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

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.

Detoxification technology and mechanism of processing with Angelicae sinensis radix in reducing the hepatotoxicity induced by rhizoma Dioscoreae bulbiferae in vivo

“…The “using Chinese botanical drugs to process other Chinese botanical drugs” method is the principle of processing the primary medicine by using a certain TCM as processing adjuvant in the processing technology, which could attenuate drug toxic reaction ( Huang et al, 2011 ; Su et al, 2016 ; Shan et al, 2018 ; Jiang T. et al, 2021 ; Zhang K. et al, 2021 ; Zhang M. et al, 2021 ; Ota and Makino, 2022 ) or (and) increase the synergistic effect ( Huang et al, 2011 ; Lu et al, 2018 ; Wang J. et al, 2019 ; Liao et al, 2021 ; Kong et al, 2022 ; Wang T. et al, 2022 ). Angelicae Sinensis Radix (ASR) is sweet in taste and warm in nature ( Chen Q. et al, 2021 ), and has been proved to have a variety of pharmacological effects such as hepatoprotective ( Hua et al, 2014 ), anti-oxidation ( Nai et al, 2021 ), and its main pharmacological components have been proved to significantly reduce liver damage induced by carbon tetrachloride ( Wang et al, 2020 ), ethanol ( Wang et al, 1997 ), and concanavalin A ( Wang et al, 2016 ).…”

Sigesbeckia orientalis Extract Ameliorates the Experimental Diabetic Nephropathy by Downregulating the Inflammatory and Oxidative Stress Signaling Pathways

“…SOE treatment may cause potential side effects in animals, as discussed in several previous studies that have examined chronic toxic effects of body organs through longterm SOE treatment. Rats were treated with SOE for 24 weeks [61] or 6 months at a dose of 5 g/kg•BW/daily [62]. Following these treatments, rats had demonstrated reduced body weight gain, histopathological damage to the liver and lung, treatment-induced oxidative stress, inflammation, and MAPK activation.…”