Update on the Benefits and Mechanisms of Action of the Bioactive Vegetal Alkaloid Berberine on Lipid Metabolism and Homeostasis

Table 3

Bioavailability of BBR in animals and humans.

Subject/research model	Diet	Dose, administration route, treatment time		Reference
Type-2 diabetic patients	No diet restriction	Berberol, each containing 558 mg of B. aristata extract titered as 85% BBR and 105 mg of S. marianum extract titered as >60% flavonolignans, 2 tablets/d, once daily, for 90 d	Low oral bioavailability of BBR can be overcome by P-glycoprotein inhibitors like herbal polyphenol. S. marianum extract	[50]
Healthy subjects	No diet restriction	400 mg, once i.g.	ng/mL, T1/2 = 29 hr,  hr, = 7.8 (hr⋅ng/ml), = 9.2 (hr⋅ng/ml)	[56]
Diabetic Kunming mice (STZ-induced)	Rodent chow	100 mg/kg, once i.g. in Rhizoma Coptidis extract and a classical Chinese prescription, Jiao-Tai-Wan	Addition of Cinnamomum cassia increased bioavailability of BBR	[16]
SD rats	Diet not specified	50 mg/kg, once i.g., free BBR or BBR loaded in solid lipid nanoparticles	Cmax = 11.1 ng/mL, T1/2 = 9.2 hr, Tmax = 2.3 hr, = 86.5 (ug⋅hr/L)  for free BBR; Cmax = 44.6 ng/mL, T1/2 = 11.5 hr, Tmax = 0.38 hr, = 179.4 (ug.hr/L) for BBR loaded in solid lipid nanoparticles	[57]
Wistar rats	Regular diet	40 mg/kg, once i.g.	BBR absorption rate in jejunum was 19.1%, 26.5%, 26.8%, and 33.6% at 10, 20, 40, and 60 min, respectively; = 37, 1879, 811, 1763, and 356 (ng⋅hr/ml) for BBR and its metabolites M1, M2, M3, and M4	[58]
SD rats	Regular diet	100 mg/kg, once i.g.	Absolute oral bioavailability was 0.36%	[59]
SD rats,	Regular diet	100 mg/kg, once i.g. in spray-dried mucoadhesive microparticle formulations (BBR-SD)	Increased by 3.5-fold and AUC by 7-fold.; = 147 ng/ml, = 1.4 hr, = 819 ng⋅hr/ml, and T1/2 = 5.95 hr for free BBR, and 509 ng/ml, 2.86 hr, 5724 ng⋅hr/ml, and 15 hr for BBR-SD	[60]
Rats with inflammatory bowel disease	Regular diet	5 mg/kg in self-nanoemulsifying drug delivery system, once daily, i.g., 7 d	Improved solubility and therapeutic efficacy in either liquid or solid form of self- nanoemulsifying drug delivery system	[61]
SD rats	Regular diet	100 mg/kg in Huang-Gui solid dispersion, once i.g.	Oral bioavailability was increased by 5-fold	[62]
Wistar rats	Regular diet	100 mg/kg in sodium caprate, or sodium deoxycholate, once i.g.	AUC was increased 41-fold by sodium caprate and 35-fold by sodium deoxycholate.	[63]
SD rats	Regular diet	25 mg/kg in self-emulsifying drug delivery system, once i.g.	Increased peak plasma concentration and AUC (0–12 hr) by 160% and 150%, respectively, and relative bioavailability 2.4-fold	[64]
Wistar rats	Regular diet	100 mg/kg in chitosan hydrochloride solution, once i.g.	Oral bioavailability was increased by 2.5-fold	[65]
Kunming mice	Regular diet	100 mg/kg in anhydrous reverse micelle delivery system, once i.g.	Enhanced oral bioavailability 2.4-fold	[66]
Wistar rats	Regular diet	100 mg/kg in D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), once i.g.	TPGS at a concentration of 2.5% increased peak serum concentration and AUC of BBR by 3-fold and 2-fold, respectively	[67]
SD rats	Regular diet	50 mg/kg in microemulsion, once i.g.	Increased oral bioavailability 6.5-fold	[68]

: area under the curve of blood BBR concentration in a pharmacokinetic study.