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Abstract Background In early 2020, COVID-19 pandemic has mobilized researchers in finding new remedies including repurposing of medicinal plant products focusing on direct-acting antiviral and host-directed therapies. In this study, we performed an in vitro investigation on the standardized Marantodes pumilum extract (SKF7®) focusing on anti-SARS-CoV-2 and anti-inflammatory activities. Methods Anti-SARS-CoV-2 potential of the SKF7® was evaluated in SARS-CoV-2-infected Vero E6 cells and SARS-CoV-2-infected A549 cells by cytopathic effect-based assay and RT-qPCR, respectively. Target based assays were performed on the SKF7® against the S1-ACE2 interaction and 3CL protease activities. Anti-inflammatory activity of the SKF7® was evaluated by nitric oxide inhibitory and TLR2/TLR4 receptor blocker assays. Results The SKF7® inhibited wild-type Wuhan (EC50 of 21.99 µg/mL) and omicron (EC50 of 16.29 µg/mL) SARS-CoV-2 infections in Vero-E6 cells. The SKF7® also inhibited the wild-type SARS-CoV-2 infection in A549 cells (EC50 value of 6.31 µg/mL). The SKF7® prominently inhibited 3CL protease activity. The SKF7® inhibited the LPS induced-TLR4 response with the EC50 of 16.19 µg/mL. Conclusions In conclusion, our in vitro study highlighted anti-SARS-CoV-2 and anti-inflammatory potentials of the SKF7®. Future pre-clinical in vivo studies focusing on antiviral and immunomodulatory potentials of the SKF7® in affecting the COVID-19 pathogenesis are warranted.

This article presents two types of phytochemical data obtained from Brucea javanica (L.) Merr. roots, a medicinal plant belonging to the Simaroubaceae family. The high-resolution LC–MS dataset comprised the chemical profile of dichloromethane extract, which was utilised to annotate 35 chemical constituents. For annotations, the measured spectral data were compared with the in-silico spectral data generated from 920 molecular structures previously reported in Simaroubaceae. Indole alkaloids, quassinoids, aliphatics and lignan were the chemical groups identified in the root extract. The second dataset provides NMR spectra (1H, 13C, COSY, HMQC and HMBC) for the six indole alkaloids previously detected in LC–MS analysis and isolated through centrifugal partition chromatography. The chemical structures of all compounds were confirmed based on NMR data as bruceolline J (compound 7), canthin-6-one-N-oxide (compound 10), bruceolline E (compound 15), 5-methoxycanthin-6-one (compound 16), canthin-6-one (compound 20), and 1‑hydroxy-11-methoxycanthin-6-one (compound 22). This phytochemical data was generated to support an ongoing anti-cancer and anti-dengue study.

Abstract Objective The purpose of this study was to profile and identify the endothelial cell biology related genes that are affected by dengue virus infection in the liver tissue of AG129 mice, with and without Carica papaya leaf juice treatment. Results The dengue fever mouse model was established by intraperitoneal inoculation of dengue virus, New Guinea C strain at 2 × 106 PFU. Daily oral administration of 1000 mg/kg freeze-dried C. papaya leaf juice (FCPLJ) was done starting from day 1 to day 3 post infection. The RNA was extracted from liver tissues harvested on day 4 post infection. The expression levels of 84 genes related to mouse endothelial cell biology were determined by qRT-PCR technique. Dengue virus infection upregulated 15 genes and downregulated two genes in the liver of AG129 mice. The FCPLJ treatment upregulated monocyte chemoattractant protein 1 and downregulated intercellular adhesion molecule 1, integrin beta 3 and fibronectin 1 genes during dengue virus infection. The data showed the potential effect of FCPLJ treatment on the expression profile of endothelial cell biology related genes in the liver of dengue virus infected-AG129 mice. Further proteomic studies are needed to determine the functional roles of the genes affected by FCPLJ treatment.

Abstract Background Carica papaya leaves have been used for traditional treatment of dengue fever and have been reported to exhibit an immunomodulatory activity by affecting the level of cytokine production in vitro and in vivo. Due to the lack of adequate in vivo evidence in dengue disease model, the present study was initiated to screen and identify the cytokines affected by freeze-dried C. papaya leaf juice (FCPLJ) treatment in AG129 mice infected with DEN-2 dengue virus. Methods The AG129 mice were fed orally with FCPLJ for 3 consecutive days after 24 h of dengue virus inoculation. Plasma cytokines were screened by using ProcartaPlex immunoassay. The gene expression in the liver was analyzed by using RT2 Profiler PCR Array. Results The results showed that FCPLJ treatment has increased the plasma CCL2/MCP-1 level during peak of viremia. Gene expression study has identified 8 inflammatory cytokine genes which were downregulated in the liver of infected AG129 mice treated with FCPLJ. The downregulated inflammatory cytokine genes were CCL6/MRP-1, CCL8/MCP-2, CCL12/MCP-5, CCL17/TARC, IL1R1, IL1RN/IL1Ra, NAMPT/PBEF1 and PF4/CXCL4. Conclusion The findings indicated the possible immunomodulatory role of FCPLJ during dengue virus infection in AG129 mice.

Abstract Background Carica papaya leaf juice (CPLJ) was well known for its thrombocytosis activity in rodents and dengue patients. However, the effect of CPLJ treatment on other parameters that could contribute to dengue pathogenesis such as nonstructural protein 1 (NS1) production and viremia level have never been highlighted in any clinical and in vivo studies. The aim of this study is to investigate the effect of freeze-dried CPLJ treatment on NS1 and viremia levels of dengue fever mouse model. Methods The dengue infection in mouse model was established by inoculation of non-mouse adapted New Guinea C strain dengue virus (DEN-2) in AG129 mice. The freeze-dried CPLJ compounds were identified by Ultra-High Performance Liquid Chromatography High Resolution Accurate Mass Spectrometry analysis. The infected AG129 mice were orally treated with 500 mg/kg/day and 1000 mg/kg/day of freeze-dried CPLJ, starting on day 1 post infection for 3 consecutive days. The blood samples were collected from submandibular vein for plasma NS1 assay and quantitation of viral RNA level by quantitative reverse transcription PCR. Results The AG129 mice infected with dengue virus showed marked increase in the production of plasma NS1, which was detectable on day 1 post infection, peaked on day 3 post-infection and started to decline from day 5 post infection. The infection also caused splenomegaly. Twenty-four compounds were identified in the freeze-dried CPLJ. Oral treatment with 500 mg/kg/day and 1000 mg/kg/day of freeze-dried CPLJ did not affect the plasma NS1 and dengue viral RNA levels. However, the morbidity level of infected AG129 mice were slightly decreased when treated with freeze-dried CPLJ. Conclusion Oral treatment of 500 mg/kg/day and 1000 mg/kg/day of freeze-dried CPLJ at the onset of viremia did not affect the plasma NS1 and viral RNA levels in AG129 mice infected with non-mouse adapted New Guinea C strain dengue virus.

The role of Carica papaya L. leaf juice in immune dysregulation caused by dengue virus infection remains unclear. This study aimed to investigate the immunomodulatory activities of the freeze-dried C. papaya leaf juice (FCPLJ) on AG129 mice infected with a clinical DENV-2 (DMOF015) isolate. The infected AG129 mice were orally treated with 500 and 1000 mg/kg/day of FCPLJ, for three days. Platelet, leukocyte, lymphocyte and neutrophil counts were microscopically determined. The level of plasma proinflammatory cytokines was measured by multiplex immunoassay. The levels of intracellular cytokines and viral RNA were determined by RT-qPCR technique. The results showed that the FCPLJ treatment increased the total white blood cell and neutrophil counts in the infected mice. The FCPLJ treatment decreased the level of GM-CSF, GRO-alpha, IL-1 beta, IL-6, MCP-1 and MIP-1 beta in the plasma of the infected mice. The intracellular IL-6 and viral RNA levels in the liver of infected mice were decreased by the FCPLJ treatment. In conclusion, this study supports the potential immunomodulatory role of the FCPLJ in a non-lethal, symptomatic dengue mouse model. Further studies on the action mechanism of the C. papaya leaf juice and its possible use as adjunctive dengue immunotherapy are warranted.

Eurycoma longifolia is one of the commonly consumed herbal preparations and its major chemical compound, eurycomanone, has been described to have antimalarial, antipyretic, aphrodisiac, and cytotoxic activities. Today, the consumption of E. longifolia is popular through the incorporation of its extract in food items, most frequently in drinks such as tea and coffee. In the current study, the characterisation of the physicochemical and pharmacokinetic (PK) attributes of eurycomanone were conducted via a series of in vitro and in vivo studies in rats and mice. The solubility and chemical stability of eurycomanone under the conditions of the gastrointestinal tract environment were determined. The permeability of eurycomanone was investigated by determining its distribution coefficient in aqueous and organic environments and its permeability using the parallel artificial membrane permeability assay system and Caco-2 cultured cells. Eurycomanone’s stability in plasma and its protein-binding ability were measured by using an equilibrium dialysis method. Its stability in liver microsomes across species (mice, rat, dog, monkey, and human) and rat liver hepatocytes was also investigated. Along with the PK evaluations of eurycomanone in mice and rats, the PK parameters for the Malaysian Standard (MS: 2409:201) standardised water extract of E. longifolia were also evaluated in rats. Both rodent models showed that eurycomanone in both the compound form and extract form had a half-life of 0.30 h. The differences in the bioavailability of eurycomanone in the compound form between the rats (11.8%) and mice (54.9%) suggests that the PK parameters cannot be directly extrapolated to humans. The results also suggest that eurycomanone is not readily absorbed across biological membranes. However, once absorbed, the compound is not easily metabolised (is stable), hence retaining its bioactive properties, which may be responsible for the various reported biological activities.

Neuroinflammation is a series of neuropathological processes as the result from the interaction with the microenvironmental cues (e.g. lipopolysaccharide (LPS) and amyloid-ß (Aß)) present at the central nervous system (CNS). The neuroinflammation will become chronic when the inflammation persists which lead to the neuronal damage and eventually neurodegeneration development. Thus, the present study aimed to determine the cytotoxic effect of vitexin compound on BV2 cells and Aß-induced BV2 cells. Cell viability assay was conducted to investigate the toxicity effect of the compound towards both cell cultures. Six concentrations of vitexin were prepared and tested. MTT assay (3-(4, 5-Dimethylthiazol-2-yl)-2, 5- diphenyltetrazolium bromide) was performed to determine the cytotoxicity of the compound. The results from both cultures were expressed as Means ± S.D where p<0.05 is considered as significant. The result from this study showed that the vitexin compound possesses cytotoxicity effect in dose-dependent manner upon exposed to both cultures. The IC50 from both cell cultures was 50µM. The result suggests that the vitexin compound is safe to be used in both conditions. This preliminary finding allows the future research to be conducted on vitexin in search for the potential treatment for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]