Luo Ke-Ke, Zhao Hai-Yu, Si Nan, Bian Bao-Lin, Xia Wen, Chen Yun-Qin, Wang Meng-Xiao, Wei Xiao-Lu, Li Xing, Qin Guang-Yuan, Yang Jian, Zhou Yan-Yan, Wang Hong-Jie
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China.
Guizhou Bailing Group Pharmaceutical Co., Ltd. Anshun 561000, China.
Zhongguo Zhong Yao Za Zhi. 2023 Feb;48(4):1124-1131. doi: 10.19540/j.cnki.cjcmm.20221008.502.
A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.
本研究采用随机、双盲、安慰剂对照、多中心Ⅱ期临床试验设计，招募符合实热火毒证型且被诊断为复发性口腔溃疡、牙龈炎和急性咽炎的受试者。共纳入240例病例，随机分为安慰剂组和黄连解毒丸组。采用中医证候量表评估黄连解毒丸治疗实热火毒证的临床疗效。采用酶联免疫吸附测定（ELISA）法测定并评估两组给药前后血浆中三磷酸腺苷（ATP）、4-羟基壬烯醛（4-HNE）和促肾上腺皮质激素（ACTH）的水平，并预测其作为临床生物标志物的应用价值。结果显示，黄连解毒丸组主要症状消失率为69.17%，安慰剂组为50.83%。黄连解毒丸组与安慰剂组比较，给药前后4-HNE差异有统计学意义（P<0.05）。黄连解毒丸组给药后4-HNE含量显著降低（P<0.05），而安慰剂组无统计学意义且呈上升趋势。给药后，黄连解毒丸组和安慰剂组ATP含量均显著降低（P<0.05），表明黄连解毒丸给药后能量代谢紊乱明显改善，机体自身修复能力也在一定程度上缓解了实热火毒证导致的ATP水平升高。黄连解毒丸组和安慰剂组给药后ACTH均显著降低（P<0.05）。结论：黄连解毒丸具有显著临床疗效，可显著改善实热火毒证所致血浆中ATP和4-HNE的异常水平，推测其为黄连解毒丸治疗实热火毒证的有效临床生物标志物。
