Table 1.
Effects of BBR presented in animal and clinical studies.
| Reference | Study Type | Population | Intervention | Effects |
|---|---|---|---|---|
| Animal studies | ||||
| Xia et al., 2011 [40] | animal model study | The type 2 diabetic rat models, n = 9 |
380 mg·kg−1·d−1/1 day (BBR), 5 weeks |
↓ glucose, FAS, body mass, TC, TG ↓ gluconeogenic genes, Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase) in liver, ↓ hepatis steatosis |
| Ge et al., 2011 [41] | animal model study | primary hepatocytes from Sprague-Dawley (SD), Zucker lean (ZL) or fatty (ZF) rats | 10, 25, 50 or 100 µM (Berberine hydrochloride in primary hepatocytes from Sprague-Dawley (SD), Zucker lean (ZL) or fatty (ZF) rats | BBR regulate genes involved in glucose and fatty acid synthesis in hepatocytes. |
| Zhang Z et al., 2014 [42] | animal model study | male mice and wild-type mice, n = 5 |
5 mg kg−1 per day (BBR). 4 weeks |
↓ body weight, % fat mass of BW, serum FAA, blood glucose, glucose AUC, serum insulin |
| Li Zhao et al., 2017 [43] | animal model study | Sprague–Dawley rats, n = 6 |
150 mg/kg body weight/1 day. 16 weeks |
↓ body mass, TG, LDL, HOMA-IR, and ↑ ISI, ↓ Raglu, GNG and hepatic lipogenesis |
| Yixuan Sun et al., 2018 [44] | animal model study | Eight-week-old male C57BL mice, n = 6 |
5 mg·kg−1·day−1/1 day (BBR), 4 weeks | ↓ liver TG, liver cholesterol, TG, plasma cholesterol, body weight |
| Yan Luo et al., 2019 [5] | animal model study | The C57BL/6J mice, n = 30 |
250 mg/kg/1 day, 12 weeks |
↓ NAS, ALT, AST, glucose, HDL, LDL, TC |
| Human studies | ||||
| Kong et al., 2004 [45] | RCT | adult hypercholesterolemic patients, n = 63 |
1 g/1 day (BBR hydrochloride), 3 months |
↓ ALT, AST, GGT, TC, TG, LDL-c |
| Xie et al., 2011 [46] | RCT | adult NAFLD and 2 diabetes patients; n = 60 | 0.3 g/1 day (BBR), 12 weeks |
↓ TG, TC, LDL, ALT ↓ liver lipid content |
| Bai et al., 2011 [47] | RCT | adult NAFLD patients, n = 68 |
0.5 g/1 day (BBR + metformin) 3 months |
↓ of level of FPG, TC, TG, LDL-C, FINS, HOMA-IR, ↑ adiponectin, ↓ IR |
| Marazzi et al., 2011 [48] | RCT | elderly hypercholesterolemic patients, n = 80 |
0.5 g/1 day (BBR + policosanol 10 mg, red yeast rice 200 mg, folic acid 0.2 mg, coenzyme Q10 2.0 mg, and astaxanthin 0.5 mg), 12 months | ↓ TC, LDL-C, IR |
| Di Pierro et al., 2012 [49] | RCT | adult 2 diabetes patients; n = 22 |
0.588 g/1 day (Berberol®, B. aristata extract titered as 85% berberine and 105 mg of S. marianum extract titered as >60% flavonolignans), 90 days |
↓ HbA1c, TC, LDL-C, HDL-C, T, FR, BMI, HOMA-IR |
| Cao et al., 2012 [50] | RCT | adult NAFLD patients, n = 78 |
0.5 g/1 day (BBR + metformin) 16 weeks |
↓ HOMA-IR, TC, TG, LDL, ALT, AST, 2hPG |
| Pérez-Rubio et al., 2013 [51] | RCT | adult MetS patients, n = 24 | 1.5 g/1 day (berberine hydrochloride), 3 months |
↓ SBP, waist circumference, TG, and total insulin secretion. ↓ waist circumference in females, SBP, TG, area under the curve (AUC) of glucose, AUC of insulin and insulinogenic index. |
| Ning et al., 2013 [52] | RCT | adult NAFLD patients; n = 44 |
0.5 g/1 day (BBR + metformin), 16 weeks |
↓ HbA1C, TC, TG |
| Manzato & Benvenut, 2014 [53] | RCT | adult dyslipidemic patients, n = 1161 |
0.5 g/1 day BBR + ed yeast rice extract 200 mg (equivalent to 3 mg monacolins), policosanol 10 mg, 0.2 mg folic acid, coenzyme Q10 2 mg, and asthaxantin 0.5 mg (Armolipid Plus, Rottapharm|Madaus) with or without diet, 16 weeks |
↓ TC, LDL-C, TG |
| Li, 2015 [54] | RCT | adult NAFLD patients, n = 96 |
0.3 g/1 day (BBR), 3 months |
↓ 2hPG, HbA1C, TC, LDL, ALT, AST |
| Yan H-M. et al., 2015 [55] | RCT | adult NAFLD patients, n = 184 |
1.5 g/1 day (BBR), 16 weeks |
↓ hepatic fat content, ALT, AST, y-GT, glucose, HOMA-IR, TC, TG, LDL-c |
| Wang et al., 2016 [56] | RCT | adult mild hyperlipemia patients, n = 97 |
0.3 g/1 day (vs. 0.9 g/1 day), 3 months |
↓ TG, TC i LDL-C, ↑ HDL-C |
| Xinxia Chang et al., 2016 [24] | RCT | adult NAFLD patients, n = 80 |
1.5 g/1 day (BBR), 16 weeks |
↓ TC, TG, LDL-c, glucose, HOMA-IR, ↓ hepatic fat content |
Abbreviations: T2DM: Type 2 Diabetes; 2hPG: 2-h post-load plasma glucose; AUC: Area Under ROC Curve; BBR: Berberine; BMI: Body Mass Index; FFA: Free Fatty Acid; FAS: Fatty Acid Synthase; FINS: Fasting Insulin; FPG: Fasting Plasma Glucose concentration; G6Pase: Glucose-6-Phosphatase; GGT: Gamma-Glutamyl Transferase; GNG: Granulomatous Amebic Encephalitis; HbA1c: Glycated hemoglobin; HOMA-IR: Homeostatic Model Assessment—Insulin Resistance; IR: Insulin Resistance; ISI: Insulin Sensitivity Index; LDL: Low-Density Lipoprotein; NAS: NAFLD Activity Score; PEPCK: Phosphoenolpyruvate Carboxykinase; Raglu: Glucose appearance; SD: Sprague-Dawley Rats; TC: Total Cholesterol; TG: Triglicerydes; y-GT: Gamma-glutamyltransferase; ZF: Zucker Fatty rats; ZL: Zucker Lean rats; ↓: lowered; ↑: elevated