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Carica papaya Leaf Extract Silver Synthesized Nanoparticles Inhibit Dengue Type 2 Viral Replication In Vitro.

ABSTRACT: The current global occurrence of dengue infection annually is approximately 400 million, with a case fatality rate of 2.5%. However, there are no antiviral agents. Carica papaya leaf extract is known for its medicinal value, due to the presence of organic compounds that possess antimicrobial, anti-inflammatory, and antioxidant activities. This study determined the anti-dengue effect of C. papaya leaf extract silver synthesized nanoparticles. In this study, aqueous and non-aqueous extractions were carried out, followed by the synthesis of silver nanoparticles as well as characterization through Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy. The in vitro anti-dengue effect was evaluated using a focus reduction neutralization test on kidney Vero E2 cell lines. In silico studies involved molecular docking to determine the potential interactions between the bioactive compounds in C. papaya leaf extract and the viral NS5 protein. C. papaya leaf methanol extract silver synthesized nanoparticle was the most promising with an IC₅₀ of 9.20 µg/mL. Molecular docking showed 5,7 dimethoxycoumarin as the best ligand, with binding energy of -7.75 kcal/mol, indicating high affinity for the NS5 protein. These results highlight that C. papaya leaf methanol extract silver synthesized nanoparticles could be used to inhibit dengue virus type 2 viral replication. However, we recommend further studies to determine their toxicity and the safety profiles.

SUBMITTER: Bere AW

PROVIDER: S-EPMC8400503 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Severe thrombocytopenia in dengue often prompts platelet transfusion primarily to reduce bleeding risk. In India, about 11-43% of dengue patients report receiving platelet transfusions which is considered scarce and expensive especially in resource limited settings. Herein, we evaluated the efficacy and safety of Carica papaya leaf extract (CPLE) in the management of severe thrombocytopenia (≤30,000/μL) in dengue infection. 51 laboratory confirmed adult dengue patients with platelet counts ≤30,000/μL were randomly assigned to either treatment (n = 26) or placebo (n = 24) group. By day 3, CPLE treated patients reported significantly (p = 0.007) increased platelet counts (482%± 284) compared to placebo (331%±370) group. In the treatment group, fewer patients received platelet transfusions (1/26 v/s 2/24) and their median time for platelets to recover to ≥ 50,000/μL was 2 days (IQR 2-3) compared to 3 days (IQR 2-4) in placebo. Overall, CPLE was safe and well tolerated with no significant decrease in mean hospitalization days. Plasma cytokine profiling revealed that by day 3, mean percent increase in TNFα and IFNγ levels in treatment group was less compared to that observed in placebos; (TNFα: 58.6% v/s 127.5%; p = 0.25 and IFNγ: 1.93% v/s 62.6% for; p = 0.12). While a mean percent increase in IL-6 levels occurred in placebos (15.92%±29.93%) by day 3, a decrease was noted in CPLE group (12.95%±21.75%; p = 0.0232). Inversely, CPLE treated patients reported a mean percent increase compared to placebo by day 3 (143% ±115.7% v/s 12.03%± 48.4%; p = 0.006). Further, by day 3, a faster clearance kinetics of viral NS1 antigenemia occurred-mean NS1 titers in treatment group decreased to 97.3% compared to 88% in placebos (p = 0.023). This study demonstrates safety and efficacy of CPLE in increasing platelet counts in severe thrombocytopenia in dengue infections. A possible immunomodulatory and antiviral activity may be attributed to CPLE treatment. These findings merit validation in larger prospective studies. Trial registration Name of the registry: Clinical Trials Registry-India (CTRI) Registration No.: CTRI-REF/2017/02/013314.

Project description:Clinical research on herbal-based dentifrice +/- mouth rinse products is very limited compared with the plethora of research on conventional oral care products under normal oral hygiene conditions. The aim of this study was to determine the anti-inflammatory effects of a novel plant Carica papaya leaf extract (CPLE) on interdental bleeding in healthy subjects. In this randomized, single-blind parallel-design study, the eligible subjects were generally healthy non-smokers, aged 18⁻26, who exhibited healthy periodontal conditions upon study entry. The participants were equally randomized into the following four groups: CPLE dentifrice, CPLE dentifrice and mouthwash, sodium lauryl sulfate (SLS)-free enzyme-containing dentifrice and SLS-free enzyme-containing dentifrice with essential oil (EO) mouthwash. Subjects were instructed to brush their teeth twice a day without changing their other brushing habits. Interdental bleeding (BOIP) was measured from inclusion (T₀) until the fourth week (T₄) of the study. Clinical efficacy was assessed after one, two, three and four weeks of home use. The analyses compared BOIP between groups and were then restricted to participants with ≥70% and then ≥80% bleeding sites at T₀. Pairwise comparisons between groups were performed at T₀ and T₄, and a logistic regression identified correlates of gingival bleeding (T₄). Among 100 subjects (2273 interdental sites), the median percentage of bleeding sites per participant at T₀ was 65%. The bleeding sites dramatically decreased in all groups between T₀ and T₄ (relative variations from -54% to -75%, p < 0.01 for all). Gingival bleeding did not significantly differ between the CPLE dentifrice and the SLS-free dentifrice +/- EO mouthwash groups (from p = 0.05 to p = 0.86), regardless of the baseline risk level. Among the CPLE dentifrice users, fewer bleeding sites were observed when toothpaste and mouthwash were combined compared to bleeding sites in those who used toothpaste alone (21% vs. 32%, p = 0.04). CPLE dentifrice/mouthwash provides an efficacious and natural alternative to SLS-free dentifrice +/-EO-containing mouthwash when used as an adjunct to mechanical oral care to reduce interdental gingival inflammation.

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Carica papaya Leaf Extract Silver Synthesized Nanoparticles Inhibit Dengue Type 2 Viral Replication In Vitro.

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