Dengue infections are still a worldwide burden, especially in Indonesia. There is no specific medication against the dengue virus. Recently, many types of research have been conducted to discover a new drug for dengue virus using natural resource extracts. Indonesia, as a tropical country, has a wide biodiversity. There are several medicinal plants in Indonesia that are believed to possess anti-dengue activity, such as Myristica fatua, Cymbopogon citratus, and Acorus calamus plants. We conducted an in vitro laboratory experiment of several extracts from Indonesian herbs combined with in silico analysis. The extracts were evaluated for safety and antiviral activity in Huh7it-1 cell lines, using a single dose of 20 µg/mL and dose-dependent (5, 10, 20, 40, 80 and 160 µg/mL) of plant extracts against dengue virus serotype 2 (DENV-2) NGC strain. The DMSO 0.1% was used as a negative control. The cytotoxic aspect was assessed by counting the cell viability, while the antiviral activity was calculated by counting the average inhibition. The selectivity index (SI) of plant extracts were performed from a ratio of CC50/EC50 value. In silico analysis was conducted to determine the free energy of binding between NS5 of dengue virus with bioactive compounds contained in Myristica fatua, Cymbopogon citratus and Acorus calamus extract plants. We determined that all extracts were not toxic against Huh7it-1 cell lines. The methanolic extracts of A. calamus, C. citratus, and M. fatua showed inhibition of DENV-2 at a dose of 20 µg/mL to 96.5%, 98.9%, and 122.7%, respectively. The dose-dependent effects showed that M. fatua has the best inhibition activity towards DENV-2. Molecular docking result showed that artesunic acid within M. fatua has the best free energy of binding (−7.2 kcal/mol), followed by homoegonol (−7.1 kcal/mol) which was slightly different from artesunic acid among others. The methanolic extracts of A. calamus, C. citratus, and M. fatua showed prospective anti-dengue activities both in vitro and in silico. Future research should be conducted to find the pure extracts of all useful herbs as a new candidate of antiviral drug.

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Caesalpinia sappan is studied for several biological activities. The aim of this research is to determine the cytotoxic and antimigratory activities of Caesalpinia sappan active fraction in combination with cisplatin on human TNBC cells (MDA-MB-231). Caesalpinia sappan heartwood was extracted with methanol. Then, several fractions of the methanol extract were obtained by using a liquid-liquid extraction method followed by column chromatography. The cytotoxicity was determined using MTT assay. Synergistic effects were analyzed by calculating the combination index (CI). Migration was examined using wound-healing assay. Levels of MMP2 activity were determined with gelatin zymography assay. The results showed that most of the fractions included in this study exhibited cytotoxic effects against MDA-MB-231 cells, and C fraction demonstrated the highest cytotoxic activity of all fractions. The combination of C-cisplatin revealed a synergistic inhibitory effect on MDA-MB-231 cell growth (CI<1). Furthermore, C fraction, alone and in combination with cisplatin, inhibited migration of MDA-MB-231 and suppressed MMP2 activity. The C fraction isolated from Caesalpinia sappan increased the cytotoxic and antimigratory activities of cisplatin on MDA-MB-231 cells. Based on these findings, the potential of Caesalpinia sappan to act as a supportive agent in metastatic TNBC treatment with cisplatin warrants further exploration.

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