Citation: Shuang Li, Penghui Yuan, Xinyi Zhang, Meiru Liu, Dezhi Yang, Linglei Kong, Li Zhang, Yang Lu, Guanhua Du. Revolutionizing sepsis therapy: Machine learning-driven co-crystallization reveals emodin's therapeutic potential[J]. Chinese Chemical Letters, ;2026, 37(2): 111289. doi: 10.1016/j.cclet.2025.111289 shu

Revolutionizing sepsis therapy: Machine learning-driven co-crystallization reveals emodin's therapeutic potential

Shuang Li ^{a, 1} ,
Penghui Yuan ^{a, b, 1} ,
Xinyi Zhang ^{a, 1} ,
Meiru Liu ^a ,
Dezhi Yang ^{a, *,} ,
Linglei Kong ^{a, *,} ,
Li Zhang ^{a, *,} ,
Yang Lu ^a ,
Guanhua Du ^a

a.
Beijing Key Laboratory of Innovative Drug Discovery and Polymorphic Research for Cerebrovascular Diseases, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
b.
School of Pharmacy, Bengbu Medical University, Bengbu 233030, China

ydz@imm.ac.cn

konglinglei@imm.ac.cn

zhangl@imm.ac.cn

Received Date: 12 January 2025
Revised Date: 16 April 2025
Accepted Date: 7 May 2025
Available Online: 1 December 2025

Figures(3)

In the pharmaceutical field, machine learning can play an important role in drug development, production and treatment. Co-crystallization techniques have shown promising potential to enhance the properties of active pharmaceutical ingredients (APIs) such as solubility, permeability, and bioavailability, all without altering their chemical structure. This approach opens new avenues for developing natural products into effective drugs, especially those previously challenging in formulation. Emodin, an anthraquinone-based natural product, is a notable example due to its diverse biological activities; however, its physicochemical limitations, such as poor solubility and easy sublimation, restricted its clinical application. While various methods have improved emodin's physicochemical properties, research on its bioavailability remains limited. In our study, we summarize cocrystals and salts produced through co-crystallization technology and identify piperazine as a favorable coformer. Conflicting conclusions from computational chemistry and molecular modeling method and machine learning method regarding the formation of an emodin-piperazine cocrystal or salt led us to experimentally validate these possibilities. Ultimately, we successfully obtained the emodin-piperazine cocrystal, which were characterized and evaluated by several in vitro methods and pharmacokinetic studies. In addition, experiments have shown that emodin has a certain therapeutic effect on sepsis, so we also evaluated emodin-piperazine biological activity in a sepsis model. The results demonstrate that co-crystallization significantly enhances emodin's solubility, permeability, and bioavailability. Pharmacodynamic studies indicate that the emodin-piperazine cocrystal improves sepsis symptoms and provides protective effects against liver and kidney damage associated with sepsis. This study offers renewed hope for natural products with broad biological activities yet hindered by physicochemical limitations by advancing co-crystallization as a viable development approach.
- Co-crystallization,
- Properties,
- Bioavailability,
- Sepsis,
- Emodin,
- Machine learning
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