Sevelamer reverses liver fibrosis by deactivation of hepatic stellate cells.

Liver fibrosis is a chronic liver disease characterized by a progressive wound healing response caused by chronic liver injury. Currently, there are no approved clinical treatments for liver fibrosis. Sevelamer is used clinically to treat hyperphosphatemia and has shown potential therapeutic effects on liver diseases. However, there have been few studies evaluating the therapeutic effects of sevelamer on liver fibrosis, and the specific mechanisms are still unclear. In this study, we investigated the antifibrotic effects of sevelamer-induced low inorganic phosphate (Pi) stress in vitro and in vivo and analyzed the detailed mechanisms. We found that low Pi stress could inhibit the proliferation of activated hepatic stellate cells (HSCs) by promoting apoptosis, effectively suppressing the migration and epithelial-mesenchymal transition (EMT) of hepatic stellate cells. Additionally, low Pi stress significantly increased the antioxidant stress response. It is worth noting that low Pi stress indirectly inhibited the activation and migration of HSCs by suppressing transforming growth factor ß (TGF-ß) expression in macrophages. In a rat model of liver fibrosis, oral administration of sevelamer significantly decreased blood phosphorus levels, improved liver function, reduced liver inflammation, and increased the antioxidant stress response in the liver. Our study revealed that the key mechanism by which sevelamer inhibited liver fibrosis involved binding to gastrointestinal phosphate, resulting in a decrease in blood phosphorus levels, the downregulation of TGF-ß expression in macrophages, and the inhibition of HSC migration and fibrosis-related protein expression. Therefore, our results suggest that sevelamer-induced low Pi stress can attenuate hepatic stellate cell activation and inhibit the progression of liver fibrosis, making it a potential option for the treatment of liver fibrosis and other refractory chronic liver diseases.

[Mechanism of gigantol in transmembrane transport in human lens epithelial cells].

Gigantol is a phenolic component of precious Chinese medicine Dendrobii Caulis, which has many pharmacological activities such as prevent tumor and diabetic cataract. This paper aimed to investigate the molecular mechanism of gigantol in transmembrane transport in human lens epithelial cells(HLECs). Immortalized HLECs were cultured in vitro and inoculated in the laser scanning confocal microscopy(LSCM) medium at 5 000 cells/mL. The fluorescence distribution and intensity of gigantol marked by fluorescence in HLECs were observed by LSCM, and the absorption and distribution of gigantol were expressed as fluorescence intensity. The transmembrane transport process of gigantol in HLECs were monitored. The effects of time, temperature, concentration, transport inhibitors, and different cell lines on the transmembrane absorption and transport of gigantol were compared. HLECs were inoculated on climbing plates of 6-well culture plates, and the ultrastructure of HLECs was detected by atomic force microscopy(AFM) during the transmembrane absorption of non-fluorescent labeled gigantol. The results showed that the transmembrane absorption of gigantol was in time and concentration-dependent manners, which was also able to specifically target HLECs. Energy and carrier transport inhibitors reduced gigantol absorption by HLECs. During transmembrane process of gigantol, the membrane surface of HLECs became rougher and presented different degrees of pits, indicating that the transmembrane transport of gigantol was achieved by active absorption of energy and carrier-mediated endocytosis.

[Mechanism of interaction between chrysin and leptin].

The study of interaction mechanism between chrysin and leptin was investigated by various spectroscopic techniques and atom force microscope. The ultraviolet spectrum presents a red shift in 200-220 nm after chrysin upon. And there is a structure alternative showed in 270 nm when the concentration ratio of chrysin and leptin in 10-15. From the fluorescence spectrum, it was found that chrysin could combine with leptin in physiological condition. The binding constant (Ka) values, at 298 K and 310 K, were (0.41±0.05)×106 and (3.26±0.46)×106 L·mol⁻¹, and the binding site number were 1.02±0.04 and 0.51±0.01, respectively. The atom force microscope results showed that the dimension of leptin molecules became more swollen after binding with chrysin because of the hydrophobicity. These results demonstrate that the mechanism of chrysin and leptin interaction could play a role in leptin adjust in human body, and it could provide a new aspect for the study of obesity treatment.

[Experimental study on Dendrobium candidum polysaccharides on promotion of hair growth].

OBJECTIVE: To observe the effect and mechanism of Dendrobium candidum polysaccharides (DCP) in promoting hair growth, in order to lay a foundation for the development and utilization of D. candidum. METHOD: The water-extraction and alcohol-precipitation method was adopted to extract DCP, and the phenol-sulphuric acid method was used to determine its content. Thirty C57BL6J mice were collected to establish the hair loss model with hair removal cream. They were randomly divided into the control group, the positive control group and the DCP group, and given 0.2 mL of ultra-pure water, minoxidil tincture and DCP (5.0 g x L(-1)) 21 days. The mice hair growth scoring standard was adopted to evaluate the hair growth of C57BL/6J mice at 7, 14 d. The hairs in unit hair-losing areas of treated C57BL/6J mice at 21 d were weighed to evaluate the effect of DCP on the promotion of hair growth. MTT assay and RT-PCR method were used to evaluate the effect of DCP on the proliferatin of HaCaT cells and the mRNA expression of VEGF in HaCaT cells. RESULT: The extraction percent of DCP was 29.87%, and its content was 79.65%. The average scores for the hair growth and weight of C57BL/6J mice of DCP group were much higher than the control group. The survival rate and mRNA expression of VEGF of HaCaT cells were much higher than the control group. CONCLUSION: DCP has the effect in promoting hair growth. Its mechanism may be related to the up-regulation of the mRNA expression of VEGF.

[Experimental study on preclinical quality control, urgent poison and irritation of Dendrobium aurantiacum eye drops, a class I new drug against diabetic cataract].

To establish a quality control method of Dendrobium aurantiacum eye drops, in order to evaluate acute toxicity, irritation and irritability and lay a foundation for its development and utilization in the future. The content of gigantol and SA in D. aurantiacum eye drops were determined by high-performance liquid chromatography (HPLC). The linear ranges of gigantol and SA were 0.040 8-1.530 0 g x L(-1) (r = 0.999 9) and 0.100 8-0.504 0 g x L(-1) (r = 0.999 9), with the average recoveries being 100.8%, 99.84%, and RSD being 1.4%, 1.8% (n = 9) respectively. The sample solution was stable at room temperature within 72 h. The acute toxicity test showed no toxic reaction of D. aurantiacum eye drops in mice. The irritating test for single-dose and multiple-dose administrations of D. aurantiacum eye drops and physiological saline in rabbit eyes and skin, as well as the allergic test in guinea pigs showed no eye irritation and skin irritation and irritability. These findings indicated that D. aurantiacum eye drops are safe and stable, with a good druggability.

[Studies on functional genes of Chinese herbal medicine].

In order to establish the foundation for modernization of Chinese herbal medicine, discovery of the functional genes related with the bioactive components of Chinese herbs and the rules of their expression was progressed for determining the regulatory mechanism, obtaining the core metabolic pathway and key regulatory factors of the medicinal components synthesis. In this article, the studies about plant's functional genes at home and abroad was introduced in three aspects: the pattern plants (rice, thaliana, etc.), the main technologic strategy (gene expression differentia, sequential tag of gene expression, DNA microarray technique and gene expression sequential analysis) and bio-informative method (comparative genomics). The current status of researches involving biosynthesis genes of flavonoids compounds and taxol, and the plant P450 genes were introduced. And the study of dendrobium functional genes conducted in authors' lab was also reviewed.