In Vi Vo and in Vi Tro Screening of the Dyslipidemic Antihypertensives, Studying the Mechanism to Modulate Signaling Srebp and Ppar in the Renal Cells, and Investigating the Cotherapy with Mountain Celery Seed Aqueous Extract in Reducing Worsen Renal F(3/3)

Hypertension is a common manifestation related with the acute and chronic kidney diseases, as a result, generally referred as “the renal hypertension”. The renal function is closely associated with the modulation of hypertension. In order to avoid the complication from cardiovascular diseases, even only at an early stage with slight degree of renal disease, an early treatment is recommended. Clinically, the therapeutic strategy for patients with renal disease normally depends on the degree of proteinuria. Currently, multiple cotherapy is recommended. The antihypertensive drugs are usually classified into five categories depending on their pharmacological action mechanism, i.e. diuretics, antiadrenergics, calcium blockers, angiotensin II receptor antagonists, and angiotensin converting enzyme inhibitors. The administration is evaluated with the cardiovascular risk and pressure index. Literally, certain antihypertensives could increase the blood triglycerides total cholesterol, the ratio of LDL/total cholesterol, and at the same time decrease the ratio of HDL/total cholesterol, while some have showed effects absolutely contrary to these. These reports are rather limited and based on only few clinical data. Dyslipidemia tends to damage kidneys. The signaling PPAR (peroxisome proliferator-activated receptor) and SREBP (sterol regulatory element binding protein) are transcriptional factors, associated with the homeostasis of lipid metabolism, are modulated by signal pathways PI3k/Akt and AMPK. Only few literature cited whether the dyslipidemia as well as the further renal damage induced by hypertensives takes the pathway via modulating these two signals. Mountain celery seed aqueous extract (MCSAE) contains 3-n-Butylphthalide with the functions of hypotensive as well as a hyocholesterolemic. The high-soluble arabinogalactan and polyphenols in MCSAE play a synergistic hypotriglyceridemic and hypocholesterolemic role in hamsters. We hypothesize that the cotherapy of antihypertensives with MCSAE could reduce the risks of renal damages and further worsen to renal fibrosis associated with antihypertensive alone therapy. This project will carry out a three-year program. In the first and the second years, the in vivo and in vitro screening of the dyslipidemic hypertensives and at the same time their relation with the PPAR and SREBP will be studied. And in the third year, we will explore the outcome of cotherapy with MCSAE to examine whether MCSAE could inhibit the renal lipid accumulation and dyslipidemia to avoid the progress to renal fibrosis.