Myricetin 3-O-beta-D-xylopyranosyl(1-2)-[alpha-L-rhamnopyranosyl-(1-6)]-beta-D-glucopyranoside

Identification of natural compounds extracted from crude drugs as novel inhibitors of hepatitis C virus.[Pubmed:34130179]

Biochem Biophys Res Commun. 2021 Aug 27;567:1-8.

Natural product-derived crude drugs are expected to yield an abundance of new drugs to treat infectious diseases. Hepatitis C virus (HCV) is an oncogenic virus that significantly impacts public health. In this study, we sought to identify anti-HCV compounds in extracts of natural products. A total of 110 natural compounds extracted from several herbal medicine plants were examined for antiviral activity against HCV. Using a Huh7-mCherry-NLS-IPS reporter system for HCV infection, we first performed a rapid screening for anti-HCV compounds extracted from crude drugs. The compounds threo-2,3-bis(4-hydroxy-3-methoxyphenyl)-3-butoxypropan-1-ol (#106) and medioresinol (#110), which were extracted from Crataegus cuneate, exhibited anti-HCV activity and significantly inhibited HCV production in a dose-dependent manner. Analyses using HCV pseudoparticle and subgenomic replicon systems indicated that compounds #106 and #110 specifically inhibit HCV RNA replication but not viral entry or translation. Interestingly, compound #106 also inhibited the replication and production of hepatitis A virus. Our findings suggest that C. cuneate is a new source for novel anti-hepatitis virus drug development.

Medioresinol as a novel PGC-1alpha activator prevents pyroptosis of endothelial cells in ischemic stroke through PPARalpha-GOT1 axis.[Pubmed:33915296]

Pharmacol Res. 2021 Jul;169:105640.

AIM: Brain microvascular endothelial cells (BMVECs), as the important structure of blood-brain barrier (BBB), play a vital role in ischemic stroke. Pyroptosis of different cells in the brain may aggravate cerebral ischemic injury, and PGC-1alpha plays a major role in pyroptosis. However, it is not known whether BMVECs undergo pyroptosis after ischemic stroke and whether PGC-1alpha activator Medioresinol (MDN) we discovered may be useful against pyroptosis of endothelial cells and ischemic brain injury. METHODS: For in vitro experiments, the bEnd.3 cells and BMVECs under oxygen and glucose-deprivation (OGD) were treated with or without MDN, and the LDH release, tight junction protein degradation, GSDMD-NT membrane location and pyroptosis-associated proteins were evaluated. For in vivo experiments, mice underwent transient middle cerebral artery occlusion (tMCAO) for ischemia model, and the neuroprotective effects of MDN were measured by infarct volume, the permeability of BBB and pyroptosis of BMVECs. For mechanistic study, effects of MDN on the accumulation of phenylalanine, mitochondrial reactive oxygen species (mtROS) were tested by untargeted metabolomics and MitoSOX Red probe, respectively. RESULTS: BMVECs underwent pyroptosis after ischemia. MDN dose-dependently activated PGC-1alpha, significantly reduced pyroptosis, mtROS and the expressions of pyroptosis-associated proteins (NLRP3, ASC, cleaved caspase-1, IL-1beta, GSDMD-NT), and increased ZO-1 and Occludin protein expressions in BMVECs. In tMCAO mice, MDN remarkably reduced brain infarct volume and the permeability of BBB, inhibited pyroptosis of BMVECs, and promoted long-term neurobehavioral functional recovery. Mechanistically, MDN promoted the interaction of PGC-1alpha with PPARalpha to increase PPARalpha nuclear translocation and transcription activity, further increased the expression of GOT1 and PAH, resulting in enhanced phenylalanine metabolism to reduce the ischemia-caused phenylalanine accumulation and mtROS and further ameliorate pyroptosis of BMVECs. CONCLUSION: In this study, we for the first time discovered that pyroptosis of BMVECs was involved in the pathogenesis of ischemic stroke and MDN as a novel PGC-1alpha activator could ameliorate the pyroptosis of endothelial cells and ischemic brain injury, which might attribute to reduction of mtROS through PPARalpha/GOT1 axis in BMVECs. Taken together, targeting endothelial pyroptosis by MDN may provide alternative therapeutics for brain ischemic stroke.

Dolominol a and B, two new neolignans from Dolomiaea souliei (Franch.) C.Shih.[Pubmed:33719777]

Nat Prod Res. 2021 Mar 15:1-8.

Two new neolignans, dolominol A (1) and dolominol B (2), together with 12 known lignans, erythro-(7S,8R)-guaiacyl-glycerol-beta-O-4'-dihydroconiferyl ether (3), threo-(7R,8R)-1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl)]-2-me thoxyphenoxy}-1,3-propanediol (4), (-)-dihydrodehydrodiconiferyl alcohol (5), (-)-massoniresinol (6), vladinol D (7), syringaresinol (8), prinsepiol (9), medioresinol (10), (+)-pinoresinol (11), 2alpha-guaicyl-4-oxo-6alpha-catechyl-3,7-dioxabicyclo [3.3.0]octane (12), cycloolivil (13), isolariciresinol (14) were isolated from Dolomiaea souliei (Franch.) C.Shih. Their structures were determined by UV, CD, HR-ESI-TOFMS, 1 D and 2 D NMR experiments. Their hepatoprotective effect against LPS-induced L-02 cells injury was also studied. Result revealed that compound 4 showed best protective effect on LPS-induced L-02 cells.

Bioactive Lignans from Hypoestes aristata.[Pubmed:32786879]

J Nat Prod. 2020 Aug 28;83(8):2483-2489.

Phytochemical investigation of extracts of the stems of Hypoestes aristata led to the isolation of nine lignans that included four known compounds, namely, hinokinin (1), savinin (2), medioresinol (3), and two cubebins (8a,b), three new butyrolactone lignans (4-6), and butyrolactol lignans 7a-c. The structures of the new compounds were established using 1D and 2D NMR and HRESIMS data. The absolute configurations of the new lignans were determined from their ECD data and the Mosher's ester method. This is the first unequivocal assignment of the absolute configuration at C-7 and C-7' of 7- and 7'-hydroxybutyrolactone lignans. The compounds were screened for inhibition of an HIV-1 protease enzyme, and compounds 1 and 6 exhibited moderate activity in this regard.

[Study on non-flavonoids chemical constituents from Spatholobi Caulis].[Pubmed:32237455]

Zhongguo Zhong Yao Za Zhi. 2020 Mar;45(5):1120-1127.

To study the non-flavonoids chemical constituents in water extract of Spatholobi Caulis. Some purification and analysis techniques like silica gel, D101-macroporous adsorptive resins, and Sephadex LH-20 column chromatographies as well as reversed phase high-performance liquid chromatography were used to isolate and analyze the phenolic acid esters and other type compounds from Spatholobi Caulis integrally. The structures of these compounds were identified by spectroscopic techniques such as nuclear magnetic resonance and high resolution mass spectrometries. Twenty-seven compounds, including phenolic acid, coumarin, lignan, terpene, alkaloid, and steroid compounds, were isolated from ethyl acetate and n-butanol fractions in water extract of Spatholobi Caulis, and they were identified as beta-sitosterol(1), feruli acid methyl ester(2), syringaresinol(3),(+)-medioresinol(4),(+)-epipinoresinol(5), p-acetylphenol(6), bolusanthin (7), evofolin B(8), salicylic acid(9), trans-p-hydroxy-cinnamic acid(10), abscisic acid(11), m-hydroxyphenol(12), C-veratroylglycol(13), p-hydroquinone(14), 8,9-dihydroxymegastigma-4,6-dien-3-one(15), p-hydroxybenzoic acid(16), 6,9-dihydroxymegastigma-4,7-dien-3-one(17), protocatechuic acid(18), protocatechuic acid methyl ester(19), 5,7-dihydroxycoumarin(20), isolariciresinol(21), nicotinic acid(22), daucosterol(23),(+)-pinoresinol(24), stigmasterol(25), allantoin(26) and koaburaside(27), respectively. Furthermore, compounds 2-15, 19-22, 24 and 26 were isolated from genus Spatholobus for the first time.

Chemical characterization of small-molecule inhibitors of monoamine oxidase B synthesized from the Acanthopanax senticosus root with affinity ultrafiltration mass spectrometry.[Pubmed:31826305]

Rapid Commun Mass Spectrom. 2020 Apr 30;34(8):e8694.

RATIONALE: Discovering and identifying new small-molecule inhibitors of monoamine oxidase B (MAO-B) could provide the potential to treat many neurodegenerative diseases. METHODS: We employed affinity ultrafiltration liquid chromatography/tandem mass spectrometry (AUF-LC/MS(n) ) to identify and characterize small-molecule inhibitors of MAO-B from a 30% ethanolic extract of Acanthopanax senticosus root (ASR). In vitro tests were performed in stimulated BV2 microglia to evaluate the anti-inflammatory effects of the ASR preparation. An in vitro enzyme activity assay, measuring half-maximal inhibitory concentrations (IC50 ) against MAO-B, determined the inhibitory activity of the potential MAO-B ligands. RESULTS: ASR treatment significantly inhibited NO release (p <0.01) and attenuated tumor necrosis factor (TNF)-alpha expression in stimulated BV2 microglia. Nine compounds were isolated from the ASR preparation as potential MAO-B inhibitors, identified as quinic acid, chlorogenic acid, isofraxidin, dicaffeoylquinic acid, pinoresinol diglucoside, medioresinol 4'-O-beta-D-glucopyranoside, eletutheroside E, syringaresinol O-beta-D-glucoside, and trihydroxyoctadecenoic acid, based on their tandem mass spectra. CONCLUSIONS: Our study provides critical data on compounds from ASR extracts which are suitable for the development of new MAO-B inhibitors as potential therapeutics for neurodegenerative diseases.

Four New Iridoid Metabolites Have Been Isolated from the Stems of Neonauclea reticulata (Havil.) Merr. with Anti-Inflammatory Activities on LPS-Induced RAW264.7 Cells.[Pubmed:31771186]

Molecules. 2019 Nov 23;24(23). pii: molecules24234271.

One new iridoid, namely neonanin C (1) one monocyclic iridoid ring-opened derivative namely neonanin D (2), two new bis-iridoid derivatives namely reticunin A (3) and reticunin B (4) with sixteen known compounds (5-20) were isolated from the stems of Neonauclea reticulata (Havil.) Merr. These new structures were determined by the detailed analysis of spectroscopic data and comparison with the data of known analogues. Compounds 1-20 were evaluated for inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages cell line. The results showed that all compounds exhibited no obvious cytotoxicity compared to the control group and five compounds including isoboonein (7), syringaresinol (10), (+)-medioresinol (12), protocatechuic acid (14) and trans-caffeic acid (15) exhibited inhibitory activities with IC50 values at 86.27 +/- 3.45; 9.18 +/- 1.90; 76.18 +/- 2.42; 72.91 +/- 4.97 and 95.16 +/- 1.20 microg/mL, respectively.

[Chemical compositions from roots of Erythrina corallodendron].[Pubmed:31602854]

Zhongguo Zhong Yao Za Zhi. 2019 Jul;44(14):3064-3069.

This project is to investigate chemical compositions from the roots of Erythrina corallodendron. Through the methods of silica gel,ODS,Sephadex LH-20 column chromatography and preparative HPLC,15 compounds were isolated from the 95% ethanol extract of the roots of E. corallodendron. Based on spectroscopic techniques,the structures of these compounds were identified as 10,11-dioxoerythraline( 1),erythrinine( 2),erythraline( 3),11-methoxyerythraline( 4),cristanines B( 5),erythratine( 6),erysotrine( 7),medioresinol( 8),( +/-)-ficusesquilignan A( 9),( +)-pinoresinol( 10),nicotinic acid( 11),dibutyl phthalate( 12),vanillic acid( 13),3-hydroxy-1-( 4-hydroxy-3-methoxyphenyl)-1-propanone( 14),and syringic acid( 15). Compounds 8-10 are isolated from genus Erythrina for the first time and all compounds are isolated from E. corallodendron for the first time. Furthermore,this paper screened the antioxidant and cytotoxic activities of the compounds using models of liver microsomal oxidation inhibition and MTT.

[Lignans from seed of Hydnocarpus anthelminthica].[Pubmed:31090297]

Zhongguo Zhong Yao Za Zhi. 2019 Apr;44(7):1397-1402.

This project is to investigate lignans from the seed of Hydnocarpus anthelminthica. Thirteen lignans were isolated from the 95% ethanol extract of the seed of H. anthelminthica, by polyamide resin, Sephadex LH-20, ODS column chromatography and preparative HPLC. Their structures were elucidated as(+)-syringaresinol(1), lirioresinol A(2),(+)-medioresinol(3),(7R,8R,8'R)-4'-guaiacylglyceryl-evofolin B(4), leptolepisol C(5),(-)-(7R,7'R,7''R,8S,8'S,8''S)-4',4''-dihydroxy-3,3',3'',5,5',5''-hexamethoxy -7,9':7',9-diepoxy-4,8''-oxy-8,8'-sesquineolignan-7'',9''-diol(6),(-)-(7R,7'R,7'' R,8S,8'S,8''S)-4',4''-dihydroxy-3,3',3'',5,5'-pentamethoxy-7,9':7',9-diepoxy-4,8' '-oxy-8,8'ses-quineolignan-7'',9''-diol(7), ceplignan(8), hydnocarpusol(9), isohydnocarpin(10),(-)-hydnocarpin(11), hydnocarpin(12), and hydnocarpin-D(13) by spectroscopic data analysis. Compounds 1-8 were obtained from the genus Hydnocarpus for the first time.

[Chemical constitutes from Clerodendrum japonicum].[Pubmed:30111024]

Zhongguo Zhong Yao Za Zhi. 2018 Jul;43(13):2732-2739.

The chemical constituents from the ethanol extract of Clerodendrum japonicum were isolated by a combination of various chromatographic techniques including column chromatography over silica gel, sephadex LH-20, ODS and reversed phase HPLC. Sixteen compounds with a pair of epimers were elucidated through the application of physicochemical properties with modern spectral analysis technology as 7alpha-hydroxy syringaresinol (1), (-)-syringaresinol (2), (-)-medioresinol (3), 2'',3''-O-acetylmartyonside (4), 2''-O-acetyl-martyonside (5), martinoside (6), monoacetyl martinoside (7)cytochalasin O (8), 9-epi-blumenol B (9), (6R, 9S) and (6R,9R)-9-hydroxy-4-megastigmen-3-one (10a10b), (6R,9S)-3-oxo-alpha-ionol (11), (-)-dehydrovomifoliol (12)megastigm-5-en-3,9-diol (13), (3R,6E,10S)-2,6,10-trimethyl-3-hydroxydodeca-6,11-diene-2,10-diol (14), (2R)-butylitaconic acid (15), 3-(3&-hydroxybutyl)-2,4,4-trimethylcyclohexa-2,5-dienone (16), (-)-loliolide (17), of which compound 1 and 15 are new natural product, the other compounds were isolated for the first time from Clerodendrum japonicum except for compounds 4, 6 and 7.

[A new lignan from rhizome of Stellera chamaejasme].[Pubmed:29751712]

Zhongguo Zhong Yao Za Zhi. 2018 Apr;43(8):1649-1653.

To investigate the chemical compounds from the rhizome of Stellera chamaejasme, nine lignans, including stellerachamin A (1), 8-hydroxypluviatolide (2), wikstromol (3), pinoresinol (4), matairesinol (5), dextrobursehernin (6), hinokinin(7), (-)-glaberide I (8) and - medioresinol (9) were isolated by various chromatographic methods. Their structures were extensively determined on basis of MS and NMR spectroscopic data analysis. Among them, compound 1 was a new lignan, and compounds 2 and 7 were isolated from Thymelaeaceae for the first time.

Bioactivities of decoctions from Plectranthus species related to their traditional use on the treatment of digestive problems and alcohol intoxication.[Pubmed:29626671]

J Ethnopharmacol. 2018 Jun 28;220:147-154.

ETHNOPHARMACOLOGICAL RELEVANCE: Decoctions of Plectranthus species are traditionally ingested after large meals for treatment of food digestion and alcohol abuse. AIM OF THE STUDY: This study aims at associating the digestion-related ethno-uses of Plectranthus species decoctions to molecular mechanism that might explain them: easing digestion (AChE inhibition) and treating hangover (ADH inhibition) MATERIAL AND METHODS: Decoctions from Plectranthus species were analysed for their alcohol dehydrogenase (ADH) inhibition and acetylcholinesterase (AChE) inhibition, related with alcohol metabolism and intestinal motility, respectively. Identification of the active components was carried out by LC-MS/MS and the docking studies were performed with AChE and the bioactive molecules detected. RESULTS: All decoctions inhibited ADH activity. This inhibition was correlated with their rosmarinic acid (RA) content, which showed an IC50 value of 19mug/mL, similar to the reference inhibitor CuCl2. The presence of RA also leads to most decoctions showing AChE inhibiting capacity. P. zuluensis decoction with an IC50 of 80mug/mL presented also medioresinol, an even better inhibitor of AChE, as indicated by molecular docking studies. Furthermore, all decoctions tested showed no toxicity towards two human cell lines, and a high capacity to quench free radicals (DPPH), which also play a helpful in the digestive process, related with their RA content. CONCLUSIONS: All activities presented by the RA-rich Plectranthus decoctions support their use in treating digestion disorders and P. barbatus could explain its use also for alleviating hangover symptoms. Medioresinol, which is present in P. zuluensis, exhibited a significant AChE inhibition and may provide, in the future, a new lead for bioactive compounds.

Four New Lignans and IL-2 Inhibitors from Magnoliae Flos.[Pubmed:28867711]

Chem Pharm Bull (Tokyo). 2017;65(9):840-847.

Four new lignans, a furofuran lignan medioresinol B (10) and three tetrahydrofuran lignans kobusinol C (16), 7'-methoxy magnostellin A (21), and mangnostellin D (23), along with 19 known lignans, were isolated from the flower buds of Magnolia biondii PAMP. The structures of the isolates were elucidated using spectroscopic analysis, mainly one- and two-dimensional NMR, high resolution-MS, and circular dichroism techniques as well as Mosher's esterification method. The anti-allergic effects of the isolated compounds were evaluated by analyzing the inhibition of interleukin-2 (IL-2) expression in Jurkat T-cells. Compounds 11-14 reduced IL-2 expression in a dose-dependent manner.

Anti-complementary constituents of Anchusa italica.[Pubmed:28438039]

Nat Prod Res. 2017 Nov;31(21):2572-2574.

Activity-guided fractionation for complement inhibitors led to the isolation of 24 known compounds from Anchusa italica. Chemical types include eight megastigmane compounds, five triterpenoid compounds, five lignan compounds, three flavonoid compounds, two alkaloid compounds and one phenthyl alcohol compound. Among which, a lignan (medioresinol), an alkaloid (5-hydroxypyrrolidin-2-one) and a flavonoid (5-hydroxyl-3', 4', 6, 7-tetramethoxy flavone) exhibited better anticomplementary effects with CH50 values ranging from 0.07 to 0.82 mM, which are plausible candidates for developing potent anticomplementary agents.