Supercritical-Carbon Dioxide Fluid Extract from Chrysanthemum indicum Enhances Anti-Tumor Effect and Reduces Toxicity of Bleomycin in Tumor-Bearing Mice

Abstract

Bleomycin (BLM), a family of anti-tumor drugs, was reported to exhibit severe side effects limiting its usage in clinical treatment. Therefore, finding adjuvants that enhance the anti-tumor effect and reduce the detrimental effect of BLM is a prerequisite. Chrysanthemum indicum, an edible flower, possesses abundant bioactivities; the supercritical-carbon dioxide fluid extract from flowers and buds of C. indicum (CISCFE) have strong anti-inflammatory, anti-oxidant, and lung protective effects. However, the role of CISCFE combined with BLM treatment on tumor-bearing mice remains unclear. The present study aimed to investigate the potential synergistic effect and the underlying mechanism of CISCFE combined with BLM in the treatment of hepatoma 22 (H22) tumor-bearing mice. The results suggested that the oral administration of CISCFE combined with BLM could markedly prolong the life span, attenuate the BLM-induced pulmonary fibrosis, suppress the production of pro-inflammatory cytokines (interleukin-6), tumor necrosis factor-α, activities of myeloperoxidase, and malondiadehyde. Moreover, CISCFE combined with BLM promoted the ascites cell apoptosis, the activities of caspases 3 and 8, and up-regulated the protein expression of p53 and down-regulated the transforming growth factor-β1 by activating the gene expression of miR-29b. Taken together, these results indicated that CISCFE could enhance the anti-cancer activity of BLM and reduce the BLM-induced pulmonary injury in H22 tumor-bearing mice, rendering it as a potential adjuvant drug with chemotherapy after further investigation in the future.

Compressed fluids and phytochemical profiling tools to obtain and characterize antiviral and anti-inflammatory compounds from natural sources

“…Camphor, borneol, phytol and eucalyptol from the edible flower Chrysantemum indicum also showed potential anti-inflammatory action against acute lung injury in mice [27], a clinical disease with excessive inflammatory response and high mortality rates, and against pulmonary inflammation caused by the anti-tumor drug used to treat rats with hepatoma tumor [8].…”

“…Moreover, the anti-inflammatory properties and chemical composition of SFE extracts of Chrysanthemum indicum have been comprehensively tackled by several authors. In these works, bioactive polyphenols were identified and quantified by HPLC-DAD, whereas terpenes profiling was carried out by GC-MS analysis [8,27,28,68]. A total of 35 compounds were identified by GC-MS, and 5 phenolics (chlorogenic acid, luteolin-7-glucoside, linarin, luteolin and acacetin) were reconfirmed and quantitatively determined by HPLC-UV [68], as illustrated in Figure 5.…”

“…In addition, interesting compounds can be obtained from food, agricultural by-products and marine sources (e.g., seaweeds and microalgae) [6]. The evaluation of natural compounds as therapeutic agents is not intended to replace synthetic drugs, but to alleviate their use and attenuate the toxic side-effects and to help to develop new candidates of future pharmaceuticals [1,7,8]. However, extraction, identification and in vitro or in vivo confirmation of their activity are challenges that need to be overcome for the development and use of these natural bioactive compounds.…”

miR‑29b suppresses proliferation and induces apoptosis of hepatocellular carcinoma ascites H22 cells via regulating TGF‑β1 and p53 signaling pathway

“…Our previous studies revealed an increased level of miR-29b in hepatoma 22 (H22) cells in ascites tumor-bearing mice treated with supercritical-carbon dioxide fluid or scutellarin administration. The treatment further decreased ascites and improved survival (12,13).…”

Chemically-Induced DNA Damage, Mutagenesis, and Cancer

“…Yang et al reported adjuvants that enhance the anti-tumor effect and reduce the detrimental effect of Bleomycin (BLM) in mice [ 9 ]. The supercritical-carbon dioxide fluid extract from flowers and buds of Chrysanthemum indicum (CISCFE) exhibits potent anti-inflammatory, anti-oxidant, and lung protective effects.…”