Wang Ziming, Wu Zihong, Xiang Qiong, Yang Jingyi, Xia Zhenzhong, Hao Aohan, Song Enfeng, Mei Shasha
Department of Traditional Chinese Medicine, Renmin Hospital of Wuhan University, Wuhan, China.
School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Front Pharmacol. 2022 Sep 7;13:979504. doi: 10.3389/fphar.2022.979504. eCollection 2022.
To systematically review the efficacy and safety of botanical drugs in the treatment of cancer-related fatigue (CRF) caused by gastric cancer (GC) and to determine the underlying pharmacological mechanisms using a network analysis. Databases such as China National Knowledge Infrastructure (CNKI), SinoMed, Wanfang, Pubmed, Embase, Cochrane Library, and Web of Science were searched for randomized controlled trials (RCTs) from inception to 18 April 2022. Methodological quality assessment was performed using the collaborative tool Cochrane, and data analysis were carried out using RevMan 5.4 and STATA 16 software. The botanical drugs with the highest frequency of use in the included studies was selected. The chemical composition, targets of action, disease targets, and shared targets of these botanical drugs were screened based on network analysis to explore the potential mechanisms of treating CRF in patients with gastric cancer (GC). A total of 13 studies that included 986 patients with gastric CRF met the inclusion criteria. The results showed that botanical drugs could improve the CRF scores of gastric CRF, including the total scores of CRF dichotomous data [Odds Ratio (OR) = 4.22; 95% confidence interval (CI) 1.67-10.68; = 0.002], the total scores of CRF continuous data [Standardized Mean Difference (SMD) = -0.98; 95% CI -1.36 to -0.60; < 0.00001], the affective subscales of Piper Fatigue Scale (PFS) scores [Weighted Mean Difference (MD) = -0.79; 95%CI -0.92 to -0.65; < 0.00001], the sensory subscales of PFS scores (MD = -0.57; 95%CI -0.77 to -0.37; < 0.00001), the behavioral subscales of PFS scores (MD = -1.05; 95% CI -1.29 to -0.82; < 0.00001), Quality of Life Questionnaire Core 30 (QLQ-C30) (MD = 10.53, 95% CI 8.26 to12.80; < 0.00001), and the Karnofsky Performance Status scale (KPS) (MD = 5.18, 95% CI 2.60 to 7.76; < 0.0001). The botanical drugs group had milder adverse effects than the control group. A total of 44 chemical components and 241 potential targets were obtained from the online database and 121 drug targets overlapped with the disease targets of CRF in patients with GC. Moreover, five key active ingredients, namely quercetin, Stigmasterol, luteolin, kaempferol, and isorhamnetin, as well as five key targets including AKT1, TP53, TNF, VEGFA, and CASP3, were screened. In addition, five key signaling pathways, including cancer, Hepatitis B, Prostate cancer, Hepatitis C, and Pancreatic cancer pathways, were obtained through enrichment analysis. The results of the study showed that botanical drugs have positive effects on CRF in patients with GC. However, more well-designed, multicenter, and large sample-sized Randomized Controlled Trials are required to evaluate the effectiveness of botanical drugs on CRF in patients with GC.
系统评价植物药治疗胃癌（GC）所致癌症相关性疲劳（CRF）的疗效和安全性，并通过网络分析确定其潜在的药理机制。检索中国知网（CNKI）、中国生物医学文献数据库（SinoMed）、万方、PubMed、Embase、Cochrane图书馆和Web of Science等数据库，查找从建库至2022年4月18日的随机对照试验（RCT）。使用Cochrane协作工具进行方法学质量评估，使用RevMan 5.4和STATA 16软件进行数据分析。选择纳入研究中使用频率最高的植物药。基于网络分析筛选这些植物药的化学成分、作用靶点、疾病靶点和共同靶点，以探索治疗胃癌患者CRF的潜在机制。共有13项研究纳入986例胃癌CRF患者，符合纳入标准。结果显示，植物药可改善胃癌CRF的CRF评分，包括CRF二分数据总分[比值比（OR）=4.22；95%置信区间（CI）1.67 - 10.68；P = 0.002]、CRF连续数据总分[标准化均数差（SMD）=-0.98；95%CI - 1.36至 - 0.60；P < 0.00001]、派珀疲劳量表（PFS）情感子量表评分[加权均数差（MD）=-0.79；95%CI - 0.92至 - 0.65；P < 0.00001]、PFS感觉子量表评分（MD=-0.57；95%CI - 0.77至 - 0.37；P < 0.00001）、PFS行为子量表评分（MD=-1.05；95%CI - 1.29至 - 0.82；P < 0.00001）、生活质量问卷核心30项（QLQ - C30）（MD = 10.53，95%CI 8.26至12.80；P < 0.00001）和卡氏功能状态量表（KPS）（MD = 5.18，95%CI 2.60至7.76；P < 0.0001）。植物药组的不良反应比对照组轻。从在线数据库中获得了44种化学成分和241个潜在靶点，其中121个药物靶点与胃癌患者CRF的疾病靶点重叠。此外，筛选出5种关键活性成分，即槲皮素、豆甾醇、木犀草素、山奈酚和异鼠李素，以及5个关键靶点，包括AKT1、TP53、TNF、VEGFA和CASP3。另外，通过富集分析获得了癌症、乙型肝炎、前列腺癌、丙型肝炎和胰腺癌等5条关键信号通路。研究结果表明，植物药对胃癌患者的CRF有积极作用。然而，需要更多设计良好、多中心、大样本量的随机对照试验来评估植物药对胃癌患者CRF的有效性。
