The compound losartan cream inhibits scar formation via TGF-ß/Smad pathway.

The role of angiotensin receptor blocker in wound healing and cutaneous fibrosis has become a hotspot in recent years. We have developed a losartan cream that is comparable to triamcinolone ointment in inhibiting scarring. Considering the effects of chitosan and asiaticoside on wound healing and scarring, we added them to the losartan cream this time and improved the formula, expecting to get a better anti-scarring effect. The effects of creams were investigated on mouse scar model with triamcinolone ointment, onion extract gel, and commercial asiaticoside cream set as positive controls. A preliminary exploration of the mechanism involved in TGF-ß/Smad pathway was performed in vivo and in vitro. With all results of anti-scarring, the compound losartan cream (containing chitosan, asiaticoside, and losartan) shows the best effect, followed by the chitosan asiaticoside cream. The treatment of the compound losartan cream inhibited expression of TGF-ß1, collagen, and Smads, and decreased phosphorylation of Smad in vivo. These inhibitory effects were also confirmed in vitro. Our findings indicated that the compound losartan cream could inhibit scarring via TGF-ß/Smad pathway. This cream might be an effective option for scar treatment.

[Purification of polyphenols from Sabina vulgaris antoine and its antioxidant properties].

OBJECTIVE: To purify polyphenols from Sabina vulgaris and to investigate its antioxidant properties. METHODS: Polyphenols were purified from Sabina vulgaris Antoine with macroporous resin HPD-700, and the quantity of polyphenols was determined by Folin-Ciocalteu colorimetry. The antioxidant properties of polyphenols were evaluated by total antioxidant capacity (T-AOC) and its activities of scavenging DPPH (1,1 diphenyl-2-picry-hydrazyl) radicals, superoxide anion (O2·-), hydroxyl free radicals (OH·) and ferric reducing antioxidant power (FRAP). RESULTS: After purification, the purity of polyphenols increased from 0.053% to 0.995%.The antioxidant properties study showed that its inhibition rate of scavenging DPPH radicals and FRAP was 151.83 U/ml and 204.59 U/ml. Its scavenging capacity for superoxide anion (O2·-) and hydroxyl free radicals (OH·) was 151.83 U/ml and 204.59 U/ml. The total antioxidant capacity was 72.68 U/ml. CONCLUSION: Polyphenols from Sabina vulgaris Antoine have high antioxidant properties, suggesting that it worth further study of its pharmacological effects.

[Influence of isoliensinine on activity of CYP3A in rats].

OBJECTIVE: To investigate the influence of isoliensinine (IL) on CYP3A enzyme activity. METHODS: A mixture metabolic system of liver microsome enzymes in vitro was developed. A HPLC method to test the metabolic activity of CYP3A was established with testosterone as a probe. The activities of CYP3A enzymes were measured with different IL concentrations and incubation time with testosterone. RESULTS: In mixture metabolic system of liver microsome enzymes, the best incubation concentration of testosterone was 200 µmol/L, the best incubation time was 210 min, in this condition the IC50 of IL for CYP3A inhibition was >1 000 µmol/L. CONCLUSION: No significant interaction between IL and CYP3A is detected, which indicates that IL might be used with CYP 3A enzyme substrates.

[Study on determination and pharmacokinetics of metabolites from Folium Mori extract in rats].

OBJECTIVE: To establish a RP-HPLC method for simultaneous determination of total quercetin, kaempferol and isorhamnetin in rat plasma after oral administration of Folium Mori extract (FME). METHODS: After a single dose of FME (110 mg/kg) was taken, rat plasma samples were collected. The samples were hydrolyzed with hydrochloric acid (c=3.0 mol/L), the mixed solution was extracted with ether acetone mixture. The total quercetin, kaempferol and isorhamnetin in plasma samples were determined by HPLC, pharmacokinetic parameters were calculated by DAS 3.0 software. RESULTS: The method was linear over the concentration ranges of 0.0545-8.70, 0.0954-14.7 and 0.0545-8.55 µg/ml for quercetin, kaempferol and isorhamnetin, respectively (r=0.9979, 0.9993, 0.9981). The absolute recoveries were 85.3%-86.1%, 79.4%-86.7% and 62.8%-89.7%, respectively and the assay recoveries were all from 94.7% to 107%. The relative standard deviation (RSD) of intra-and inter-day were less than 9.5% and 9.8%, respectively. The main pharmacokinetic parameters were as follows: T(1/2z) was 92.7, 67.9 and 54.2 h; Tmax was 0.400, 0.400 and 3.87 h; AUC(0-∞) was 68.0, 67.5 and 32.8 mg/h/L; MRT(0-∞) was 128, 85.2 and 72.0 h for quercetin, kaempferol and isorhamnetin, respectively. CONCLUSION: The method established in this study is accurate, reliable and reproducible, and can be applied for determination of total quercetin, kaempferol and isorhamnetin in rat plasma after oral administration of FME; the pharmacokinetic studies showed that the distribution of drugs is rapid and elimination is very slow.