Table 2.

Past studies exploring antichlamydial properties of polyphenolic compounds.

Antimicrobial Agent	Chlamydial Species	Study Design	Effects	Reference
Flavones (×8), Flavonols (×8), Flavonones (×2), Isoflavones (×4), Synthetic flavonoids (×4), Natural coumarins (×5), Synthetic courmarins (×10), Catechins (×5), Phenolic acids (×5), Gallates (×5), Stilbene (×1)	C. pneumoniae (K7)	In vitro Pre-inoculation: incubated with cells for 24 h prior to EB inoculation. Post-inoculation: administered at 0 h post inoculation (p.i.).	From 57 compounds, at 50 μM: 21 were highly active, 16 active, 6 moderately active, and 14 inactive. 10 compounds achieved an MIC of 50 μM or less with luteolin being 8.8 μM and dodecyl gallate being 18 μM. Gallates was the most active group. Some compounds accumulated inside cells or in cell membranes and cause inhibition when present only prior to infection. Compound structural variations, either free from sugar moieties, or with greater hydrophobicity, were found to be more active. All compounds were non-toxic to the host cells.	[43]
Polyphenon 70S: Epigallocatechin (18.3%), Epicatechin (8.6%), Epigallocatechin gallate (35.9%), Epicatechin gallate (11.2%), Gallocatechin gallate (3.5%)	C. trachomatis (D), (L2) C. Pneumoniae (AR-39), (AC-43)	In vitro Pre-treatment: incubated with EBs for 30, 60, or 90 min prior to inoculation. Post-inoculation: administered at 0 h p.i.	Polyphenon 70S, post-incubation, 100% inhibition of chlamydial inclusions, at 0.5 mg/mL, with toxicity to host cells at 0.25 mg/mL. Pre-incubation, 100% inhibition, at 0.4–1.6 mg/mL, with no toxicity to host cells.	[47]
Catechin, Epicatechin, Epigallocatechin, Epicatechin gallate, Epigallocatechin gallate	C. pneumoniae (AR-39)	In vitro Pre-treatment: incubated with EBs for 90 min prior to inoculation.	Inhibition was observed for concentrations from 0.4 to >6.4 mg/mL. Most active compounds were epigallocatechin gallate and epicatechin gallate, followed by epicatechin. Catechin and epigallocatechin exhibited intermediate activity. Epicatechin was the least toxic.	[48]
Luteolin, Octyl gallate, Quercetin	C. pneumoniae (K7)	In vivo Pre- & Post-inoculation: administered daily for 3 days prior to inoculation; administered daily for 12 days p.i. (mice)	Luteolin suppressed inflammation in lung tissue, C. pneumoniae-specific antibodies, and the presence of chlamydia in lung tissue. Octyl gallate had no significant effect on infection. Quercetin increased the inflammatory responses and the chlamydial load in the lungs.	[49]
Baicalin	C. trachomatis (D)	In vitro Post-inoculation: administered at 24 h p.i.	Blocks the infection of Hep-2 cells. Down-regulates the production of the chlamydia-secreted protein (CPAF). CPAF degradation of host transcription factors RFX5 may allow chlamydia to escape efficient immune detection. Baicalin may assist the host immune system to detect the chlamydial infection.	[51]
Betulin, Betulin derivatives (×32)	C. pneumoniae (CWL-029)	In vitro Post-inoculation: administered at 0 h p.i.	At a concentration of 1 μM, three derivatives showed >80% growth inhibition, and 15 compounds 20%–80% growth inhibition. Betulin dioxime exhibited an MIC of 1 μM, and achieved 50% inhibition at 290 nM. Compounds were well tolerated by host cells.	[52]
Corn mint extract (Mentha arvensis): Rosmarinic acid (5.2%), Linarin (6.0%), Acacetin-acetylglucoside-rhamnoglycoside (2.5%) Pure compounds: Rosmarinic acid, Linarin, Acacetin	C. pneumoniae (CWL-029), (K7)	In vitro Post-inoculation: administered at 0 h p.i. In vivo Pre- & Post-inoculation: administered daily for 3 days prior to inoculation; administered daily for 10 days p.i. (mice)	For corn mint extract, at 256 μg/mL, 73% inhibition of chlamydial inclusions was achieved for strain CWL-029, and 90% for strain K7, with ~78% host cell viability. Pure compound, inhibition at 100 μg/mL for strain CWL-029: linarin 100%, acacetin 97%, and rosmarinic acid 73%, with ~99% host cell viability. Pure compound, inhibition at 100 μg/mL for strain K7: linarin 62%, acacetin 81%, and rosmarinic acid 74%. In vivo, corn mint extract in nutritionally relevant dosages resulted in reduced inflammatory responses to chlamydial infection.	[53]
Peppermint tea extracts (Mentha × piperita L.): Eriocitrin, 12-Hydroxyjasmonate sulfate, Luteolin-O-rutinoside, Rosmarinic acid, Salvianolic acid B, Trace polyphenols, Trace plant acids	C. pneumoniae (K7)	In vitro Post-inoculation: administered at 0 h p.i.	Seven tea extracts were shown to be active against C. pneumoniae. At 250 μg/mL, from 20.7% to 69.5% inhibition. Higher content of luteolin and apigenin glycosides showed high activity. Host cell viability after the 72 h exposure to tea extracts ranged from 82.4% to 99.4%.	[54]
Isoflavones: Biochanin A, Formononetin, Genistein, Daidzein, Genistin, Daidzin	C. trachomatis (K), (L2) C. Pneumoniae (K7)	In vitro Post-inoculation: administered at 0 h p.i.	Biochanin A at 50 μM, complete inhibition of C. pneumoniae. Biochanin A, IC50: C. trachomatis—62 μM; C. pneumoniae—12 μM. No harmful effects on host cell viability. Biochanin A methylated hydroxyl group provides improved the antichlamydial activity. Biochanin A does not affect C. pneumoniae in its extracellular (EB) form. Oromucosal buccal dosage forms improve dissolution of biochanin A and allow for permeation of porcine buccal tissue.	[55]
Polyphenols: Quercetin, Luteolin, Rhamnetin, Octyl gallate Coadministrants: Doxycycline, Verapamil (Ca2+), Isradipine (Ca2+), Thapsigargin (Ca2+)	C. pneumoniae (CWL-029)	In vitro Post-inoculation: administered at 0 h p.i.	Quercetin, luteolin, rhamnetin and octyl gallate did not improve the antichlamydial effect of doxycycline. Some coadministration combinations of Ca2+ modulators with phenolic compounds resulted in potentiation of the antichlamydial effect of phenolic compounds. More antagonistic combinations were found than synergic or additive combinations.	[56]
Polyphenols: Resveratrol, Quercetin Coadministrants: Clarithromycin, Ofloxacin	C. pneumoniae (CWL-029)	In vitro Pre-inoculation: incubated with cells for 24 h prior to inoculation.	Resveratrol at 40 μM and quercetin at 20 μM exhibited significant growth inhibition in presence of clarithromycin or ofloxacin compared to controls. Immunomodulatory effects via strong inhibition of the IL-23 levels with coadministration of resveratrol or quercetin and ofloxacin or clarithromycin.	[57]