treatment. Differential metabolites related to C. arietinium treatment, including acylcarnitines, amino acid related metabolites and organic acids, were further used to indicate relevant pathways in T2D rats, including glyoxylate and dicarboxylate metabolism, tricarboxylic acid cycle, vitamin B6 metabolism and energy metabolism. CONCLUSIONS: In summary, C. arietinium treatment could effectively alleviate diabetic symptoms and regulate metabolic disorders in T2D rats.

Effects of Hydroxysafflor Yellow A on the PI3K/AKT Pathway and Apoptosis of Pancreatic ß-Cells in Type 2 Diabetes Mellitus Rats.

BACKGROUND AND AIM: Type 2 diabetes mellitus (T2DM), a complex metabolic disease, has become a major public health issue around the world. Hydroxysafflor yellow A (HSYA) is the major active chemical ingredient of Carthamus tinctorius L. (safflower), which is widely used in patients with cardiovascular and cerebrovascular diseases in China. The aim of this study was to investigate the anti-diabetic effect and potential mechanism of HSYA on the high-fat diet (HFD) and streptozotocin (STZ-)-induced T2DM rats. MATERIALS AND METHODS: T2DM rats were induced by feeding HFD (60% fat) for four weeks followed by intraperitoneal injection of a low dose of streptozocin (35mg/kg). The T2DM rats were treated with HSYA (120mg/kg) or metformin (90mg/kg) for eight weeks. Biochemical analysis, histological analysis and Western blot analysis were conducted after 8 weeks of intervention. RESULTS: The treatment with HSYA evidently reduced fasting-blood glucose and insulin resistance in T2DM rats, indicated by results from fasting-blood glucose, oral glucose tolerance test, fasting insulin levels and histology of pancreas islets. The Western blot results revealed that HSYA reversed the down-regulation of PI3K and AKT in liver. The TUNEL assay analysis of pancreatic tissue showed that HSYA could inhibit the apoptosis of pancreatic ß-cells to a certain extent. Moreover, HSYA-treatment increased the levels of glycogen synthase and hepatic glycogen and improved lipid metabolism by reducing the triglyceride, total and low-density lipoprotein cholesterol levels, even though it did not change the rats' body weights. CONCLUSION: The results of this study suggested that HSYA could promote PI3K/Akt activation and inhibit the apoptosis of pancreatic ß-cells directly or indirectly, which might be the underlying mechanisms in HSYA to improve insulin resistance and regulate glycolipid metabolism in T2DM rats.

Acupuncture as adjuvant therapy for diabetic foot: A protocol for systematic review.

BACKGROUND: Diabetic foot (DF) problems are common throughout the world, about one-fourth of them develop a foot ulcer and serious cases would suffer from amputation, which seriously affects the patient's work and life. Previous studies indicated that acupuncture as adjuvant therapy would be effective in treating DF. However, these studies have no consistent results. Therefore, the aim of our study was to explore the efficacy and safety of acupuncture as adjuvant therapy for DF. METHODS: The randomized controlled trials associated with acupuncture therapy (or as adjuvant therapy) for DF will be included. We will search 6 electronic databases relevant to health sciences, including PubMed, Embase, the Cochrane Library, the Chinese databases Sino-Med, CNKI, and WANFANG database. All searches were from databases inception to March 30, 2019. The primary outcomes are the total curative effective rate, and the hemodynamic parameter and adverse events will be deemed as secondary outcomes. The Stata15.1 software and Review Manager (RevMan 5.3; Cochrane Collaboration, Copenhagen, Denmark) will be used for analysis, to assess the bias risk, subgroup analysis, and data synthesis. RESULTS: In this systematic review and meta-analysis, we will synthesize the studies to assess the safety and efficacy of acupuncture as adjuvant therapy for DF. CONCLUSION: The summary of our study will clarify whether acupuncture as adjuvant therapy could be an efficient method for DF.

Berberine ameliorates colonic damage accompanied with the modulation of dysfunctional bacteria and functions in ulcerative colitis rats.

Intestinal flora imbalance is one of the potential pathogenesis of inflammatory bowel diseases, and the study aims to discover the effect of berberine on the composition and function of gut microbiota in ulcerative colitis (UC) rats. UC rats were induced by dextran sulfate sodium (DSS) and administrated with berberine. Colonic morphological changes and claudin-1 protein of colon tissues were primarily examined to validate the protective effects brought by berberine treatment. Then the composition and function of gut microbiota were analyzed, accompanied with quantitative analysis of serum amino acids. The results showed that berberine could not only ameliorate the colonic damages in DSS-induced UC rats but also regulate the gut microbiota by increasing lactic acid-producing bacteria and carbohydrate hydrolysis bacteria as well as decreasing conditional pathogenic bacteria. Accordingly, the relevant functions of above bacteria were improved, including the metabolism and biosynthesis of amino acids, capability of DNA replication and repair, carbohydrate digestion and absorption and glycolysis/gluconeogenesis. Furthermore, the serum amino acids were regulated and showed high correlation with the gut microbiota after berberine treatment. In conclusion, the study confirms the effect of berberine on ameliorating the colonic damage and highlights some specific bacteria and relevant functions linked with berberine treatment, exploring the potential of gut microbiota as a diagnostic biomarker or a therapeutic target in UC treatment.

LC-MS-based metabolomics analysis of Berberine treatment in ulcerative colitis rats.

Inflammatory bowel disease (IBD) is often accompanied by metabolic imbalance and Berberine can relieve the symptoms of IBD, but the mechanism is still unclear. To explore the relationship between IBD, metabolism and Berberine, dextran sulfate sodium-induced ulcerative colitis (UC) model was built and urine and feces samples were analyzed with ultra-performance liquid chromatography combined with quadrupole-time-of-flight mass spectrometry, followed by multivariate statistical analyses. Targeted metabolomics was applied to verify and supplement the result of amino acids tested by non-targeted metabolomics. The study found that Berberine could ameliorate UC and improve metabolic disorders. The level of 4 metabolites increased and 35 decreased in urine and these metabolites mainly belong to amino acid, glucide, organic acid and purine. Besides, Berberine could reduce the level of 5 metabolites and raise the level of 7 metabolites in feces, which mainly belong to amino acid and lipid. Additionally, these altered metabolites were mainly related to amino acids metabolism, purine metabolism, vitamin metabolism, lipid metabolism and citrate cycle pathways. Furthermore, microbiome metabolism may be regulated by Berberine in UC. In general, this study provides a useful approach for exploring the mechanism of Berberine in the treatment of UC from the perspective of metabolomics.

Shen-Ling-Bai-Zhu-San alleviates functional dyspepsia in rats and modulates the composition of the gut microbiota.

The pathogenesis of functional dyspepsia (FD) is multifactorial, and the gut microbiota may play a significant role. Shen-Ling-Bai-Zhu-San (SLBZS), a traditional Chinese herbal medicine, has been widely used in the treatment of FD, and appears to influence the gut microbiota. Therefore, we hypothesized that SLBZS would alleviate dyspeptic symptoms by adjusting the composition of the gut microbiota. To test this hypothesis, we aimed to evaluate the effects of SLBZS on FD and elucidate the mechanism that underlies the interactions between gut microbiota and FD during SLBZS treatment. We employed a rat model of FD induced by multiple forms of chronic mild stimulation. 16S rRNA gene sequencing and shotgun metagenomic sequencing were used to analyze the microbial communities in fecal samples from the rats. We found that the SLBZS improved dyspeptic symptoms in FD rats, such as weight loss, decreased intestinal motility, reduced absorptive capacity. Moreover, the SLBZS treatment reversed gut dysbiosis in FD. With SLBZS treatment, FD biomarkers including Prevotella, Mucispirillum and Akkermansia were decreased while SCFA-producing bacteria such as Adlercreutzia and Clostridium, and sulfate-reducing bacteria Desulfovibrio were enriched. Additionally, SLBZS normalized the dysregulated function of the microbiome, upregulating the pathways of energy metabolism and decreasing the oxidative stress as well as bacterial pathogenesis. Our study demonstrated that SLBZS could ameliorate dyspepsia, and amend the dysregulated composition and function of the gut microbial community, providing insight into the mechanism of SLBZS treatment for FD from the perspective of gut microbiota.

Zengye decoction induces alterations to metabolically active gut microbiota in aged constipated rats.

Zengye decoction (ZYD), a traditional Chinese medicinal formula, has been used in the treatment of various chronic diseases, such as constipation and skin dryness syndrome. Clinically, the specific mechanisms and targets of ZYD for treating disease remain unclear. The present study was undertaken to investigate the effects of ZYD on the gut microbiota and host metabolites in aged constipated rats and the relationship between the intestinal microbiota and the host. Rats were divided randomly into three groups, the control group (n = 10), recovery group (n = 10) and ZYD group (n = 10). First, the aged constipation model was established for the ZYD group and recovery group. Then, rats in the ZYD group were treated with ZYD. Urinary and faecal samples of each animal were collected in microcentrifuge tubes. Next, 16s rRNA gene sequencing was employed to analyse the composition of the gut microbiome in faecal samples and afterwards the metabolic function of the altered gut microbiota was predicted. Additionally, 1H NMR profiling was used to detect the alterations of host metabolites in urine and faecal samples to verify the metabolic function results obtained from sequencing. As a result, ZYD reduced the level of harmful bacteria, such as Desulfovibrio, Ruminococcus, Prevotella and Dorea, and increased the abundance of Oxalobacter, Clostridium and Roseburia. The functional prediction of changes in the gut microbiota induced by ZYD revealed that ZYD promoted energy storage, regulated amino acid metabolism, inhibited methane metabolism, strengthened the physiological function of glutathione and reduced bacterial toxin. The 1H NMR profiles revealed that ZYD regulated the carbohydrates, short chain fatty acids, amino acids and amines in the aged constipated rats. In addition, most metabolic changes observed were related to the function of intestinal microbiota. These results suggest that ZYD can regulate the intestinal microbiota of constipated rats to normal levels and change the endogenous metabolites of the host through the intestinal microbiota to achieve therapeutic effects.

The efficacy of oral Zhizhu Kuanzhong, a traditional Chinese medicine, in patients with postprandial distress syndrome.

BACKGROUND AND AIM: The treatment of patients with functional dyspepsia (FD) remains unsatisfactory. We assessed the efficacy of Zhizhu Kuanzhong (ZZKZ) capsule, a traditional Chinese medicine formula, in patients with postprandial distress syndrome (PDS) of FD. METHODS: The study was designed as a multicenter, randomized, double-blinded, controlled clinical trial. Three-hundred ninety-two patients with PDS defined by Rome III criteria from 16 centers in China were randomly assigned to receive either ZZKZ or placebo. The proportion of the responders at 4 weeks after randomization was considered primary endpoint. Secondary endpoint was the symptom score reduction of each dyspeptic symptom relative to the baseline at 4 weeks after randomization in all subjects. RESULTS: In terms of the primary endpoint, the proportion of the responders concerning the composite PDS symptom score was 38.8% and 54.7% in placebo group and ZZKZ group, respectively (P = 0.003), in per protocol analysis at 4 weeks after randomization. Concerning the individual evaluated upper gastrointestinal symptoms, only postprandial fullness and early satiety showed significant difference in symptom score reduction at 4 weeks after randomization between placebo and ZZKZ groups. CONCLUSIONS: Zhizhu Kuanzhong is superior to placebo in the treatment of PDS with FD. The exact mechanisms by which ZZKZ improves symptoms remain to be established (http://www.chictr.org.cn/ChinCTR-TRC-14004714).

Huang-Lian-Jie-Du-Decoction Ameliorates Hyperglycemia and Insulin Resistant in Association With Gut Microbiota Modulation.

Background: Huang-Lian-Jie-Du-Decoction (HLJDD), a prescription of traditional Chinese medicine, has been clinically used to treat diabetes for thousands of years and its mechanism was reported to be related to gut microbiota. However, no study has explored the effect of HLJDD on the gut microbiota in type 2 diabetes mellitus (T2DM) yet. Therefore, in this study, we investigated the modulation of gut microbiota induced by HLJDD treatment in T2DM in order to unveil the underlying mechanism. Methods: A combination of high-fat diet (HFD) and streptozotocin (STZ) was used to induce T2DM in rats. Bacterial communities in the fecal samples from the control group, the T2DM model group, and the HLJDD-treated T2DM group were analyzed by 16S gene sequencing, followed with a subset sample analyzed by shotgun sequencing. Results: The HLJDD treatment significantly ameliorated hyperglycemia and inflammation in T2DM rats. Additionally, our results indicated that HLJDD treatment could not only restore the gut dysbiosis in T2DM rats, which was proved by an increasing amount of short chain fatty acids (SCFAs)-producing and anti-inflammatory bacteria such as Parabacteroides, Blautia, and Akkermansia as well as a decreasing amount of conditioned pathogenic bacteria (e.g., Aerococcus, Staphylococcus, and Corynebacterium), but also modulate the dysregulated function of gut microbiome in T2DM rats, including an up-regulation in bile acid biosynthesis as well as a reduction in glycolysis/gluconeogenesis and nucleotide metabolism. Conclusion: HLJDD treatment could ameliorate hyperglycemia and restore the dysregulated microbiota structure and function to a normal condition mainly by increasing SCFAs-producing bacteria and reducing conditioned pathogenic bacteria in T2DM rats, which provides insights into the mechanism of HLJDD treatment for T2DM from the view of gut microbiota.

Carnosic acid regulates cell proliferation and invasion in chronic myeloid leukemia cancer cells via suppressing microRNA-708.

PURPOSE: Carnosic acid (CA) is an important polyphenol mainly isolated from the famous spice and the medicinal plant Rosmarinus officinalis. CA has been shown to exhibit tremendous pharmacological properties which include, but are not limited to, anticancer, antioxidant and anti-inflammatory activities. The current study was designed to evaluate the anticancer effects of CA against chronic myeloid leukemia (CML) which is one of the rare but deadly malignancies both in men and women. METHODS: CML KBM-7 cell line was used in this study. Cell viability was assessed by MTT assay. Apoptosis was detected by DAPI and annexin V/PI staining, cell cycle analysis by flow cytometry and cell invasion by Boyden chamber assay. The microRNA-780 expression was determined by quantitative RT-PCR. RESULTS: Our results indicated that CA exhibits significant anticancer activity on CML KBM-7 cells with an IC50 of 25 µM. The anticancer activity was due to induction of apoptosis and cell cycle arrest. Moreover, it was observed that CA inhibits the proliferation and invasion of CML KBM-7 cells which could mainly be due to downregulation of microRNA- 780 expression as indicated by the quantitative RT-PCR analysis. CONCLUSION: Taken together, we propose that carnosic acid could prove a potential lead compound in the treatment of CML and deserves further in vitro as well as in vivo study.

Effect of Zishen Jiangtang Pill, a Chinese Herbal Product, on Rats with Diabetic Osteoporosis.

Diabetic osteoporosis (DO) is a complication of diabetes. Zishen Jiangtang Pill (ZJP) is a Chinese herbal product which has been used in clinic to maintain blood glucose level and bone density for decades. However, the evidence about its mechanism on diabetes and osteoporosis is still unknown. The aim of this study is to investigate therapeutic effect of ZJP on DO in streptozotocin- (STZ-) induced rats. Rats were randomly assigned to 4 groups: one control group (CON), one model group (MOD), and two ZJP treatment groups (1.5 and 3.0 g/kg/d). All rats were treated for 8 weeks. Results showed that ZJP decreased the blood glucose level during OGTT and prevented the changes of FBG and Fins. Similarly, ZJP inhibited the changes of BCa, P, TRACP-5b, CTX-1, BALP, and BGP and the reduction of BMD. In parallel, 1H-NMR metabolomic studies showed that ZJP significantly altered the metabolic fingerprints of blood and urine level. These findings suggest that ZJP can effectively improve glucose metabolism, abnormal bone metabolism, and metabolic disorders in DO rats, which may be a useful alternative medicine for DO therapy.