Perlolyrine

Analysis of Herbal Mechanisms and Prescriptions for Chronic Cerebral Circulatory Insufficiency Based on Data Mining and Network Pharmacology.[Pubmed:33475051]

Comb Chem High Throughput Screen. 2021 Jan 20. pii: CCHTS-EPUB-113500.

BACKGROUND: Traditional Chinese medicine has accumulated rich resources and experience through clinical research to explore the prevention and treatment of chronic cerebral circulatory insufficiency, but current medicine lacks in-depth research and confirmation on the established protocols and mechanism of prescribed TCMs at the macro and micro levels. OBJECTIVE: To explore the prescription of Chinese medicines for the treatment of chronic cerebral circulation insufficiency (CCCI) and to explore the mechanism of core drugs. METHODS: 229 Chinese prescriptions for CCCI were collected from CNKI, CBM, VIP and WANFANG databases. Analyze the frequency and association rules of drugs and to extract the core drugs by TCMISSV2.5 software. The active ingredients and targets were obtained by TCMSP, and genes of CCCI were collected from the DisGeNET, OMIM, DrugBank disease databases. The intersection targets of herbal medicine and disease was imported into the STRING database for PPI network. The key targets were screened by network topology algorithm. The Systems Dock website was used to verify the molecular docking. The GOEAST and DAVID tools were used to perform GO and KEGG pathway analysis with the key target genes. RESULTS: 117 drugs involved in 229 prescriptions were identified, 2 core drugs were identified. We identified 8 active ingredients, which were mandenol, myricanone, Perlolyrine, senkyunone, wallichilide, sitosterol, beta-sitosterol and stigmasterol. 371 herbal targets predicted and 335 disease targets. The enrichment analysis showed that the core herbal medicines could prevent CCCI by 15 key signaling pathways. CONCLUSION: There are direct or indirect connections in key signaling pathways, which not only participate in energy metabolism, hormone regulation, signal transduction, but also play a role in the comprehensive intervention of nervous system, immune system, circulatory system and other systems, which is consistent with the comprehensive pathogenesis of CCCI induced by multiple factors.

Flazin as a Promising Nrf2 Pathway Activator.[Pubmed:31668063]

J Agric Food Chem. 2019 Nov 20;67(46):12844-12853.

Flazin is a beta-carboline-derived alkaloid found in Japanese fermented foods. Here, the potential of flazin as an antioxidant food was studied with particular reference to its effect on the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) system in human hepatocytes (C3A). Flazin and flazin analogues including the decarboxylated derivative Perlolyrine were chemically synthesized and compared with each other and with chlorogenic acid and curcumin. Among these compounds, flazin showed the lowest cytotoxicity (IC50 < 500 muM) and the highest capacity to activate the Keap1-Nrf2 system. It provided the largest (>3-fold of the control) cytoprotection ability against a pro-oxidant, although its radical absorbance capacity was relatively low. Flazin increased the expressions of Nrf2-dependent phase II enzyme genes and their products (NQO1, GSTP, and GSH proteins). The strong cytoprotection ability of flazin associated with low logP (0-3) is shared by sulforaphane and 3,5-dihydroxy-4-methoxybenzyl alcohol, suggesting the potential value of flazin and flazin-rich foods for the prevention of oxidation-related health disorders.

[A new benzophenone isolated from fibrous roots of Anemarrhena asphodeloides].[Pubmed:31090296]

Zhongguo Zhong Yao Za Zhi. 2019 Apr;44(7):1392-1396.

Five compounds were isolated from the fibrous roots of Anemarrhena asphodeloides by silica gel, Sephadex LH-20 and semi-HPLC column chromatography. On the basis of physic-chemical properties and spectroscopic data analysis, these compounds were identified as methyl 2-[2,4-dihydroxy-3-(4-hydroxybenzoyl)-6-methoxyphenyl]acetate(1), 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoate(2), Perlolyrine(3),syringaresinol-4'-O-beta-D-glucoside(4) and 4',6-dihydroxy-4-methoxybenzophenone-2-O-(2''),3-C-(1'')-1''-desoxy-alpha-L-fruct ofuranoside(5). Among them, 1 was a new benzophenone. Compounds 2-5 were isolated from this plant for the first time. Compound 1 was tested for neuroprotective effects against H_2O_2-induced damage in SH-SY5 Y cells.

Design and synthesis of furyl/thineyl pyrroloquinolones based on natural alkaloid perlolyrine, lead to the discovery of potent and selective PDE5 inhibitors.[Pubmed:29505934]

Eur J Med Chem. 2018 Apr 25;150:30-38.

Based on Perlolyrine (1), a natural alkaloid with weak PDE5 potency from the traditional Chinese aphrodisiac plant Tribulus terrestris L., a series alpha-substituted tetrahydro-beta-carboline (THbetaC) derivatives were synthesized via T(+)BF4(-)-mediated oxidative C-H functionalization of N-aryl THbetaCs with diverse potassium trifluoroborates. Following Winterfeldt oxidation afforded the corresponding furyl/thienyl pyrroloquinolones, of which 5-ethylthiophene/ethylfuran derivatives 20a-b were identified as the most potent and selective PDE5 inhibitors. Among the enantiomers, (S)-20a and (S)-20b (IC50=0.52 and 0.39nM) were found to be more effective than their (R)-antipode, display favorable pharmacokinetic profiles, exert in vitro vasorelaxant effects on the isolated thoracic aorta, and exhibit in vivo efficacy in the anesthetized rabbit erectile model.

Isolation and identification of a humanTRPV1 activating compound from soy sauce.[Pubmed:28095752]

Biosci Biotechnol Biochem. 2017 May;81(5):987-994.

Transient receptor potential vanilloid 1 (TRPV1) was identified as a receptor of capsaicin, which is a pungent ingredient in hot red peppers. Due to its relevance for nociception, a physiological and pharmacological study of TRPV1 has also been developed. Therefore, it is important to enrich scientific knowledge regarding the TRPV1 activating or inhibiting compounds. In this study, we fractionated soy sauce based on the human TRPV1 (hTRPV1) activity using column chromatography and purified 5-(9H-pyrido[3,4-b]indol-1-yl)-2-furanmethanol (Perlolyrine) as an hTRPV1-activating compound. Additionally, Perlolyrine activates the human transient receptor potential ankyrin 1 (hTRPA1). The EC50 of hTRPV1 and hTRPA1 were 2.87 and 1.67 mumol L(-1), respectively. HPLC quantification of soy sauces showed that they contain 2.22-12.13 mumol L(-1) of Perlolyrine. The sensory evaluation revealed that Perlolyrine has taste modification effect. The results of this study, for the first time, suggest that Perlolyrine induces the activation of hTRPV1 and hTRPA1.

Isolation and Identification of an Antiproliferative Compound from Fructose-Tryptophan Maillard Reaction Products.[Pubmed:27041128]

J Agric Food Chem. 2016 Apr 20;64(15):3041-7.

This study was performed to isolate and identify a compound with antiproliferative activity against human stomach cancer cell lines, from fructose-tryptophan Maillard reaction products (MRPs). The MRPs, prepared from a fructose-tryptophan solution heated at 130 degrees C for 2 h, were fractionated into five solvent fractions: n-hexane, chloroform, ethyl acetate, butanol, and water. The highest antiproliferative activity was found in the chloroform fraction (85.93% at 200 mug/mL), and the active compound from this chloroform fraction was purified by silica gel column chromatography, TLC, and preparative HPLC. The antiproliferative activity (IC50) of the active compound was 42.24 mug/mL, and the active compound was identified as Perlolyrine (C16H10N2O2) by (1)H/(13)C NMR, DEPT, HMBC, and LC-ESI-MS. Therefore, this research may be useful in developing Perlolyrine as a functional therapeutic agent.

Transition-metal-catalyzed C-H bond functionalizations: feasible access to a diversity-oriented beta-carboline library.[Pubmed:24523206]

Chemistry. 2014 Mar 17;20(12):3408-14.

Diversification of the beta-carboline skeleton has been demonstrated to assemble a beta-carboline library starting from the tetrahydro-beta-carboline framework. This strategy affords feasible access to heteroaryl-, aryl-, alkenyl-, or alkynyl-substituted beta-carbolines at the C1, C3, or C8 position through three categorically different types of transition-metal-catalyzed CC bond-forming reactions, in the presence of multiple potentially reactive positions. These site-selective functionalizations include; 1) the Cu-catalyzed C1/C3-selective decarboxylative C sp 3C sp 2 and C sp 3Csp coupling of hexahydro-beta-carboline-3-carboxylic acid with a CH bond of a heteroarene or terminal alkyne; 2) the chelation-assisted Pd-catalyzed C1/C8-selective CH arylation of hexahydro-beta-carboline with aryl boron reagents; and 3) the chelation-assisted Pd-catalyzed C1/C3-selective oxidative CH/CH cross-coupling of beta-carboline-N-oxide with arenes, heteroarenes, or alkenes. The saturated structural feature of the hexahydro-beta-carboline framework can increase reactivity and control site selectivity. The robustness of these approaches has been demonstrated through the synthesis of hyrtioerectine analogues and Perlolyrine. We believe that these strategies could provide inspiration for late-stage diversifications of bioactive core scaffolds.

Alkaloids from the mangrove-derived actinomycete Jishengella endophytica 161111.[Pubmed:24451190]

Mar Drugs. 2014 Jan 21;12(1):477-90.

A new alkaloid, 2-(furan-2-yl)-6-(2S,3S,4-trihydroxybutyl)pyrazine (1), along with 12 known compounds, 2-(furan-2-yl)-5-(2S,3S,4-trihydroxybutyl)pyrazine (2), (S)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (3), (S)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (4), (4S)-4-(2-methylbutyl)-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbalde hyde (5), (S)-4-benzyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (6), flazin (7), Perlolyrine (8), 1-hydroxy-beta-carboline (9), lumichrome (10), 1H-indole-3-carboxaldehyde (11), 2-hydroxy-1-(1H-indol-3-yl)ethanone (12), and 5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde (13), were isolated and identified from the fermentation broth of an endophytic actinomycetes, Jishengella endophytica 161111. The new structure 1 and the absolute configurations of 2-6 were determined by spectroscopic methods, J-based configuration analysis (JBCA) method, lactone sector rule, and electronic circular dichroism (ECD) calculations. Compounds 8-11 were active against the influenza A virus subtype H1N1 with IC50 and selectivity index (SI) values of 38.3(+/-1.2)/25.0(+/-3.6)/39.7(+/-5.6)/45.9(+/-2.1) mug/mL and 3.0/16.1/3.1/11.4, respectively. The IC50 and SI values of positive control, ribavirin, were 23.1(+/-1.7) mug/mL and 32.2, respectively. The results showed that compound 9 could be a promising new hit for anti-H1N1 drugs. The absolute configurations of 2-5, 13C nuclear magnetic resonance (NMR) data and the specific rotations of 3-6 were also reported here for the first time.

Chemical constituents of Arisaema franchetianum tubers.[Pubmed:23106482]

J Asian Nat Prod Res. 2013;15(1):71-7.

A novel pyrrolidine alkaloid, (2R*,3S*,5S*)-N,2-dimethyl-3-hydroxy-5-(10-phenyldecyl)pyrrolidine (1), and 17 known compounds were isolated from Arisaema franchetianum Engl. (Araceae) tubers. The 17 compounds were bergenin (2), emodin (3), caffeic acid (4), nobiletin (5), 3-O-beta-d-galactopyranosyl-hederagenin 28-O-beta-d-xylopyranosyl(1 --> 6)-beta-d-galactopyranosyl ester (6), coniferin (7), qingyangshengenin (8), methylconiferin (9), syringaresinol 4'-O-beta-d-glucopyranoside (10), gagaminine (11), Perlolyrine (12), (S)-1-(1'-hydroxyethyl)-beta-carboline (13), 1-(beta-carboline-1-yl)-3,4,5-trihydroxy-1-pentanone (14), 1-methoxycarbonyl-beta-carboline (15), indolo[2,3-alpha]carbazole (16), 4-hydroxycinnamic acid methyl ester (17), and methyl 4-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethyl] ferulate (18). The inhibitory activities of compound 1 and its N-methyl derivative (1a) against porcine respiratory and reproductive syndrome virus (PRRSV), human leukemic K562 cells, and human breast cancer MCF-7 cells were evaluated. Compounds 1 [50% inhibited concentration (IC(50)) = 12.5 +/- 0.6 muM] and 1a (IC(50) = 15.7 +/- 0.9 muM) were cytotoxic against K562 cells. Compound 1a also had a weak effect on PRRSV with an IC(50) value of 31.9 +/- 6.0 muM [selectivity index (SI) = 18.7].

25 years of natural product R&D with New South Wales agriculture.[Pubmed:18007515]

Molecules. 2005 Oct 31;10(10):1232-41.

Following recent NSW Government restructuring, the Department of Agriculture now exists in a composite form along with Forestry, Fisheries and Minerals in the new NSW Department of Primary Industries. This paper outlines some of the highlights of secondary metabolite R&D accomplished in the 25 years since the essential oil research unit was transferred from the Museum of Applied Arts & Sciences, Sydney to NSW Agriculture's Wollongbar Agricultural Institute on the NSW north coast. The essential oil survey was continued, typing the Australian flora as a suitable source of isolates such as myrtenal (Astartea), myrtenol (Agonis), methyl chavicol(Ochrosperma), alpha-phellandren-8-ol (Prostanthera), methyl myrtenate (Darwinia), methyl geranate (Darwinia), kessane (Acacia), cis-dihydroagarofuran (Prosthanthera), protoanemonin (Clematis), isoamyl isovalerate (Micromyrtus), methyl cinnamate (Eucalyptus) and bornyl acetate (Boronia). Many of these components are used, or have potential use in the fragrance, flavour, medicinal plant or insect attraction fields. Two weeds toxic to livestock in the Central West of the State are also harvested commercially as medicinal plants. Measurement of hypericin concentrations in the various plant parts of St John's Wort (Hypericum perforatum) over two seasons has shown that the weed can be effectively managed by grazing sheep during the winter months when toxin levels are low. Syntheses of beta-carbolines tribulusterine and Perlolyrine have shown that the former alkaloid was misidentified in the literature and hence not the toxic principle responsible for Tribulus staggers in sheep. Poor quality (high 1,8-cineole - low terpinen-4-ol) oil bearing tea tree (Melaleuca alternifolia) plantations have been established to the detriment of many a tea tree farmer. Analytical methods developed to check leaf quality at an early age indicated precursor sabinene constituents that convert to the active terpinen-4-ol both as the leaf matures or as the precursors are distilled for oil production. Tea tree's major insect pest, pyrgo beetle (Paropsisterna tigrina), was seen to selectively metabolize only 1,8-cineole from it's monoterpenoid-rich diet. Characterization of these and other metabolites from myrtaceous herbivores showed a species specific production of predominately ring hydroxylated products, some of which were attractive when bioassayed against adult beetles.

[Studies on urinary metabolites of perlolyrine in rats].[Pubmed:12903518]

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2000 Apr;22(2):154-8.

OBJECTIVE: To study the metabolism of Perlolyrine in rats, which is an active ingredient from the traditional Chinese herb, Ligusticum Wallichii Franch. METHODS: After administration of Perlolyrine and deuterated Perlolyrine, the rat urines were hydrolyzed with glucuronidase, basified with NaHCO3-Na2CO3, extracted with ethyl ether--iso-propyl alcohol. The organic phases (neutral and basic fractions) were concentrated for trimethylsilyl (TMS) derivatives. The aqueous phase were acidified with sulfuric acid, taken to dryness and extracted with methanol (water soluble acidic fractions) and concentrated for TMS derivatives. The TMS derivatives were determined by gas chromatograph mass spectrometry (GC-MS). RESULTS: Perlolyrine and one metabolite were found from the neutral and basic fractions, and two different metabolites were found from the water soluble acidic fractions. CONCLUSIONS: It was proposed that the major metabolic pathways of Perlolyrine were that the hydroxylation of Perlolyrine and the oxidation of its hydroxylmethyl group.

Pharmacokinetics of perlolyrine in rats by stable isotope dilution in conjunction with GC-MS.[Pubmed:11360678]

Acta Pharmacol Sin. 2000 Jul;21(7):660-2.

AIM: To determine the pharmacokinetics of Perlolyrine in rats. METHODS: The plasma concentration and pharmacokinetic parameters of Perlolyrine were determined by gas chromatography-mass spectrometry (GC-MS) with selected ion (m/z 247 and m/z 248) and [2-(15) N] Perlolyrine (m/z 248) as internal standard. RESULTS: The concentration-time profile of Perlolyrine after ig Perlolyrine 2 mg.kg-1 fitted a two-compartment open model in rats. The pharmacokinetic parameters were T1/2 alpha = 0.33 h, T1/2 beta = 4.52 h, T1/2 (ka) = 0.14 h, Tmax = 0.35 h, Cmax = 18.84 micrograms/L, K12 = 0.88 h-1, K21 = 0.42 h-1, K10 = 0.32 h-1, V/F = 109.22 L.kg-1, AUC = 112.68 micrograms.h.L-1. CONCLUSION: The method was constant, sensitive, and accurate. It provides a useful method for the determination of pharmacokinetics of Perlolyrine which are important for clinical use of Perlolyrine.