This study will investigate whether the addition of Quercetin or Alpha-Lipoic Acid (ALA) to standard metformin therapy can improve symptoms, hormone levels, metabolic health, and quality of life in women with polycystic ovary syndrome (PCOS). Over 3 months, participants will be randomly assigned to one of three groups: metformin alone, metformin plus Quercetin, or metformin plus ALA. Researchers will measure changes in hormones, blood sugar, cholesterol, and antioxidant markers, as well as quality of life and medication adherence. Physical measurements and side effects will also be recorded to assess safety and overall benefit.

Start Date20 Sep 2025

Sponsor / Collaborator

University of Al-Mustansiriyah

CTR20242631

/ CompletedPhase 1

一项在轻、中度肾功能损害受试者与匹配的肾功能正常对照受试者中评价HTD1801药代动力学的I期、开放标签、平行组、单次给药研究

[Translation] A Phase I, open-label, parallel-group, single-dose study evaluating the pharmacokinetics of HTD1801 in subjects with mild to moderate renal impairment and matched controls with normal renal function

首要目的：在轻度和中度肾功能损害受试者与匹配的肾功能正常对照受试者中确定HTD1801的单次给药PK特征。次要目的：1、在轻度和中度肾功能损害受试者与匹配的肾功能正常对照受试者中评估HTD1801的安全性和耐受性；2、在轻度和中度肾功能损害受试者与匹配的肾功能正常对照受试者中评估HTD1801的血浆蛋白结合情况；3、评估基线肾功能与PK参数之间的关系。

[Translation]

Primary objective: To determine the single-dose PK characteristics of HTD1801 in subjects with mild and moderate renal impairment and matched control subjects with normal renal function. Secondary objectives: 1. To evaluate the safety and tolerability of HTD1801 in subjects with mild and moderate renal impairment and matched control subjects with normal renal function; 2. To evaluate the plasma protein binding of HTD1801 in subjects with mild and moderate renal impairment and matched control subjects with normal renal function; 3. To evaluate the relationship between baseline renal function and PK parameters.

Start Date02 Sep 2024

Sponsor / Collaborator

Hightide Therapeutics, Inc.

CTR20242600

/ CompletedPhase 1

[14C-B]HTD1801在健康受试者中的单中心、非随机、开放、单次给药的物质平衡研究

[Translation] [14C-B] A single-center, non-randomized, open-label, single-dose mass balance study of HTD1801 in healthy subjects

主要研究目的： 1) 定量分析男性健康受试者单次口服[14C-B]HTD1801后，排泄物（尿液和粪便）中的总放射性量，获得人体放射性的累积排泄率； 2) 鉴定男性健康受试者单次口服[14C-B]HTD1801后人体内的代谢产物，确定主要生物转化途径和主要代谢产物结构； 3) 考察男性健康受试者单次口服[14C-B]HTD1801后，全血和血浆中总放射性的分配情况以及血浆总放射性的药代动力学。次要研究目的： 1) 采用已验证的液相色谱-串联质谱法（LC-MS/MS）定量分析血浆中的小檗碱及其主要代谢产物（如适用）的浓度，获得小檗碱及其主要代谢产物（如适用）的药动学参数； 2) 评价[14C-B]HTD1801单次给药后男性健康受试者的安全性。

[Translation]

Main study objectives: 1) To quantitatively analyze the total radioactivity in excreta (urine and feces) after a single oral administration of [14C-B]HTD1801 to healthy male subjects, and obtain the cumulative excretion rate of radioactivity in the human body; 2) To identify the metabolites in the human body after a single oral administration of [14C-B]HTD1801 to healthy male subjects, and determine the main biotransformation pathways and the structures of the main metabolites; 3) To investigate the distribution of total radioactivity in whole blood and plasma and the pharmacokinetics of total radioactivity in plasma after a single oral administration of [14C-B]HTD1801 to healthy male subjects. Secondary study objectives: 1) To quantitatively analyze the concentration of berberine and its main metabolites (if applicable) in plasma using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and obtain the pharmacokinetic parameters of berberine and its main metabolites (if applicable); 2) To evaluate the safety of healthy male subjects after a single administration of [14C-B]HTD1801.

Start Date12 Aug 2024

Sponsor / Collaborator

Hightide Therapeutics, Inc.

100 Clinical Results associated with AMPK x NLRP3

100 Translational Medicine associated with AMPK x NLRP3

0 Patents (Medical) associated with AMPK x NLRP3

433

Literatures (Medical) associated with AMPK x NLRP3

01 Apr 2026·TISSUE & CELL

Coupling regulation the pyroptosis and polarization of macrophage: Novel insights into the pathogenesis and immunotherapy of osteoarthritis

Review

Author: Song, Chao ; Su, Zhengwen ; Liu, Zongchao ; Hou, Xianghan ; Chen, Jingwen ; Liu, Tao ; Luo, Yingjin ; He, Yuheng ; Li, Feilong ; Hao, Pandeng

The pathological mechanism of osteoarthritis (OA) has evolved from being viewed as "simple mechanical wear" to being recognized as a chronic inflammatory disease driven by immune responses, metabolic imbalance, and mechanical stress. Synovial macrophages play a central role in the remodeling of the immune microenvironment, and their heterogeneity along with the imbalance between M1/M2 polarization can synergistically enhance joint inflammation, reprogram cartilage metabolism, and exacerbate tissue damage. Signaling networks such as NF-κB/MAPK, JAK/STAT, PI3K/Akt/mTOR-AMPK, Nrf2, Notch, and Wnt/β-catenin collectively regulate their polarization spectrum and functional states. The NLRP3 inflammasome-caspase-1-GSDMD axis-mediated pyroptosis serves as a key driver of disease initiation and progression, establishing a "polarization-metabolism-pyroptosis" tripartite pathological framework. The tripartite interaction among chondrocytes, fibroblast-like synoviocytes, and macrophages (CC-FLS-MC) further forms a cross-cellular inflammatory amplification network.Targeting these mechanisms, intervention strategies focus on multi-level immune modulation, including blocking the NLRP3-caspase-1-GSDMD pyroptosis axis, regulating macrophage polarization and metabolic reprogramming, and developing cell/nanocarrier-based drug delivery systems. Specific approaches encompass small-molecule inhibitors (e.g., NLRP3 and pyroptosis inhibitors), Nrf2/PPARγ agonists, MSC- or M2 macrophage-derived exosomes, and biomimetic nanoplatforms. These strategies aim to achieve "inhibition of the M1-pyroptosis-inflammatory cascade and promotion of M2-repair-metabolic reprogramming." In summary, comprehensive immune regulation targeting the coupling of macrophage polarization and pyroptosis, along with its metabolic basis, holds promise for providing new theoretical foundations and translational pathways for disease-modifying therapies and precision management of OA.

01 Feb 2026·INTERNATIONAL IMMUNOPHARMACOLOGY

Paeoniflorin suppresses cardiomyocyte pyroptosis and ameliorates diabetic cardiomyopathy by AMPK/Nrf2/NLRP3 pathway

Article

Author: Ren, Shan ; Lin, Yan ; Wu, Fengkai ; Liu, Hongyu ; Zhao, Yu ; Yang, Xue ; Liu, Yang ; Wang, Yingwanqi ; Wang, Jun ; Li, Guangwei ; Xiao, Wei ; Zhang, Huixiang

Investigating potential pharmaceutical agents for diabetic cardiomyopathy (DCM) represents a crucial avenue in diabetes research. Paeoniflorin (PF), derived from plants belonging to the Paeonia genus, has demonstrated potential in addressing cardiovascular conditions; however, its precise mechanism is still uncertain. This research employs various techniques, including MTT assay, ELISA, immunofluorescence, siRNA transfection technology, RT-qPCR, Western blot, and echocardiography, to investigate the protective impacts of PF on type I diabetic mice and H9C2 cells under high glucose conditions, emphasizing inflammatory responses and pyroptosis. Both the animal and cellular results indicated that PF can ameliorate abnormalities of cardiomyocyte surface area and the expressions of collagen type I, ANP, and BNP, while ameliorating cardiac function. Concurrently, PF downregulated the levels of various proteins, including NLRP3, Caspase-1, C-Caspase-1, GSDMD, GSDMD-N, as well as reducing the levels of interleukin-1 beta (IL-1β), interleukin-18 (IL-18), and lactate dehydrogenase (LDH). These results imply that PF may alleviate high glucose-induced myocardial hypertrophy and fibrosis, ameliorate cardiac function, and mitigate cardiomyocyte pyroptosis and inflammatory responses. The study reveals that the cardioprotective effects of PF anti-inflammation and anti-pyroptosis may be closely associated with the AMPK/Nrf2/NLRP3 pathway. This research elucidates the mechanism of PF in treating DCM by inhibiting pyroptosis and inflammatory responses, thereby providing new insights for the clinical prevention and treatment of DCM.

14 Jan 2026·JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

Natural Dietary Flavonoid Apigenin Mitigates Ulcerative Colitis via Modulating the AMPK/NF-κB/NLRP3 Signaling Axis

Article

Author: Mao, Zhongyi ; Yang, Yinan ; Qi, Guihong ; Zhao, Wenli ; Li, Peng ; Zou, Lin-En ; Mao, Xiaoshuang ; Yang, Ying ; Zhou, Mengsha ; Sun, Shihao

Ulcerative colitis (UC) is a challenging inflammatory disease with higher relapse and lower remission rates, urgently requiring effective and safe complementary treatment options. Apigenin (Api), a natural flavonoid from parsley and celery, exhibits potent antioxidant and anti-inflammatory activities. In mice with 2.5% DSS-induced acute colitis, Api markedly alleviated weight loss, colon shortening, and elevated DAI scores, while restoring mucosal integrity and reducing oxidative stress and inflammation. Mechanistically, Api can directly bind to AMPK to activate it, thereby alleviating oxidative stress and suppressing the NF-κB pathway, which in turn inhibits NLRP3 inflammasome activation. Moreover, Api directly binds to NLRP3, thereby inhibiting inflammasome activation. Through dual targeting of AMPK and NLRP3, Api cooperatively suppresses oxidative stress and inflammation in UC mice. Collectively, these findings demonstrate that Api protects against colitis via modulation of the AMPK/NF-κB/NLRP3 axis, highlighting its potential as a natural anti-inflammatory agent for intestinal health.

News (Medical) associated with AMPK x NLRP3

15 Dec 2022

·www.prnewswire.com

HighTide Therapeutics and Quotient Sciences Announce Agreement to Conduct a 14C Human ADME Program for HTD1801

Integrated Synthesis-to-Clinic® Program Will Support HTD1801's Clinical Development and Regulatory Submission Package ROCKVILLE, Md., SHENZHEN, China and NOTTINGHAM, England, Dec. 15, 2022 /PRNewswire/ -- HighTide Therapeutics, Inc. ("HighTide"), a globally integrated clinical-stage biopharmaceutical company focusing on novel multifunctional therapeutics for metabolic and digestive diseases, and Quotient Sciences, a drug development and manufacturing accelerator, have signed an agreement to support HighTide's HTD1801 program. The agreement will see Quotient Sciences perform a 14C human absorption, distribution, metabolism, and excretion (ADME) study for HighTide's lead drug candidate, HTD1801, to generate data to support HTD1801's clinical development. HTD1801 is a first-in-class new molecular entity. HighTide's continued clinical progress with HTD1801 includes an ongoing Phase 2 study for the treatment of type 2 diabetes (T2DM), the initiation of a global Phase 2b study for the treatment of nonalcoholic steatohepatitis (NASH), and the successful end-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) for primary sclerosing cholangitis (PSC). The U.S. FDA has granted HTD1801 Fast Track designation in both NASH and PSC. Quotient Sciences will be providing a fully integrated Synthesis-to-Clinic® program, from radiosynthesis of the 14C-labeled drug substance to the design and conduct of the human ADME study and delivery of the final clinical study report. The company is currently commencing radiochemistry activities and finalizing the clinical study design. Mark Egerton, PhD, CEO of Quotient Sciences, said: "We are excited to share our expertise in 14C-enabled drug development with HighTide to support their HTD1801 program, which has the potential to help many patients suffering from T2DM, NASH, and PSC worldwide. Our unique Synthesis-to-Clinic offering streamlines the entire human ADME process by integrating radiolabeled formulation development, real-time drug product manufacturing, and clinical testing in a single program of work led by a single project manager, reducing timelines and getting new medicines to patients faster." Liping Liu, PhD, Founder and CEO of HighTide, added: "We are very pleased to enter this collaboration with Quotient Sciences. Both parties have extensive expertise and experience in their respective fields. The study will help us better understand the ADME properties of HTD1801 to continue to advance our global clinical development programs. We expect the alliance to greatly facilitate our clinical progress by completing the ADME program in a more streamlined, time- and cost-effective manner." About Quotient Sciences Quotient Sciences is a drug development and manufacturing accelerator providing integrated programs and tailored services across the entire development pathway. Cutting through silos across a range of drug development capabilities, we save precious time and money in getting drugs to patients. Everything we do for our customers is driven by an unswerving belief that ideas need to become solutions, and molecules need to become cures, fast. Because humanity needs solutions, fast. For more information, please visit quotientsciences.com. About HighTide Therapeutics HighTide is a globally integrated clinical-stage biopharmaceutical company focusing on the discovery and development of innovative multifunctional therapies for metabolic and digestive diseases with significant unmet medical needs. The company's lead drug candidate, HTD1801, is a first-in-class new molecular entity, currently in clinical development for the treatment of type 2 diabetes (T2DM), nonalcoholic steatohepatitis (NASH), and primary sclerosing cholangitis (PSC). HTD1801 has received Fast Track designation from the U.S. FDA for both NASH and PSC, as well as Orphan Drug designation for PSC. In China, HTD1801 has been included in the National Major New Drug Innovation Program. For more information, please visit . SOURCE Quotient Sciences

Fast TrackPhase 2Orphan Drug

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