Grape seed extract proanthocyanidins downregulate HIV-1 entry coreceptors, CCR2b, CCR3 and CCR5 gene expression by normal peripheral blood mononuclear cells

• Published in: Biological research 2002, Vol.35 (3-4), p.421-431
• Main Authors: Nair, Madhavan P, Kandaswami, Chithan, Mahajan, Supriya, Nair, Harikrishna N, Chawda, Ram, Shanahan, Thomas, Schwartz, Stanley A
• Format: Article
• Language: English
• Subjects: Anthocyanins - pharmacology; Antioxidants - pharmacology; BIOLOGY; Gene Expression Regulation, Viral - drug effects; HIV-1 , human immunodeficiency virus-1 GSE,- Grape Seed Extract; HIV-1 - drug effects; HIV-1 - genetics; Humans; Leukocytes, Mononuclear - drug effects; PBMC, peripheral blood mononuclear cells; Plant Extracts - pharmacology; Proanthocyanidins; Receptors, CCR2; Receptors, CCR3; Receptors, CCR5 - drug effects; Receptors, CCR5 - genetics; Receptors, Chemokine - drug effects; Receptors, Chemokine - genetics; Reverse Transcriptase Polymerase Chain Reaction; RT- PCR - reverse transcriptase polymerase chain reaction; Seeds - chemistry; Vitis - chemistry
• ISSN: 0716-9760; 0716-9760; 0717-6287
• DOI: 10.4067/S0716-97602002000300016

Flavonoids and related polyphenols, in addition to their cardioprotective, anti-tumor, anti-inflammatory, anti-carcinogenic and anti-allergic activities, also possess promising anti-HIV effects. Recent studies documented that the beta-chemokine receptors, CCR2b, CCR3 and CCR5, and the alpha-chemokine receptors, CXCR1, CXCR2 and CXCR4 serve as entry coreceptors for HIV-1. Although flavonoids and polyphenolic compounds elicit anti-HIV effects such as inhibition of HIV-1 expression and virus replication, the molecular mechanisms underlying these effects remain to be clearly elucidated. We hypothesize that flavonoids exert their anti-HIV effects, possibly by interfering at the HIV co-receptor level. We investigated the effect of flavonoid constituents of a proprietary grape seed extract (GSE) on the expression of HIV-1 coentry receptors by immunocompetent mononuclear leukocytes. Our results showed that GSE significantly downregulated the expression of the HIV-1 entry co-receptors, CCR2b, CCR3 and CCR5 in normal PBMC in a dose dependent manner. Further, GSE treated cultures showed significantly lower number of CCR3 positive cells as quantitated by flow cytometry analysis which supports RT-PCR gene expression data. Investigations of the mechanisms underlying the anti-HIV-1 effects of grape seed extracts may help to identify promising natural products useful in the prevention and/or amelioration of HIV-1 infection.