New indolequinazoline alkaloids from the fruits of Tetradium ruticarpum.

In this research, five new indolequinazoline alkaloids (1-5), along with six known indolequinazoline alkaloids (6-11) were obtained from the fruits of Tetradium ruticarpum. Their structures were elucidated through comprehensive spectroscopic data of 1D and 2D NMR, HRESIMS and ECD spectra. Additionally, all isolates were assayed for their SIRT1 inhibitory activities in vitro and compounds 2, 7, 10 and 11 exhibited activities with IC50 values ranged from 43.16 to 118.35 µM.

Asiaticasics A-O, structurally intriguing coumarins from Toddalia asiatica with potential inflammatory inhibitory activity.

Ethyl acetate fraction of Toddalia asiatica was fractionated to yield fifteen previously undescribed prenylated coumarins, asiaticasics A-O (1-15) along with nine (16-24) known derivatives. The structures of these undescribed coumarins were established by spectroscopic analysis and reference data. Biological activity evaluation showed that compound 3 with the IC50 value of 2.830 µM and compound 12 with the IC50 value of 0.682 µM owned anti-inflammatory activity by detecting the rate of lactate dehydrogenase release in pyroptosis J774A.1 cells. The results showed that the expression of Caspase-1 and IL-1ß was decreased in a dose-dependent manner in the compound 12 treatment group, suggesting that compound 12 may reduce pyroptosis by inhibiting NLRP3 inflammasome. To further determine that compound 12 treatment can inhibit macrophage pyroptosis, morphological observation was performed and the results were consistent with the bioactivity evaluation.

Limonoids and alkaloids from Tetradium austrosinense (Hand.-Mazz.) T.G.Hartley.

A pair of new enantiomeric indolopyridoquinazoline-type alkaloids, (+)-1,7S,8R- and (-)-1,7R,8S-trihydroxyrutaecarpine (3a and 3b), and a new limonoid-tyrosamine hybrid, austrosinin (8), along with six known alkaloids and limonoids, were isolated from the stems with leaves of Tetradium austrosinense. Their structures were elucidated on the basis of analysis of MS, NMR, ECD and time-dependent density functional theory-based electronic circular dichroism (TDDFT-ECD) calculations, as well as proposed biosynthetic pathway. An anti-inflammatory bioassay in vitro showed 8 had significant immunosuppressive effect against the production of pro-inflammatory cytokine TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.

Phytochemistry and Biological Activities of Murraya Species.

Murraya is a plant genus within the Rutaceae family comprising over 17 species, which are widely distributed in Asia, Australia, and the Pacific Islands. Furthermore, these species have been used in traditional medicine to treat fever, pain, and dysentery. Several reports have also extensively studied the leaves, seeds, stembark, and bark of Murraya from 1965 to 2023 to explore their natural product composition. Various phytochemical studies have revealed the isolation of 413 compounds recorded, comprising coumarins, terpenoids, flavonoids, and aromatics, as well as alkaloids, which constitute the largest proportion (46.9%). These isolated compounds have long been known to exhibit different bioactivities, such as cytotoxic and anti-inflammatory properties. Cytotoxic activity has been observed against HCT 116, HeLa, HepG2, and other cell lines. Previous studies have also reported the presence of antifungal, hepatoprotective, antihyperlipidemic, antidiarrheal, and antioxidant effects. Therefore, this review provides a comprehensive overview of Murraya species, highlighting their phytochemistry, biological activities, and potential as a source of active natural compounds.

The complete chloroplast genome of Aegle marmelos and its phylogenetic analysis.

Aegle marmelos (L.) Correa 1800, a plant belonging to the Rutaceae family, is extensively used in Tibetan medicine. We employed Illumina HiSeq reads to assemble the complete chloroplast (cp) genome of A. marmelos, which spans 144,538 bp. The genome comprises 114 genes, including 75 protein-coding genes, 31 tRNA genes, and 8 rRNA genes. It is characterized by four regions: The large single-copy (LSC) region (74,253 bp), the inverted repeat A (IRa) region (26,015 bp), the small single-copy (SSC) region (18,255 bp), and the inverted repeat B (IRb) region (26,015 bp). Phylogenomic analysis demonstrated a close relationship between A. marmelos and Citrus. The assembly of The cp genome in this study serves as a foundation for conservation efforts and phylogenetic investigations of A. marmelos, paving the way for future experimentation.

B-seco Limonoids with anti-inflammatory activity from Tetradium fraxinifolium (Hook.) T.G.Hartley.

Fraxinifolines A-F (1-6), six new B-seco limonoids, together with four known A,D-di-seco ones, were isolated from the twigs with leaves of Tetradium fraxinifolium. Their structures with absolute configurations were elucidated on the basis of analysis of MS, NMR, single-crystal X-ray diffraction and biogenetic pathway. An anti-inflammatory bioassay in vitro showed limonoids 1-3 had significant immunosuppressive effect against the production of pro-inflammatory cytokines (IL-1ß and/or TNF-α) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.

Larvicidal constituents from Poncirus trifoliata root extracts.

In the search for effective and environmentally friendly mosquito control agents, we have examined natural sources, such as microbes and plants, and the synthetic analogs of natural products. These plants and microbes have evolved in their ecological niches to produce defensive compounds against other competing organisms in their surroundings such as microbes, plants, and insects as a means to enhance their survival. Thus, some of these plants and microbes have bioactive compounds with insecticidal, fungicidal, and phytotoxic activities. In our previous research, we successfully isolated bioactive constituents from natural sources. We have carried out synthetic modifications and total synthesis of marginally active isolated compounds to achieve significantly higher active compounds. We have focused on plants in the Rutaceae family as the members of this family are known to possess bioactive compounds with algicidal, antifungal, insecticidal, and fungicidal activities. In this article, we report the isolation and structure elucidation of mosquito larvicidal constituents from Poncirus trifoliata (Rutaceae) root extract.

Alkylamides from Zanthoxylum armatum DC. and their neuroprotective activity.

Zanthoxylum armatum DC. is an important medicinal plant, and its pericarps are commonly used as a natural spice in Asian countries. In this study, fifteen alkylamides were isolated and elucidated from the pericarps of Z. armatum, including five undescribed alkylamides (1-5) and ten known compounds (6-15). The molecular structures of all compounds were elucidated by 1D and 2D NMR spectroscopic analysis and mass spectrometry, among which the absolute configuration of compound 15 was determined by the Mo2(OAc)4-induced circular dichroism method. Moreover, all compounds were screened for their neuroprotective activity against H2O2-induced oxidative stress in human neuroblastoma SH-SY5Y cells for the evaluation of their neuroprotective activity. Especially, compounds 2-4 expressed potential neuroprotective activity, and further research showed that the cell viability was significantly enhanced in a concentration dependent manner when the cells were treated for 6 h. Moreover, compounds 2-4 could decrease reactive oxygen species accumulation. This paper enriched structure types of alkylamides in Zanthoxylum armatum.

A review of citrus plants as functional foods and dietary supplements for human health, with an emphasis on meta-analyses, clinical trials, and their chemical composition.

Fruits, flowers, leaves, essential oils, hydrosols, and juices of citrus spp. Are utilized to prepare various forms of food products. Along with their nutritional values, in the health industry, different parts of the plants of the citrus genus have been used as supplements or remedies to prevent or control diseases. This review focused on reported meta-analyses and clinical trials on the health benefits of citrus plants as functional foods. Also, chemical compounds of various citrus species were reviewed. The following information sources were used for data collection: Google Scholar, the Web of Science, Scopus, and PubMed. Various keywords, including "citrus AND chemical compounds," "citrus AND phytochemicals," "citrus species," "citrus AND meta-analysis," "nutritional and therapeutical values of citrus spp.," "clinical trials AND citrus," "clinical trials AND Rutaceae," "health benefits of citrus spp.," "citrus edible or non-edible applications," and scientific names of the citrus plants were utilized to collect data for the review. The scientific name and common name of all twenty-eight citrus species, along with any of the above keywords, were also searched in the mentioned databases. Scientific papers and data sources were sought to review and discuss the citrus plant's nutritional and therapeutic importance. Several meta-analyses and clinical trials have reported beneficial effects of citrus spices on a variety of cancer risks, cardiovascular risk factors, neurologic disorders, urinary tract conditions, and gastrointestinal tract conditions. They have shown anxiolytic, antimicrobial, and pain-alleviating effects. Some of them can be helpful in managing obesity and cardiovascular risk factors.

Coumarins from Rutaceae: Chemical diversity and biological activities.

Rutaceae is a family expressed by approximately 2100 species distributed in 154 genera widespread in tropical and temperate regions of Australasia, America, and South Africa. Substantial species of this family are employed as folk medicines. The literature describes the Rutaceae family as a great source of natural and bioactive compounds like terpenoids, flavonoids, and, especially, coumarins. To data, 655 coumarins were isolated and identified from Rutaceae in the past twelve years and, most of them, showed different biological and pharmacological activities. There are studies with coumarins from Rutaceae indicating that these compounds showed activity against cancer, inflammation, infectious diseases, and in the treatment of endocrinal and gastrointestinal conditions. Although coumarins are considered versatile bioactive molecules, until the present, there is no compiled information about coumarins from the Rutaceae family demonstrating the potency of these compounds in all dimensions and chemical similarities among the genera. The present review covers the relevant studies dealing with isolation of Rutaceae coumarins from 2010 until 2022 and outlines the current data on pharmacological activities these coumpounds. Additionally, the chemical disposition and similarity among Rutaceae genera are also statistically discussed employing PCA and HCA methods.

Structurally diverse sulphur-containing amides from Glycosmis craibii with their potential antiproliferative activities.

Fourteen new sulphur-containing amides, glycocramides A-N (1-14), as well as nine known analogues (15-23) were isolated and characterized from Glycosmis craibii Tanaka. The chemical structures of new sulphur-containing amides 1-14 were ambiguously elucidated by extensive spectroscopic methods, while the known compounds 15-23 were identified by the comparison of their experimental spectral data with those described data in the literatures. The antiproliferative effects of all isolated sulphur-containing amides were evaluated in vitro. As a result, part of sulphur-containing amides showed remarkable inhibitory effects against MGC-803 cell line with IC50 values ranging from 13.12 ± 0.10 to 20.03 ± 0.13 µM. These research results suggest that the sulphur-containing amides are potentially to be developed as a new natural anti-tumor drugs.

New flavone, and cytotoxicity activity of Rauia resinosa ethanolic extract and constituents.

The ethanolic extract from leaves of Rauia resinosa, Rutaceae, provided a new flavone, 5-hydroxy-5',6,7-trimethoxy-3',4'-methylenedioxyflavone (1), in addition to four known compounds: 3',4',5,5',7-pentamethoxyflavone (2), 5,7,8-trimethoxy-3'4'-methylenedioxyflavone (3), 3',4',5,7,8-pentamethoxyflavone (4) and ß-sitosterol (5). The structures of all compounds were established on the basis of spectroscopic methods, mainly 1D and 2D NMR, UPLC-DAD-MS and UPLC-ESI-MS/MS, involving comparison with literature data. Cytotoxicity of leaves and stems extracts, their fractions and compounds (2), (3), (4) and (5) were evaluated against T24 (bladder carcinoma), TOV-21-G (ovarian adenocarcinoma) and HepG2 (liver carcinoma) cell lines.

A new C-C linked benzophenathridine-2-quinoline dimer, and the antiplasmodial activity of alkaloids from Zanthoxylum holstzianum.

The CH2Cl2/MeOH (1:1) extract of Zanthoxylum holstzianum stem bark showed good antiplasmodial activity (IC50 2.5 ± 0.3 and 2.6 ± 0.3 µg/mL against the W2 and D6 strains of Plasmodium falciparum, respectively). From the extract five benzophenanthridine alkaloids [8-acetonyldihydrochelerythrine (1), nitidine (2), dihydrochelerythine (3), norchelerythrine (5), arnottianamide (8)]; a 2-quinolone alkaloid [N-methylflindersine (4)]; a lignan [4,4'-dihydroxy-3,3'-dimethoxylignan-9,9'-diyl diacetate (7)] and a dimer of a benzophenanthridine and 2-quinoline [holstzianoquinoline (6)] were isolated. The CH2Cl2/MeOH (1:1) extract of the root bark afforded 1, 3-6, 8, chelerythridimerine (9) and 9-demethyloxychelerythrine (10). Holstzianoquinoline (6) is new, and is the second dimer linked by a C-C bond of a benzophenanthridine and a 2-quinoline reported thus far. The compounds were identified based on spectroscopic evidence. Amongst five compounds (1-5) tested against two strains of P. falciparum, nitidine (IC50 0.11 ± 0.01 µg/mL against W2 and D6 strains) and norchelerythrine (IC50 value of 0.15 ± 0.01 µg/mL against D6 strain) were the most active.

Five Rutaceae family ethanol extracts alleviate H2O2 and LPS-induced inflammation via NF-κB and JAK-STAT3 pathway in HaCaT cells.

This study was designed to investigate the effects of five Rutaceae family ethanol extracts (FRFEE): Citrus medica Linn (CML), Citrus aurantium L. Cv. Daidai (CAD), Citrus medica Linn. var. sarcodactylis (Noot.) Swingle (CMS),Citrus sinensis L. Osbeck (CSO) and Zanthoxylum bungeanum Maxim (ZBM) on retarding the progression of H2O2 and LPS-induced HaCaT cells. Cell inflammatory injury model was established by H2O2 and LPS. The alleviative effects of FRFEE were evaluated by detecting the activity of superoxide dismutase (SOD), glutathione (GSH) and the generation of reactive oxygen species (ROS). The inflammatory signaling pathways of NF-κB and JAK-STAT3 were detected by Western blotting, the mRNA expression levels of inflammatory factors and skin barrier factors were detected by RT-PCR. 50% ethanol extracts of five medicinal and food homologous herbs of Rutaceae family showed different levels of anti-oxidant and anti-inflammatory activities. The FRFEE effectively improved SOD and GSH content and decreased ROS levels. Meanwhile, FRFEE strongly suppressed two inflammatory signaling pathways NF-κB and JAK-STAT3. The RT-PCR examination of inflammatory factors and skin barrier factor revealed significant anti-inflammatory effects of FRFEE. It was worth noting that among the five extracts, Zanthoxylum bungeanum Maxim extract had the best anti-inflammatory and anti-oxidation effects. In addition, it could strongly inhibit the expression of psoriasis factor CCL20. In summary, these results suggested that Zanthoxylum bungeanum Maxim extract could be used as an anti-psoriatic agent in the treatment of psoriasis among FRFEE.

Undescribed protolimonoids from the root bark of Dictamnus dasycarpus Turcz.

Nine undescribed protolimonoids, including two apotirucallane and seven tirucallane triterpenoids, as well as five known compounds, were isolated from the root bark of Dictamnus dasycarpus Turcz. Their structures were elucidated by extensive spectroscopic analysis. Compounds 4-8, with an undescribed 22,25-epoxytirucallene part, were established their absolute configuration by single-crystal X-ray diffraction of 4. Such compounds might provide evidence for the degradation of protolimonoids to limonoids, bridging an oxidative cleavage biogenetic pathway between these structurally diverse triterpenoids. None of them showed anti-inflammatory, hepatoprotective, or monoamine oxidase B inhibitory activity.

Acyl-Nω-methylserotonins and Branched-chain Acylserotonins in Lemon and Other Citrus Seeds-New Lipids with Antioxidant Properties and Potential Pharmacological Applications.

We have found 15 previously unknown compounds in seeds of lemon and other citrus species, such as tangerine, grapefruit and pomelo. The structure of these compounds was characterized by HR-MS spectrometry, fluorescence spectroscopy and chemical synthesis. These compounds were predominantly long-chain (C20-C25), saturated acyl-Nω-methylserotonins with the main contribution of C22 and C24 homologues, usually accounting for about 40% and 30% of all acylserotonins, respectively. The other, previously undescribed, minor compounds were branched-chain acylserotonins, as well as normal-chain acylserotonins, recently found in baobab seed oil. Within the seed, acylserotonins were found nearly exclusively in the inner seed coat, where probably their biosynthesis proceeds. On the other hand, lemon seedlings contained only trace amounts of these compounds that were not found in adult leaves. The compounds identified in the present studies were shown to have antioxidant properties in vitro, using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. In the investigated reaction in hexane, Me-C22 and Me-C24-serotonins were less active than n-C22 and n-C24-serotonins and δ-tocopherol, while branched-chain acylserotonins (iso-C21 and -C25) showed higher antioxidant activity than all the normal-chain compounds. On the other hand, all these compounds showed a similar but considerably lower antioxidant activity in acetonitrile than in hexane.

Chemical constituents from the roots of Zanthoxylum bungeanum Maxim. and their neuroprotective activities.

Twenty-two isolates, including two previously undescribed compounds identified as benzoyltembamide (1) and P-benzoyphenethyl anisate (21), were isolated and identified from a methanol extract of the roots of Zanthoxylum bungeanum Maxim. (Rutaceae) using diverse chromatographic materials and pre-HPLC. Their structures were elucidated on the basis of spectroscopic and spectrometric data analysis such as HR-ESI-MS, 1D and 2D NMR, IR and UV, as well as single-crystal X-ray diffraction for crystalline compounds. All the compounds (except for compound 16) were isolated from the roots of Z. bungeanum for the first time. Selected compounds were evaluated for their antioxidant activities. Compound 18 attenuated the H2O2-induced cytotoxicity and blocked the accumulation of ROS in SH-SY5Y cells, and exhibited potent neuroprotective activity.

Anti-inflammatory constituents from the stems and leaves of Glycosmis ovoidea Pierre.

Seven undescribed compounds, including four acridones, two coumarins, and a phenylpropanoid, together with 13 known acridone analogues were isolated from the ethanolic extract of the stems and leaves of Glycosmis ovoidea Pierre. Their structures were elucidated on the basis of comprehensive analysis of 1D and 2D NMR and HRESIMS spectroscopic data, and the absolute configurations were assigned by comparison of the experimental and calculated ECD data. Five compounds showed moderate inhibitory effects on nitric oxide production stimulated by lipopolysaccharide in BV-2 microglial cells with IC50 values in the range of 18.30-30.84 µM, and three compounds showed potent inhibition on 5-lipoxygenase (5-LOX) with IC50 values in the range of 2.08-10.26 µM. The possible binding sites of the active compounds with 5-LOX were further performed by molecular docking.

Cytotoxic constituents of Glycosmis ovoidea collected in Vietnam.

Compounds derived from natural sources have been major contributors to the area of cancer chemotherapy for decades. As part of an ongoing effort to discover anticancer drug leads from tropical plants, a large-scale collection of Glycosmis ovoidea Pierre (Rutaceae), was made at Nui Chua National Park, Vietnam. Activity-guided fractionation of the chloroform-soluble fractions led to the isolation of nine coumarins, including the new compound, 1-(7-methoxy-2-oxo-2H-chromen-8-yl)-3-methyl-1-oxobut-2-en-2-yl (S)-2-methylbutanoate (1). An close analogue of 1, namely, kincuongin (2), was deemed as non-cytotoxic (IC50 > 10 µM) against five different cancer cell lines. However, co-administration of kimcuongin (2) showed an approximately 100 times potentiation of the MCF-7 breast cancer cell cytotoxicity of the previously reported flavonoid, 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone (10). To provide a mechanistic basis for the cancer cell line inhibition enhancement observed, an initial in silico study on compound 10 indicated that it interacts with isoforms of the NF-κB complex. In a confirmatory western blot experiment conducted, kimcuongin (2) was found to potentiate the effects of flavone 10 in inhibiting both NF-κB and PARP-1. In vivo investigations using a zebrafish (Danio rerio) model showed that compounds 2, 3, 5, and 6 did not exhibit any discernible toxicity at concentrations up to 50 µM.

Chemical Constituents of the Stem Bark of the Hybrid Plant Citrus × paradisi Macfad. (Rutaceae).

The stem bark of Citrus × paradisi Macfad. (Rutaceae) gave (23S)-isolimonexic acid (1), limonin (2), citracridone II (3), citpressine II (4), citpressine I (5), grandisine (6), 2-hydroxynoracronycine (7), citracridone I (8), 5-methoxyseselin (9), umbelliferone (10), scopoletin (11), naringenin (12), apigenin (13), friedelin (14), agrostophyllinone (15) and stigmasterol-3-O-ß-D-glucopyranoside (16). The structures of the compounds were determined using NMR and MS spectroscopic data, and by comparison with published data. The relative configuration of 1 was proposed as (23S)-isolimonexic acid using NOE studies. Hydrogenation reaction of compound 3 led to the new derivative 3',4'-dihydrocitracridone II (3a). Cytotoxicity activities against the human adenocarcinoma alveolar basal epithelial cell lines A549 and the Caucasian prostate adenocarcinoma cell lines PC3, using the MTT assays showed that the methanol crude extract was significant with IC50 values of 30.1 and 31.7 µg/mL, respectively, with the positive control, doxorubicin giving an IC50 of 0.9 µM. In addition, compounds 3, 7 and 8 gave moderate cytotoxic activities with IC50 values of 33.1, 31.2 and 32.5 µM for A549 cells and 35.7, 33.8 and 34.9 µM for PC3 cells, respectively. The hydrogenated 3a was less active than 3, suggesting that the presence of the double bond in pyrans is important for structure-activity relationship.