Antifibrotic effects of hypocalcemic vitamin D analogs in murine and human hepatic stellate cells and in the CCl4 mouse model.

Liver cirrhosis is a life-threatening consequence of liver fibrosis. The aim of this study was to investigate the antifibrotic potential of clinically available vitamin D analogs compared to that of calcitriol in vitro and in vivo. Murine hepatic stellate cells, Kupffer cells, and human LX-2 cells were treated with vitamin D analogs, and the profibrotic behavior of these cells was studied. In vivo liver fibrosis was induced using CCl4 until measurable fibrosis was established. Animals were then treated with calcitriol and paricalcitol. Vitamin D and its analogs showed antifibrotic effects in vitro. Treatment with active vitamin D (calcitriol, CAL) and its analogs reduced the protein expression of α-smooth muscle actin (α-SMA) in mHSC. In human LX-2 cells alfacalcidol reduced transforming growth factor-ß (TGF-ß) induced platelet-derived growth factor receptor-ß protein expression and contractility while paricalcitol (PCT), in its equipotent dose to CAL, reduced TGF-ß induced α-SMA protein expression, and ACTA2 and TGF-ß mRNA expression. No effects of a treatment with vitamin D and its analogs were observed in Kupffer cells. In vivo, PCT-treated mice had significantly lower calcium levels than CAL-treated mice. CAL and PCT reduced the hepatic infiltration of CD11b-positive cells and alanine transaminase levels, while PCT but not CAL significantly inhibited fibrosis progression, with a favorable side effect profile in the CCl4 model. We conclude that hypocalcemic vitamin D analogs should be considered in future studies investigating vitamin D for the treatment of liver fibrosis.

Algicidal effects of four Chinese herb extracts on bloom-forming Microcystis aeruginosa and Chlorella pyrenoidosa.

Extracts from four Chinese herbs, Phellodendri chinensis cortex, Artemisia annua L., Scutellaria baicalensis G. and Citrus reticulate peel were tested for their algicidal effects on Microcystis aeruginosa and Chlorella pyrenoidosa. The results showed that M. aeruginosa was more susceptible than C. pyrenoidosa. The growth of M. aeruginosa was significantly inhibited (p < 0.05) by the four herb extracts. Among the four herbs, P. chinensis cortex and S. baicalensis had the greatest inhibitory effects on M. aeruginosa, followed by C reticulate peel and A. annua. The 50% effective concentrations (EC50) of S. baicalensis, P chinensis cortex, C. reticulate peel and A. annua were 0.87, 0.88, 5.27 and 1 1.16 gherb L-1, respectively. The growth of C. pyrenoidosa was moderately inhibited by the herb extracts individually. The EC5o concentrations for S. baicalensis, P. chinensis cortex, C. reticulate peel andA. annua were 8.67, 11.67, 12.81 and 12.44 g herb L-1', respectively. Extract from S. baicalensis displayed stronger algicidal effects on C. pyrenoidosa than the other three herbs, although no lethal effect on C. pyrenoidosa was observed during the cultivation period. Compared with corresponding individual extract at the same dosage, the binary mixtures of the four herb extracts enhanced the algicidal effects on M. aeruginosa. The maximum inhibitory rates of all binary mixtures of the four herb extracts were all above 92% during the 10-day incubation. The results demonstrate that Chinese herbs, such as P. chinensis cortex or S. baicalensis and their combinations, could offer an effective alternative for mitigating outbreaks of harmful algal blooms in water bodies.