Inhibitory effect of food-functioned phytochemicals on dysregulated inflammatory pathways triggered by SARS-CoV-2: a mechanistic review.

Inflammatory cascades of the dysregulated inflammatory pathways in COVID-19 can cause excessive production of pro-inflammatory cytokines and chemokines leading to cytokine storm syndrome (CSS). The molecular cascades involved in the pathways may be targeted for discovery of new anti-inflammatory agents. Many plant extracts have been used clinically in the management of COVID-19, however, their immunosuppressive activities were mainly investigated based on in silico activity. Dietary flavonoids of the extracts such as quercetin, luteolin, kaempferol, naringenin, isorhamnetin, baicalein, wogonin, and rutin were commonly identified as responsible for their inhibitory effects. The present review critically analyzes the anti-inflammatory effects and mechanisms of phytochemicals, including dietary compounds against cytokine storm (CS) and hyperinflammation via inhibition of the altered inflammatory pathways triggered by SARS-CoV-2, published since the emergence of COVID-19 in December 2019. Only a few phytochemicals, mainly dietary compounds such as nanocurcumin, melatonin, quercetin, 6-shagoal, kaempferol, resveratrol, andrographolide, and colchicine have been investigated either in in silico or preliminary clinical studies to evaluate their anti-inflammatory effects against COVID-19. Sufficient pre-clinical studies on safety and efficacy of anti-inflammatory effects of the phytochemicals must be performed prior to proper clinical studies to develop them into therapeutic adjuvants in the prevention and treatmemt of COVID-19 symptoms.

Data on LC-MS profile of Brucea javanica (L.) Merr. and the NMR data of its major indole alkaloids.

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 1­hydroxy-11-methoxycanthin-6-one (compound 22). This phytochemical data was generated to support an ongoing anti-cancer and anti-dengue study.

Carica papaya Leaf Juice for Dengue: A Scoping Review.

The potential therapeutic effect of Carica papaya leaf juice has attracted wide interest from the public and scientists in relieving dengue related manifestations. Currently, there is a lack of evaluated evidence on its juice form. Therefore, this scoping review aims to critically appraise the available scientific evidence related to the efficacy of C. papaya leaf juice in dengue. A systematic search was performed using predetermined keywords on two electronic databases (PubMed and Google Scholar). Searched results were identified, screened and appraised to establish the association between C. papaya and alleviating dengue associated conditions. A total of 28 articles (ethnobotanical information: three, in vitro studies: three, ex vivo studies: one, in vivo study: 13, clinical studies: 10) were included for descriptive analysis, which covered study characteristics, juice preparation/formulations, study outcomes, and toxicity findings. Other than larvicidal activity, this review also reveals two medicinal potentials of C. papaya leaf juice on dengue infection, namely anti-thrombocytopenic and immunomodulatory effects. C. papaya leaf juice has the potential to be a new drug candidate against dengue disease safely and effectively.

Preliminary study on the expression of endothelial cell biology related genes in the liver of dengue virus infected mice treated with Carica papaya leaf juice.

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.

Effect of freeze-dried Carica papaya leaf juice on inflammatory cytokines production during dengue virus infection in AG129 mice.

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.

The effect of freeze-dried Carica papaya leaf juice treatment on NS1 and viremia levels in dengue fever mice model.

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.

Anti-infective activities of 11 plants species used in traditional medicine in Malaysia.

Treatment of drug resistant protozoa, bacteria, and viruses requires new drugs with alternative chemotypes. Such compounds could be found from Southeast Asian medicinal plants. The present study examines the cytotoxic, antileishmanial, and antiplasmodial effects of 11 ethnopharmacologically important plant species in Malaysia. Chloroform extracts were tested for their toxicity against MRC-5 cells and Leishmania donovani by MTT, and chloroquine-resistant Plasmodium falciparum K1 strain by Histidine-Rich Protein II ELISA assays. None of the extract tested was cytotoxic to MRC-5 cells. Extracts of Uvaria grandiflora, Chilocarpus costatus, Tabernaemontana peduncularis, and Leuconotis eugenifolius had good activities against L. donovani with IC50 < 50 µg/mL. Extracts of U. grandiflora, C. costatus, T. peduncularis, L. eugenifolius, A. subulatum, and C. aeruginosa had good activities against P. falciparum K1 with IC50 < 10 µg/mL. Pinoresinol isolated from C. costatus was inactive against L. donovani and P. falciparum. C. costatus extract and pinoresinol increased the sensitivity of Staphylococcus epidermidis to cefotaxime. Pinoresinol demonstrated moderate activity against influenza virus (IC50 = 30.4 ±â€¯11 µg/mL) and was active against Coxsackie virus B3 (IC50 = 7.1 ±â€¯3.0 µg/mL). ß-Amyrin from L. eugenifolius inhibited L. donovani with IC50 value of 15.4 ±â€¯0.01 µM. Furanodienone from C. aeruginosa inhibited L. donovani and P. falciparum K1 with IC50 value of 39.5 ±â€¯0.2 and 17.0 ±â€¯0.05 µM, respectively. Furanodienone also inhibited the replication of influenza and Coxsackie virus B3 with IC50 value of 4.0 ±â€¯0.5 and 7.2 ±â€¯1.4 µg/mL (Ribavirin: IC50: 15.6 ±â€¯2.0 µg/mL), respectively. Our study provides evidence that medicinal plants in Malaysia have potentials as a source of chemotypes for the development of anti-infective leads.

Effect of selected local medicinal plants on the asexual blood stage of chloroquine resistant Plasmodium falciparum.

BACKGROUND: The development of resistant to current antimalarial drugs is a major challenge in achieving malaria elimination status in many countries. Therefore there is a need for new antimalarial drugs. Medicinal plants have always been the major source for the search of new antimalarial drugs. The aim of this study was to screen selected Malaysian medicinal plants for their antiplasmodial properties. METHODS: Each part of the plants were processed, defatted by hexane and sequentially extracted with dichloromethane, methanol and water. The antiplasmodial activities of 54 plant extracts from 14 species were determined by Plasmodium falciparum Histidine Rich Protein II ELISA technique. In order to determine the selectivity index (SI), all plant extracts demonstrating a good antiplasmodial activity were tested for their cytotoxicity activity against normal Madin-Darby Bovine Kidney (MDBK) cell lines by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. RESULTS: Twenty three extracts derived from Curcuma zedoaria (rhizome), Curcuma aeruginosa (rhizome), Alpinia galanga (rhizome), Morinda elliptica (leaf), Curcuma mangga (rhizome), Elephantopus scaber (leaf), Vitex negundo (leaf), Brucea javanica (leaf, root and seed), Annona muricata (leaf), Cinnamomun iners (leaf) and Vernonia amygdalina (leaf) showed promising antiplasmodial activities against the blood stage chloroquine resistant P. falciparum (EC50 < 10 µg/ml) with negligible toxicity effect to MDBK cells in vitro (SI ≥10). CONCLUSION: The extracts belonging to eleven plant species were able to perturb the growth of chloroquine resistant P. falciparum effectively. The findings justified the bioassay guided fractionation on these plants for the search of potent antimalarial compounds or formulation of standardized extracts which may enhance the antimalarial effect in vitro and in vivo.