Monteillier Aymeric, Cretton Sylvian, Ciclet Olivier, Marcourt Laurence, Ebrahimi Samad Nejad, Christen Philippe, Cuendet Muriel
School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, CMU, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland.
Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran.
J Ethnopharmacol. 2017 May 5;203:214-225. doi: 10.1016/j.jep.2017.03.048. Epub 2017 Mar 28.
Waltheria indica L. is traditionally used in several countries against inflammatory related diseases and cancer, mainly as a decoction of the aerial parts.
The transcription factor NF-κB is known to induce tumor promotion and progression and is considered a major player in inflammation-driven cancers. Therefore, inhibitors of this pathway possess cancer chemopreventive and chemotherapeutic activities. This study aimed first to confirm the use of Waltheria indica as a traditional anti-inflammatory remedy by assessing the NF-κB inhibitory activity and then to identify the major bioactive compounds. The isolated compounds were also tested for their QR inducing property, a complementary strategy in cancer chemoprevention able to target tumor initiation. Finally, the relevance of in vitro results was examined by investigating the occurrence of the active compounds in traditional preparations.
Compounds were isolated from the dichloromethane extract of the aerial parts using flash chromatography and semi-preparative HPLC. NF-κB inhibitory activity of pure compounds from Waltheria indica was assessed using a luciferase reporter assay in HEK293 cells. Their QR inducing activity was also assessed in Hepa1c1c7 cells.
Twenty-nine compounds, of which 5 are new, were obtained from the dichloromethane extract and tested for their cancer chemoprevention activity. Eleven compounds inhibited NF-κB and/or induced QR in the low to mid µM range. Chrysosplenol E (20) was active in both tests. Two of the most potent NF-κB inhibitors, waltherione A (4) and waltherione C (5), as well as 20 were found in the traditional decoction, in which 4 and 5 were major compounds.
The presence of potent NF-κB inhibitors and QR inducing compounds in the decoction of the aerial parts of Waltheria indica supports its traditional use in inflammatory-related diseases and cancer chemoprevention.
在多个国家，人们传统上使用印度刺蒴麻来治疗炎症相关疾病和癌症，主要是将地上部分煎成汤剂使用。
已知转录因子NF-κB可促进肿瘤发展和进展，被认为是炎症驱动型癌症的主要因素。因此，该信号通路的抑制剂具有癌症化学预防和化疗活性。本研究首先通过评估NF-κB抑制活性来证实印度刺蒴麻作为传统抗炎药物的用途，然后鉴定主要的生物活性化合物。还测试了分离出的化合物诱导醌还原酶（QR）的特性，这是癌症化学预防中一种能够靶向肿瘤起始的补充策略。最后，通过研究传统制剂中活性化合物的存在情况，考察体外实验结果的相关性。
使用快速柱色谱和半制备型高效液相色谱从地上部分的二氯甲烷提取物中分离化合物。在HEK293细胞中使用荧光素酶报告基因检测法评估印度刺蒴麻纯化合物的NF-κB抑制活性。还在Hepa1c1c7细胞中评估了它们诱导QR的活性。
从二氯甲烷提取物中获得了29种化合物，其中5种为新化合物，并对它们的癌症化学预防活性进行了测试。11种化合物在低至中微摩尔范围内抑制NF-κB和/或诱导QR。金腰子酚E（20）在两项测试中均有活性。在传统汤剂中发现了两种最有效的NF-κB抑制剂，刺蒴麻酮A（4）和刺蒴麻酮C（5），以及化合物20，其中4和5是主要成分。
印度刺蒴麻地上部分汤剂中存在有效的NF-κB抑制剂和诱导QR的化合物，这支持了其在炎症相关疾病和癌症化学预防方面的传统用途。
