Anti-fibrotic mechanism of Sedum sarmentosum total flavanones in inhibiting activation of HSC by regulating Smads / 中国中药杂志

This paper was aimed to observe the interventional effect of Sedum sarmentosum total flavanones on hepatic fibrosis and its possible mechanism through the subcutaneous injection of CCl_4 in rats. Sixty male SD rats were randomly divided into normal control group, model group, low-dose, medium-dose, high-dose S. sarmentosum total flavanones groups(100, 200, 400 mg·kg~(-1)) and silymarin group(200 mg·kg~(-1)). The model of liver fibrosis was established by subcutaneous injection of rats with 40% CCl_4. After the modeling, the drug groups were intragastrically administered with corresponding drugs once a day for consecutively five weeks, while the normal group and the model group were given 0.9% sodium chloride solution during the same period. After the experiment, the general conditions of rats and the pathological changes of liver tissues were observed, and the contents of serum ALT, AST, HA and LN were measured. Besides, the expressions of the protein and relevant mRNA of Smad2/3, Smad4 and α-SMA in rats were detected. Compared with model group, S. sarmentosum total flavanones could significantly increase the rats' body weight, inhibit the increase of liver and spleen index in rats of liver fibrosis, reduce the levels of ALT, AST, HA and LN, and alleviate pathological changes. Meanwhile, compared with the model group, the protein expressions of Smad2/3, Smad4 and α-SMA as well as relevant mRNA expressions in S. sarmentosum total flavanones group were obviously decreased, while Smad7 expression was markedly increased. As a result, S. sarmentosum total flavanones could significantly alleviate CCl_4-induced liver fibrosis, and its anti-hepatic fibrosis mechanism may be related to intervention with Smads pathway, so as to inhibit the activation of HSC.

Simultaneous Determination of 8 Components in Total Flavanones of Sedum sarmentosum Bunge by UPLC-MS/MS / 中国药房

OBJECTIVE:To establish a method for simultaneous determination of hyperoside,quercitrin,luteoloside, kaempferol,quercetin,rutin,luteolin and isorhamnetin in total flavanones of Sedum sarmentosum Bunge. METHODS:UPLC-MS/MS method was adopted. The determination was performed on ZOBAX SB C18column with mobile phase consisted of methanol-5 mmol/L ammonium formate aqueous solution(45:55,V/V)at the flow rate of 0.4 mL/min. The column temperature was 30 ℃, and sample size was 2 μL. The electrospray ionization source(ESI)was used;ion source temperature was 400 ℃;desolvation temperature was 300 ℃;desolvation gas flow was 600 L/h;capillary voltage was 3 000 V;nebuliser pressure was 45 psi;the work mode was multiple reaction monitoring mode;detection mode was negative ion mode. The established method was used to determine the contents of 8 components in 3 batches of total flavanones of Sedum sarmentosum Bunge. RESULTS:The linear ranges of hyperoside,quercitrin,luteoloside,kaempferol,quercetin,rutin,luteolin and isorhamnetin were 10.0-640.0,0.5-32.0, 4.5-288.0,8.0-512.0,50.0-3 200.0,2.0-128.0,12.5-800.0 and 25.2-1 612.8 ng/mL(r≥0.991 4),respectively. The limits of detection were 5.0,0.25,2.25,4.0,25.0,1.0,6.25 and 12.6 ng/mL,respectively.The limits of quantitation were 10.0,0.5,4.5, 8.0,50.0,2.0,12.5 and 25.2 ng/mL,separately. RSDs of precision,stability(24 h)and reproducibility tests were no more than 4.3%(n=6). The recoveries were 95.9%-100.6%,and RSDs were 1.5%-3.8%(n=6). The contents of hyperoside,quercitrin, luteoloside,kaempferol,quercetin,rutin,luteolin and isorhamnetin in 3 batches of total flavanones of Sedum sarmentosum Bunge were 507.88-560.37,42.95-50.36,63.52-71.80,1 695.10-1 753.27,10 569.28-10 612.99,25.76-30.13,2 795.22-2 877.43 and 4 869.55-4 971.30 μg/g,respectively. CONCLUSIONS:The established method can be used for simultaneous determination of 8 components in total flavanones of Sedum sarmentosum Bunge.