3,5-Dihydroxy-4-methoxybenzoic acid

Rec. Nat. Prod. 2019,13(1): 71-80.

Chemical Constituents and Anti-influenza Viral Activity of the Leaves of Vietnamese Plant Elaeocarpus tonkinensis.[Reference: WebLink]

Various Elaeocarpus species including Elaeocarpus tonkinensis have been important medicinal plants that used in traditional medication system and mainly used to cure nervous system-related disorders. However, their antiviral potential has not been reported yet.
METHODS AND RESULTS:
During the screening of medicinal plant extracts with the antiviral activity against influenza viruses, we found that E. tonkinensis extract has strong antiviral activity. Through organic solvent partition and repeated column chromatography using SiO2, C-18 and Sephadex LH-20, a total of nine compounds were purified from the methanol extract of E. tonkinensis. Their chemical structures were determined by NMR and MS spectral data to be trolliamide (1), gallic acid (2), urolithin M-5 (3), hydroquinone (4), 2,4-dihydroxybenzoic acid (5), 3,5-Dihydroxy-4-methoxybenzoic acid (6), corilagin (7), chebulagic acid (8), and shikimic acid (9). Their antiviral activity against influenza virus strains A/Puerto Rico/8/34 (H1N1; PR8), A/Hong Kong/8/68 (H3N2; HK) and B/Lee/40 (Lee) was examined on the basis of cytopathic effect (CPE) assay. Among them, compounds 2, 3, 4, 7, and 8 significantly inhibited viral replication in a dose-dependent manner with EC50 values ranging from 7.8 to 59.6 μg/mL against influenza A and/or B viruses with selectivity indices above 5.0.
CONCLUSIONS:
This study suggests that the botanical materials of E. tonkinensis could be promising inhibitors of influenza A and B viruses and applied to the development of a novel herbal medicine.

Toxicology, 1979, 14(3):217-227.

Toxic interaction between narcotic analgesics and inhibitors of catechol-O-methyltransferase.[Reference: WebLink]

A lethal synergism between morphine and tropolone, an inhibitor of catechol-O-methyltransferase, was previously noted in adult male Holtzman rats.
METHODS AND RESULTS:
The present research demonstrates that this phenomenon generalizes across factors of sex, age, strain (Sprague-Dawley, Wistar) and species (Swiss albino mice). Acute toxicity was also significantly increased (1.5–1.9 times) in the case of codeine, methadone, meperidine and levorphanol, but to a lesser extent than for morphine (4.0 times) in the S-D strain. Another COMT inhibitor, 3,5-Dihydroxy-4-methoxybenzoic acid, interacted with morphine in S-D rats to an equal degree as did tropolone. Post-treatment with 1 mg/kg of naloxone in rats or naltrexone in mice reduced the high lethality associated with morphine plus tropolone. There was a pronounced lowering of whole brain norepinephrine (NE) level after morphine plus tropolone in Wistar rats with doses of each component that alone caused no change in NE. Brain dopamine (DA) was elevated by tropolone and by its combination with morphine. Each drug alone caused slight lowering of brain serotonin. Enhancement by tropolone of the toxicity of (+)-amphetamine in mice and rats was of similar magnitude as for morphine.
CONCLUSIONS:
The possible role of brain NE and/or DA in the sensitivity to acute toxic effects of opioids in rodents is suggested by these data, as well as a parallel in this regard with amphetamine-type stimulants.