BACKGROUND: Infectious diarrhea (ID) is a highly prevalent disease worldwide that poses a substantial risk to human well-being. In China, numerous clinical studies have investigated the efficacy of Gegen Qinlian decoction (GGQLD) in treating ID. However, there is a need for additional rigorous and evidence-based medical research to enhance physicians\' confidence in their prescribing practices.
METHODS: Seven Chinese and English databases were systematically searched. The Cochrane Risk of Bias tool was used to assess the quality of the included studies. Meta-analysis was conducted using RevMan 5.3, and Stata 16.0 was used for the sensitivity analysis. Trial sequential analysis was performed using TSA v0.9, and GRADEprofiler was utilized to evaluate the quality of evidence.
RESULTS: A total of 12 randomized controlled trials (RCTs) involving 1,240 patients were included. The meta-analysis demonstrated that the combination of GGQLD with conventional Western medicine had better effects on clinical efficacy (relative risk [RR] = 1.15, 95% confidence interval [CI] [1.10, 1.20]), duration of diarrhea symptoms (weighted mean difference [WMD] = -10.96, 95% CI [-11.97, -9.96]), duration of abdominal pain symptoms (WMD = -12.01, 95% CI [-14.12, -9.90]), duration of fever symptoms (WMD = -11.91, 95% CI [-13.39, -10.43]), interleukin-6 levels (WMD = -113.59, 95% CI [-113.03, -108.14]), and tumor necrosis factor-α levels (WMD = -62.18, 95% CI [-65.25, -59.11]) and that no significant adverse reactions occurred (RR = 0.45, 95% CI [0.10, 1.97]). The sample size of the included studies reached the expected size. The quality of evidence for outcome indicators was rated as low or very low.
CONCLUSIONS: The combination of GGQLD with conventional Western medicine demonstrates promising efficacy and safety in treating ID. Nonetheless, more high-quality RCTs are required to confirm this conclusion.
Infektiöse Diarrhö (ID) ist eine Krankheit mit weltweit hoher Prävalenz und erheblichem Risiko für das menschliche Wohlergehen. In China ist die Wirksamkeit von Gegen Qinlian Decoction (GGQLD) zur Behandlung der ID in zahlreichen klinischen Studien untersucht worden. Es besteht jedoch zusätzlich Bedarf an methodisch strenger, evidenzbasierter medizinischer Forschung, um das Vertrauen der Ärzteschaft für ihre Verordnungspraxis zu stärken. Sieben chinesisch- und englischsprachige Datenbanken wurden systematisch durchsucht. Mit dem Cochrane-Verzerrungsrisiko-Tool wurde die Qualität der eingeschlossenen Studien beurteilt. Die Metaanalyse wurde mit RevMan 5.3 durchgeführt und die Sensitivitätsanalyse mit Stata 16.0. Eine sequenzielle Studienanalyse erfolgte mit TSA v0.9 und die Qualitätsbeurteilung der Evidenz mit GRADEprofiler. Insgesamt 12 randomisierte kontrollierte Studien (RCTs) mit 1‘240 Teilnehmenden wurden untersucht. Die Metaanalyse ergab, dass die Kombination aus GGQLD mit konventioneller westlicher Medizin bessere Effekte auf die klinische Wirksamkeit (RR = 1.15, 95%-KI [1.10; 1.20]), Dauer der Diarrhösymptome (WMD = −10.96, 95%-KI [−11.97; −9.96]), Dauer der Bauchschmerzsymptome (WMD = −12.01, 95%-KI [−14.12; −9.90]), Dauer der Fiebersymptome (WMD = −11.91, 95%-KI [−13.39; −10.43]), Interleukin-6-Werte (WMD = −113.59, 95%-KI [−113.03, −108.14]) und Tumornekrosefaktor-α-Werte (WMD = −62.18, 95%-KI [−65.25; −59.11]) zeigte und dass keine signifikanten Nebenwirkungen auftraten (RR = 0.45, 95%-KI [0.10; 1.97]). Der Stichprobenumfang der eingeschlossenen Studien erreichte die erwartete Größe. Die Qualität der Evidenz im Hinblick auf Outcome-Messgrößen wurde als niedrig bis sehr niedrig eingestuft. Die Kombination aus GGQLD und konventioneller westlicher Medizin zur Behandlung der ID zeigt vielversprechende Wirksamkeit und Sicherheit. Es sind jedoch noch RCTs von hoher Qualität erforderlich, um diese Schlussfolgerung zu bestätigen.

BACKGROUND: Diabetic cardiomyopathy (DCM) is a common diabetes complication with limited medications. Gegen Qinlian decoction (GQD) has been used in the treatment of diabetes and its related complications in China for several decades.
OBJECTIVE: In this study, network pharmacology was employed to predict the active ingredients, key targets, and pathways involved in the treatment of DCM by GQD and to validate it by animal experiments.
METHODS: The active ingredients of GQD were retrieved from TCMSP and published literature. DCM-related gene targets were searched in Drugbank, Genecards, Disgenet, and OMIM disease databases. Protein-protein interaction networks were constructed using the STRING database and Cytoscape. GO analysis and KEGG pathway enrichment analysis were performed using the Metascape platform. Moreover, a diabetic mouse model was established to evaluate the therapeutic effects of GQD by measuring serum biochemical markers and inflammation levels. Finally, the expression of predicted key target genes was determined using real-time quantitative PCR.
RESULTS: A total of 129 active ingredients were screened from GQD. Moreover, 146 intersecting genes related to DCM were obtained, with key targets, including AKT1, TNF, IL6, and VEGFA. Lipid and atherosclerosis, AGE-RAGE, PI3K-AKT, and MAPK pathways were identified. Blood glucose control, decreased inflammatory factors, and serum CK-MB levels were restored after GQD intervention, and the same occurred with the expressions of PPAR-γ, AKT1, APOB, and GSK3B genes.
CONCLUSIONS: Quercetin, kaempferol, wogonin, 7-methoxy-2-methyl isoflavone, and formononetin may exert major therapeutic effects by regulating key factors, such as AKT1, APOE, and GSK3B, in the inflammatory reaction, glycolipid oxidation, and glycogen synthesis related signaling pathways.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: GQD improved type 2 diabetes primarily by modulating the abundance of Faecalibacterium in the gut microbiota, alleviating metabolic disorders and the inflammatory state.
UNASSIGNED: Registry No. ChiCTR-IOR-15006626.

UNASSIGNED: To investigate Gegen Qinlian Decoction (GQD) combined with metformin for treatment of patients with Type-2 Diabetes Mellitus (T2DM).
UNASSIGNED: This retrospective observational study reviewed the clinical data of 89 patients diagnosed with T2DM in the Department of Acupuncture and Massage, Hainan Medical University from January 2021 to June 2022. Patients were non-randomized and divided into two groups based on the treatment received: observation group (n=41, GQD combined with metformin); control group (n=48, metformin only). Fasting blood glucose levels (FBG), traditional Chinese medicine (TCM) syndrome scores, clinical effect, blood glucose time in range and adverse reactions were compared between the two groups.
UNASSIGNED: There were no statistically significant differences in age, gender, BMI and duration of T2DM between the two groups (P>0.05). The FBG, 2h glucose, HbA1c levels and TCM syndrome scores of the two groups were significantly lower post-treatment (P<0.001) with a greater decrease in the observation group (P<0.001). The observation group was more clinically efficacious than the control group post-treatment (92.68% vs. 77.08%; P<0.05). Blood glucose time in range and the incidence of adverse reactions were lower in the observation group than the control group (P<0.001 and P<0.05).
UNASSIGNED: GQD combined with metformin can significantly reduce FBG, 2h glucose and HbA1c levels, and improve TCM syndrome, with good clinical efficacy, shorter blood glucose time in range and less adverse reactions.

This study established a mouse model of ulcerative colitis and explored the serum transitional components of Gegen Qinlian Decoction by UHPLC-Q-Orbitrap-MS. Based on the exact relative molecular weight and MS/MS spectrum, 55 prototype components and 59 metabolites were identified from the model group, while 18 prototype components and 35 metabolites from the control group. The prototype components in serum were mainly flavonoids and the characteristic components of the model group were alkaloids. Glucuronidation, sulfonation, and glycosylation have been confirmed to be the main metabolic types in vivo. The results of comparative analysis of differences indicated that puerarin, baicalin, wogonoside, wogonin, chrysin, oroxylin A, berberine, berberrubine, and palmatine were the characteristic components in model state, which at the same time, were confirmed by pharmacological studies to be the serum pharmacodynamic material basis of Gegen Qinlian Decoction in the treatment of ulcerative colitis. This study has provided reference for explaining the metabolic transformation pattern and mechanism of action of Gegen Qinlian Decoction in vivo.

To investigate the effect of Gegen Qinlian Decoction(GQD) on enzyme activity, gene expression and methylation level of fatty acid synthase(FASN) in adipose tissue from rats with insulin resistance induced by high-fat diet. The 60% fat-powered high-fat diet was continuously given to male SD rats to induce the insulin resistance model. Then, they were divided into five groups randomly and administrated by gavage every day for 16 weeks with following drugs respectively: 10 mL·kg~(-1)water for control group(C) and insulin resistance model control group(IR), 1.65 g·kg~(-1)GQD per day for low-dose group(GQDL), 4.95 g·kg~(-1)GQD per day for medium-dose group(GQDM), 14.85 g·kg~(-1)GQD per day for high-dose group(GQDH), and 5 mg·kg~(-1) rosiglitazone per day for rosiglitazone group(RGN). Epididymal adipose tissue was taken to determine enzyme activity of FASN by colorimetric method, mRNA expression level of Fasn by quantitative Real-time PCR(Q-PCR) and CpGs methylation level between +313 and +582 by bisulfite sequencing PCR(BSP). These results showed that Fasn expression was significantly lowered in IR model rats compared with the control rats(P<0.01). Enzymatic activity and CpGs methylation level of Fasn in IR group showed downward trends. Low and medium-dose GQD can increase enzyme activity of FASN(P<0.05). Moreover, low-dose GQD increased the total CpGs methylation level of Fasn fragment between +313 and +582 in insulin resistance rats(P<0.05). For GQDM group, the methylation frequency of CpGs at positions +506 and +508(P<0.01) as well as the methylation frequency of CpGs on the binding sites of transcription factorzinc finger protein 161(P<0.05) were significantly increased. The methylation frequency of CpG at +442 position was positively correlated with Fasn expression(P<0.01, r=0.735), and methylation frequencies of CpGs at +345 and +366 positions were positively associated to enzyme activity of FASN respectively(P<0.05, r=0.479; P<0.01, r=0.640). In conclusion, GQD can reverse enzyme activity of FASN and methylation level of Fasn in adipose tissue of insulin resistant rats, and CpG sites at positions +506 and +508 may be the targets of GQD. The methylation level of CpGs at + 345 and + 366 sites were possibly related to FASN activity, while methylation of CpG at + 442 site may be closely correlated with mRNA level of Fasn. In addition, GQD did not significantly change mRNA expression level of Fasn, but effectively reversed enzymatic activity, suggesting that GQD may regulate the post transcriptional expression of Fasn.

BACKGROUND: Gegen Qinlian Decoction (GQD) is a classic traditional Chinese medicine prescription that is widely used to clinically treat diabetes mellitus. It is composed of Pueraria lobata (Willd.) Ohwi (ge gen), Scutellaria baicalensis Georgi (huang qin), Coptidis chinensis Franch. (huang lian), and Glycyrrhiza uralensis Fisch. (gan cao). However, the active ingredients in GQD and their mechanism of action are unclear.
OBJECTIVE: In this study, we aimed to verify the efficacy of GQD in improving insulin resistance (IR) in diabetic mice and used network pharmacology to identify potential targets and pathways underlying its mechanism of action.
METHODS: A mouse model of diabetes was created by feeding mice a high-fat diet followed by an intraperitoneal injection of streptozotocin. These type II diabetic mice were administered either a clinical dose or a high dose of GQD, after which blood glucose and serum insulin levels were measured to assess its effects on IR. Network pharmacology was used to construct a \'component-pathway-target\' network to elucidate the likely targets and pathways modulated in common by GQD components. Furthermore, mRNA transcript levels and protein expression levels of oestrogen receptor alpha (ESR1) were determined.
RESULTS: The in vivo experiment showed that GQD markedly decreased blood glucose and increased serum insulin levels in type II diabetic mice. Network pharmacology and bioinformatics analysis indicated that GQD regulated 82 corresponding proteins and 59 relevant biological pathways associated with diabetes. One such target was ESR1, which was significantly decreased at both the mRNA and protein levels in diabetic mice, but whose levels were significantly increased by GQD treatment.
CONCLUSIONS: This project provides a scientific basis for understanding the effectiveness of multi-component, multi-target compound formulas, as well as a new strategy for investigating therapeutic drugs for type II diabetes and other diseases.