ABSTRACT
In order to provide rationale for selection of good germplasm in Rubus chingii, main effective medicinal ingredients of green fruit such as gallic acid, ellagic acid, kaempferol-3-rutinoside, astragalin and tiliroside were measured using UPLC for the samples collected from Chun'an county of Zhejiang province, and such parameters as soluble solid contents of ripe fruit of some samples were also measured to study variation among individuals and correlation. It has been found that there were differences among individuals in the contents of gallic acid, ellagic acid, kaempferol-3-rutinoside, astragalin and tiliroside, which ranged from 0.010 2%-0.027 4%, 0.089 5%-0.291 1%, 0.010 5%-0.114 8%, 0.005 8%-0.041 2% and 0.010 9%-0.086 3%, respectively, with a CV of 18.60%, 27.02%, 44.23%, 44.17% and 47.29%, respectively. Gallic acid was positively correlated with ellagic acid, but negatively with kaempferol-3-rutinoside and astragalin significantly. Significantly positive correlation existed between kaempferol-3-rutinoside, astragalin and linden glycoside as well as between ellagic acid and fruit shape index of ripe fruit and between linden glycoside and the content of soluble solids. 51.35% of the individuals had a content of soluble solids more than 15%. Therefore, abundant variations have been found among individuals in effective medicinal ingredients in R. chingii, which shows great potential for selection, but only do 7.61% of the individuals meet the requirement of Chinese pharmacopoeia in terms of the contents of effective medicinal ingredients. Therefore, selection could be first performed in terms of fruit shape index of ripe red fruit, followed by the contents of ellagic acid and kaempferol-3-rutinoside measured. The individuals, in which the contents of effective medicinal ingredients don't meet the requirement of Chinese pharmacopoeia, could be considered for the selection in terms of edible fresh fruit.
Subject(s)
Humans , Ellagic Acid , Fruit , Glycosides , Plant Extracts , RubusABSTRACT
<p><b>BACKGROUND</b>Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) targeted treatment has been a standard therapy for advanced non-small cell lung cancer (NSCLC), but it is not tolerated well by all patients. In China, some studies have reported that traditional Chinese medicinal herbs (TCMHs) may increase efficacy and reduce toxicity when combined with EGFR-TKI, but outside of China few studies of this kind have been attempted.</p><p><b>OBJECTIVE</b>This study is intended to systematically review the existing clinical evidence on TCMHs combined with EGFR-TKI for treatment of advanced NSCLC.</p><p><b>SEARCH STRATEGY</b>PubMed, the Cochrane Library, the Excerpta Medica Database (EMBASE), the China BioMedical Literature (CBM), and the China National Knowledge Infrastructure (CNKI) and web site of the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), the World Conference of Lung Cancer (WCLC) were searched; the search included all documents published in English or Chinese before October 2013.</p><p><b>INCLUSION CRITERIA</b>We selected randomized controlled trials based on specific criteria, the most important of which was that a TCMH plus EGFR-TKI treatment group was compared with an EGFR-TKI control group in patients with advanced NSCLC.</p><p><b>DATA EXTRACTION AND ANALYSIS</b>The modified Jadad scale was used to assess the quality of studies. For each included study, patient characteristics, treatment details, therapeutic approach and clinical outcomes were collected on a standardized form. When disagreements on study inclusion or data extracted from a study emerged, the consensus of all coauthors provided the resolution. The clinical outcome metrics consisted of objective response rate (ORR; complete response + partial response divided by the total number of patients), disease control rate (DCR; complete response + partial response + no change divided by the total number of patients), survival rate, improved or stabilized Karnofsky performance status (KPS), and severe toxicity. RevMan 5.0 software was used for data syntheses and analyses. Risk ratio (RR) and 95% confidence interval (CI) were calculated; if the hypothesis of homogeneity was not rejected (P>0.1, I(2)<50%), the fixed-effect model was used to calculate the summary RR and the 95% CI. Otherwise, a random-effect model was used.</p><p><b>RESULTS</b>In this review, 19 studies were included based on the selection criteria. Of them, 13 studies were of high quality and 6 studies were of low quality, according to the modified Jadad scale. When the TCMH plus EGFR-TKI treatment groups were compared with the EGFR-TKI control groups the meta-analysis demonstrated a statistically significant higher ORR (RR 1.34; 95% CI 1.15 to 1.57; P=0.000 2), DCR (RR 1.18; 95% CI 1.09 to 1.27; P<0.000 1), one-year survival rate (RR 1.21; 95% CI 1.01 to 1.44; P=0.04), 2-year survival rate (RR 1.91; 95% CI 1.26 to 2.89; P=0.002) and improved or stable KPS (RR 1.38; 95% CI 1.26 to 1.51; P<0.000 01). Severe toxicity for rash was decreased (RR 0.55; 95% CI 0.32 to 0.94; P=0.03), as were nausea and vomiting (RR 0.17; 95% CI 0.04 to 0.72; P=0.02) and diarrhea (RR 0.46; 95% CI 0.24 to 0.89; P=0.02). Sensitivity analysis indicated that findings of the meta-analysis were robust to study quality. In the funnel plot analysis, asymmetry was observed, and publication bias was indicated by Egger's test (P=0.03).</p><p><b>CONCLUSION</b>TCMH intervention can increase efficacy and reduce toxicity when combined with EGFR-TKI for advanced NSCLC, although this result requires further verification by more well designed studies.</p>