Page 79 - MI-2-2
P. 79
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
35
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
37
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
50
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
39
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,
51
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

