Bergenin monohydrate

Evaluation of Intestinal Absorption and Bioavailability of a Bergenin-Phospholipid Complex Solid Dispersion in Rats.[Pubmed:29556829]

AAPS PharmSciTech. 2018 May;19(4):1720-1729.

Bergenin (BN) is a Biopharmaceutics Classification System class IV (BCS IV) drug with poor hydrophilicity and lipophilicity and is potentially eliminated by the efflux function of P-glycoprotein (P-gp). These factors may explain its low oral bioavailability. In the present study, a BN-phospholipid complex solid dispersion (BNPC-SD) was prepared by solvent evaporation and characterized based on differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, infrared diffraction, solubility, octanol-water partition coefficient, and in vitro dissolution. To investigate how P-gp can inhibit BN absorption in vivo, the P-gp inhibitor verapamil was co-administered with BNPC-SD to Sprague Dawley rats. By in situ single-pass intestinal perfusion, the membrane permeability of BN from BNPC-SD was higher than that of BN given alone and was improved further by co-administered verapamil. A pharmacokinetics study was done in Sprague Dawley rats, with plasma BN levels estimated by high-performance liquid chromatography. Cmax and AUC0 --> t values for BN were significantly higher for BNPC-SD than for BN given alone and were increased further by verapamil. Thus, the relative oral bioavailability of BNPC-SD as well as BNPC-SD co-administered with verapamil was 156.33 and 202.46%, respectively, compared with the value for BN given alone. These results showed that BNPC-SD can increase the oral bioavailability of BCS IV drugs.

Preparation of bergenin - Poly (lactic acid) polymers and in vitro controlled release studies.[Pubmed:29705111]

Int J Biol Macromol. 2018 Sep;116:354-363.

The efficacy of bergenin prepared with osmotic-pump-controlled release is much lower than expected. In this study, biodegradable polylactic acid is used to modify bergenin and immobilize it with chemical methods. Bergenin-PLA obtained by this method has low molecular weight and good thermal stability, as well as prolonged in vitro release time along with increased molecular weight. Biocompatibility tests and in vitro antitumor tests showed that bergenin-PLA at a ratio of 1:30 has good biological properties and low cytotoxicity at t three concentrations, and its antitumor activity was significantly increased compared to bergenin. The chemical immobilization of bergenin not only provides a good mode of administration for patients but also provides a good foundation for the sustained release of drugs over time.

Bergenin, Acting as an Agonist of PPARgamma, Ameliorates Experimental Colitis in Mice through Improving Expression of SIRT1, and Therefore Inhibiting NF-kappaB-Mediated Macrophage Activation.[Pubmed:29375382]

Front Pharmacol. 2018 Jan 12;8:981.

Bergenin, isolated from the herb of Saxifraga stolonifera Curt. (Hu-Er-Cao), has anti-inflammatory, antitussive and wound healing activities. The aim of the present study was to identify the effect of bergenin on experimental colitis, and explored the related mechanisms. Our results showed that oral administration of bergenin remarkably alleviated disease symptoms of mice with dextran sulfate sodium (DSS)-induced colitis, evidenced by reduced DAI scores, shortening of colon length, MPO activity and pathologic abnormalities in colons. Bergenin obviously inhibited the mRNA and protein expressions of IL-6 and TNF-alpha in colon tissues, but not that of mucosal barrier-associated proteins occludin, E-cadherin and MUC-2. In vitro, bergenin significantly inhibited the expressions of IL-6 and TNF-alpha as well as nuclear translocation and DNA binding activity of NF-kappaB-p65 in lipopolysaccharide (LPS)-stimulated peritoneal macrophages and RAW264.7 cells, which was almost reversed by addition of PPARgamma antagonist GW9662 and siPPARgamma. Subsequently, bergenin was identified as a PPARgamma agonist. It could enter into macrophages, bind with PPARgamma, promote nuclear translocation and transcriptional activity of PPARgamma, and increase mRNA expressions of CD36, LPL and ap2. In addition, bergenin significantly up-regulated expression of SIRT1, inhibited acetylation of NF-kappaB-p65 and increased association NF-kappaB-p65 and IkappaBalpha. Finally, the correlation between activation of PPARgamma and attenuation of colitis, inhibition of IL-6 and TNF-alpha expressions, NF-kappaB-p65 acetylation and nuclear translocation, and up-regulation of SIRT1 expression by bergenin was validated in mice with DSS-induced colitis and/or LPS-stimulated macrophages. In summary, bergenin could ameliorate colitis in mice through inhibiting the activation of macrophages via regulating PPARgamma/SIRT1/NF-kappaB-p65 pathway. The findings can provide evidence for the further development of bergenin as an anti-UC drug, and offer a paradigm for the recognization of anti-UC mechanisms of compound with similar structure occurring in traditional Chinese medicines.