Enhancement of hepatoprotective activity of limonin from citrus seeds against acetaminophen-induced liver injury by HSCCC purification and liposomal encapsulation

Wanling Yang; Yiyao Liang; Yujie Liu; Yunan Yao; Zhiqian Yu; Baizhong Chen; Yi Cai; Minyan Wei; Guodong Zheng

doi:10.1016/j.fitote.2024.105899

Enhancement of hepatoprotective activity of limonin from citrus seeds against acetaminophen-induced liver injury by HSCCC purification and liposomal encapsulation

Fitoterapia. 2024 Mar 11:175:105899. doi: 10.1016/j.fitote.2024.105899. Online ahead of print.

Authors

Wanling Yang¹, Yiyao Liang¹, Yujie Liu¹, Yunan Yao¹, Zhiqian Yu¹, Baizhong Chen², Yi Cai³, Minyan Wei⁴, Guodong Zheng⁵

Affiliations

¹ Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510645, China.
² Guangdong Xinbaotang Biological Technology Co., Ltd, Guangdong, Jiangmen 529000, China.
³ Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510645, China. Electronic address: yicaisysu@163.com.
⁴ Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510645, China. Electronic address: weiminyan@163.com.
⁵ Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510645, China. Electronic address: gd200237@126.com.

PMID: 38471575
DOI: 10.1016/j.fitote.2024.105899

Abstract

Limonin is a natural tetracyclic triterpenoid compound in citrus seeds that presents hepatoprotective effects but is often discarded as agricultural waste because of its low content and low solubility. Herein, limonin with high purity (98.11%) from citrus seeds was obtained via purification by high-speed counter-current chromatography (HSCCC) and recrystallization. Limonin-loaded liposomes (Lip-LM) prepared by thin film hydration and high pressure homogenization method to enhance its solubility and hepatoprotective effect on APAP-induced liver injury (AILI). Lip-LM appeared as lipid nanoparticles under a transmission electron microscope, and showed well dispersed nano-scale size (69.04 ± 0.42 nm), high encapsulation efficiency (93.67% ± 2.51%), sustained release, fine stability. Lip-LM also exhibited significantly better hepatoprotective activity on AILI than free limonin in vivo. In summary, Lip-LM might be used as a potential hepatoprotective agent in the form of dietary supplement and provide an effective strategy to improve the potential value of citrus seeds.

Keywords: AILI; Citrus seeds limonin; HSCCC; Liposomes; Solubility.