Metabolomics Reveals the Mechanisms for the Pulmonary Toxicity of Siegesbeckia orientalis L. and the Toxicity-Reducing Effect of Processing.

Ting Jiang,Junfang Su,Zhiping Qiao,Gang Cao,Linsheng Liu,Tingxiu Zhao,Mi Zhang,Tao Su

doi:10.3389/fphar.2021.630319

Abstract

Siegesbeckia orientalis L. (SO) is a commonly used Chinese medicinal herb. It has long been used as a remedy in traditional Chinese medicine (TCM) for symptoms that resemble inflammatory joint disorders. However, it is slightly toxic. According to the TCM theory, processing can reduce the toxicity of the herbs. Here, we performed metabolomics to determine whether processing with rice wine reduces the toxicity of raw SO, and to explore the mechanisms underlying the raw SO–induced toxicity and the toxicity-reducing effect of processing. Our results showed that raw SO has long-term toxicity in rats. It significantly elevated the serum level of LDH and caused histopathological damages in the lung tissues. It is worth noting that the LDH level in the PSO group was lower than that in the raw SO group, and the damages in lung tissues were relatively mild in PSO-treated rats, suggesting that processing reduces the pulmonary toxicity of the raw. Moreover, a total of 32 significantly changed metabolites were identified. Based on the MetaboAnalyst pathway analysis, we found that two characteristic metabolic pathways including alanine, aspartate and glutamate metabolism and glycerophospholipid metabolism were only changed in the raw SO group, while histidine metabolism was only changed in the PSO group, which suggests that induction of oxidative stress contributes to raw SO–induced pulmonary toxicity, and free radical scavenging might be responsible for the toxicity-reducing effect of processing. Our data shed new light on how raw SO induces pulmonary toxicity and how the toxicity can be reduced by processing. This study not only provides scientific justifications for the traditional processing theory of SO, but also helps to optimize the processing protocol and the clinical drug combination of SO.

Highlights

Siegesbeckia orientalis L. (SO), a traditional Chinese medicinal herb, was recorded to be able to eliminate the wind-dampness and soothe painful joints, and to be slightly toxic in Xinxiu Bencao (657–659 A.D., Tang Dynasty in China)
The serum levels of aspartate transaminase (AST), alanine transaminase (ALT), Urea, creatine kinase (CK), and lactate dehydrogenase (LDH) were measured in each rat every month
ALT and AST are the markers of hepatic damage; Urea is a marker of renal damage; CK is a marker of cardiac damage

Summary

Introduction

Siegesbeckia orientalis L. (SO), a traditional Chinese medicinal herb, was recorded to be able to eliminate the wind-dampness and soothe painful joints (the State Commission of Chinese Pharmacopoeia, 2020), and to be slightly toxic in Xinxiu Bencao (657–659 A.D., Tang Dynasty in China). (SO), a traditional Chinese medicinal herb, was recorded to be able to eliminate the wind-dampness and soothe painful joints (the State Commission of Chinese Pharmacopoeia, 2020), and to be slightly toxic in Xinxiu Bencao (657–659 A.D., Tang Dynasty in China). SO is commonly used in managing traditional Chinese medicine (TCM) symptoms that resemble joint inflammatory disorders such as rheumatoid arthritis (RA). Chemical studies have revealed that SO contains terpenoids, glycosides, etc. Toxicological studies have demonstrated that the water extract of SO has acute toxicity in animals (Guan et al, 2007). Reversible pulmonary toxicity of SO is observed in a subacute toxicity study in mice (Guan et al, 2008). Up to now, the longterm toxicity of SO remains unknown, and the mechanisms underlying the raw SO–induced toxicity is still not fully understood

Methods

Results

Discussion

Conclusion