A new method to evaluate the dose-effect relationship of a TCM formula Gegen Qinlian Decoction: “Focus” mode of integrated biomarkers

transduction cascades, which jointly optimized the expression of target gene profiles to promote fatty acid oxidation and accelerate glucose uptake and utilization than PPARg full agonist rosiglitazone without stimulating PPARa activity. Thus, GQD showed antidiabetic/or antihyperglycemic effects, partially through regulating adipocytic PPARa and PPARg signaling systems to maintaining balanced glucose and lipid metabolisms. This study provides a new insight into the anti-diabetic effect of GQD as a PPARa/g dual agonist to accelerate the clinical use.

Section: Animal Model and Drug Administrationsupporting

confidence: 91%

Gegen Qinlian Decoction Coordinately Regulates PPARγ and PPARα to Improve Glucose and Lipid Homeostasis in Diabetic Rats and Insulin Resistance 3T3-L1 Adipocytes

Zhu

et al. 2020

“…1) GQD improves insulin resistance. Oral administration of 1.357, 4.071, and 6.785 g/kg GQD water extract (300 mg/kg/d of metformin was used as positive control) for 60 days protected pancreatic tissue and improved the insulin sensitivity index of twelve T2DM model animals (Huang et al, 2017). For example, in the minimal active dose, i.e., 1.357 g/kg/d, treated group, insulin sensitivity index decreased from higher than 2.5 to lower than 2.0 (p < 0.01) (Huang et al, 2017).…”

Section: Nonalcoholic Fatty Liver Diseasementioning

confidence: 99%

“…Oral administration of 1.357, 4.071, and 6.785 g/kg GQD water extract (300 mg/kg/d of metformin was used as positive control) for 60 days protected pancreatic tissue and improved the insulin sensitivity index of twelve T2DM model animals (Huang et al, 2017). For example, in the minimal active dose, i.e., 1.357 g/kg/d, treated group, insulin sensitivity index decreased from higher than 2.5 to lower than 2.0 (p < 0.01) (Huang et al, 2017). Integrated system pharmacology and bioinformatics analysis revealed the Hub targets (including PPARG, RELA, EGFR, CASP3, VEGFA, AR, ESR1, and CCND1) and signaling pathways (including insulin signaling, endocrine resistance, TNF signaling, PI3K-Akt signaling, AMPK signaling, MAPK signaling, NF-κB signaling, HIF-1 signaling, apoptosis, and VEGF signaling pathways) involved in the underlying mechanisms of GQD in improving diabetic insulin resistance (Cao et al, 2020).…”

Section: Nonalcoholic Fatty Liver Diseasementioning

confidence: 99%

Constituents, Pharmacokinetics, and Pharmacology of Gegen-Qinlian Decoction

2021

Gegen-Qinlian decoction (GQD) is a classic traditional Chinese medicine (TCM) formula. It is composed of four TCMs, including Puerariae Lobatae Radix, Scutellariae Radix, Coptidis Rhizoma, and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle. GQD is traditionally and clinically used to treat both the “external and internal symptoms” of diarrhea with fever. In this review, key words related to GQD were searched in the Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), and other databases. Literature published mainly from 2000 to 2020 was screened and summarized. The main constituents of GQD could be classified into eight groups according to their structures: flavonoid C-glycosides, flavonoid O-glucuronides, benzylisoquinoline alkaloids, free flavonoids, flavonoid O-glycosides, coumarins, triterpenoid saponins, and others. The parent constituents of GQD that enter circulation mainly include puerarin and daidzein from Puerariae Lobatae Radix, baicalin and wogonoside from Scutellariae Radix, berberine and magnoflorine from Coptidis Rhizoma, as well as glycyrrhetinic acid and glycyrrhizic acid from Glycyrrhizae Radix et Rhizoma Praeparata cum Melle. GQD is effective against inflammatory intestinal diseases, including diarrhea, ulcerative colitis, and intestinal adverse reactions caused by chemotherapeutic agents. Moreover, GQD has significant effects on metabolic diseases, such as nonalcoholic fatty liver and type 2 diabetes. Furthermore, GQD can be used to treat lung injury. In brief, the main constituents, the pharmacokinetic and pharmacological profiles of GQD were summarized in this review. In addition, several issues of GQD including effective constituents, interactions between the constituents, pharmacokinetics, interaction potential with drugs and pharmacological effects were discussed, and related future researches were prospected in this review.

“…Furthermore, it can control fasting and postprandial blood glucose and bring them to a desirable level ( Cao et al, 2010 ; Lian et al, 2015 ; Huang et al, 2019 ). However, due to the complex composition of herbs, the unclear mechanism of TCM formulas ( Shao et al, 2021 ; Yuan et al, 2021 ; Yun et al, 2021 ), and a lack of scientific data to support the dose-response relationship ( Huang et al, 2017 ; Ge et al, 2018 ), the clinical dosage modification usually lacks standardization and has become a bottleneck for detailed studies on TCM.…”

Section: Introductionmentioning

confidence: 99%

Dosage Modification of Traditional Chinese Medicine Prescriptions: An Analysis of Two Randomized Controlled Trials

Zhou

Zheng

et al. 2021

Traditional Chinese medicine (TCM) prescriptions lack standardization due to the complex composition of the prescribed herbs, the unclear mechanism of the formulas, and a lack of scientific data to support the dose-response relationship. Here, we proposed a new clinical strategy of dosage modification for TCM prescriptions to evaluate the clinical efficacy and guide the clinical medication. This study used two TCM prescriptions for the treatment of newly diagnosed type 2 diabetes mellitus (T2DM) to explore the key indications and the most appropriate critical values of dosage modification by analyzing two randomized controlled trials (RCTs). In this study, the indications refer to a change in the indicators from baseline at a certain time point (week 4, week 8, week 12), which could predict the change in outcome indicators, and the critical values refer to the change ranges closely related to the decrease in HbA1c at week 12. In Study 1, the correlation analysis between the change range of indicators at three time points (weeks 4, 8, and 12) from baseline and the decrease in HbA1c at week 12 from baseline (HbA1c 012) was carried out to screen the related indications. Next, we evaluate the related indications and the respective critical values to determine the key indicators, indications, and the most appropriate critical value. We conducted a correlation between the change range of key indicators (obtained from the result of Study 1) at three time points from baseline and HbA1c 012 to screen the key indications in the drug group, high-dose group, and low-dose group in Study 2. Key indications with critical values were determined to investigate the most appropriate critical value in the three groups separately. In Study 1, the key indicator was FBG, the key indication was FBG 04, and the most appropriate critical value was 0.5 mmol/L. In Study 2, the key indication was FBG 04 and the most appropriate critical value was 0.6 mmol/L in the drug group. In the high-dose group, the key indication was FBG 04, and the most appropriate critical value was 0.3 mmol/L. In the low-dose group, the key indication was FBG08, and the most appropriate critical value was 0.1 mmol/L. In addition, we summarized a verification strategy for dosage modification.