[Translation] A single-center, randomized, double-blind, single- and multiple-dose escalation study to evaluate the safety, tolerability, pharmacokinetics, and food effects of HPN-01 enteric-coated capsules in healthy Chinese subjects.

主要目的：考察健康受试者单、多次口服给予HPN-01肠溶胶囊的安全性和耐受性；次要目的：评价健康受试者单、多次口服给予HPN-01肠溶胶囊的药代动力学特性；评价食物对健康受试者单次服用HPN-01肠溶胶囊后药代动力学特性的影响；

[Translation]

Main purpose: To investigate the safety and tolerability of HPN-01 enteric-coated capsules after single and multiple oral administration to healthy subjects; Secondary purpose: To evaluate the pharmacokinetic properties of HPN-01 enteric-coated capsules after single and multiple oral administration to healthy subjects; To evaluate the effect of food on the pharmacokinetic properties of HPN-01 enteric-coated capsules after single administration to healthy subjects;

Start Date23 Apr 2021

Sponsor / Collaborator

Shanghai Hepuhua Pharmaceutical Technology Co Ltd

NCT04481594 / Unknown statusPhase 1

A Randomized, Double-Blind, Placebo Controlled, Sequential Parallel Group, Single and Multiple Ascending Doses (SAD/MAD) Study Following Oral Administration in Healthy Subjects to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HPN-01

This study is a randomized, double-blind, placebo-controlled first-in-human study in which the safety, tolerability, pharmacokinetics and pharmacodynamics of orally administered HPN-01 will be evaluated in healthy subjects

Start Date08 Sep 2020

Sponsor / Collaborator

Hepanova, Inc.Startup

100 Clinical Results associated with SREBF1 x SREBP-2

100 Translational Medicine associated with SREBF1 x SREBP-2

0 Patents (Medical) associated with SREBF1 x SREBP-2

620

Literatures (Medical) associated with SREBF1 x SREBP-2

01 Dec 2024·Environmental Pollution

Lower-dose vs high-dose oral bisphenol S action of lipid metabolism in liver of male SD rat via mediating different SREBP isoforms

Article

Author: Ru, Shaoguo ; Wu, Dehua ; Peng, Hongyuan ; Wang, Weiwei ; Su, Enping ; Wang, Bo ; Li, Jiali

Bisphenol S (BPS) is commonly used for the industrial production of thermal paper, polycarbonate plastics, epoxy resins and other materials. Studies have reported that BPS can lead to triglyceride (TAG) or/and cholesterol (CHO) accumulation in the liver in zebrafish and mice, but the reasons for the different types of lipids that accumulate in the liver following BPS exposure are unclear. Here, the influences of lower-dose (10 mg/kg body weight/day) and high-dose (50 mg/kg body weight/day) BPS exposure to male SD rats on the accumulation of different lipids in the liver were explored. The results indicated that BPS treatment increased the levels of acetyl-CoA and glycogen in the liver. A lower dose of BPS upregulated the mRNA and protein expression levels of sterol regulatory element-binding protein 1 (srebp1), which is involved in the de novo synthesis of TAG in the liver, thus promoting the synthesis of glycerides (diacetylglyceride and TAG). However, a higher dose of BPS induced CHO accumulation, but inhibited the mRNA expression of genes (i.e., srebp2, hmgcr and hmgcs) involved in the de novo synthesis of CHO in the liver. Excessive accumulation of glycerides and CHO led to destruction of the physiological structure of rat liver, causing disorders in liver function. Our data provide new insight into the different mechanisms by which glyceride and CHO accumulate in the liver after BPS exposure.

01 Nov 2024·Biomedicine & Pharmacotherapy

The potential role of transcription factor sterol regulatory element binding proteins (SREBPs) in Alzheimer's disease

Review

Author: Fan, Panpan ; Zhao, Qingchun ; Chen, Huanhua ; Lin, Junjie ; Gu, Yujia ; Zhou, Lijun ; Xu, Zihua ; Li, Xinzhu ; Wang, Weiyi ; Zheng, Fangyuan ; Liu, Siyuan ; Yang, Aizhu

Sterol regulatory element binding proteins (SREBPs) are a series of cholesterol-related transcription factors. Their role in regulating brain cholesterol biosynthesis, amyloid accumulation, and tau tangles formation has been intensively studied in protein-protein interaction analysis based on genes in clinical databases. SREBPs play an important role in maintaining cholesterol homeostasis in the brain. There are three subtypes of SREBPs, SREBP-1a stimulates the expression of genes related to cholesterol and fatty acid synthesis, SREBP-1c stimulates adipogenesis, and SREBP-2 stimulates cholesterol synthase and LDL receptors. SREBP-2 is activated in response to cholesterol depletion and stimulates a compensatory upregulation of cholesterol uptake and synthesis. Previous studies have shown that inhibition of SREBP-2 reduces cholesterol and amyloid accumulation, and new research suggests that SREBPs play a multifaceted role in Alzheimer's disease. Here, we highlight the importance of SREBPs in AD, in terms of multiple pathways regulating cholesterol in the brain, and primarily demonstrate the potential of SREBP-2 inhibitors. There was a trend towards a significant increase in the expression levels of different SREBP isoforms in AD patients compared to healthy controls. Therefore, there is a close link between SREBPs and AD, and this review analyses the potential role of SREBPs in the treatment of AD. In addition, we systematically reviewed the research progress of SREBPs in AD, and this review will provide more innovative insights into the pathogenesis and treatment of AD and new strategies for drug development in AD.

01 Oct 2024·The Journal of Steroid Biochemistry and Molecular Biology

β-sitosterol alleviates high fatty acid-induced lipid accumulation in calf hepatocytes by regulating cholesterol metabolism

Article

Author: Li, Zhendong ; Loor, Juan J ; Xu, Chuang ; Zhang, Bingbing ; Wang, Shuang ; Mauck, John ; Jia, Bin ; Yang, Wei ; Yang, Mingmao ; Fan, Wenwen ; Tian, Yan

A significant reduction in plasma concentration of cholesterol during early lactation is a common occurrence in high-yielding dairy cows. An insufficient synthesis of cholesterol in the liver has been linked to lipid accumulation caused by high concentrations of fatty acids during negative energy balance (NEB). As ruminant diets do not provide quantitative amounts of cholesterol for absorption, phytosterols such as β-sitosterol may serve to mitigate the shortfall in cholesterol within the liver during NEB. To gain mechanistic insights, primary hepatocytes were isolated from healthy female 1-day old calves for in vitro studies with or without 1.2 mM fatty acids (FA) to induce metabolic stress. Furthermore, hepatocytes were treated with 50 μM β-sitosterol with or without FA. Data were analyzed by one-way ANOVA with subsequent Bonferroni correction. Results revealed that calf hepatocytes treated with FA had greater content of non-esterified fatty acids (NEFA) and triacylglycerol (TAG), and greater mRNA and protein abundance of the lipid synthesis-related SREBF1 and FASN. In contrast, mRNA and protein of CPT1A (fatty acid oxidation) and the cholesterol metabolism-related targets SREBF2, HMGCR, ACAT2, APOA1, ABCA1 and ABCG5 was lower. Content of the antioxidant-related glutathione (GSH) and activities of superoxide dismutase (SOD) also was lower. Compared with FA challenge alone, 50 μM β-sitosterol led to greater mRNA and protein abundance of SREBF2, HMGCR, ACAT2 and ABCG5, and greater content of GSH and activity of SOD. In contrast, compared with the FA group, the mRNA and protein abundance of SREBF1 and ACC1 and the content of TAG and NEFA in the β-sitosterol + FA group were lower. Overall, β-sitosterol can promote cholesterol metabolism and reduce oxidative stress while reducing lipid accumulation in hepatocytes challenged with high concentrations of fatty acids.

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