Echinacea in infection

Abstract

Ongoing studies have developed strategies for identifying key bioactive compounds and chemical profiles in Echinacea with the goal of improving its human health benefits. Antiviral and antiinflammatory-antipain assays have targeted various classes of chemicals responsible for these activities. Analysis of polar fractions of E. purpurea extracts showed the presence of antiviral activity, with evidence suggesting that polyphenolic compounds other than the known HIV inhibitor, cichoric acid, may be involved. Antiinflammatory activity differed by species, with E. sanguinea having the greatest activity and E. angustifolia, E. pallida, and E. simulata having somewhat less. Fractionation and studies with pure compounds indicate that this activity is explained, at least in part, by the alkamide constituents. Ethanol extracts from Echinacea roots had potent activity as novel agonists of TRPV1, a mammalian pain receptor reported as an integrator of inflammatory pain and hyperalgesia and a prime therapeutic target for analgesic and antiinflammatory drugs. One fraction from E. purpurea ethanol extract was bioactive in this system. Interestingly, the antiinflammatory compounds identified to inhibit prostaglandin E(2) production differed from those involved in TRPV1 receptor activation.

FIGURE 1

Ability of Echinacea purpurea ethanol extract (PI621307) to inhibit HIV replication. Data shown represent the mean ± SEM for each data point from 3 different experiments with triplicate samples in each experiment.

FIGURE 2

Inhibition of HIV infectivity by Echinacea purpurea fractions. (A) Ability of 7 HPLC-separated fractions (100 μg/mL) to inhibit HIV infection (white bars) or cytotoxicity (black bars). Each bar represents the mean of triplicates. The antiviral activity found in fraction 1 that is highlighted with an asterisk showed efficacy against HIV-1 as determined by a Student’s t test comparing the untreated and treated samples (P = 0.0001). (B) HPLC analysis of E. purpurea fraction 1. Phenolic acid standards were run to allow identification of compounds.

FIGURE 3

Antiviral activity and cytotoxicity associated with subfractions 1–9 from Echinacea purpurea fraction 1. All HIV infectivity (white bars) and cytotoxicity (black bars) assays were performed with 100 μg/mL of the fraction or subfraction. Values represent the mean ± SEM for 2 experiments performed in triplicate. Asterisks represent findings that are significantly different from control infections as determined by a Student’s t test (P = 0.0001).

FIGURE 4

Extracts of Echinacea species from different harvest dates were studied at 15 μg/mL for their effects on prostaglandin E₂ (PGE₂) production. Data (originally ng/mL PGE₂) were normalized to the DMSO-lipopolysaccharide (LPS)–treated control and are presented as means ± 95% CIs. E. angustifolia, E. pallida, and E. sanguinea (P < 0.001) reduced PGE₂ production compared with medium + DMSO controls. Data shown are with LPS; studies were conducted without LPS, but PGE₂ values were not altered by Echinacea. *P < 0.05 compared with medium + LPS + DMSO in a Dunnett multiple-comparison test. Redrawn from reference (8).

FIGURE 5

Preparative HPLC fractions of Echinacea angustifolia soxhlet ethanol extract were assessed for reduction of prostaglandin E₂ (PGE₂) production and are presented as means ± 95% CIs. All treatments are shown with lipopolysaccharide (LPS) because the fractions did not alter PGE₂ production in the absence of LPS. Fractions 1 and 3 significantly reduced LPS-induced PGE₂ production. n = 3. **P < 0.05, representative of a Dunnett multiple-comparison test.

FIGURE 6

Relative potency of 70% ethanol Echinacea extracts (0.25 mg/mL) on TRPV1 (mean ± SEM, n ≥ 4 independent oocytes for each value). Current responses were normalized in each cell to responses obtained with capsaicin (10 μmol/L). Spinach extract (0.25 mg/mL) was used as the control. *P < 0.05, **P < 0.01, significantly different when compared with spinach control (Student’s t test). Extracts evoked no responses in water-injected cells.