Effects of rhubarb extract on radiation induced lung toxicity via decreasing transforming growth factor-beta-1 and interleukin-6 in lung cancer patients treated with radiotherapy
ABSTRACT Radiation induced lung toxicity (RILT) is the main adverse effect in the radiation therapy of lung cancer. However, the optimal management of RILT has not been defined. In this paper, we investigated the effects of rhubarb extract on RILT, pulmonary function (PF), transforming growth factor-beta-1 (TGF-beta1), and interleukin-6 (IL-6) in lung cancer patients treated with radiotherapy.
We conducted a randomized, double-blind, placebo-controlled trial. Eighty consecutive patients were randomly enrolled into two groups: trial group and control group. The trial group received three-dimensional conformal radiation therapy (3D-CRT) plus rhubarb (at a dose of 20 mg kg(-1) once a day) for 6 weeks. The control group received 3D-CRT plus a placebo containing starch for 6 weeks. Plasma TGF-beta1 and serum IL-6 were measured in all patients before, every 2 weeks during, and at 6 weeks after the completion of the treatment. RILT and PF were evaluated at 6 weeks and 6 months after the end of the treatment, respectively. The differences of TGF-beta1, IL-6, RILT, and PF between the two groups were analysed.
The incidence of RILT in the trial group was significantly lower than that in the control group at 6 weeks and 6 months after treatment (32.4% versus 56.7% at week 6, and 27.0% versus 52.8% at month 6, both P<0.05). The plasma TGF-beta1 levels in the trial group were significantly lower than that in the control group during and after the treatment (P<0.05 or 0.01, respectively). The serum IL-6 levels in the trial group were significantly lower than that in the control group during the treatment (all P<0.01). The forced vital capacity (FVC), forced expiratory volume at 1s (FEV1) at 6 weeks and the diffusion capacity for carbon monoxide (DLCO) at 6 months in the trial group were significantly improved compared to the control group (P<0.05 or 0.01, respectively).
The rhubarb extract significantly attenuated RILT and improved PF, probably by decreasing the level of TGF-beta1 and IL-6. These results may be of value for the prophylaxis of RILT, but the exact mechanisms underlying these prophylactic effects remain to be further explored.
- SourceAvailable from: Yuwen Qiu
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- "Total rhubarb anthraquinones (TRAs), active therapeutic components that have been isolated from rhubarb roots (Rheum palmatum L. or Rheum tanguticum Maxim.), have been widely used in traditional Chinese medicine for centuries. Recent studies have demonstrated many pharmacological properties of rhubarb extracts , such as purgative (Peigen et al., 1984; Xu et al., 2011), anti-inflammatory (Cuellar et al., 2001; Gao et al., 2011), liver protection (Zhao et al., 2009), and attenuation of radiation-induced lung toxicity (Yu et al., 2008). Despite its therapeutic value, potential side effects of rhubarb extracts have been shown in experimental studies. "
ABSTRACT: Aloe-emodin (AE; 1,8-dihydroxy-3-hydroxymethyl-9,10-anthracenedione) is one of the primary active compounds in total rhubarb anthraquinones (TRAs), which induce nephrotoxicity in rats. However, it is still not known whether AE has a similar effect on human kidney cells. In this study, 3-(4,5,-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays showed that AE decreases the viability of HK-2 cells (a human proximal tubular epithelial cell line) in a dose- and time-dependent manner. AE induced G2/M arrest of cell cycle in HK-2 cells, which was detected with propidium iodide (PI) staining. This apoptosis was further investigated by Hoechst staining, transmission electron microscopy (TEM), DNA fragmentation, and Annexin V/PI staining. Apoptosis of the cells was associated with caspase 3 activation, which was detected by Western blot analysis and a caspase activity assay. In addition, changes in the endoplasmic reticulum (ER) ultrastructure as observed by TEM showed the effects of AE on ER. Treatment with AE also resulted in an increase in eukaryotic initiation factor-2α (eIF-2α) phosphorylation, X-box binding protein 1 (XBP1) mRNA splicing, c-Jun N-terminal kinase (JNK) phosphorylation, glucose-regulated protein (GRP) 78 and CAAT/enhancer-binding protein-homologous protein (CHOP) accumulation. These results suggest that AE induces ER stress in HK-2 cells, which is involved in AE-induced apoptosis. In conclusion, AE induces apoptosis in HK-2 cells, and the ER stress is involved in AE-induced apoptosis in vitro. The implications of the toxic effects of AE for clinical use are unclear and these findings should be taken into account in the risk assessment for human exposure.Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 12/2011; 50(3-4):1149-58. DOI:10.1016/j.fct.2011.12.018 · 2.61 Impact Factor
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- "The rhubarb extract from Rheum officinale significantly attenuated radiation induced lung toxicity and improved pulmonary function (Yu et al., 2008). Polygonum multiflorum water extract exerts a preventive effect against cognitive deficits in Alzheimer's disease (Um et al., 2006). "
ABSTRACT: Medicinal plants belonging to the family Polygonaceae in Chinese pharmacopoeia possess important medicinal efficacy in traditional Chinese medicines. DNA barcodes are first used to discriminate the Polygonaceae in Chinese pharmacopoeia and their adulterants. DNA samples, extracted from thirty-eight specimens belonging to eighteen species in Polygonaceae, were used as templates. Eight candidate barcodes were amplified by polymerase chain reaction. Sequence analysis was accomplished by CodonCode Aligner V 2.06 and DNAman V 6. Species identification was performed using MEGA V 4.0. The amplification efficiency of six candidate DNA barcodes (rbcL, trnH-psbA, ndhJ, rpoB, rpoC1, accD) was 100%, while the efficiency of YCF5 and nrITS was 56% and 44%, respectively. The interspecific divergence was highest for the trnH-psbA (20.05%), followed by the nrITS (14.01%) across all species pairs, while intraspecific variation both within populations and between populations was absent (0.0%). The trnH-psbA can not only distinguish ten species of Polygonaceae in Chinese pharmacopoeia, but also recognize eight other species of Polygonaceae including their adulterants. Our findings show that DNA barcoding is an efficient tool for identification of Polygonaceae in Chinese pharmacopoeia and their adulterants.Journal of ethnopharmacology 07/2009; 124(3):434-9. DOI:10.1016/j.jep.2009.05.042 · 2.94 Impact Factor
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- "The relative contents of rhein and emodin in TRAs (used in our labs) are about 19% and 27%, respectively, and the chemical structures of them are shown in Fig. 1. Recent studies revealed that rhubarb extracts are able to attenuate acute pancreatitis, liver fibrosis and radiation-induced lung toxicity by decreasing the level of transforming growth factor-beta-1 (TGF-␤1)(Yu et al., 2007; Zhan et al., 2000; Zhao et al., 2004). Moreover, experimental studies have suggested that emodin exerts antiproliferative effects in several cancer cell lines through mitochondria (Srinivas et al., 2003), activation of caspase 3 and caspase 9 (Lee, 2001; Srinivas et al., 2003), but independent of reactive oxygen species (ROS) production (Chen et al., 2002). "
ABSTRACT: Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone) and rhein (4,5-dihydroxyanthraquinone-2-carboxyl acid) are two main active compounds in total rhubarb anthraquinones (TRAs), which showed nephrotoxicity in Sprague Dawley (S.D.) rats in our previous study. However, it is unknown yet whether emodin and rhein have cytotoxic effects on kidney. To address this issue, HK-2 cells, a human proximal tubular epithelial cell line, were treated with different concentrations of emodin or rhein, and cell viability and morphological changes were investigated. The ratio of hypodiploid cells and the activity of caspase 3 protease were also detected. Results showed that addition of emodin but not rhein at concentrations above 40microM for 24h reduced cell viability and induced apoptosis in HK-2 cells. Additionally, emodin at apoptosis-inducing concentrations caused expression of cathepsin B (CB) protein and activation of CB protease. Addition of CB inhibitor, CA-074, significantly attenuated the ratio of hypodiploid and apoptotic cells, partially blocked caspase 3 activation and inhibited reduction of cell viability induced by emodin. These data indicate that emodin possesses cytotoxic effects on HK-2 cells partially through induction of CB protein and activation of CB protease.Toxicology Letters 10/2008; 181(3):196-204. DOI:10.1016/j.toxlet.2008.05.013 · 3.36 Impact Factor