Novel Antiviral Efficacy of Hedyotis diffusa and Artemisia capillaris Extracts against Dengue Virus, Japanese Encephalitis Virus, and Zika Virus Infection and Immunoregulatory Cytokine Signatures

Abstract

Currently, there are no specific therapeutics for flavivirus infections, including dengue virus (DENV) and Zika virus (ZIKV). In this study, we evaluated extracts from the plants Hedyotis diffusa (HD) and Artemisia capillaris (AC) to determine the antiviral activity against DENV, ZIKV, and Japanese encephalitis virus (JEV). HD and AC demonstrated inhibitory activity against JEV, ZIKV, and DENV replication and reduced viral RNA levels in a dose–responsive manner, with non-cytotoxic concentration ranging from 0.1 to 10 mg/mL. HD and AC had low cytotoxicity to Vero cells, with CC50 values of 33.7 ± 1.6 and 30.3 ± 1.7 mg/mL (mean ± SD), respectively. The anti-flavivirus activity of HD and AC was also consistent in human cell lines, including human glioblastoma (T98G), human chronic myeloid leukemia (K562), and human embryonic kidney (HEK-293T) cells. Viral-infected, HD-treated cells demonstrated downregulation of cytokines including CCR1, CCL26, CCL15, CCL5, IL21, and IL17C. In contrast, CCR1, CCL26, and AIMP1 were elevated following AC treatment in viral-infected cells. Overall, HD and AC plant extracts demonstrated flavivirus replication inhibitory activity, and together with immunoregulatory cytokine signatures, these results suggest that HD and AC possess bioactive compounds that may further be refined as promising candidates for clinical applications.

Natural Products and Derivatives as Potential Zika virus Inhibitors: A Comprehensive Review

“…They inhibited virus replication and reduced viral RNA levels in a concentration-dependent manner in the range from 0.1 to 10 mg/mL in Vero cells. Both extracts presented anti- flavivirus activity in other human cell lines, including human glioblastoma (T98G), human chronic myeloid leukemia (K562), and human embryonic kidney (HEK-293T) cells [ 87 ].…”

Role of phytocompounds as the potential anti-viral agent: an overview

“…It has four serotypes, meaning a person can be infected four times. An Ayurvedic polyherbal concoction called Nilavembu Kudineer (NVK) with Andrographis paniculata as the main constituent and other extracts from Mollugo cerviana (Molluginaceae), Piper nigrum (Piperaceae), Zingeber officinale (Zingeberaceae), Cyperus rotandus (Cyperaceae), Trichosanthes cucumerina , Santalum album , Vetiveria zizanioides (Piperaceae), and V. zizanioides Hedyotis diffusa and Artemisia capillaris had been reported to show good anti-DENV and anti-CHIKV during infection in vitro (Mao et al 2022 ; Jain et al 2020 ). Baicalein and fisetin phytoactive compounds had been shown to impede replication at different stages.…”

“…It can also be transmitted through sexual contact, organ transplantation, from mother to fetus during pregnancy, and transfusion of blood and blood products by WHO, 2023 . It has no specific anti-viral treatment, but in recent years, researchers have detected curcumin and pinocembrin found in turmeric, and tea extracts from Hedyotis diffusa and Artemisia capillaris are found to have replication repressive effect (Mao et al 2022 ), respectively in having anti-ZIKV effects (Akbar et al 2018 ; Lee et al 2019 ). Extract from endemic plants, Aphloia theiformis (Aphloiceae) and Psiloxylon mauritianum (Myrtaceae), found at Reunion Island, inhibited ZIKV adherence to cell surface makings by both anti-ZIKV and anti-DENV (Clain et al 2019 , 2018 ).…”

“…Various plants are valuable assets, which are to be explored, especially in emerging resistant infectious diseases (Idriss et al 2023a , b ; Mukhtar et al 2008 ). Undeniably, plant-derived phytoactive compounds are potential therapeutic metabolites with the power to obstruct, control viral uptake, attach to surface receptors, and compete for pathways of activation of intracellular signals (Mao et al 2022 ; Ghosh et al 2009 ; Kapoor et al 2017 ; Khan et al 2005 ; Mohapatra and Dar 2010 ).…”

Network pharmacology, bioinformatics, and experimental validation to identify the role of Hedyotis diffusa willd against gastric cancer through the activation of the endoplasmic reticulum stress

“…In traditional Chinese medicine, Hedyotis diffusa Willd (Family Rubiaceae) is commonly known as Bai Hua She Cao (BHSSC) in pinyin. According to contemporary pharmacological research, BHSSC possesses a wide range of pharmacological properties, including anti-inflammatory [ 4 ], hepatoprotective effect [ 5 , 6 ], antiviral efficacy [ 7 ], antioxidant [ 8 ] and neuroprotective [ 9 ], anti-tumor [ 10 ], and other biological activities.…”