Abstract

BackgroundThe dried fruits of Forsythia suspensa has generally been used to clear heat and detoxify in traditional Korean and Chinese medicine. Oxaliplatin is a first-line treatment chemotherapeutic agent for advanced colorectal cancer, but it induces peripheral neuropathy as an adverse side effect affecting the treatment regimen and the patient’s quality of life. The present study was conducted to evaluate the neuroprotective effects of an aqueous extract of F. suspensa fruits (EFSF) on oxaliplatin-induced peripheral neuropathy.MethodsThe chemical components from EFSF were characterized and quantified using the ultra-high performance liquid chromatography-diode array detector system. The cytotoxicities of anticancer drugs in cancer cells and PC12 cells were assessed by the Ez-Cytox viability assay. To measure the in vitro neurotoxicity, the neurite outgrowth was analyzed in the primary dorsal root ganglion (DRG) cells, and neural PC12 cells that were differentiated with nerve growth factor. To evaluate the in vivo neuroprotective activity, the von Frey test was performed in six-week-old male mice (C57BL/6) receiving EFSF (60–600 mg/kg) in the presence of 20–30 mg/kg cumulative doses of oxaliplatin. Thereafter, the mice were euthanized for immunohistochemical staining analysis with an antibody against PGP9.5.ResultsEFSF attenuated the cytotoxic activities of the various anticancer drugs in neural PC12 cells, but did not affect the anticancer activity of oxaliplatin in human cancer cells. Oxaliplatin remarkably induced neurotoxicities including cytotoxicity and the inhibited neurite outgrowth of DRG and neural PC12 cells. However, the co-treatment of EFSF (100 μg/ml) with oxaliplatin completely reversed the oxaliplatin-induced neurotoxicity. Forsythoside A, the major component of EFSF, also exerted remarkable neuroprotective effects against the oxaliplatin-induced neurotoxicity. In addition, EFSF (60–200 mg/kg) significantly alleviated the oxaliplatin-induced mechanical allodynia and loss of intra-epidermal nerve fiber to the levels of the vehicle control in the mouse peripheral neuropathy model.ConclusionsEFSF could be considered a useful herbal medicine for the treatment of peripheral neuropathy in cancer patients receiving chemotherapy with oxaliplatin.

Highlights

  • The dried fruits of Forsythia suspensa has generally been used to clear heat and detoxify in traditional Korean and Chinese medicine

  • To determine the major components of the extract of F. suspensa fruits (EFSF), its ultra-high performance liquid chromatography (UHPLC) chromatogram was scanned and compared to the standard chemical (STD) peak of forsythoside A (FSA) which has been described as a marker component of Forsythiae Fructus in the Korea and Chinese Pharmacopoeia [1, 2]

  • The results indicate that EFSF contains about 12.5% of FSA, and that FSA can be used as a marker component of EFSF

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Summary

Introduction

The dried fruits of Forsythia suspensa has generally been used to clear heat and detoxify in traditional Korean and Chinese medicine. The present study was conducted to evaluate the neuroprotective effects of an aqueous extract of F. suspensa fruits (EFSF) on oxaliplatin-induced peripheral neuropathy. Many studies have been done on the phytochemicals, pharmacological evaluation and quantitative analyses of Forsythiae suspensa [3, 4]. It was demonstrated that the FSAcontaining organic fraction of F. suspensa fruit exerted neuroprotective effects on rotenone-induced neurotoxicity in PC12 cells as well as in a rotenone-induced neurodegenerative rat model through antioxidant and antiinflammatory activities, suggesting its application in the treatment of Parkinson’s disease [17]. The neuroprotective effect of F. suspensa or FSA on chemotherapyinduced peripheral neuropathy (CIPN) is not known yet

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