First-in-class drug oroxylin A tablets for treating hepatic and gastrointestinal disorders: from preclinical development to clinical research.
10.1016/S1875-5364(25)60910-1
- Author:
Chengju LUO
1
;
Xuhong LI
2
;
Yuan GAO
3
;
Junyi YANG
1
;
Weiming FANG
1
;
Libin WEI
4
Author Information
1. Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
2. Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Productivity Promotion Center, Department of Science and Technology of Jiangsu Province, Nanjing 210042, China.
3. Public Laboratory Platform, China Pharmaceutical University, Nanjing 210009, China.
4. Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China. Electronic address: wlbiws_1986@aliyun.com.
- Publication Type:Review
- Keywords:
First-in-class drug;
Gut-liver axis;
Hepatic and gastrointestinal disorders;
Oroxylin A;
Preclinical to clinical phases
- MeSH:
Humans;
Flavonoids/pharmacokinetics*;
Tablets;
Animals;
Gastrointestinal Diseases/drug therapy*;
Liver Diseases/drug therapy*;
Drug Development;
Clinical Trials as Topic;
Scutellaria baicalensis/chemistry*
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(7):801-814
- CountryChina
- Language:English
-
Abstract:
Oroxylin A (OA) is a natural flavonoid primarily derived from the plants Oroxylum indicum and Scutellaria baicalensis. Currently, OA is obtainable through chemical synthesis and exhibits polypharmacological properties, including anti-cancer, anti-inflammatory, anti-microbial, and multi-organ protective effects. The first-in-class drug OA tablets are presently undergoing phase Ib/IIa clinical trials for hepatocellular carcinoma (HCC) treatment. Substantial evidence suggests that OA demonstrates therapeutic potential against various hepatic and gastrointestinal (GI) disorders, including HCC, hepatic fibrosis, fatty liver disease, hepatitis, liver injury, colitis, and colorectal cancer (CRC). OA exerts its therapeutic effects primarily by modulating several crucial signaling pathways, including those associated with apoptosis, oxidative stress, inflammation, glucolipid metabolism, and fibrosis activation. The oral pharmacokinetics of OA is characterized by phase II metabolism, hydrolysis, and enterohepatic recycling. This review provides a comprehensive overview of the critical stages involved in the development of OA tablets, presenting a holistic perspective on the progression of this first-in-class drug from preclinical to clinical phases. It encompasses the synthesis of active pharmaceutical ingredients, pharmacokinetics, pharmacological efficacy, toxicology, drug delivery, and recent advancements in clinical trials. Importantly, this review examines the potential mechanisms by which OA may influence the gut-liver axis, hypothesizing that these interactions may confer health benefits associated with OA that transcend the limitations posed by its poor bioavailability.
