ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats （SHR）. In this experiment， 50 SHR rats were randomly grouped as follows： model （n=8）， captopril （0.01 g·kg^-1） （n=6）， low-dose blank Fufang Lingjiao Jiangya pills （0.342 g·kg^-1） （n=6）， high-dose blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1） （n=6）， low-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， high-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）， low-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， and high-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）. Additionally， 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration， 3 h post administration， and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions， 48 SHR rats were randomly grouped as follows： model， blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1）， antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1）， 2× goat horn-containing Fufang Lingjiao Jiangya pills （0.824 g·kg^-1）， 4× goat horn Fufang Lingjiao Jiangya pills （0.969 g·kg^-1）， and 6× goat horn Fufang Lingjiao Jiangya pills （1.112 g·kg^-1）. The normal group included 8 WKY rats， and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks， and blood pressure was recorded at various time points （pre-administration， 3 h post administration， and on days 4， 7， 10， and 14 of administration）. Serum levels of angiotensin-converting enzyme （ACE）， angiotensin Ⅱ（Ang Ⅱ）， renin， and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart， kidney， and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2， angiotensin Ⅱ type 1 receptor （AT1R）， and angiotensinogen （AGT） in the kidney tissue were determined by Western blot， while the expression of nuclear factor （NF）-κB p65 and Toll-like receptor 4 （TLR4） in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group， all treatment groups showed lowered blood pressure （P<0.05， P<0.01）， and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group， the model group showed elevated serum levels of ACE， Ang Ⅱ， renin， and IL-6， while the elevations were declined in the Fufang Lingjiao Jiangya pills groups （P<0.05， P<0.01）. Pathological changes in the heart， kidney， and thoracic aorta were alleviated in all the treatment groups， with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R， AGT， NF-κB p65， and TLR4 and up-regulated protein levels of ACE2 （P<0.05， P<0.01） compared with model group， with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system （RAAS） and TLR4/NF-κB signaling pathways.

[Objective]To investigate the protective effect of Wuling Powder on hyperlipidemic(HLP) mice and the underlying mechanism.[Methods]Forty-eight male ICR mice were randomly divided into six groups:normal,model,Ezetimibe and Wuling Powder low,middle,high dose groups. Mice in all groups were treated with a high-fat diet for 8 weeks,except for normal group. Meanwhile,the mice in drug intervention groups were treated with Ezetimibe or Wuling Powder. General physical signs of mice in each group were observed and recorded,total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C) and total bile acid(TBA) were detected. Liver lipid deposition was detected by hematoxylin-eosin(HE) staining and oil red staining. Cholesterol ester transfer protein(CETP) and recombinant phospholipid transfer protein(PLTP) was detected with enzyme-linked immunosorbent assay(ELISA). Immunohistochemistry was used to detect the expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Ultra-high performance liquid chromatograph coupled triple quadrupole mass spectrometer(UPLC-MS/MS) was applied to measure bile acid(BAs) levels in liver tissue. Expression of intestine Takeda G protein-coupled receptor 5(TGR5) and farnesoid X receptor(FXR1) was detected with fluorescence analysis.[Results]Wuling Powder could inhibit the increase in body weight of mice induced by high-fat diet. In the 4th week,low dose group of Wuling Powder reduced TC level(P<0.01),each group of Wuling Powder reduced the level of TG(P<0.01);in the 8th week,high dose of Wuling Powder could increase the level of TG(P<0.05),there was no statistical significance in the level of TC,HDL-C and LDL-C(P>0.05). Wuling Powder could reduce hepatic cell fat vacuoles and number of lipid droplets;middle and high doses of Wuling Powder could increase the level of PLTP(P<0.01),low and high doses of Wuling Powder could increase the level of CETP(P<0.05,P<0.01),reduce serum level of TBA,and increase immunohistochemical detection of CYP7A1 expression in the liver(P<0.01),and restore disorders in BAs metabilism,at the same time,simultaneously reducing the levels of TGR5 and FXR1 in the intestine.[Conclusion]Wuling Powder can reduce the level of blood lipids in HLP mice,and its mechanism may be related to promote the reverse transport of cholesterol by increasing the levels of CETP and PLTP,and regulate liver BAs metabolism balance of HLP mice.

[Objective]To investigate the protective effect of Wuling Powder on hyperlipidemic(HLP) mice and the underlying mechanism.[Methods]Forty-eight male ICR mice were randomly divided into six groups:normal,model,Ezetimibe and Wuling Powder low,middle,high dose groups. Mice in all groups were treated with a high-fat diet for 8 weeks,except for normal group. Meanwhile,the mice in drug intervention groups were treated with Ezetimibe or Wuling Powder. General physical signs of mice in each group were observed and recorded,total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C) and total bile acid(TBA) were detected. Liver lipid deposition was detected by hematoxylin-eosin(HE) staining and oil red staining. Cholesterol ester transfer protein(CETP) and recombinant phospholipid transfer protein(PLTP) was detected with enzyme-linked immunosorbent assay(ELISA). Immunohistochemistry was used to detect the expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Ultra-high performance liquid chromatograph coupled triple quadrupole mass spectrometer(UPLC-MS/MS) was applied to measure bile acid(BAs) levels in liver tissue. Expression of intestine Takeda G protein-coupled receptor 5(TGR5) and farnesoid X receptor(FXR1) was detected with fluorescence analysis.[Results]Wuling Powder could inhibit the increase in body weight of mice induced by high-fat diet. In the 4th week,low dose group of Wuling Powder reduced TC level(P<0.01),each group of Wuling Powder reduced the level of TG(P<0.01);in the 8th week,high dose of Wuling Powder could increase the level of TG(P<0.05),there was no statistical significance in the level of TC,HDL-C and LDL-C(P>0.05). Wuling Powder could reduce hepatic cell fat vacuoles and number of lipid droplets;middle and high doses of Wuling Powder could increase the level of PLTP(P<0.01),low and high doses of Wuling Powder could increase the level of CETP(P<0.05,P<0.01),reduce serum level of TBA,and increase immunohistochemical detection of CYP7A1 expression in the liver(P<0.01),and restore disorders in BAs metabilism,at the same time,simultaneously reducing the levels of TGR5 and FXR1 in the intestine.[Conclusion]Wuling Powder can reduce the level of blood lipids in HLP mice,and its mechanism may be related to promote the reverse transport of cholesterol by increasing the levels of CETP and PLTP,and regulate liver BAs metabolism balance of HLP mice.