Sari Defi Kartika, Jeelani Ghulam, Ilmi Hilkatul, Tumewu Lidya, Wahyuni Ratna, Widyawaruyanti Aty, Nozaki Tomoyoshi, Hafid Achmad Fuad
Center of Natural Product Medicine Research and Development, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.
Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan.
BMC Complement Med Ther. 2024 Dec 18;24(1):416. doi: 10.1186/s12906-024-04717-6.
Neglected tropical diseases (NTDs) afflict nearly 2 billion people worldwide and are caused by various pathogens, such as bacteria, protozoa, and trypanosoma, prevalent in tropical and subtropical regions. Among the 17 NTDs recognized by the World Health Organization (WHO), protozoal infections caused by Plasmodium, Entamoeba, Leishmania, and Trypanosoma are particularly prominent and pose significant public health. Indonesia, endowed with a rich biodiversity owing to its tropical climate, harbors numerous plant species with potent biological activities that hold promise for therapeutic interventions. Hence, efforts have been directed towards exploring Indonesian plant extracts and isolated compounds for their potential in combating protozoal diseases.
This study evaluated the antiprotozoal properties of 48 plant extracts sourced from the Cratoxylum, Diospyros, and Artocarpus genera. These extracts were screened using cell-based assays against Plasmodium falciparum (Pf), Entamoeba histolytica (Eh), Leishmania donovani (Ld), Trypanosoma brucei rhodesiense (Tbr), and Trypanosoma cruzi (Tc).
Extracts derived from the roots of Cratoxylum arborescens, obtained through dichloromethane extraction, exhibited significant activity against protozoa, with an IC value ranging from 0.1 to 8.2 µg/mL. Furthermore, cochinchinone C was identified as an active compound capable of inhibiting the growth of Pf, Eh, Ld, and Tbr, Tc trypomastigote, and Tc epimastigote with IC values of 5.8 µM, 6.1 µM, 0.2 µM, 0.1 µM, 0.7 µM, and 0.07 µM, respectively. Cochinchinone C is the first compound reported to exhibit activity against protozoal neglected tropical diseases, showing low cytotoxicity with a selectivity index greater than 10 when tested against carcinoma and normal cell lines. This suggests indicating its potential as a candidate for further drug development. This is the first report of cochinchinone C's activity against these protozoans.
These findings establish cochinchinone C as a strong candidate for antiprotozoal drug development, highlighting the untapped therapeutic potential of Indonesia's rich plant biodiversity.
被忽视的热带病(NTDs)影响着全球近20亿人,由各种病原体引起,如细菌、原生动物和锥虫,在热带和亚热带地区普遍存在。在世界卫生组织(WHO)认可的17种被忽视的热带病中,由疟原虫、溶组织内阿米巴、利什曼原虫和锥虫引起的原生动物感染尤为突出,并构成重大公共卫生问题。印度尼西亚因其热带气候拥有丰富的生物多样性,蕴藏着许多具有强大生物活性的植物物种,有望用于治疗干预。因此,人们一直致力于探索印度尼西亚植物提取物和分离化合物在对抗原生动物疾病方面的潜力。
本研究评估了来自黄牛木属、柿属和波罗蜜属的48种植物提取物的抗原生动物特性。这些提取物通过基于细胞的试验,针对恶性疟原虫(Pf)、溶组织内阿米巴(Eh)、杜氏利什曼原虫(Ld)、布氏罗得西亚锥虫(Tbr)和克氏锥虫(Tc)进行筛选。
通过二氯甲烷萃取从黄牛木的根中获得的提取物对原生动物表现出显著活性,IC值范围为0.1至8.2μg/mL。此外,柯钦醌C被鉴定为一种活性化合物,能够抑制Pf、Eh、Ld、Tbr以及Tc滋养体和Tc前鞭毛体的生长,IC值分别为5.8μM、6.1μM、0.2μM、0.1μM、0.7μM和0.07μM。柯钦醌C是首个被报道对被忽视的热带原生动物疾病具有活性的化合物,在针对癌细胞系和正常细胞系进行测试时,显示出低细胞毒性,选择性指数大于10。这表明其有潜力作为进一步药物开发的候选物。这是柯钦醌C对这些原生动物活性的首次报道。
这些发现确立了柯钦醌C作为抗原生动物药物开发的有力候选物,突出了印度尼西亚丰富植物生物多样性中尚未开发的治疗潜力。