Pyrogallol

Int J Oncol. 2002 Jul;21(1):187-92.

Identification of pyrogallol as an antiproliferative compound present in extracts from the medicinal plant Emblica officinalis: effects on in vitro cell growth of human tumor cell lines.[Pubmed: 12063567]

In this study we compared the in vitro antiproliferative activity of extracts from medicinal plants toward human tumor cell lines, including human erythromyeloid K562, B-lymphoid Raji, T-lymphoid Jurkat, erythroleukemic HEL cell lines. Extracts from Emblica officinalis were the most active in inhibiting in vitro cell proliferation, after comparison to those from Terminalia arjuna, Aphanamixis polystachya, Oroxylum indicum, Cuscuta reflexa, Aegle marmelos, Saraca asoka, Rumex maritimus, Lagerstroemia speciosa, Red Sandalwood. Emblica officinalis extracts have been studied previously, due to their hepatoprotective, antioxidant, antifungal, antimicrobial and anti-inflammatory medicinal activities.
METHODS AND RESULTS:
Gas chromatography/mass spectrometry analyses allowed to identify Pyrogallol as the common compound present both in unfractionated and n-butanol fraction of Emblica officinalis extracts.
CONCLUSIONS:
Antiproliferative effects of Pyrogallol were therefore determined on human tumor cell lines thus identifying Pyrogallol as an active component of Emblica officinalis extracts.

Bioorg Med Chem Lett. 2008 Mar 1;18(5):1567-72.

Pyrogallol and its analogs can antagonize bacterial quorum sensing in Vibrio harveyi.[Pubmed: 18262415]

Bacteria can coordinate community-wide behaviors through quorum sensing, that is, the secretion and sensing of autoinducer (AI) molecules. Bacterial quorum sensing is implicated in the regulation of pathologically relevant events such as biofilm formation, bacterial virulence, and drug resistance. Inhibitors of bacterial quorum sensing could therefore be useful therapeutics. Herein we report for the first time the discovery of several Pyrogallol compounds as single digit micromolar inhibitors of bacterial quorum sensing in Vibrio harveyi.

Drug Metab Dispos . 2015 Aug;43(8):1181-9.

Ginsenosides Regulate PXR/NF-κB Signaling and Attenuate Dextran Sulfate Sodium-Induced Colitis[Pubmed: 25986850]

Abstract Pregnane X receptor (PXR) activation exhibits anti-inflammatory effects via repressing nuclear factor-κB (NF-κB); however, its overactivation may disrupt homeostasis of various enzymes and transporters. Here we found that ginsenosides restore PXR/NF-κB signaling in inflamed conditions without disrupting PXR function in normal conditions. The effects and mechanisms of ginsenosides in regulating PXR/NF-κB signals were determined both in vitro and in vivo. Ginsenosides significantly inhibited NF-κB activation and restored the expression of PXR target genes in tumor necrosis factor-α-stimulated LS174T cells. Despite not being PXR agonists, ginsenosides repressed NF-κB activation in a PXR-dependent manner. Ginsenosides significantly increased the physical association between PXR and the NF-κB p65 subunit and thereby decreased the nuclear translocation of p65. Ginsenoside Rb1 and compound K (CK) were major bioactive compounds in the regulating PXR/NF-κB signaling. Consistently, ginsenosides significantly attenuated dextran sulfate sodium-induced experimental colitis, which was associated with restored PXR/NF-κB signaling. This study indicates that ginsenosides may elicit anti-inflammatory effects via targeting PXR/NF-κB interaction without disrupting PXR function in healthy conditions. Ginsenoside Rb1 and CK may serve as leading compounds in the discovery of new drugs that target PXR/NF-κB interaction in therapy for inflammatory bowel disease.

Mutat Res. 2013 Aug 15;755(2):81-9.

Methanol extract from the stem of Cotinus coggygria Scop., and its major bioactive phytochemical constituent myricetin modulate pyrogallol-induced DNA damage and liver injury.[Pubmed: 23830930]

The present study was undertaken to investigate the hepatoprotective effect of the methanol extract of Cotinus coggygria Scop. in rats exposed to the hepatotoxic compound Pyrogallol.
METHODS AND RESULTS:
Assessed with the alkaline version of the comet assay, 1000 and 2000mg/kg body weight (bw) of the extract showed a low level of genotoxicity, while 500mg/kg bw of the extract showed no genotoxic potential. Quantitative HPLC analysis of phenolic acids and flavonoids in the methanol extract of C. coggygria showed that myricetin was a major component. To test the hepatoprotective effect, a non-genotoxic dose of the C. coggygria extract and an equivalent amount of synthetic myricetin, as present in the extract, were applied either 2 or 12h prior to administration of 100mg/kg bw of Pyrogallol. The extract and myricetin promoted restoration of hepatic function by significantly reducing Pyrogallol-induced elevation in the serum enzymes AST, ALT, ALP and in total bilirubin. As measured by the decrease in total score and tail moment, the DNA damage in liver was also reduced by the extract and by myricetin. Our results suggest that pro-surviving Akt activity and STAT3 protein expression play important roles in decreasing DNA damage and in mediating hepatic protection by the extract.
CONCLUSIONS:
These results suggest that myricetin, as a major component in the extract, is responsible for the antigenotoxic and hepatoprotective properties of the methanol extract of C. coggygria against Pyrogallol-induced toxicity.

Toxicology. 2013 Dec 15;314(2-3):202-8.

Contact sensitizing potential of pyrogallol and 5-amino-o-cresol in female BALB/c mice.[Pubmed: 24172597]

Hair dye components such as Pyrogallol and cresol have been shown previously to promote allergic reactions such as rashes, dermal inflammation, irritation and dermatitis.
METHODS AND RESULTS:
The objective of this study was to determine the contact sensitization potential of Pyrogallol (PYR) and 5-amino-o-cresol (AOC) when applied dermally to female BALB/c mice. Measurement of the contact hypersensitivity response was initially accomplished using the local lymph node assay. For PYR, significant increases in the proliferation of lymph node cells were observed at concentrations of 0.5% (w/v) and higher. For AOC, borderline increases, albeit significant, in auricular lymph node cell proliferation were observed at 5% and 10%. Results from the irritancy assay suggested that PYR, but not AOC, was an irritant. To further delineate whether PYR was primarily an irritant or a contact sensitizer, the mouse ear swelling test (MEST) was conducted. A significant increase in mouse ear thickness was observed at 72h following challenge with 0.5% PYR in mice that had been sensitized with 5% PYR. In contrast, no effects were observed in the MEST in mice sensitized and challenged with the highest achievable concentration of AOC (10%). Additional studies examining lymph node subpopulations and CD86 (B7.2) expression by B cells further support the indication that PYR was a sensitizer in BALB/c mice.
CONCLUSIONS:
The results demonstrate that PYR is both a sensitizer and an irritant in female BALB/c mice. However, the contact sensitization potential of AOC is minimal in this strain of mouse.

Int Immunopharmacol. 2008 Dec 10;8(12):1672-80.

Pyrogallol, an active compound from the medicinal plant Emblica officinalis, regulates expression of pro-inflammatory genes in bronchial epithelial cells.[Pubmed: 18760383]

The most relevant cause of morbidity and mortality in cystic fibrosis (CF) patients is the lung pathology characterized by chronic infection and inflammation sustained mainly by Pseudomonas aeruginosa (P. aeruginosa). Innovative pharmacological approaches to control the excessive inflammatory process in the lung of CF patients are thought to be beneficial to reduce the extensive airway tissue damage. Medicinal plants from the so-called traditional Asian medicine are attracting a growing interest because of their potential efficacy and safety. Due to the presence of different active compounds in each plant extract, understanding the effect of each component is important to pursue selective and reproducible applications.
METHODS AND RESULTS:
Extracts from Emblica officinalis (EO) were tested in IB3-1 CF bronchial epithelial cells exposed to the P. aeruginosa laboratory strain PAO1. EO strongly inhibited the PAO1-dependent expression of the neutrophil chemokines IL-8, GRO-alpha, GRO-gamma, of the adhesion molecule ICAM-1 and of the pro-inflammatory cytokine IL-6. Pyrogallol, one of the compounds extracted from EO, inhibited the P. aeruginosa-dependent expression of these pro-inflammatory genes similarly to the whole EO extract, whereas a second compound purified from EO, namely 5-hydroxy-isoquinoline, had no effect.
CONCLUSIONS:
These results identify Pyrogallol as an active compound responsible for the anti-inflammatory effect of EO and suggest to extend the investigation in pre-clinical studies in airway animal models in vivo, to test the efficacy and safety of this molecule in CF chronic lung inflammatory disease.

Cutan Ocul Toxicol. 2013 Sep;32(3):234-40.

Pyrogallol-associated dermal toxicity and carcinogenicity in F344/N rats and B6C3F1/N mice.[Pubmed: 23231012]

Pyrogallol (CAS No. 87-66-1), a benzenetriol used historically as a hair dye and currently in a number of industrial applications, was nominated to the National Toxicology Program (NTP) for testing based on the lack of toxicity and carcinogenicity data.
METHODS AND RESULTS:
Three-month and two-year toxicity studies to determine the toxicity and carcinogenicity of Pyrogallol when applied to naïve skin (i.e. dermal administration) were conducted in both sexes of F344/N rats and B6C3F1/N mice. In the three-month studies, adult rodents were administered Pyrogallol in 95% ethanol five days per week for 3 months at doses of up to 150 mg/kg body weight (rats) or 600 mg/kg (mice). Based on the subchronic studies, the doses for the two-year studies in rats and mice were 5, 20 and 75 mg/kg of Pyrogallol. All mice and most rats survived until the end of the three-month study and body weights were comparable to controls. During the two-year study, survival of dosed rats and male mice was comparable to controls; however survival of 75 mg/kg female mice significantly decreased compared to controls. The incidences of microscopic non-neoplastic lesions at the site of application were significantly higher in all dosed groups of rats and mice and in both the 3-months and two-year studies. In the two-year study, hyperplasia, hyperkeratosis and inflammation tended to be more severe in mice than in rats, and in the mice they tended to be more severe in females than in males. The incidence of squamous cell carcinoma at the site of application (SOA) in 75 mg/kg female mice and SOA squamous cell papillomas in 75 mg/kg male mice were greater than controls.
CONCLUSIONS:
Pyrogallol was carcinogenic in female mice and may have caused tumors in male mice.