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

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 POD-induced 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.

Consistency evaluation of Chaihuang granules based on pharmacokinetics and metabolomics.

Consistency evaluation of Traditional Chinese Medicinal preparations (TCMPs) with complex chemical composition is challenging. Chaihuang granules (CHG), as a well-known TCMP, consists of Chaihu (Bupleuri Radix) and Huangqin (Scutellariae Radix) extract. In this work, we used pharmacokinetics and metabolomics to evaluate consistency of CHG products from two different manufacturers. In the pharmacokinetic study, a liquid chromatography tandem mass spectrometry (LC-MS/MS) method was applied to determine the plasma concentration-time profiles of baicalin in rat plasma. Pharmacokinetic parameters, including the maximum concentration in blood (Cmax), area under the curve (AUC), the time to reach Cmax (Tmax), and half-life (T1/2), were calculated to assess the consistency preliminarily. And there was no significant difference in these pharmacokinetic parameters between the two CHG. In LC-MS-based metabolomics, the metabolic response profiles changes based on relative distance values (RDV) to different CHG products were compared. Meanwhile, the kinetic process of 31 differential endogenous metabolites that altered by CHG were determined. Metabolomics data showed the similar metabolic regulation effects to rats of the two formulations. Both pharmacokinetic and metabolomics results indicated there was no significant difference between CHG products. Furthermore, metabolic pathways significantly altered by CHG were elucidated, including phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, phenylalanine metabolism, and sphingolipid metabolism. Pharmacokinetics combined with metabolomics could provide a comprehensive perspective for consistency evaluation of CHG.