1-Methoxy-2,3-methylenedioxyxanthone

Normalization of the H3K9me2/H3K14ac-DeltaFosB pathway in the nucleus accumbens underlying the reversal of morphine-induced behavioural and synaptic plasticity by Compound 511.[Pubmed:36252464]

Phytomedicine. 2023 Jan;108:154467.

BACKGROUND: Although opioid agonist-based treatments are considered the first-line treatment for opioid use disorders, nonopioid alternatives are urgently needed to combat the inevitable high relapse rates. Compound 511 is a formula derived from ancient traditional Chinese medical literature on opiate rehabilitation. Previously, we observed that Compound 511 could effectively prevent the acquisition of conditioned place preference (CPP) during early morphine exposure. However, its effects on drug-induced reinstatement remain unclear. PURPOSE: This study aims to estimate the potential of Compound 511 for the therapeutic intervention of opioid relapse in rodent models and explore the potential mechanisms underlying the observed actions. STUDY DESIGN/METHODS: The CPP and locomotor sensitization paradigm were established to evaluate the therapeutic effect of Compound 511 treatment on morphine-induced neuroadaptations, followed by immunofluorescence and western blot (WB) analysis of the synaptic markers PSD-95 and Syn-1. Furthermore, several addiction-associated transcription factors and epigenetic marks were examined by qPCR and WB, respectively. Furthermore, the key active ingredients and targets of Compound 511 were further excavated by network pharmacology approach and experimental validation. RESULTS: The results proved that Compound 511 treatment during abstinence blunted both the reinstatement of morphine-evoked CPP and locomotor sensitization, accompanied by the normalization of morphine-induced postsynaptic plasticity in the nucleus accumbens (NAc). Additionally, Compound 511 was shown to exert a selectively repressive influence on morphine-induced hyperacetylation at H3K14 and a reduction in H3K9 dimethylation as well as DeltaFosB activation and accumulation in the NAc. Finally, two herbal ingredients of Compound 511 and six putative targets involved in the regulation of histone modification were identified. CONCLUSION: Our findings indicated that Compound 511 could block CPP reinstatement and locomotor sensitization predominantly via the reversal of morphine-induced postsynaptic plasticity through epigenetic mechanisms. Additionally, 1-Methoxy-2,3-methylenedioxyxanthone and 1,7-dimethoxyxanthone may serve as key ingredients of Compound 511 by targeting specific epigenetic enzymes. This study provided an efficient nonopioid treatment against opioid addiction.

[Chemical constituents of Polygala tenuifolia root].[Pubmed:25857159]

Zhong Yao Cai. 2014 Sep;37(9):1594-6.

OBJECTIVE: To study the chemical constituents from the root of Polygala tenuifolia. METHODS: Silica gel,Sephadex LH-20 and ODS chromatographic techniques were used to study the chemical constituents of Polygala tenuifolia, and the chemical structures were elucidated by application of spectral data. RESULTS: Eight-compounds were obtained and their structure were identified as 7-hydroxy-1-Methoxy-2,3-methylenedioxyxanthone(1), 1, 7-dihydroxy-2, 3-dimethoxyxanth one(2), 1,3,6-trihydroxy-2, 7-dimethoxyxanthone(3),7-hydroxy-1,2, 3-trimethoxyxanthone(4), 1,2,3,6, 7-pentamethoxyxanthone(5), 1,3, 7-trihydroxy-2, 6-dimethanoxyxanthone (6),7-hydroxy-1-methoxyxanthone(7) and 1,7-dihydroxy-3,4-dimethoxyxanthone(8). CONCLUSION: Compounds 1,6,7 and 8 are isolated from Polygala tenuifolia for the first time.

[Chemical constituents in roots of Polygala fallax and their anti-oxidation activities in vitro].[Pubmed:16110862]

Zhongguo Zhong Yao Za Zhi. 2005 Jun;30(11):827-30.

OBJECTIVE: To study the chemical constituents in roots of P. fallax and their anti-oxidation activities in vitro. METHOD: Column chromatographic techniques were employed for isolation and purification of chemical constituents of the plant. The structures were elucidated on the basis of the spectral evidence and the physical and chemical character. The isolated compounds were screened with four anti-oxidation models in vitro. RESULT: Seven xanthones, 1,7-dihydroxy-2,3-methylenedioxyxanthone (1), 1-Methoxy-2,3-methylenedioxyxanthone (2), 3-hydroxy-1,2-dimethoxyxanthone (3), 1,6,7-trihydroxy-2,3-dimethoxyxanthone (4), 7-hydroxy-1-Methoxy-2,3-methylenedioxyxanthone (5), 1,3-dihydroxy-2-methoxyxanthone (6) and 1,3,7-trihydroxy-2-methoxyxanthone (7), were isolated from the roots of P. fallax. And compounds 1 - 7 showed different anti-oxidation activities in the different pharmacological models. CONCLUSION: Compounds 2, 3, 5 and 7 were isolated from this plant for the first time. Xanthones from this plant showed anti-oxidation activities. The pharmacological activities of the pure compounds from this plant were also reported for the first time.

Xanthones from the roots of Polygala caudata and their antioxidation and vasodilatation activities in vitro.[Pubmed:15856419]

Planta Med. 2005 Apr;71(4):372-5.

Three new xanthones, 2-hydroxy-1,6,7-trimethoxyxanthone (1), 1,4-dimethoxy-2,3-methylenedioxyxanthone (2), and 7-hydroxy-1,2-dimethoxyxanthone (3), together with five known compounds, 2,7-dihydroxy-1-methoxyxanthone (4), 1-Methoxy-2,3-methylenedioxyxanthone (5), 7-hydroxy-1-methoxyxanthone (6), euxanthone (1,7-dihydroxyxanthone) (7), and gentitein (1,3,7-trihydroxyxanthone) (8), were isolated from the roots of Polygala caudata. Their structures were established on the basis of spectral evidence. In the antioxidation activity screening in vitro with luminol chemiluminescence methods, compounds 1 - 5 and 7 and 8 showed H2O2 scavenger activity, with a scavenging effect of 58.4 - 94.5% at 10 microg/mL, and 26.0 - 84.7% at 2 microg/mL. Compounds 4 and 8 also exhibited scavenging effects on the reactive oxygen free radicals produced by macrophage respiratory bursts, with a scavenging effect of 71.7% and 63.4% at 10 microg/mL, 41.2% and 47.8% at 2 microg/mL, respectively. In the vasodilatation assay, compounds 4 - 7 exhibited relaxing activity on the contractions evoked by KCl in Wistar rat thoracic aorta rings in a dose-dependent manner.

[Studies on chemical constituents of Polygala arillata buch-ham].[Pubmed:11498872]

Yao Xue Xue Bao. 1997 May;32(5):360-2.

Two new compounds were isolated from the roots of Polygala arillata Buch-Ham. On the basis of chemical reactions and spectral (UV, IR, MS, 1HNMR, DIFNOE, 13CNMR) analysis, they were identified as 1,3-dihydroxy-2-methoxyxanthone(I) and 7-hydroxy-1-Methoxy-2,3-methylenedioxyxanthone(II). Pharmacological study indicated that I and II have inhibitory effect on aldose reductase activity.