Liu Xin, Xi Ruofan, Cheng Linyan, Wang Yi, Nie Yiwen, Yan Ge, Guo Dongjie, Guo Wanjun, Du Ting, Lu Hanzhi, Wang Peiyao, Zhu Jianyong, Li Fulun
Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
Department of Pharmacy Research, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
Heliyon. 2024 May 16;10(10):e31376. doi: 10.1016/j.heliyon.2024.e31376. eCollection 2024 May 30.
Palmoplantar warts (PWs) are a usual skin disease associated with human papillomavirus (HPV) that can affect patients' quality of life. The traditional Chinese medicine (TCM) Weiren Xiaoyou formula (WRXYF) is a relatively gentle and effective therapy that has achieved good therapeutic effects in clinical practice, but its mechanism has not yet been studied.
A meta-analysis was carried out to identify the potential advantages of topical TCM for PW treatment. Clinical cases suggested that WRXYF was an effective therapeutic agent against PWs. Network pharmacology was utilized to predict potential targets for the main bioactive compound, tanshinone IIA (Tan IIA), in WRXYF. High-performance liquid chromatography with electrospray mass spectrometry (HPLC/ESI-MS) was applied to detect major components. The bioactivity of Tan IIA against PWs was then validated with quantitative polymerase chain reaction (q-PCR), fluorescence hybridization (FISH), electron microscopy and Western blotting.
A meta-analysis was conducted on 10 randomized clinical trials (RCTs) involving 2260 participants suggested that topical TCM could more effectively treat PWs than conventional medications. Network pharmacology identified Tan IIA as a candidate agent from 17 major compounds assessed by HPLC/ESI-MS because of its stable binding with 10 PW targets. HPV2, HPV27, and HPV57 were the main infectious strains in tissues obtained from PW patients and in HPV-infected HaCaT cells. Tan IIA treatment effectively destroyed viral particles and reduced the viral copy numbers of the three HPV subtypes. The results shown that Tan IIA has the ability to halt the cell cycle of HPV-infected HaCaT cells specifically in the G/G phase. A total of 6 cell cycle-related proteins were regulated after Tan IIA treatment, demonstrating the role of Tan IIA in inhibiting the cell cycle.
Tan IIA, the primary bioactive constituent in WRXYF, enhances PWs by halting the cell cycle in the G/G phase via modulation of the p53 signaling pathway.
掌跖疣（PWs）是一种常见的与人类乳头瘤病毒（HPV）相关的皮肤疾病，会影响患者的生活质量。中药维任消疣方（WRXYF）是一种相对温和且有效的疗法，在临床实践中取得了良好的治疗效果，但其作用机制尚未得到研究。
进行一项荟萃分析以确定局部应用中药治疗掌跖疣的潜在优势。临床病例表明WRXYF是治疗掌跖疣的有效药物。利用网络药理学预测WRXYF中主要生物活性化合物丹参酮IIA（Tan IIA）的潜在靶点。采用高效液相色谱-电喷雾质谱联用（HPLC/ESI-MS）检测主要成分。然后通过定量聚合酶链反应（q-PCR）、荧光杂交（FISH）、电子显微镜和蛋白质免疫印迹法验证Tan IIA对掌跖疣的生物活性。
对10项涉及2260名参与者的随机临床试验（RCT）进行荟萃分析，结果表明局部应用中药比传统药物能更有效地治疗掌跖疣。网络药理学从通过HPLC/ESI-MS评估的17种主要化合物中确定Tan IIA为候选药物，因为它与10个掌跖疣靶点具有稳定的结合。HPV2、HPV27和HPV57是从掌跖疣患者组织和HPV感染的HaCaT细胞中分离出的主要感染毒株。Tan IIA治疗有效破坏了病毒颗粒并降低了这三种HPV亚型的病毒拷贝数。结果表明Tan IIA能够特异性地使HPV感染的HaCaT细胞在G/G期停止细胞周期。Tan IIA处理后共调节了6种细胞周期相关蛋白，证明了Tan IIA在抑制细胞周期中的作用。
WRXYF中的主要生物活性成分Tan IIA通过调节p53信号通路使细胞周期在G/G期停滞，从而增强对掌跖疣的治疗效果。
