Total saponins from stems and leaves of Panax quinquefolius L. ameliorate podophyllotoxin‐induced myelosuppression and gastrointestinal toxicity

Abstract

Podophyllotoxin (POD), a natural lignan distributed in podophyllum species, possesses significant antitumor and antiviral activities. But POD often causes serious side effects, such as myelosuppression, gastrointestinal toxicity, neurotoxicity, hepatic and renal dysfunction, and even death, which not only hinder its clinical application but also threaten the patient's health. Therefore, an effective treatment against POD-induced toxicity is important. Our preliminary study found that the total saponins from the stems and leaves of Panax quinquefolius L. (PQS) could significantly reduce the death of mice caused by POD. To reveal how PQS can alleviate PODinduced toxicity, further study was needed. Peripheral blood cell analysis, diarrhea score, and histological examination demonstrated that PQS could relieve myelosuppression and gastrointestinal side effects induced by POD. Then, metabolomics was performed to investigate the possible protective mechanism of PQS on POD-induced myelosuppression and gastrointestinal toxicity. Metabolomics analysis showed that metabolic changes caused by POD could be reversed by PQS to some extent; 23 metabolites altered significantly after POD exposure, and 11 metabolites significantly reversed by PQS pretreatment. Metabolic pathway analysis suggested that PQS might exhibit its protective effects by rebalancing disordered arginine, glutamine, and unsaturated fatty acid metabolism.

Research progress on metabolomics in the quality evaluation and clinical study ofPanax ginseng

“…Among them, ginsenoside is considered the main active ingredient for its efficacy and can be divided into three categories according to the position and number of glycol groups on its aglycones, the majority of which are dammarane and oleanolic acid (Chang et al, 2016;Chen & Cui, 2002;Choi, 2008;Sun et al, 2018;Zhang et al, 2022;Zhang et al, 2021). among different metabolites; therefore, the mechanism of drugs can be further revealed (Chen et al, 2015;Sun et al, 2018;Zhou et al, 2021).…”

“…Presently, more than 300 active components have been isolated, such as ginsenosides, polysaccharides, volatile oils, organic acids, alkaloids, amino acids, trace elements, and vitamins (Wang et al, 2018; Wang et al, 2021). Among them, ginsenoside is considered the main active ingredient for its efficacy and can be divided into three categories according to the position and number of glycol groups on its aglycones, the majority of which are dammarane and oleanolic acid (Chang et al, 2016; Chen & Cui, 2002; Choi, 2008; Sun et al, 2018; Zhang et al, 2022; Zhang et al, 2021).…”

Preliminary metabolomics-based predictive models for myelosuppression in breast cancer patients with different anthracycline chemotherapy

“…Decreased levels of the EPA in breast adipose tissue may increase the risk of breast cancer in ammation which will leading to poor prognosis[48].Oxoglutarate is associated with multiple metabolic pathways, including arginine synthesis, butyrate metabolism, citric acid cycle, and alanine, aspartate, and glutamate metabolism. Studies have shown that arginine metabolism disorders are associated with myelosuppression induced by podophyllotoxin[49]. Oxoglutarate can be generated by the oxidative decarboxylation of isocitrate, and animal model have shown that the citrate intermediate succinate can increase hemoglobin, platelet and neutrophil levels and improve chemotherapy-induced myelosuppression[50].…”