[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.

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

660

Literatures (Medical) associated with SREBF1 x SREBP-2

01 Jun 2025·The Journal of Nutritional Biochemistry

Exposure to bisphenol A and sodium nitrate found in processed meat induces endocrine disruption and dyslipidemia through PI3K/AKT/SREBP pathway in zebrafish larvae

Article

Author: Nayak, Santosh Pushpa Ramya Ranjan ; Pasupuleti, Mukesh ; Arockiaraj, Jesu ; Ramamurthy, Karthikeyan ; Rajagopal, Rajakrishnan ; Das, Anamika

Meat is a staple in many cultural diets, and the consumption of processed meats has increased significantly worldwide. The widespread use of sodium nitrate (NaNO₃) as a preservative and the unintentional leaching of bisphenol A (BPA) from packaging into meats have raised health concerns. This study evaluates the combined toxicity of BPA and NaNO₃ despite their individual safety assessments. Our findings reveal that coexposure to BPA and NaNO₃ at levels found in processed meats induces mortality and malformations in zebrafish larvae. The combined exposure triggers oxidative stress, lipid peroxidation, dyslipidemia, inflammation, and apoptosis. Network toxicology analysis elucidates the molecular mechanisms underlying metabolic dysfunction caused by these substances. Dysregulation of genes related to thyroid function (tsh-β, dio-1, thr-b) and inflammation (tnf-α, il-1β, il-6, nfκb) was observed in the co-exposure group. Additionally, this group exhibited increased lipid accumulation, elevated cholesterol and triglyceride levels, and dysregulation of essential lipid metabolism genes (srebp2, pcsk9). Co-exposure also impaired larval motility and behavior, evidenced by hypolocomotion and reduced acetylcholinesterase levels. Further gene expression analysis showed increased levels of pi3k and akt, two major signaling molecules. Ultimately, the simultaneous exposure to BPA and NaNO₃ leads to disruptions in the endocrine system and abnormal lipid levels via activating the PI3K/AKT/SREBP pathway.

01 Apr 2025·Journal of Ethnopharmacology

Saffron and its active constituents ameliorate hypercholesterolemia by inhibiting PCSK9 and modulating Sortilin, LDLR, and SREBP-2 signaling in high fat diet induced hypercholesterolemic C57BL/6 mice

Article

Author: Sj, Aditya Rao ; Siddiq A, Aisha ; Martin, Asha ; Dileep, Shaik Abdul ; Singam, Siva Sankara Reddy

ETHNOPHARMACOLOGICAL RELEVANCESaffron (Crocus sativus L.) has long been used in Ayurveda, Iranian, and Chinese traditional medicine as a natural remedy for hypercholesterolemia, obesity, and liver disorders though its therapeutic mechanism remains unclear.AIM OF THE STUDYThis study explores the mechanism by which saffron extract (SE), crocin (CN), and crocetin (CR) mitigate high fat diet (HFD) induced hypercholesterolemia and hepatic inflammation in C57BL/6 mice, focusing on their inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9).MATERIALS AND METHODSC57BL/6 mice (N = 10/group) were fed either a, normal diet, HFD, or HFD supplemented with SE, CN, CR, or atorvastatin for 12 weeks. Plasma lipids and inflammatory markers were measured. Histopathological changes were assessed via H&E and Sudan black staining. Gene expression was analyzed using qRT-PCR, and ligand-protein interactions were studied using molecular docking, simulation, and thermophoresis.RESULTSHFD-fed mice exhibited dyslipidemia, liver damage, and inflammation, which SE, CN, and CR significantly improved. Treatments reduced cholesterol, triglycerides, and reactive oxygen species, reversed fatty liver degeneration, and downregulated PCSK9 and sortilin expression while upregulating LDLR. They suppressed transcription factors SREBP-1C and SREBP-2 and reduced inflammatory markers, including TNF-α, while increasing IL-10 expression. CR reduced plasma PCSK9 secretion by 39.9 % (p < 0.05). Docking and simulation studies confirmed the strong binding potential of CR and CN to PCSK9.CONCLUSIONSaffron and its active components (CN and CR) are novel natural PCSK9 inhibitors that effectively ameliorate hypercholesterolemia by modulating sortilin, LDLR and SREBP-2 pathway, potentially opening the way for developing new therapeutic approaches for managing cholesterol related disorders.

01 Apr 2025·Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

D-allulose enhances lipid oxidation in HepG2 cells via peroxisome proliferator-activated receptor α (PPARα)

Article

Author: Haas, Michael J ; Mooradian, Arshag D ; Batch, Jennifer ; Graham, Lauren ; Warda, Firas

Lipid accumulation in hepatocytes in non-alcoholic steatohepatitis (NASH) is attributed partly to loss of insulin-responsiveness and/or an increased pro-inflammatory state. Since the rare sugar D-allulose has insulin mimetic and anti-inflammatory properties, its effects on lipid accumulation in liver-derived cells was tested. In HepG2 cells exposed to 200 μM oleic acid for 72 h, D-allulose treatment decreased intracellular lipid accumulation with an IC₅₀ = 0.45 ± 0.07 mM. A similar effect was observed in cells treated with 10 μM gemfibrozil. D-allulose and gemfibrozil treatment increased oleic acid β-oxidation. Both D-allulose and gemfibrozil increased peroxisome proliferator-activated receptor α (PPARα) expression (two-fold) relative to control cells, while retinoid X receptor was unchanged. D-allulose and gemfibrozil increased PPARα-dependent genes including those involved in fatty acid β-oxidation (acyl-coenzyme A oxidase 1, long-chain-fatty-acid-coenzyme A ligase 5, and carnitine palmitoyltransferase 1 A). D-allulose and gemfibrozil also increased PPARα reporter gene expression and phosphorylation (Serine 12) which were both inhibited by the mitogen-activated protein (MAP) kinase inhibitor PD098059. Other MAP kinase inhibitors, including SB203580, SP600125, and BIX10289 had no effect on reporter gene expression. Oleic acid treatment, but not D-allulose or gemfibrozil, decreased sterol response element binding protein 1 and sterol response element binding protein 2 expression relative to cells not exposed to oleic acid, while peroxisome proliferator-activated receptor γ expression did not change. These results indicate that D-alluose mimics gemfibrozil effects on lipid content in HepG2 cells by promoting fatty acid β-oxidation via PPARα.

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