Effect of RG (Coptis root and ginseng) formula in patients with type 2 diabetes mellitus: a study protocol for a randomized controlled and double-blinding trial.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a common metabolic disease with significant health, social, and economic consequences. Traditional Chinese medicine (TCM) could effectively regulate blood sugar and influence gut microbiota in T2DM patients. Preliminary studies showed that the Coptis root and ginseng (RG) formula could relieve insulin resistance and prevent the progression of diabetes in mice. OBJECTIVES: The purpose of this study is to explore the efficacy and safety of RG formula in the treatment of adult patients with T2DM, as well as observing its effects on gut microbiota. METHODS AND ANALYSIS: This trial is a randomized, double-blind, placebo-controlled study. A total of 60 participants will be randomized in a 1:1 ratio into an experiment group (RG formula) and a control group (placebo). Patients in both groups will be given diabetes education and basic blood glucose control. Glucose-lowering drugs with significant influence on gut microbiota will be avoided. This trial will last 25 weeks including 1-week run-in, 12-week intervention, and 12-week follow-up visit. The primary outcome is the change in the HbA1c. The secondary outcomes comprise the change in the fasting blood glucose (FBG), postprandial blood glucose (PBG), fasting insulin (FIL), fasting C-peptide(C-P), insulin resistance index (IRI), inflammatory factors, and species abundance of gut microbiota between the two groups. Safety of medication will also be evaluated. The correlation analysis will be explored between the glycemic indicators, inflammatory factors, and abundance of gut microbiota. DISCUSSION: This study will provide the clinical evidence for the efficacy of RG formula in regulating blood sugar and influencing gut microbiota, which will be beneficial to form the integrated therapeutic regimen in T2DM with TCM. TRIAL REGISTRATION: "Clinical Study on the Intervention of Coptis Root and Ginseng," Chinese Clinical Trials Registry ChiCTR 2100042126 . Registered on 14 January 2021.

Safety evaluation of main alkaloids from Rhizoma Coptidis.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhizoma Coptidis (RC), a widely used traditional Chinese medicine, has been used for the treatment of heat-clearing and detoxifying, but there is very little information on its safety. AIM OF THE STUDY: To provide information on the safety of RC, we evaluated the toxicity of the crude RC and RC alkaloids (berberine, coptisine, palmatine and epiberberine) including cytotoxicity, acute toxicity in mice and sub-chronic toxicity in rats. MATERIALS AND METHODS: The cytotoxicity of RC alkaloids was tested in HepG2 and 3T3-L1 cells by the MTT assay. The acute toxicity of RC alkaloids was tested in mice and the mortality was calculated at the end of experiment. For sub-chronic toxicity study, the rats were treated with the RC alkaloids at a dose of 156 mg/kg/day and RC at a dose of 521 mg/kg/day for 90 days. Mortality, clinical signs, body weight changes, organ weights, urinalysis and hematological parameters, gross necropsy and histopathology were monitored during the study period. RESULTS: The cell assay indicates that the IC(50) values of berberine, coptisine, palmatine and epiberberine in HepG2 cells were 48.17, 64.81, 112.80 and 120.58 µg/mL, which in 3T3-L1 cells were 41.76, 56.48, 84.32 and 104.18 µg/mL, respectively. In the acute toxicity assay, the LD(50) values of four alkaloids were 713.57, 852.12, 1533.68 and 1360 mg/kg, respectively. However, in the sub-chronic toxicity study, no mortality and morbidity were observed which could be related to RC alkaloids and RC treatment. Besides, there was no abnormality in clinical signs, body weights, organ weights, urinalysis, hematological parameters, gross necropsy and histopathology in any of the animals after the oral administration of RC alkaloids and RC. CONCLUSIONS: Taking these results together, we came to the conclusion that the toxicity of berberine is the maximum and palmatine is the minimal in four RC alkaloids. The currently recommended doses of RC alkaloids and RC consumed are relatively safe.

A multidisciplinary approach to the toxicologic problems associated with the use of herbal medicines.

In Hong Kong, a multidisciplinary team consisting of a pharmacist, a chemical pathologist, a scientific officer, and a physician has jointly provided an advisory service on herbal safety to healthcare professionals of all public hospitals since August 2000. This paper reports the first 2 years of experience of this team to emphasize the importance of a multidisciplinary approach to herbal poisoning. Twenty referrals received from the public hospitals from August 2000 to June 2002 were reviewed. The diagnosis of herbal toxicity was made after consideration of the temporal relationship between exposure to the herb and the occurrence of the adverse event and the exclusion of other causes. The causal relationship was seen as much stronger if the herb's pharmacological effects could fully explain the adverse event, if there were similar previous reports, and if the toxicological analysis findings were supportive. In 10 patients, the adverse events were deemed unlikely to be related to the use of herbal medicines. In 3 patients, it was concluded that the adverse events were possibly related to the use of herbal medicines. In 7 patients, the causal relationship was seen to be much stronger because the adverse events in these patients simply reflected the pharmacological effects of the herbs consumed and specific toxic ingredients were isolated from herbal residues and patients' urine or serum. The clinical problems arising from the use of herbal medicines included the Aristolochia species causing acute renal failure (n = 1), aconite roots causing aconitine poisoning (n = 2), the Datura species causing anticholinergic poisoning (n = 1), and "yulan" (Stephania sinica) causing tetrahydropalmatine poisoning (n = 3). The 4 patients with acute renal failure and tetrahydropalmatine poisoning received these toxic herbs, which were not listed in the prescriptions, as a result of poor dispensing practice or for other reasons. Toxicological problems associated with the use of herbal medicines are complex and may be easily overlooked. A multidisciplinary team of experts should be made available to provide advice to frontline healthcare professionals.