Chemometric-guided chemical marker selection: A case study of the heat-clearing herb Scrophularia ningpoensis

Lung-Shuo Wang; Po-Jen Chen; Wen-Chi Cheng; Yu-Chia Chang; Mohamed El-Shazly; Lo-Yun Chen; Bo-Rong Peng; Chun-Han Su; Pei-Tzu Yen; Tsong-Long Hwang; Kuei-Hung Lai

doi:10.3389/fpls.2023.1153710

Chemometric-guided chemical marker selection: A case study of the heat-clearing herb Scrophularia ningpoensis

Front Plant Sci. 2023 Mar 17:14:1153710. doi: 10.3389/fpls.2023.1153710. eCollection 2023.

Authors

Lung-Shuo Wang^{1

2

3}, Po-Jen Chen⁴, Wen-Chi Cheng⁵, Yu-Chia Chang^{6

7}, Mohamed El-Shazly⁸, Lo-Yun Chen⁵, Bo-Rong Peng⁵, Chun-Han Su⁹, Pei-Tzu Yen^{2

10}, Tsong-Long Hwang^{6

7

11

12

13}, Kuei-Hung Lai^{5

14

15}

Affiliations

¹ The School of Chinese Medicine for Post Baccalaureate, I-Shou University, Kaohsiung, Taiwan.
² Cornucopia Traditional Medicine Clinic, Tainan, Taiwan.
³ Department of Chinese Medicine, Sin-Lau Hospital, Tainan, Taiwan.
⁴ Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
⁵ Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
⁶ Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
⁷ Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
⁸ Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt.
⁹ Department of Food Science, College of Human Ecology, Fu Jen Catholic University, New Taipei City, Taiwan.
¹⁰ Jian Sheng Tang Chinese Medicine Clinic, Kaohsiung, Taiwan.
¹¹ Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
¹² Department of Chemical Engineering, Ming Chi University of Technology, New Taipei City, Taiwan.
¹³ Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
¹⁴ PhD Program in Clinical Drug Development of Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
¹⁵ Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan.

Abstract

The selection of medicinal plants' chemical markers focuses on bioactivity as the primary goal, followed by the nature of secondary metabolites, their stability, and availability. However, herbal medicines are valued for their complex and holistic pharmacological effects. A correct chemical marker can be carefully selected by a systematic clarification of their chemical-biological relationships. In the current study, the multi-informative molecular networking (MIMN) approach was employed to construct the anti-inflammatory metabolomic pattern of a heat-clearing herb, Scrophularia ningpoensis Hemsl. (S. ningpoensis). The MIMN molecular families characterized by cinnamic acid glycosides showed a higher bioactivity score compared with the other two major chemical classes (iridoid glycosides and iridoid-cinnamic acid glycosides). The Global Natural Product Social Molecular Networking (GNPS) and Reaxys database were used to assist in the putative annotation of eighteen metabolites from the bioactive and non-bioactive molecular families. The anti-inflammatory validation step was based on the detection of reactive oxygen species (ROS) generation by activated human neutrophils. All compounds from the bioactive MIMN molecular families dose-dependently inhibited the total ROS generation promoted by fMLF (IC₅₀: 0.04-0.42 μM), while the compounds from non-bioactive MIMN clusters did not show any significant anti-inflammatory effect. The ROS-dependent anti-inflammatory activity of these cinnamic acid glycosides was attributed to their oxygen radical scavenging ability. The most abundant cinnamic acid glycoside, angoroside C (IC₅₀: 0.34 μM) was suggested to be selected as a chemical marker for S. ningpoensis. In this study, the MIMN platform was applied to assist in the chemical marker selection of S. ningpoensis. The correct selection of markers will aid in the compilation and revision of herbal monographs and pharmacopeias resulting in the precise analysis and classification of medicinal plants on a scientific basis.

Keywords: ROS-dependent anti-inflammation; Scrophularia ningpoensis Hemsl.; chemical markers; multi-informative molecular networking; neutrophil.

Grants and funding

The grants that supported this work were from the Chang Gung Memorial Hospital (CMRPF1M0101, CMRPF1M0131, CMRPG3J0231~3, EMRPD1N0551, CMRPF1J0051~3, and BMRP450), the Chang Gung University of Science and Technology (ZRRPF3K0111), Ministry of Education (DP2-111-21121-01-N-01-03), the National Science and Technology Council (MOST 106-2320-B-255-003-MY3, MOST 108-2320-B-255-003-MY3, MOST 109-2327-B-255-001, MOST 111-2321-B-255-001, MOST 111-2321-B-182-001, MOST 110-2320-B-038-013, MOST 110-2320-B-038-034, and MOST 111-2320-B-038-040-MY3), and Taipei Medical University (TMU109-AE1-B15), Taiwan.