Inhibitory effect and mechanism of total flavonoids from Melicope pteleifolia on transplanted tumor of colorectal cancer in nude mice / 中国药房

OBJECTIVE To study the inhibitory effect and mechanism of total flavonoids from Melicope pteleifolia （TF-MPL） on transplanted tumor of colorectal cancer in nude mice. METHODS The transplanted tumor model of colorectal cancer was induced by injecting 0.2 mL colorectal cancer cell LoVo subcutaneously via the right armpit of nude mice. After successful modeling， nude mice were randomly divided into model group， 5-fluorouracil group （positive control， 10 mg/kg）， TF-MPL high- dose and low-dose groups （25， 12.5 mg/kg）； a normal group （normal saline containing 0.3% carboxymethyl cellulose sodium） without modeling was additionally set up， with 6 mice in each group. Each group was intraperitoneally injected with the corresponding drug solution/solvent for 21 consecutive days. The inhibitory rate of the transplanted tumor， liver and spleen index， and the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in serum were detected after the last medication； the morphological changes of tumor tissue were observed； immunohistochemical staining was used to detect protein expressions of Toll- like receptor 4 （TLR4） and nuclear factor-κB subunit p65 （NF-κB p65） in tumor tissue of nude mice. Western blot assay was used to detect protein expressions of TLR4， myeloid differentiation factor 88 （MyD88）， TNF receptor-associated factor 6 （TRAF6）， interleukin-1 receptor-associated kinase 1 （IRAK-1）， NF-κB p65 and caspase-3 in tumor tissue of nude mice. RESULTS Compared with the model group， TF-MPL high-dose group showed a significant decrease in tumor weight （inhibitory rate of 36.91%）， liver and spleen index， serum levels of TNF-α and IL-6 and protein expressions of TLR4， MyD88， TRAF6，IRAK-1 and NF- κB p65 （P＜0.05 or P＜0.01）； the expression of caspase-3 protein was increased significantly （P＜0.05）， and more tumor cell shrinkage and deformation， nuclear pyknosis and fragmentation were observed. CONCLUSIONS TF-MPL can significantly inhibit the growth of transplanted tumor of colorectal cancer in nude mice， the mechanism of which may be associated with reducing inflammatory response， inhibiting TLR4/MyD88/NF-κB signaling pathway， and promoting apoptosis in colorectal cancer cells.

Molecular networking-based discovery of anti-inflammatory chromene dimers from Melicope pteleifolia.

With the aid of a feature-based molecular networking strategy, five undescribed C2 and C1 symmetric chromene dimers, namely, melptelchromenes A-E, were isolated from the leaves of Melicope pteleifolia. Four asymmetric dimers were found to be racemates and were resolved by chiral phase HPLC analyses. Their structures, including absolute configurations, were elucidated by HRMS, NMR spectroscopy, and quantum mechanical calculations of ECD spectra and NMR chemical shifts. Melptelchromenes A-D possess a unique ethylidene linkage via two 2H-chromene cores, while melptelchromene E represents the first example of a dimeric chromene featuring a 1,3-diarylbutan-1-ol moiety. Of these compounds, 6,6'-linked dimeric chromenes showed nitric oxide inhibitory activities on lipopolysaccharide-induced RAW 264 cells, and (-)- and (+)-melptelchromene E were the two most potent compounds (IC50, 3.0 and 5.1 µM, respectively).

Three quinolinone alkaloid - phenylpropanoid adducts from Melicope pteleifolia.

Preliminary in vitro cytotoxic test on different extracts of Melicope pteleifolia collected at Dak Nong province, Vietnam showed that the n-hexane one was the most potent. From this n-hexane extract, three new quinolinone alkaloid-phenylpropanoid derivatives (1-3) and three known compounds (4-6) were isolated. Based on NMR and HR-MS analysis, their chemical structures were elucidated as melicoptines A-C (1-3), flindersine (4), 3,4,5-trimethoxybenzoic acid (5) and (24S)-methylcholestan-1α,3ß-diol (6). Isolated compounds (1-4) were evaluated for their anti-bacterial and cytotoxic activities against human non-small cell lung cancer (A549), human cervical cancer (HeLa), human Burkitt's lymphoma (Raji) and normal fibroblasts (NIH-3T3). All of them were inactive.

Pharmacological Properties of 2,4,6-Trihydroxy-3-Geranyl Acetophenone and the Underlying Signaling Pathways: Progress and Prospects.

2,4,6-Trihydroxy-3-geranyl acetophenone (tHGA) is a bioactive phloroglucinol compound found in Melicope pteleifolia (Champ. ex Benth.) T.G.Hartley, a medicinal plant vernacularly known as "tenggek burung". A variety of phytochemicals have been isolated from different parts of the plant including leaves, stems, and roots by using several extraction methods. Specifically, tHGA, a drug-like compound containing phloroglucinol structural core with acyl and geranyl group, has been identified in the methanolic extract of the young leaves. Due to its high nutritional and medicinal values, tHGA has been extensively studied by using various experimental models. These studies have successfully discovered various interesting pharmacological activities of tHGA such as anti-inflammatory, endothelial and epithelial barrier protective, anti-asthmatic, anti-allergic, and anti-cancer. More in-depth investigations later found that these activities were attributable to the modulatory actions exerted by tHGA on specific molecular targets. Despite these findings, the association between the mechanisms and signaling pathways underlying each pharmacological activity remains largely unknown. Also, little is known about the medicinal potentials of tHGA as a drug lead in the current pharmaceutical industry. Therefore, this mini review aims to summarize and relate the pharmacological activities of tHGA in terms of their respective mechanisms of action and signaling pathways in order to present a perspective into the overall modulatory actions exerted by tHGA. Besides that, this mini review will also pinpoint the unexplored potentials of this compound and provide some valuable insights into the potential applications of tHGA which may serve as a guide for the development of modern medication in the future.

The complete chloroplast genome of Melicope pteleifolia (Champ. ex Benth.) T. G. Hartley (Rutaceae).

Melicope pteleifolia, an important medicinal and horticultural plant, has antipyretic, anti-inflammatory, and analgesic effects. Here, the complete chloroplast genome of M. pteleifolia was sequenced and its phylogenetic relationship was investigated. The complete chloroplast genome of M. pteleifolia was 159,014 bp in size, including a pair of inverted repeat regions (IR, 27,640 bp), a large single copy region (LSC, 85,124 bp), and a small single copy region (SSC, 18,610 bp). The GC content of the chloroplast genome was 38.3%. A total of 133 genes were annotated, including 88 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. Phylogenetic analysis revealed that M. pteleifolia clusters together with species of Toddalia, Zanthoxylum, Tetradium, Phellodendron, and Casimiroa.

The third complete chloroplast genome of Melicope pteleifolia (Rutaceae): a widely used folk medicinal herb.

Melicope pteleifolia commonly known as thin evodia, is an herb used to therapy eczema, dermatitis, and other ailments in traditional Chinese medicine. Here, we reported the third complete chloroplast genome of M. pteleifolia based on next-generation sequencing. The third chloroplast genome of M. pteleifolia is 158,933 bp in length consisting of large and small single-copy regions of length 85,020 and 18,607 bp, separated by two IR regions of 27,683 bp. The overall GC content was 38.30%. De novo assembly and annotation showed the chloroplast genome of M. pteleifolia encodes 134 genes, including 89 protein-coding genes, 37 tRNA genes, and eight rRNA genes. A huge intraspecies variation was found with 248 SNPs and 97 INDELs among three assemblies of M. pteleifolia. Phylogenetic tree indicated that three assemblies of M. pteleifolia form a clade, sister to the genus Phellodendron and Casimiroa.

The phytochemistry, pharmacology and applications of Melicope pteleifolia: A review.

ETHNOPHARMACOLOGY RELEVANCE: The leaves, stems and roots of Melicope pteleifolia (Champ. ex Benth.) T.Hartley (MP; Rutaceae, called sanyaku in Chinese; syn.: Euodia lepta), have been used traditionally for the treatment of sore throat, rheumatism, eczema, dermatitis, bruises, and insect, rat, snake bites based on traditional Chinese medicine concepts. AIM OF THIS STUDY: This paper aims to provide a comprehensive and critical analysis of studies on MP and focusing on potential relationships between traditional uses and pharmacological effects, assessing the therapeutic potential as a medicine. MATERIALS AND METHODS: Relevant data on MP were retrieved using the keywords "Melicope pteleifolia", "pharmacology", "toxicity" and "applications" in databases including "Pubmed", "SciFinder", "Springer", "Elsevier", "Wiley", "Web of Science", "Google Scholar", "China Knowledge Resource Integrated databases (CNKI)", "PhD" and "MSc dissertations", and a hand-search. RESULTS AND DISCUSSION: The heat-clearing, dampness-removing and gallbladder-normalizing actions of MP have been linked to biomedical concepts like anti-inflammatory, antioxidant and hepatoprotective activities. The latter is potentially based on the presence of furaquinoline alkaloids, phenylpropanoids and flavonoids. Analgesic, antimicrobial and anti-tumor effects have also been reported. Currently limited evidence is available relating to potential toxicological risks especially of aqueous extracts with so far no reports signalling specific risks. Although some studies on the pharmacodynamics of MP have been reported, studies on action mechanisms of MP are still rare. CONCLUSIONS: In the future and prior to initiating clinical trials, the safety, in vitro and in vivo pharmacology, and mechanism of action of MP needs to be assessed, including a focus on the link between traditional uses and modern applications. In addition, phytochemical and biological studies need to conduct on flowers and fruits of MP. Furthermore, strict quality control measures are needed in the studies investigating any aspect of the pharmacology, chemistry and biology of MP.

Transcriptomic data analyses of Melicope pteleifolia via Illumina high-throughput sequencing technology / 中草药

Objective: To obtain the transcriptome sequence database of Melicope pteleifolia. Methods: The transcriptome sequencing and systematic bioinformatics analysis were carried out using the second generation high-throughput sequencing platform Illumina HiSeqTM 2000 with mixed root, stem and leaf samples of M. pteleifolia. Results: A total of 47 045 040 high quality sequences (clean reads) were obtained by transcriptome sequencing analysis. A total of 67 956 unigenes were assembled by Trinity de novo, with an average length of 787 nt. BLAST analysis showed that 42 749 (61.92%), 31 152 (45.84%), 26 563 (39.09%), and 17 481 (25.72%) unigenes were annotated in NR, Swiss port, KOG and KEGG databases respectively, and 47 groups were involved in three GO classification: biological process, cellular component and molecular function. A total of 9807 unigenes were annotated to 130 KEGG metabolic pathways, 19 secondary metabolic pathways were screened. Twenty-five different KOG functional groups were obtained by the analysis of KOG functional classification. It was predicted that there were 56 families of higher plant transcription factors. A total of 7 748 simple sequence repeats (SSRs) were found by MISA software. The number (4 117) of the tri-nucleotide SSRs was the richest, with a frequency of 53.1%, and the number of the penta-nucleotide SSRs was relatively small, accounting for 2.2%. Conclusion: The transcriptome information characteristics of root, stem, and leaf of M. pteleifolia can be obtained by high-throughput Illumina sequencing technology and bioinformatics analysis, which will lay a foundation for further research on functional gene mining, secondary metabolic pathway analysis and regulation mechanism of M. pteleifolia.

Pteleifolols A-E, acetophenone di-C-glycosides and a benzopyran dimer from the leaves of Melicope pteleifolia.

Four new acetophenone di-C-glycosides, pteleifolols A-D (1-4) and a new dimeric benzopyran, pteleifolol E (5), were isolated from the leaves of Melicope pteleifolia. Seven known compounds, including 2,4,6-trihydroxyacetophenone-3,5-di-C-glucopyranoside (6), were also isolated. Structures of the new compounds (1-5) were established by using spectroscopic and spectrometric techniques, including 1D and 2D nuclear magnetic resonance (NMR), UV, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) data. Pteleifolols A-D (1-4) were E-p-coumaroyl, Z-p-coumaroyl, E-feruloyl, and benzoyl esters of 6, respectively. Pteleifolol E (5) was a dichromene dimerized through a C2 unit.

Chemical constituents from Melicope pteleifolia leaves.

Five acetophenones bearing spiroketal-hexofuranoside rings, one di-C-glycosidic acetophenone and two benzopyrans, along with 16 known compounds were isolated from the leaves of Melicope pteleifolia. Structures of all the isolates were elucidated using extensive spectroscopic methods, including 1D, 2D-NMR and HRESIMS. All the isolates were also evaluated for their neuraminidase inhibitory activities against H1N1, H9N2, wild-type H1N1 and oseltamivir-resistant H1N1 (H274Y mutation) virus strains. Of the isolates, tamarixetin 3-robinobioside was found to exhibit the strongest enzymatic inhibition (IC50 24.93 ± 3.46, 23.19 ± 5.41, 26.67 ± 5.16 and 40.16 ± 4.50 µM, respectively). Selected candidates, kaempferol 3-robinobioside, kaempferol 3-O-ß-d-glucopyranosyl (1 â†’ 2)-α-d-xylopyranoside and tamarixetin 3-robinobioside, also showed moderate reductions in H1N1-induced cytopathic effects on MDCK cells.

Research progress in Melicope pteleifolia / 中草药

Melicope pteleifolia belongs to the family Rutaceae, Sect. Tetradium (Lour.) Engl. plants, which is widely distributed in Guangxi, Guangdong, Hainan, Jiangxi, Fujian, Guizhu, Yunnan, and other provinces. The main components are volatile oils and alkaloids. M. pteleifolia has been reported that it has antipyretic, analgesic, anti-inflammatory effects, and so on. In this paper, the investigation of documents, chemical components, and pharmacological effects is reviewed, which can provide a theoretical basis for further research of M. pteleifolia.

A New Phenylated Flavone from Melicope pteleifolia / 中草药·英文版

Objective To study the constituents in Melicope pteleifolia. Methods Plant material was isolated with 80% EtOH. Compounds were separated with chromatographic methods and their structures were elucidated on the basis of spectral analysis (EI-MS, 1H-NMR, and 13C-NMR) and chemical evidence. Results Five compounds were isolated from petrol ether or ethyl acetate soluble fraction. Their structures were identified as 3,5,3'-trihydroxy-4'-methoxy-7-(3-methylbut-2-enyloxy) flavone (pteleifolosin C, 1), 3,7-dimethoxyl kaempferol (kamatakenin, 2), vanillic acid (3), tricosanoic acid tetradecyl ester (4), and p-sitosterol (5), respectively. Conclusion Compound 1 is a new structure named pteleifolosin C. Compounds 2-4 are isolated from this plant for the first time.