Damnacanthol

In silico and in vivo study of anti-inflammatory activity of Morinda longissima (Rubiaceae) extract and phytochemicals for treatment of inflammation-mediated diseases.[Pubmed:38493905]

J Ethnopharmacol. 2024 Jun 28;328:118051.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, the plant Morinda longissima Y.Z.Ruan (Rubiaceae) is used by ethnic people in Vietnam for the treatment of liver diseases and hepatitis. AIM OF THE STUDY: The study was designed to assess the efficacy of the 95% ethanolic extract of Morinda longissima roots (MLE) in experimental immune inflammation. The phytochemical variation of root extract and the chemical structures of natural compounds were also investigated using HPLC-DAD-HR-MS analysis. MATERIALS AND METHODS: Three different doses (100, 200, and 300 mg/kg b.w.) of MLE were chosen to determine anti-inflammatory activity. The mice were given orally extracts and monitored their behavior and mortality for 14 days to evaluate acute toxicity. The volume of the paw and the histopathological evaluation were carried out. The polyphenolic phytoconstituents of MLE extract were identified using LC/MS analysis. The anti-inflammatory efficacy in silico and molecular docking simulations of these natural products were evaluated based on their cyclooxygenase (COX)-1 and 2 inhibitory effects. RESULTS: This investigation showed the 95% ethanolic extract of Morinda longissima roots was found non-toxic up to 2000 mg/kg dose level in an acute study, neither showed mortality nor treatment-related signs of toxicity in mice. Eight anthraquinones and anthraquinone glycosides of Morinda longissima roots were identified by HPLC-DAD-HR-MS analysis. In the in vivo experiments, MLE was found to possess powerful anti-inflammatory activities in comparison with diclofenac sodium. The highest anti-inflammatory activity of MLE in mice was observed at a dose of 300 mg/kg body weight. The in silico analysis showed that seven out the eight anthraquinones and anthraquinone glycosides possess a selectivity index R(COX-2/COX-1) lower than 1, indicating that these compounds are selective against the COX-2 enzyme in the following the order: rubiadin-3-methyl ether < morindone morindone-6-methyl ether < morindone-5-methyl ether < Damnacanthol < rubiadin < Damnacanthol-3-O-beta-primeveroside. The natural compounds with the best selectivity against the COX-2 enzyme are quercetin (9), rubiadin-3-methyl ether (7), and morindone (4), with R(COX2/COX1) ratios of 0.02, 0.03, and 0.19, respectively. When combined with the COX-2 protein in the MD research, quercetin and rubiadin-3-methyl ether greatly stabilized the backbone proteins and ligands. CONCLUSION: In conclusion, the anthraquinones and ethanolic extract of Morinda longissima roots may help fight COX-2 inflammation. To develop novel treatments for inflammatory disorders linked to this one, these chemicals should be investigated more in the future.

A new iridoid glucoside from the roots of Morinda officinalis.[Pubmed:37232117]

J Asian Nat Prod Res. 2023 Dec;25(12):1223-1228.

A new iridoid glucoside, moridoside (1), and nine known compounds, asperulosidic acid (2), 6-O-epi-acetylscandoside (3), geniposidic acid (4), 2-hydroxymethylanthraquinone (5), 2-hydroxymethyl-3-hydroxyanthraquinone (6), Damnacanthol (7), lucidine-omega-methyl ether (8), 2-hydroxy-1-methoxyanthraquinone (9), and 3,8-dihydroxy-1,2-dimethoxyanthraquinone (10) were isolated from the methanol extract of Morinda officinalis How. roots. Their structural identification was carried out based on the spectroscopic evidence. All compounds were evaluated for their nitric oxide (NO) production inhibitory activities in LPS-stimulated RAW264.7 macrophages. Compounds 5-7 significantly inhibited the production of NO with IC(50) values of 28.4, 33.6, and 30.5 muM, respectively.

Inhibition of Nitric Oxide Production in LPS-Stimulated RAW 264.7 Macrophages and 15-LOX Activity by Anthraquinones from Pentas schimperi.[Pubmed:27093247]

Planta Med. 2016 Sep;82(14):1246-51.

The anti-inflammatory activity of a coumarin and nine anthraquinone derivatives, 3-hydroxy-1-methoxy-2-methylanthraquinone (1), 2-hydroxymethyl anthraquinone (2), schimperiquinone B (3), cleomiscosin A (4), damnacanthal (5), 1,2-dihydroxy anthraquinone (6), Damnacanthol (7), 3-hydroxy-2-hydroxymethyl anthraquinone (8), 1-hydroxy-2-methoxyanthraquinone (9), and 2-hydroxymethyl-3-O-prenylanthraquinone (10), isolated from the roots of Pentas schimperi were determined. The anti-15-lipoxygenase activity and nitric oxide production inhibition on lipopolysaccharide-activated macrophages RAW 264.7 cells were determined as indicators of anti-inflammatory activity. The Griess assay was used to measure nitric oxide production and the ferrous oxidation-xylenol orange assay was used to determine the 15-lipoxygenase inhibitory activity. All the compounds significantly decreased nitrite + nitrate accumulation in lipopolysaccharide-stimulated RAW 264.7 cells in a concentration-dependent manner with 85.67 % to 119.75 % inhibition of nitrite + nitrate production at 20 microg/mL. Most of the compounds had a moderate inhibitory effect on 15-lipoxygenase activity. Compounds 8 and 10 were the most potent inhibitor both in nitrite + nitrate production with respective IC50 values of 1.56 microM and 6.80 microM. Compounds 2, 7, and 8 had good anti-15-lipoxygenase activity with respective IC50 values of 13.80 microM, 14.80 microM, and 15.80 microM compared to quercetin, which was used as a standard lipoxygenase inhibitor (IC50 of 16.80 microM). Our study revealed 3-hydroxy-2-hydroxymethyl anthraquinone and Damnacanthol as potent inhibitors of both 15-lipoxygenase activity and nitric oxide production. Further studies are needed in order to envisage its possible future use as a therapeutic alternative against inflammatory diseases.

Cytotoxicity of anthraquinones from the roots of Pentas schimperi towards multi-factorial drug-resistant cancer cells.[Pubmed:26115800]

Invest New Drugs. 2015 Aug;33(4):861-9.

INTRODUCTION: Multidrug resistance in cancer represents a major problem in chemotherapy. The present study was designed to assess the cytotoxicity of anthraquinones from Pentas schimperi, namely damnacanthal (1), Damnacanthol (2), 3-hydroxy-2-hydroxymethyl anthraquinone (3) and schimperiquinone B (4) against nine drug-sensitive and multidrug resistant (MDR) cancer cell lines. METHODS: The resazurin reduction assay was used to evaluate the cytotoxicity of the above compounds, whilst caspase-Glo assay was used to detect the activation of caspases enzymes by compounds 1 and 2. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species were all analyzed via flow cytometry. RESULTS: Anthraquinones 1 and 2 displayed cytotoxic effects with IC50 values below 81 muM on all the nine tested cancer cell lines whilst 3 and 4 displayed selective activities. The recorded IC50 values for compounds 1 and 2 ranged from 3.12 muM and 12.18 muM (towards leukemia CCRF-CEM cells) and from 30.32 muM and 80.11 muM (towards gliobastoma U87MG.DeltaEGFR cells) respectively, and from 0.20 muM (against CCRF-CEM cells) to 195.12 muM (against CEM/ADR5000 cells) for doxorubicin. Compounds 1 and 2 induced apoptosis in CCRF-CEM leukemia cells, mediated by the disruption of the MMP and increase in ROS production. CONCLUSIONS: Anthraquinones from Pentas schimperi and mostly 1 and 2 are potential cytotoxic natural products that deserve more investigations to develop novel antineoplastic drugs against multifactorial drug resistant cancers.

[Anthraquinones from the roots of Knoxia valerianoides].[Pubmed:22308688]

Zhongguo Zhong Yao Za Zhi. 2011 Nov;36(21):2980-6.

OBJECTIVE: To investigate the chemical constituents of the roots of Knoxia valerianoides and their biological activities. METHOD: The anthraquinones were isolated by using a combination of various chromatographic techniques including column chromatography over silica gel, Sephadex LH-20, and reversed-phase HPLC. Structures of the isolates were identified by their physical-chemical properties and spectroscopic analysis including 2D NMR and MS. Antioxidant, anti-HIV, neuroprotective, and cytotoxic activities were screened by using cell-based models. RESULT: Twenty-two constituents were isolated from an ethanolic extract of the roots of K. valerianoides. Their structures were identified as nordamnacanthal (1), ibericin (2), rubiadin (3), Damnacanthol (4), 2-ethoxymethylknoxiavaledin (5), 3-hydroxymorindone (6), knoxiadin (7), 2-formyl knoxiavaledin (8), lucidin (9), xanthopurpurin (10), 1, 3-dihydroxy-2-methoxy-9, 10- anthraquinone (11), lucidin(-methyl ether (12), digiferruginol (13), 3-hydroxy-2-methyl-9,10-anthraquinone (14), rubiadin-1-methyl ether (15), 6-methoxylucidin (-ethyl ether (16), 1,3,6-trihydroxy-2-methyl-9,10-anthraquinone (17), 1,3-dihydroxy-2-hydroxy methyl-6-methoxy-9,10-anthraquinone (18), 1,3,6-trihydroxy-2-methoxymethyl-9,10- anthraquinone (19), 3,6-dihydroxy-2- hydroxymethyl-9,10-anthraquinone (20), and 1,6-dihydroxy-2-methyl-9,10-anthra quinone (21). In the in vitro assays, at a concentration of 1 x 10(-5) mol x L(-1), no compounds were active against human cancer cell lines (HCT-8, Bel7402, BGC-823, A549, and A2780), deserum and glutamate induced PC12-syn cell damage, LPS induced NO production in macrophage, Fe2+-cystine induced rat liver microsomal lipid peroxidation, HIV-1 replication, and protein tyrosine phosphatase 1B (PTP1B). CONCLUSION: Compounds 9-21 were obtained from the roots of K. valerianoides for the first time.

Antiplasmodial quinones from Pentas longiflora and Pentas lanceolata.[Pubmed:21979929]

Planta Med. 2012 Jan;78(1):31-5.

The dichloromethane/methanol (1:1) extracts of the roots of Pentas longiflora and Pentas lanceolata showed low micromolar (IC(50) = 0.9-3 microg/mL) IN VITRO antiplasmodial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of PLASMODIUM FALCIPARUM. Chromatographic separation of the extract of PENTAS LONGIFLORA led to the isolation of the pyranonaphthoquinones pentalongin (1) and psychorubrin (2) with IC(50) values below 1 microg/mL and the naphthalene derivative mollugin (3), which showed marginal activity. Similar treatment of Pentas lanceolata led to the isolation of eight anthraquinones ( 4-11, IC(50) = 5-31 microg/mL) of which one is new (5,6-dihydroxyDamnacanthol, 11), while three--nordamnacanthal (7), lucidin-omega-methyl ether (9), and Damnacanthol (10)--are reported here for the first time from the genus Pentas. The compounds were identified by NMR and mass spectroscopic techniques.

Anthraquinones from the roots of Knoxia valerianoides inhibit the formation of advanced glycation end products and rat lens aldose reductase in vitro.[Pubmed:20195820]

Arch Pharm Res. 2010 Feb;33(2):209-14.

Eight known compounds, lucidin (1), lucidin-omega-methyl ether (2), rubiadin (3), Damnacanthol (4), 1,3,6-trihydroxy-2-methoxymethylanthraquinone (5), 3,6-dihydroxy-2-hydroxymethyl-9,10-anthraquinone (6), 1,3,6-trihydroxy-2-hydroxymethyl-9,10-anthraquinone 3-O-beta-primeveroside (7), and vanillic acid (8), were isolated from EtOAc- and n-BuOH-soluble fractions of the roots of Knoxia valerianoides. The structures of 1-8 were identified by analysis of spectroscopic data as well as by comparison with published values. All the isolates were subjected to in vitro bioassays to evaluate advanced glycation end products (AGEs) formation and rat lens aldose reductase (RLAR) inhibitory activity. Compound 5 showed the most potent inhibitory activity (IC(50) = 52.72 microM) against AGEs formation. Compounds 1, 2, and 8 also showed potent inhibitory activity on AGEs formation with IC(50) values of 79.28, 62.79, and 93.93 microM, respectively, compared with positive control, aminoguanidine (IC(50) = 962 microM). While, compounds 1 and 5-7 showed strong inhibitory activity against RLAR with IC(50) values of 3.35, 3.04, 6.39, and 2.05 microM, respectively.

New anthraquinone glycosides from the roots of Morinda citrifolia.[Pubmed:19233251]

Fitoterapia. 2009 Apr;80(3):196-9.

Six new anthraquinone glycosides: digiferruginol-1-methylether-11-O-beta-gentiobioside (1); digiferruginol-11-O-beta-primeveroside (2); Damnacanthol-11-O-beta-primeveroside (3); 1-methoxy-2-primeverosyloxymethyl-anthraquinone-3-olate (4); 1-hydroxy-2-primeverosyloxymethyl-anthraquinone-3-olate (5); and 1-hydroxy-5,6-dimethoxy-2-methyl-7-primeverosyloxyanthraquinone (6) were isolated from Morinda citrifolia (Rubiaceae) roots together with four known anthraquinone glycosides. The structures of the new compounds were established using spectral methods. For five of the new compounds, the sugar is attached via the hydroxymethyl group of the anthraquinone C-2 carbon. This type of bond is rarely found for anthraquinone glycosides isolated from natural sources.

Antimicrobial anthraquinones from Morinda angustifolia.[Pubmed:18621113]

Fitoterapia. 2008 Dec;79(7-8):501-4.

Investigation on Morinda angustifolia resulted in the isolation of a new anthraquinone, 1,8-dihydroxy-2-methyl-3,7-dimethoxyanthraquinone (1), along with five known analogues, lucidin 3-O-beta-primeveroside (2), 1,3-dihydroxy-2-methylanthraquinone (3), lucidin- omega -ethyl ether (4), lucidin-omega-butyl ether (5) and Damnacanthol (6). The new compound demonstrated significant antimicrobial activity against Bacillus subtilis, Escherichia coli, Micrococcus luteus, Sarcina lutea, Candida albicans and Saccharomyces sake.

Chemical constituents of Morinda citrifolia roots exhibit hypoglycemic effects in streptozotocin-induced diabetic mice.[Pubmed:18451522]

Biol Pharm Bull. 2008 May;31(5):935-8.

The hypoglycemic effects of the chemical constituents of Morinda citrifolia roots was evaluated in streptozotocin (STZ)-induced diabetic mice. The CHCl3, EtOAc, n-BuOH and H2O soluble phases of the MeOH extract of M. citrifolia roots were administrated orally to STZ-induced diabetic mice. Only the n-BuOH soluble phase showed a significant reduction of the blood glucose levels. From the biologically active n-BuOH soluble phase, two iridoids and three anthraquinones were isolated as main constituents. These compounds were identified by spectroscopic analysis to be deacetylasperulosidic acid (1), asperulosidic acid (2), Damnacanthol-3-O-beta-D-primeveroside (3), lucidin 3-O-beta-D-primeveroside (4) and morindone-6-O-beta-D-primeveroside (5). 3 and 4 exhibited the hypoglycemic effects, which were anthraquinones with no substituents in one aromatic ring.

Three new and antitumor anthraquinone glycosides from Lasianthus acuminatissimus MERR.[Pubmed:16508180]

Chem Pharm Bull (Tokyo). 2006 Mar;54(3):297-300.

Three new anthraquinone glycosides, lasianthuoside A (1), B (2), and C (3), were isolated from the root of Lasianthus acuminatissimus MERR., The structural elucidation of these anthraquinones was mainly established on the basis of 1D and 2D NMR and HR-MS spectroscopic analysis. Ten known compounds, Damnacanthol (4), Damnacanthol 11-methyl ether (5), Damnacanthol-3-O-beta-D-primeveroside (6), asperuloside (7), asperulosidic acid (8), deacetyl asperulosidic acid (9), a nonglycosidic iridoid (10), 2,6-dimethoxy-4-hydroxyphenol-1-O-beta-D-glucopyranoside (11), tachioside (methoxyhydroquinone-4-O-beta-D-glucopyranoside) (12), and isotachioside (methoxyhydroquinone-1-O-beta-D-glucopyranoside) (13) were also identified for the first time from this plant in the course of the phytochemical and spectroscopic investigation. In addition to this report, a preliminary evaluation of 13 compounds in treating rheumatoid arthritis and antitumor effects of six anthraquinones are presented.

Natural anthraquinones probed as Type I and Type II photosensitizers: singlet oxygen and superoxide anion production.[Pubmed:15629252]

J Photochem Photobiol B. 2005 Jan 14;78(1):77-83.

The photosensitizing properties of six anthraquinones (AQs): soranjidiol (1), soranjidiol-1-methyl ether (2), rubiadin (3), rubiadin-1-methyl ether (4), damnacanthal (5) and Damnacanthol (6), isolated from leaves and stems of Heterophyllaea pustulata Hook. f. (Rubiaceae) were studied. By means of photobiological and photophysical methods in vitro, the type of photosensitization that these metabolites are capable of producing was determined. Whereas the photosensitized generation of superoxide anion radical (O(2)(-)) (Type I) was evaluated in leukocyte suspensions, singlet molecular oxygen ((1)O(2)) production (Type II) was examined in organic solution. In addition, the quantum yield of (1)O(2) (Phi) in chloroform was measured for those AQs that generate it. It was established that 4 behaves exclusively as a Type I photosensitizer. By contrast, the others AQs act by both types of mechanisms, among which 5 showed the largest Phi of (1)O(2).

Pharmacological and toxicological activity of Heterophyllaea pustulata anthraquinone extracts.[Pubmed:13678245]

Phytomedicine. 2003;10(6-7):569-74.

Benzenic extracts from both stems and leaves of Heterophyllaea pustulata showed the most significant activity in vivo in the Brine Shrimp Lethally Test (BST), relative to others of different polarity. They were therefore selected for in vitro antimicrobial activity studies. Bacteriostatic activity against Micrococcus luteus ATCC 9341 was detected, selectively inhibiting both oxacillin-sensitive and -resistant Staphylococcus aureus, among several gram-positive and gram-negative bacterial species tested. Antifungal activity against important opportunist microorganisms and against those involved in superficial mycosis, all from nosocomial origin was also detected. A chemical screening revealed the presence of anthraquinones as major compounds. Among them, we identified damnacanthal, rubiadin, 2-hydroxy-3-methyl anthraquinone, soranjidiol, rubiadin-1-methyl ether, and Damnacanthol in the benzenic stem extract. The benzenic leaf extract shows a similar chemical composition, except for damnacanthal, Damnacanthol, soranjidiol-1-methyl ether, and 3 anthraquinones whose structures have not yet been elucidated. Acute toxicity studies revealed a low toxicity in mice for the anthraquinonic extracts, as measured in the LD50 value (123 mg/kg body wt. i.v.), and death was not observed at doses of up to 4000 mg/kg body wt. s.c.

Anthraquinones from Neonauclea calycina and their inhibitory activity against DNA topoisomerase II.[Pubmed:9657055]

Biol Pharm Bull. 1998 Jun;21(6):641-2.

In a series of searches for DNA topoisomerase II inhibitors from naturally occurring compounds, a wood extract of Neonauclea calycina MERR. (Rubiaceae) showed a moderate effect in vitro. Purification of the extract resulted in the isolation of seven known anthraquinones. The structures were characterized as damnacanthal, rubiadin 1-methyl ether, nordamnacanthal, morindone, Damnacanthol, lucidin 3-O-primeveroside and morindone 6-O-primeveroside by spectral analysis, respectively. Damnacanthal and morindone showed an intensive inhibitory effect against topoisomerase II (IC50: 20 micrograms/ml and 21 micrograms/ml).

[Structure correction and synthesis of subspinosin].[Pubmed:2239332]

Yao Xue Xue Bao. 1990;25(3):173-7.

"Subspinosin" isolated from the root of Damnacanthus subspinosus Hand-Mazz (Rubiaceae) and deduced as 3-ethoxymethyl-2-hydroxy-1-methoxyan-thraquinone 1 by Li et al in 1981, should be corrected as 2-ethoxymethyl-3-hydroxy-1-methoxyanthraquinone 5 by comparison with the synthetic compound. Since 5 is already known as Damnacanthol-omega-ethyl ether, the name "Subspinosin" for 1 (not yet a natural isolate) should be abandoned in order to acknowledge this priority, and, what is more, to avoid confusion. The anthraquinones 1 and 5 were synthesized by condensation of phthalic anhydride with 3-methylcatechol or 2-methylresorcinol in fused AlCl3/NaCl (5:1), followed sequentially by selective acetylation, methylation, bromination and condensation with sodium ethoxide.