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Planta Med 2024; 90(11): 858-863
DOI: 10.1055/a-2363-5033
Biological and Pharmacological Activity
Original Papers

An In Silico-Guided Approach for Assessing Herb-Drug Interaction Potential: A Case Study with Cudrania tricuspidata Leaf Extracts

Jeong In Seo 
1   Pharmacomicrobiomics Research Center and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-Do, Republic of Korea
,
Young Beom Kwak
2   Department of Pharmaceutical Engineering, Inje University, Gimhae, South Korea
,
Seong Eun Cho
1   Pharmacomicrobiomics Research Center and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-Do, Republic of Korea
,
Hye Hyun Yoo
1   Pharmacomicrobiomics Research Center and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-Do, Republic of Korea
› Author AffiliationsThis research was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIT) (RS-2023-00217123) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (RS-2023 – 00 271 578).
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Abstract

Cudrania tricuspidata leaf extracts have long been utilized as traditional oriental medicines across Asian countries like Korea, China, and Japan. These extracts are renowned for their therapeutic benefits in addressing inflammation, tumors, obesity, and diabetes, maintaining their status as a pivotal folk remedy. Given the rising trend of combining medicinal herbs with conventional medications, it is imperative to explore the potential herb-drug interactions. However, there is a dearth of research on evaluating the herb-drug interactions of C. tricuspidata leaf extracts. Also, the intricate chemical composition of medicinal herbs presents methodological hurdles in establishing causal relationships between their constituents and herb-drug interactions. To overcome these challenges, a combined in silico and in vitro workflow was developed and effectively applied to evaluate the potential herb-drug interaction of C. tricuspidata leaf extracts along with the associated chemical factors. In in vitro CYP inhibition assays, C. tricuspidata leaf extracts exhibited potent inhibition of CYP1A2 and CYP2C8, with quercetin, kaempferol, and their glycosides identified as the major constituents. In silico analysis based on the prediction tools (ADMETlab 2.0 and pkCSM) identified key contributors to CYP inhibition, quercetin and kaempferol. Additionally, molecular docking analysis validated the binding of ligands (quercetin and kaempferol) to proteins (CYP1A2 and CYP2C8). These findings suggest that C. tricuspidata leaf extracts could inhibit CYP1A2 and CYP2C8, aiding in understanding the herb-drug interaction potential of C. tricuspidata leaf extracts for safe clinical application. Furthermore, this approach can be broadly applied to study herb-drug interactions of various medicinal herbs, enhancing their therapeutic benefits and reducing adverse reactions by considering chemical profiles relevant to herb-drug interaction potential in herbal preparations.

Keywords

Cudrania tricuspidata - herb-drug interactions - cytochrome P450 - in silico - in vitro - quercetin - kaempferol - flavonoids - Moraceae

Supporting Information

    Information on selected probe substrates and their respective CYP enzyme-specific metabolites, CYP activity inhibition by positive controls, inhibitory effect of CLE on CYP-specific metabolite formation in HLMs, predicted outcomes for CYP inhibitory constituents in CLE based on pkCSM analysis, and each analytical method using LC-MS/MS, HPLC-DAD, and LC-QTOF/MS are available as Supporting Information.

  • Supporting Information


Publication History

Received: 22 April 2024

Accepted after revision: 09 July 2024

Accepted Manuscript online:
09 July 2024

Article published online:
06 August 2024

© 2024. Thieme. All rights reserved.

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