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Microbes & Immunity                                                   Biological activity of Amazonian plants



            gene product is responsible for the elevated expression of   cells treated with LM extract at all-time points (p-value
            IL-6, IL-8, and IL-10, among other cytokines in primate   ranging from 0.0156 to 0.0131). SIV-infected leukocytes,
            leukocyte  cells  used  in  these  experiments.   Moreover,   even when treated with plant extracts, expressed very
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            IL-8 and IL-6 expression are positively correlated to   low levels of IL-10. IL-10 expression was detected only at
            clinical symptoms and disease progression in HIV/AIDS   the 144-h and 240-h time points in cells treated with OH
            patients. 36,37  The results obtained in this study corroborate   extract. At the initial stage of the experiment, cells treated
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            with those of Dwivedi et al.,  who analyzed a cohort of   with plant extracts produced more cytokines than in SIV-
            HIV  reservoir  patients  and  found  that  HIV  unspliced   infected cells alone (data not shown), except for IL-6, for
            RNA was significantly associated with IL-10 signaling, as   which no statistically significant difference was observed.
            well as other factors such as toll-like receptor 4/microbial   These in vitro results align with the data obtained from the
            translocation and IL-1/NLR family pyrin domain     clinical study on HIV-1-infected adolescents.
            containing  3 inflammasome.  In the  experiments,  IL-10   Whereas betulinic acid has been identified in several
            was  poorly  expressed  in  SIV-infected  cells  (Figure  7),   Lycania species, such as  Licania tomentosa,  Licania
            regardless of prior treatment with plants extracts, but it was   heteromorpha,  Licania  carii,  Licania  pyrifolia,  Licania
            abundantly secreted by uninfected cells, whether treated   cruegeriana, and Licania licaniaeflora, 41-45  niruriflavone has
            with plant extracts or not. This suggests that in this in vitro   thus far been isolated only from Licania arianeae. 46
            system, HIV unspliced RNA is rare or absent. If reduced
            IL-10 production by EHLC treated with LM and OH      Many authors found that derivatives of betulinic acid
            extracts, and subsequently challenged with SIV infection   inhibit the in vitro cytopathic effects of HIV-induced cell
            triggers lentiviral RNA splicing, the compounds from these   syncytia formation, suggesting that its anti-HIV activity
            plants could be potentially candidates for antiretroviral   occurs at the level of virus glycoprotein-cell receptor
            therapy, stimulating HIV replication in latently infected   interactions. 47-49  This finding was later corroborated
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            cells in drug-resistant patients. 39               by Aiken and Chen,  who reported that betulinic acid
                                                               inhibits the in vitro fusion of the HIV glycoprotein with
              As a point of reference, despite in an in vivo context, the   the host cell receptor and also hampers virion maturation.
            clinical research conducted by Ka’e et al. on HIV-1 infected   Betulinic acid, which has been isolated from LM, exerts
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            adolescents in Cameroon undergoing  antiretroviral   both mechanisms. In contrast, niruriflavone is known for
            therapy, quantified a high expression of pro-inflammatory   its antioxidant activity and has not been associated with
            cytokines, including IFN-γ and IL-6, as well as anti-  antiretroviral  activity.   The  other  compounds  obtained,
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            inflammatory  cytokines  IL-4  and  IL-10.  Furthermore,   (-)-gallocatechin and 4’-O-methyl-epigallocatechin, have
            when considering additional parameters, including data   been shown to inhibit the HIV-1 reverse transcriptase. 52-55
            from uninfected subjects, the study identified inflammatory
            cytokines (IFN-γ and IL-12), anti-inflammatory cytokines   Despite the crude extract of OH was not fractionated
            (IL-4 and IL-10), and inflammation-related cytokines   in this study, many reports have documented its isolated
            (IL-6 and IL-1β) as markers indicative of successful viral   compounds. 23,24  Among them, the bioflavonoids,
            suppression in comparison to viral persistence. In this   agathisflavone, epicatechin, 6-C-glycopyranosyl-luteolin,
            study, it was observed that  extracts from OH and LM,   and amentoflavone, despite being derived from different
            regardless of SIVmac251 infection status, induced IFN-γ   plants, have exhibited in vitro anti-HIV activity through
            production. Notably, EHLC treated with OH and infected   distinct mechanisms. 54,55  In addition, luteolin and apigenin
            with SIV exhibited significantly higher IFN-γ expression   have been shown to inhibit HIV enzymes, such as the
            (p=0.0073) at the 144-h time point compared to other   protease, RNase H, and integrase. 55,56
            treatment conditions. Regarding IL-6, both plant extracts   5. Conclusion
            induced its expression under different treatments. However,
            uninfected EHLC treated with OH extract demonstrated   The experiments preliminarily demonstrate the mitotic,
            significantly higher IL-6 expression compared to other   immune-modulating, and SIV-suppressive properties of
            treatments, with or without SIV infection. Overall, SIV-  Amazonian medicinal extracts from the plants LM and
            infected leukocytes produced more IL-6 when treated   OH. For the most part, OH extract had the best mitotic
            with OH extract than in those treated with LM extract.   activity, while LM extract provided the most protection
            With respect to anti-inflammatory cytokines, SIV-infected   against SIV cytopathicity. Regarding cytokines secretion
            leukocytes treated with OH extract exhibited significantly   in SIV-infected EHLC, OH extract was generally the
            higher IL-4 expression than other treatments across all   most effective in inducing expression, except for IL-8,
            analyzed time intervals (p-value ranging from 0.0208 to   where no significant difference was observed between
            0.0040). Secretion of IL-10 by EHLC was restricted in   the two plant extracts. IL-10 expression in infected cells


            Volume 2 Issue 2 (2025)                         71                               doi: 10.36922/mi.8367
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