Evidence and possible mechanism of <i>Scutellaria baicalensis</i> and its bioactive compounds for hepatocellular carcinoma treatment

Traditional Chinese medicines have been reported to have outstanding effects in the treating of hepatocellular carcinoma. Scutellaria baicalensis (S. baicalensis) has demonstrated anti-tumor, anti-angiogenic, and anti-inflammatory properties. Baicalein, wogonin, and baicalin are the main pharmacologically bioactive compounds of S. baicalensis. Eight electronic databases were searched to select articles published from their inception to 30 May 2022. For selected articles, clinical and preclinical data was obtained on the use of S. baicalensis and its bioactive compounds in hepatocellular carcinoma therapy. Statistical analyses were performed using RevMan version 5.3 and Stata software. Quality assessment of the studies was performed using Cochrane and Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE)’s risk of bias tools. Seven clinical and 17 preclinical in vivo studies along with 31 in vitro studies were included in this research. Meta-analysis showed that a Chinese herbal medicine preparation, with S. baicalensis as the sovereign herb, combined with Transcatheter arterial chemoembolization (TACE) or primary treatment, could lead to a significantly improved tumor objective response rate (Risk ratio (RR) = 1.57, 95% confidence interval (CI): [1.30, 1.90], p < 0.00001). Scutellaria baicalensis-based extracts (standard mean difference (SMD) = –0.86, 95%CI: [–1.20, −0.53], p < 0.00001), baicalein (SMD = –4.80, 95%CI: [–6.66, − 2.95], p < 0.00001), baicalin (SMD = –2.28, 95%CI [–3.26, −1.30], p < 0.00001) and wogonin (SMD = –1.41, 95%CI [–2.26, −0.57], p < 0.00001) slowed tumor growth in vivo. These outcomes might be linked to the mechanism by which S. baicalensis promotes apoptosis, induces autophagy, and blocks the expression of vascular endothelial growth factor (p < 0.05). Based on experimental and clinical evidence, we believe that S. baicalensis and its bioactive compounds have therapeutic potential and plausible mechanisms of action against hepatocellular carcinoma, in terms of efficacy and safety.据报道，传统中药在肝细胞癌（hepatocellular carcinoma）的治疗中展现出卓越疗效。黄芩（Scutellaria baicalensis，S. baicalensis）已被证实具备抗肿瘤、抗血管生成及抗炎特性。黄芩素（baicalein）、汉黄芩素（wogonin）与黄芩苷（baicalin）是黄芩主要的药理活性成分。 本研究检索了8个电子数据库，筛选自建库起始至2022年5月30日发表的相关文献。提取纳入文献中关于黄芩及其活性成分用于肝细胞癌治疗的临床与临床前研究数据。采用RevMan 5.3版软件及Stata软件开展统计学分析，使用科克伦（Cochrane）偏倚风险工具与实验动物系统评价中心（Systematic Review Centre for Laboratory Animal Experimentation，SYRCLE）的偏倚风险评估工具对纳入研究进行质量评价。 本研究共纳入7项临床研究、17项体内临床前研究及31项体外研究。Meta分析结果显示，以黄芩为君药的中药制剂联合经导管动脉化疗栓塞术（Transcatheter arterial chemoembolization，TACE）或作为一线治疗方案时，可显著提升肿瘤客观缓解率（风险比（Risk ratio，RR）=1.57，95%置信区间（confidence interval，CI）：[1.30, 1.90]，p<0.00001）。以黄芩提取物（标准均数差（standard mean difference，SMD）=–0.86，95%CI：[–1.20, −0.53]，p<0.00001）、黄芩素（SMD=–4.80，95%CI：[–6.66, −2.95]，p<0.00001）、黄芩苷（SMD=–2.28，95%CI：[–3.26, −1.30]，p<0.00001）及汉黄芩素（SMD=–1.41，95%CI：[–2.26, −0.57]，p<0.00001）均可在体内抑制肿瘤生长。上述效应可能与黄芩介导的细胞凋亡促进、自噬诱导及血管内皮生长因子（vascular endothelial growth factor，VEGF）表达阻断机制相关（p<0.05）。 基于现有实验与临床证据，本研究认为黄芩及其活性成分在肝细胞癌治疗中具备治疗潜力，且其作用机制在疗效与安全性层面均具有合理性。