[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

635

Literatures (Medical) associated with SREBF1 x SREBP-2

01 Jan 2025·Animal Reproduction Science

Acute heat stress regulates estradiol synthesis in ovine ovarian granulosa cells through the SREBPs/MVK–LHR pathway

Article

Author: Cao, Shaoxian ; Li, Yinxia ; Qian, Yong ; Shu, Jiaao ; Zhang, Jun ; Ding, Qiang ; Wang, Huili ; Meng, Chunhua ; Zhang, Jianli ; Li, Fan

The adverse effects of heat stress on reproductive performance of sheep are becoming increasingly severe. Previous research has revealed that heat stress decreases both cholesterol and estradiol content; however, regulation of estradiol by cholesterol and its regulatory mechanism under heat stress are unclear. Mevalonate kinase (MVK), a key cholesterol synthesis pathway enzyme, binds to the luteinizing hormone receptor (LHR; a key gene regulating hormone synthesis) mRNA. In this study, ovine ovarian granulosa cells (GCs) were used in an in vitro model. To elucidate the underlying molecular mechanism, immunofluorescence, quantitative reverse transcription polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay, and an RNA electrophoretic mobility shift assay (REMSA) were used to investigate whether the decrease in cholesterol caused by acute heat stress resulted in a decrease in estradiol synthesis. Acute heat stress reduced the cholesterol content in ovine ovarian GCs, which transactivated the cholesterol synthesis pathway corresponding to the gene expression of sterol regulatory element-binding protein (SREBP-1A), SREBP-2, and MVK. Upregulated MVK increased the MVK-LHR mRNA complex, which caused LHR mRNA decay and downregulation, further leading to the downregulation of CYP19A1 and a decrease in estradiol. The cholesterol synthesis inhibitor, PF-429242, alleviated the decrease in estradiol synthesis caused by acute heat stress. Overall, acute heat stress caused a decrease in total cholesterol, which transactivated the expression of cholesterol synthesis genes, such as SREBP-1A, SREBP2, and MVK, increasing the MVK-LHR complex, downregulating LHR expression, and further decreasing estradiol.

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·Food Research International

Compound oolong tea ameliorates lipid accumulation through AMPK-PPAR pathway of hepatic lipid metabolism and modulates gut microbiota in HFD induced mice

Article

Author: Shi, Xiaolei ; Liu, Jun ; Huang, Hao ; Zhao, Jin ; Yuan, Yiwei ; Gong, Mingxiu ; Xu, Qianqian

Based on the modified traditional Chinese formula, Compound Oolong tea (WLT) is composed of six herbal medicines which have beneficial effects. The present study aimed to assess the effects of WLT on lipid metabolism and gut microbiota in the mouse obesity model.Totally 32 mice were randomized into 4 groups including normal control (NC), high-fat diet model (HFD), positive control (PC) receiving atorvastatin 10 mg/kg/d, and WLT group with WLT water extra 300 mg/kg/d. The HFD, PC, WLT groups were fed a High-fat Diet. The results show that body weight, Lee's index, liver index and fat index were reduced in WLT. Moreover, the accumulation of TC, TG, and LDL-C were lower, and the level of serum HDL-C in WLT was higher than HFD. The activities of ALT and AST were reduced, and the glucose tolerance was improved in WLT. Furthermore, the relative gene expression of hepatic such as Pparγ, Lxr, Srebp-1c, Srebp-2, Scd-1, Acc-1, Fas were upregulated, and Hmgcr was downregulated in WLT compared to HFD. The relative protein expression of PPARγ, SREBP-1, FAS, and SCD-1 were decreased, and p-AMPK/AMPK and p-ACC-1/ACC-1 were increased in WLT compared with HFD. In addition, the diversity of gut microbiota was increased in mice, with an increase in Bacteroidota and a decrease in Firmicutes and Desulfovibrionales were decreased in WLT, compared with HFD. Briefly, WLT improves hepatic lipid metabolism through the AMPK-PPAR pathway and regulates the gut microbiome. These findings suggest that WLT could potentially be used as a functional food ingredients for preventing obesity.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis