Research on Anti-inflammatory Targets and Mechanisms of alkaloids in Picrasma quassioides Benn Through Network Pharmacology

Abstract This study aimed to investigate the molecular mechanism of Picrasma quassioides Benn against inflammation by means of network pharmacology. The paper will provide a reference for multi-target and multi-channel treatment of inflammation with traditional Chinese medicine. Through screening and analysis, 11 active ingredients and 109 anti-inflammation prediction targets were obtained and constructed a compound-target network. The targets such as VEGFA, TLR4 and STAT3 may play a crucial role. Network enrichment analysis showed that the 109 potential targets constitute a number of pathways or inflammatory reactions closely related to inflammation, including NF-κB signaling pathway and MAPK signaling pathway. The docking results indicated that the binding energy of Picrasidine Y and the inflammatory factors VEGFA is the highest. This study predicted the role of multiple active compounds in the alkaloids of Picrasma in the inflammatory response, and provided a theoretical basis for the anti-inflammatory mechanism of Picrasma

1-Methoxycarbony-β-carboline from Picrasma quassioides exerts anti-angiogenic properties in HUVECs in vitro and zebrafish embryos in vivo / 中国天然药物

Angiogenesis is a crucial process in the development of inflammatory diseases, including cancer, psoriasis and rheumatoid arthritis. Recently, several alkaloids from Picrasma quassioides had been screened for angiogenic activity in the zebrafish model, and the results indicated that 1-methoxycarbony-β-carboline (MCC) could effectively inhibit blood vessel formation. In this study, we further confirmed that MCC can inhibit, in a concentration-dependent manner, the viability, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro, as well as the regenerative vascular outgrowth of zebrafish caudal fin in vivo. In the zebrafish xenograft assay, MCC inhibited the growth of tumor masses and the metastatic transplanted DU145 tumor cells. The proteome profile array of the MCC-treated HUVECs showed that MCC could down-regulate several angiogenesis-related self-secreted proteins, including ANG, EGF, bFGF, GRO, IGF-1, PLG and MMP-1. In addition, the expression of two key membrane receptor proteins in angiogenesis, TIE-2 and uPAR, were also down-regulated after MCC treatment. Taken together, these results shed light on the potential therapeutic application of MCC as a potent natural angiogenesis inhibitor via multiple molecular targets.

1-Methoxycarbony-β-carboline from Picrasma quassioides exerts anti-angiogenic properties in HUVECs in vitro and zebrafish embryos in vivo / 中国天然药物

Angiogenesis is a crucial process in the development of inflammatory diseases, including cancer, psoriasis and rheumatoid arthritis. Recently, several alkaloids from Picrasma quassioides had been screened for angiogenic activity in the zebrafish model, and the results indicated that 1-methoxycarbony-β-carboline (MCC) could effectively inhibit blood vessel formation. In this study, we further confirmed that MCC can inhibit, in a concentration-dependent manner, the viability, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro, as well as the regenerative vascular outgrowth of zebrafish caudal fin in vivo. In the zebrafish xenograft assay, MCC inhibited the growth of tumor masses and the metastatic transplanted DU145 tumor cells. The proteome profile array of the MCC-treated HUVECs showed that MCC could down-regulate several angiogenesis-related self-secreted proteins, including ANG, EGF, bFGF, GRO, IGF-1, PLG and MMP-1. In addition, the expression of two key membrane receptor proteins in angiogenesis, TIE-2 and uPAR, were also down-regulated after MCC treatment. Taken together, these results shed light on the potential therapeutic application of MCC as a potent natural angiogenesis inhibitor via multiple molecular targets.

Simultaneous determination of 4 alkaloids and a flavonoid in Picrasmae Ramulus et Folium by RP-HPLC / 中国中药杂志

A RP-HPLC method was developed to evaluate the quality of Picrasmae Ramulus et Folium by simultaneous determination of five constituents including 1-hydroxymethyl-beta-carboline (1), 1-methoxicabony-beta-carboline (2), 4-methoxy-5-hydroxy-canthin-6-one (3), 4, 5-dimethoxy-canthin-6-one (4) and maackiain (5) in Picrasmae Ramulus et Folium. The samples were separated on a Kromasil RP-C18 (4.6 mm x 250 mm, 5 microm) column eluted with acetonitrile and 0.1% phosphoric acid as mobile phases in gradient mode. The detection wavelength was set at 254 nm. The calibration curves and linearity of the above five standards were determined as (1) Y = 6 525.6X + 37.25 (0.009-1.780 microg, r = 0.996 8), (2) Y = 3 662.3X + 41.55 (0.005-0.920 microg, r = 0.999 5), (3) Y = 3763.1X + 146.87 (0.015-3.060 microg, r = 0.999 0), (4) Y = 2 174.1X + 21.52 (0.003-0.620 microg, r = 0.999 5), and (5) Y = 276.25X + 7.65 (0.010-1.960 microg, r = 0.998 9), respectively. The method is simple and repeatable, and can be used for the quality assessment of Picrasmae Ramulus et Folium.

Parámetros micrográficos para la identificación de hojas, corteza y leño de Picrasma crenata (Vell.) Engl. (Simaroubaceae) / Micrographic parameters for the identification of leaves, bark and wood of Picrasma crenata (Vell.) Engl. (Simaroubaceae)

Picrasma crenata (Vell.) Engler (Simaroubaceae) es un árbol de bajo porte conocido popularmente como "palo amargo" o "quina brava", que habita en el noreste de la Argentina, principalmente en la provincia de Misiones. En la medicina tradicional el leño se emplea en forma de infusión, como antimalárico, antipalúdico, antisifilítico y tónico; se lo utiliza también como insecticida en la elaboración de tinturas alcohólicas como sustituto de Quassia amara, para el tratamiento de la pediculosis. El objetivo de este trabajo fue realizar un estudio morfoanatómico de la corteza, el leño y las hojas de P. crenata con el fin de obtener caracteres de valor diagnóstico que permitan una correcta identificación de la especie. Se efectuaron cortes transversales y longitudinales de material fresco que fue incluido en parafina de los tres órganos de la planta, y se colorearon con Safranina-Fast Green y Violeta de Cresilo. Los resultados mostraron que: la corteza se halla constituida por 5-7 peridermis de disposición imbrincada, el floema se halla interrumpido por numerosos radios muy sinuosos y torsionados; el leño, de color blanco amarillento, tiene crecimiento semianular a anular con porosidad difusa no uniforme; las hojas son compuestas, sus folíolos oval elípticos, alternos, presentan mesófilo dorsiventral, estomas anomocíticos solo en la epidermis inferior, tricomas simples y una cavidad esquizolisígena en el parénquima central del nervio medio. (AU)

Study on chemical constituents of Picrasma quassioides / 中国中药杂志

To study the chemical constituents of Picrasma quassioides. The chemical constituents were isolated and purified by chromatographic methods over Sephadex LH-20 and silica gel column, and structurally elucidated by spectral analysis, including UV, IR, MS, 1H-NMR, 13C-NMR. Fourteen compounds were obtained and identified as trifolirhizin(1), maackiain(2), 3', 7-dihydroxy-4'-methoxylisoflavone(3), umbelliferone(4), emodin(5), nigakilactone F(6), picrasin B(7),picraqualide B (8),4-methoxy-5-hydroxycanthin-6-one(9), 4,5-dimethoxycanthin-6-one (10),5-methoxycanthin-6-one(11), 11-hydroxycanthin-6-one(12) , 1-methoxycarbonyl-beta-carboline(13), 1-hydroxymethyl-beta-carboline(14). Compounds 1-5 are reported from the first time for the genus Pricrasma.

Fingerprint research and multi-component quantitative analysis of Kumu injection by HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To establish the HPLC chromatographic fingerprint of Kumu injection and to simultaneously determine the contents of three beta-carboline alkaloids, comprehensively evaluating the immanent quality of Kumu injection.</p><p><b>METHOD</b>The chromatographic analysis was performed on a Phenomenex Gemini C18 ( 4.6 mm x 250 mm, 5 microm) column with the gradient elution solvent system composed of methanol and 30 mmol x L(-1) aqueous ammonium acetate (adjusted with glacial acetic acid to pH 4.5). Similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine (2004 A) was used in data analysis.</p><p><b>RESULT</b>Sixteen co-possessing peaks were selected as the fingerprints of Kumu injection, and 7 peaks were identified by chemical reference substances. There were good similarities between the standard fingerprint chromatogram and each fingerprint chromatogram from the eleven samples for their similarity coefficients were not less than 0.9. Three kinds of beta-carboline alkaloids were separated well. The correlation coefficients were 0.999 9. The linear ranges of three components were 0.020 0-0.300 0, 0.102 0-1.530 0, 0.015 2-0. 228 0 microg, respectively, and the average recoveries ranged were from 99.5% to 102%.</p><p><b>CONCLUSION</b>The method of fingerprint combined with quantitative analysis is sensitive, selective, and provide scientific basis for quality control of Kumu Injection.</p>

Estudio de genotoxicidad de Picrasma crenata (Vell.) Engl. - Simaroubaceae - / Genotoxicity study on Picrasma crenata (Vell.) Engl. - Simaroubaceae -

En la medicina popular se utiliza el leño de Picrasma crenata en infusión como pediculicida y como tónico amargo no astringente. Los principios activos responsables de la actividad son los quasinoides. Los objetivos de este trabajo son: determinar la actividad de las infusiones sobre el desarrollo de raíces y la división celular mediante el Test de Allium cepa; analizar la correlación de las concentraciones y los parámetros macro y microscópicos e interpretar la posible genotoxicidad de la infusión. Las concentraciones empleadas fueron 2,5 mg%; 5,0 mg%, 10,0 mg%, 20,0 mg% y 40,0 mg%. Se observó una correlación estadísticamente significativa de las concentraciones con las longitudes de las raíces y las anomalías macroscópicas; además, una correlación significativa de los índices mitóticos con las longitudes de las raíces y las anomalías microscópicas. Así, se puede inferir que los extractos en las concentraciones ensayadas podrían presentar actividad genotóxica.

Infusions of Picrasma crenata woods are used in folk medicine against lice and as a non astringent bitter tonic. The active principles responsible for the activity are the quasinoides. The objectives of this work are: to establish the activity of the infusions on the development by roots and the cellular division by means of the Test of Allium cepa; to analyze the correlation of the concentrations with macro and microscopic parameters and to conclude about the possible genotoxicity of the infusion. The used concentrations were 2.5 mg%; 5,0 mg%, 10,0 mg%, 20,0 mg% and 40,0 mg%. A statistically significant correlation between the concentrations and the roots lengths and macroscopic aberrations and a significant correlation between the mitotic index and the roots lengths and microscopic aberrations have been observed. Thus, it is possible to deduce that the extracts in the tested concentrations could present genotoxic activity.

Isolation and in vitro antimalarial activity of hexane extract from Thai Picrasma javanica B1 stembark.

The in vitro antimalarial activities against Plasmodium falciparum K1 of four extracts from the stembark of Picrasma javanica B1; ie water, methanol, chloroform and hexane extracts were studied using a modification of the [3H]hypoxanthine incorporation method. It was found that the hexane extract showed in vitro antimalarial activity with IC50 of 3.3 microg/ml. The extract was further fractionated using quick column chromatography, resulting in ten fractions. Fraction V was the most effective against P. falciparum K1 with IC50 of 4.4 microg/ml. Further isolation of fraction V using a column chromatographic technique provided six fractions. According to 1H- and 13C-NMR spectra, it could be concluded that the major compound in fraction V-3 was beta-sitosterol. Unfortunately, the antimalarial activity of beta-sitosterol could not be determined because of its low solubility in DMSO. However, fractions V-2 and V-4 still showed in vitro antimalarial activities with IC50 of 2.8 and 3.4 microg/ml, respectively. The further fractionation of these two active fractions could lead to promising candidates as antimalarial agents.