HuangQin Decoction Attenuates CPT-11-Induced Gastrointestinal Toxicity by Regulating Bile Acids Metabolism Homeostasis

Abstract

Irinotecan (CPT-11) is a potent chemotherapeutic agent, however, its clinical usage is often limited by the induction of severe gastrointestinal (GI) toxicity, especially late-onset diarrhea. HuangQin Decoction (HQD), commonly used for the treatment of GI ailments, has been proved could significantly ameliorate the intestinal toxicity of CPT-11. To reveal the mechanisms of CPT-11-induced toxicity and the modulation effects of HQD, a previous untargeted metabolomics study was performed and the results indicated that HQD may protect the GI tract by altering the metabolism of bile acids (BAs). Nevertheless, the untargeted assays are often less sensitive and/or efficient. In order to further confirm our previous findings, here in this paper, serum and tissues metabolic profiles of 17 BAs were analyzed using liquid chromatography-tandem mass spectrometry based targeted metabolomics. The results indicated that serum and tissues levels of most BAs were significantly decreased after CPT-11 administration, except some hydrophobic BAs. Co-treatment with HQD could markedly attenuate CPT-11-induced GI toxicity and reverse the alterations of hydrophobic BAs. Despite the fact that the BAs pool size remained unchanged, the balance of BAs had shifted leading to decreased toxicity after HQD treatment. The present study demonstrated for the first time that the precise interaction between HQD, CPT-11-induced intestinal toxicity and BAs’ homeostasis.

Wen-Luo-Tong Decoction Attenuates Paclitaxel-Induced Peripheral Neuropathy by Regulating Linoleic Acid and Glycerophospholipid Metabolism Pathways

“…Metabolomics has been used as important technique for interpreting pharmacological mechanisms of TCM formulae under the guidance of systematic theory (Li et al, 2011 ; Li and Zhang, 2013 ). Indeed, there have been an increasing number of TCM studies applying metaboliomics (Lu et al, 2014 ; Cao et al, 2015 ; Wang et al, 2015 , 2017 ). Wen-Luo-Tong (WLT) is an herbal formula ointment for topical application.…”

Evidence for Shikonin acting as an active inhibitor of human carboxylesterases 2: Implications for herb–drug combination

“…Consequently, alteration of hCE2 activity may lead to the fluctuation of intestinal SN‐38 concentration, which would determine the risk of intestinal toxicity (X. W. Wang, Zhu, & Markowitz, ; Xiao et al, ). Although a large number of clinical drugs, such as loperamide vhydrochloride, cholestyramine, and levofloxacin, have been regarded as the promising options for the prevention of delayed diarrhea caused by CPT‐11, the improper mechanism and dosage are common causes for treatment failure (X. Wang et al, ). Moreover, herbal medicine PHY906 has been reported to attenuate the intestinal toxicity induced by CPT‐11 (Cui et al, ; Lam et al, ).…”

“…Although a large number of clinical drugs, such as loperamide vhydrochloride, cholestyramine, and levofloxacin, have been regarded as the promising options for the prevention of delayed diarrhea caused by CPT-11, the improper mechanism and dosage are common causes for treatment failure (X. Wang et al, 2017). Moreover, herbal medicine PHY906 has been reported to attenuate the intestinal toxicity induced by CPT-11 (Cui et al, 2017;Lam et al, 2010).…”

Systems Pharmacology Based Strategy for Q-Markers Discovery of HuangQin Decoction to Attenuate Intestinal Damage

“…LC-IT-TOF/MS was used to clarify which active compounds are actually existing in water decoction of HQD. One milliliter of standard decoction HQD ( Wang X. et al, 2017 ) was dissolved in a suitable amount of 80% (v/v) methanol with the assistant dissolve effect of DMSO by ultra-sonication and subsequently centrifuged (16000 rpm, 4°C) for 10 min. The supernatants were filtered and analyzed on a ZORBAX SB-C18 rapid resolution HT (2.1 mm × 100 mm, 1.8 μm) (Agilent Technologies).…”

“…HuangQin decoction (HQD) is a basic formula listed in Treatise on Exogenous Febrile Disease written by Zhongjing Zhang. It has been widely used in China for more than 1800 years on the treatment of gastrointestinal (GI) ailments, including diarrhea, abdominal spasms, vomiting, and nausea ( Wang X. et al, 2017 ). Recent studies have revealed that PHY906, a modified formulation derived from HQD, could ameliorate chemotherapy-induced GI toxicity and enhance the therapeutic efficacy of irinotecan, capecitabine and other antitumor drugs ( Lam et al, 2010 ; Saif et al, 2010 ; Wang et al, 2011 ).…”