The Flavonoid, Quercetin, Inhibits HIV-1 Infection in Normal Peripheral Blood Mononuclear Cells

Abstract

Problem statement: Flavonoids and related polyphenols, have been known to possess cardioprotective, anti-tumor, anti-inflammatory, anti-allergic and anti-viral activities. Previous studies have shown that flavonoid, quercetin significantly downregulates expression of pro-inflammatory cytokines in cultured cells via modulation of NFκB and p38MAPK signaling pathways. In the current study, we hypothesize that quercetin exerts anti-HIV activity by differential modulation of pro-and anti-inflammatory cytokine expression in normal PBMCs. Approach: Cultures of PBMC received either different concentrations of quercetin (1-50 µM) or media alone. The anti-HIV effects of quercetin was evaluated in an in vitro infection model by quantitaing the HIV-1 LTR gene suppression by quantitative Real Time PCR, HIV-1 p24 antigen production by ELISA and viral infectivity by MAGI cell assay. Results: Our results showed that quercetin significantly downregulates p24 antigen production, LTR gene expression and viral infectivity in a dose dependent manner (5-50 µM) as compared to HIV infected untreated control PBMCs. Further, we reported that quercetin significantly downregulated the expression of the pro-inflammatory cytokine, TNF-α with concomitant upregulation of anti-inflammatory cytokine IL-13 as determined by measurement of gene expression and protein production. A higher level of IL-13 is known to inhibit TNF-α production and also HIV-1 infection. Thus, differential modulation of pro-and anti-inflammatory cytokines could be one of the possible mechanisms for the anti-HIV effects of quercetin. Conclusion: Better understanding of the mechanisms underlying the anti-HIV effects of quercetin may help to develop a new neutraceutical agent useful in the treatment of HIV-1 infected subjects in conjunction with conventional therapeutic regimens.

Effect of the pretreatment with acerola (Malpighia emarginata DC.) juice on ethanol-induced oxidative stress in mice – Hepatoprotective potential of acerola juice

“…30 Polyphenols have been associated to prevention of degenerative diseases in human and this was mainly attributed to their antioxidant properties. 31 Among the phenolics, anthocyanin and flavonol contents were further determined in acerola juice. The major anthocyanins identified in acerola varieties were cyanidin-3-rhamnoside and pelargonidin-3-rhamnoside.…”

Oxidative Stress, Redox Regulation and Elite Controllers of HIV Infection: Towards a Functional Cure

“…Flavonoids (quercetin) was reported to exhibit both anti-infective and antireplicative HIV abilities. Quercetin significantly downregulates p24 antigen production, LTR gene expression and viral infectivity in a dose-dependent manner (5-50 mM) and further downregulation of the expression of the pro-inflammatory cytokine TNF-α with concomitant upregulation of anti-inflammatory cytokine IL-13 [93]. A higher level of IL-13 is known to inhibit TNF-α production and also HIV-1 infection.…”

Nature nominee quercetin's anti‐influenza combat strategy—Demonstrations and remonstrations

“…107 Researchers have concluded that quercetin's antiviral activity is a result of a variety of multiple actions. Some of the primary mechanisms may include one or more of the following: (1) reducing the ability of a virus to infect cells (infectability), 108 (2) inhibiting the ability of infected cells to replicate and reproduce, 108 and (3) reducing resistance of infected cells to pharmaceutical drug therapy. 109 It is reported that within each of these categories, quercetin has demonstrated (in vivo) chemical interactions of multiple cellular pathways that inhibit or promote the production of critical viral proteins.…”