Toonanoronoids A-E, five new limonoids from Toona ciliata var. yunnanensis.

Five new B-seco-limonoids, namely toonanoronoids A-E (1-5), in conjunction with three previously reported compounds, were isolated from the EtOAc extract of the twigs and leaves of Toona ciliata var. yunnanensis. Their structures were elucidated through comprehensive spectroscopic and X-ray crystallographic analysis. The cytotoxic activities of new compounds against five human tumor cell lines (HL-60, SMMC-7721, A549, MCF-7, and SW480) were screened, Compounds 4 and 5 exerted inhibition toward two tumor cell lines (HL-60, SW-480) with IC50 values between 1.7 and 5.9 µM.

Nimbolide: promising agent for prevention and treatment of chronic diseases (recent update).

Background: Nimbolide, a bioactive compound derived from the neem tree, has garnered attention as a potential breakthrough in the prevention and treatment of chronic diseases. Recent updates in research highlight its multifaceted pharmacological properties, demonstrating anti-inflammatory, antioxidant, and anticancer effects. With a rich history in traditional medicine, nimbolide efficacy in addressing the molecular complexities of conditions such as cardiovascular diseases, diabetes, and cancer positions it as a promising candidate for further exploration. As studies progress, the recent update underscores the growing optimism surrounding nimbolide as a valuable tool in the ongoing pursuit of innovative therapeutic strategies for chronic diseases. Methods: The comprehensive search of the literature was done until September 2020 on the MEDLINE, Embase, Scopus and Web of Knowledge databases. Results: Most studies have shown the Nimbolide is one of the most potent limonoids derived from the flowers and leaves of neem (Azadirachta indica), which is widely used to treat a variety of human diseases. In chronic diseases, nimbolide reported to modulate the key signaling pathways, such as Mitogen-activated protein kinases (MAPKs), Wingless-related integration site-ß (Wnt-ß)/catenin, NF-κB, PI3K/AKT, and signaling molecules, such as transforming growth factor (TGF-ß), Matrix metalloproteinases (MMPs), Vascular Endothelial Growth Factor (VEGF), inflammatory cytokines, and epithelial-mesenchymal transition (EMT) proteins. Nimbolide has anti-inflammatory, anti-microbial, and anti-cancer properties, which make it an intriguing compound for research. Nimbolide demonstrated therapeutic potential for osteoarthritis, rheumatoid arthritis, cardiovascular, inflammation and cancer. Conclusion: The current review mainly focused on understanding the molecular mechanisms underlying the therapecutic effects of nimbolide in chronic diseases.

Alliaxylines A-E: five new mexicanolides from the stem barks of Dysoxylum alliaceum (Blume) Blume ex A.Juss.

A total of five new mexicanolides (1-5), namely alliaxylines A-E, together with two known limonoids 6 and 7, were isolated and identified from Dysoxylum alliaceum (Blume) Blume ex. A.Juss. (Meliaceae). The structures of these compounds were elucidated based on extensive spectroscopic analyses, including HR-ESI-MS, UV, IR, 1D, and 2D NMR, as well as theoretical stimulation of NMR shifts with the DP4 + algorithm. Consequently, this study aimed to examine cytotoxic activities of these compounds against MCF-7 and A549 cell lines. The results implied that compound 2 was the most potent against the two tested cells, with IC50 values of 34.95 ± 0.21 and 44.39 ± 1.03 µM.

Ceramicines U-Z from Chisocheton ceramicus and structure-antimalarial activity relationship study.

Ceramicines are a series of limonoids which were isolated from the barks of Malaysian Chisocheton ceramicus (Meliaceae), and were known to show various biological activity. Six new limonoids, ceramicines U-Z (1-6), with a cyclopentanone[α]phenanthrene ring system with a ß-furyl ring at C-17 were isolated from the barks of C. ceramicus. Their structures were determined on the basis of the 1D and 2D NMR analyses, and their absolute configurations were investigated by CD spectroscopy. Ceramicine W (3) exhibited potent antimalarial activity against Plasmodium falciparum 3D7 strain with IC50 value of 1.2 µM. In addition, the structure-antimalarial activity relationship (SAR) of the ceramicines was investigated to identify substituent patterns that may enhance activity. It appears that ring B and the functional groups in the vicinity of rings B and C are critical for the antimalarial activity of the ceramicines. In particular, bulky ester substituents with equatorial orientation at C-7 and C-12 greatly increase the antimalarial activity.

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.

Erythrocarpines IN, new limonoids from the barks of Chisocheton erythrocarpus and their neuroprotective effects against hydrogen peroxide in NG108-15 cells.

A phytochemical study on the bark of Chisocheton erythrocarpus Hiern (Meliaceae) has led to the isolation of six new phragmalin-type limonoids named erythrocarpines I - N (1-6) along with one known limonoid, erythrocarpine F (7). Their structures were fully characterized by spectroscopic methods. The pre-treatment of NG108-15 cells with 1-5, 7 (2 h) demonstrated low to good protective effects against H2O2 exposure; 1 (83.77% ± 1.84 at 12.5 µM), 2 (69.07 ± 2.01 at 12.5 µM), 3 (80.38 ± 2.1 at 12.5 µM), 4 (62.33 ± 1.95 at 25 µM),5 (58.67 ± 1.85 at 50 µM) and 7 (66.07 ± 2.03 at 12.5 µM). Interestingly, 1 and 3 demonstrated comparable protective effects to positive control epigallocatechin gallate (EGCG) with similar cell viability capacity (≈ 80%), having achieved that at lower concentration (12.5 µM) than EGCG (50 µM). Collectively, the results suggested the promising use of 1 and 3 as potential neuroprotective agents against hydrogen peroxide-induced cytotoxicity in neuronal model.

Antiplasmodial and Antileishmanial Activities of a New Limonoid and Other Constituents from the Stem Bark of Khaya senegalensis.

Plasmodium falciparum and Leishmania sp. resistance to antiparasitic drugs has become a major concern in malaria and leishmaniasis control. These diseases are public health problems with significant socioeconomic impacts, and mostly affect disadvantaged populations living in remote tropical areas. This challenge emphasizes the need to search for new chemical scaffolds that preferably possess novel modes of action to contribute to antimalarial and antileishmanial research programs. This study aimed to investigate the antimalarial and antileishmanial properties of a methanol extract (KS-MeOH) of the stem bark of the Cameroonian medicinal plant Khaya senegalensis and its isolated compounds. The purification of KS-MeOH led to the isolation of a new ordered limonoid derivative, 21ß-hydroxybourjotinolone A (1a), together with 15 known compounds (1bc-14) using a repeated column chromatography. Compound 1a was obtained in an epimeric mixture of 21α-melianodiol (1b) and 21ß-melianodiol (1c). Structural characterization of the isolated compounds was achieved with HRMS, and 1D- and 2D-NMR analyses. The extracts and compounds were screened using pre-established in vitro methods against synchronized ring stage cultures of the multidrug-resistant Dd2 and chloroquine-sensitive/sulfadoxine-resistant 3D7 strains of Plasmodium falciparum and the promastigote form of Leishmania donovani (1S(MHOM/SD/62/1S). In addition, the samples were tested for cytotoxicity against RAW 264.7 macrophages. Positive controls consisted of artemisinin and chloroquine for P. falciparum, amphotericin B for L. donovani, and podophyllotoxin for cytotoxicity against RAW 264.7 cells. The extract and fractions exhibited moderate to potent antileishmanial activity with 50% inhibitory concentrations (IC50) ranging from 5.99 ± 0.77 to 2.68 ± 0.42 µg/mL, while compounds displayed IC50 values ranging from 81.73 ± 0.12 to 6.43 ± 0.06 µg/mL. They were weakly active against the chloroquine-sensitive/sulfadoxine-resistant Pf3D7 strain but highly potent toward the multidrug-resistant PfDd2 (extracts, IC50 2.50 ± 0.12 to 4.78 ± 0.36 µg/mL; compounds IC50 2.93 ± 0.02 to 50.97 ± 0.37 µg/mL) with selectivity indices greater than 10 (SIDd2 > 10) for the extract and fractions and most of the derived compounds. Of note, the limonoid mixture [21ß-hydroxylbourjotinolone A (1a) + 21α-melianodiol (1b) + 21ß-melianodiol (1c)] exhibited moderate activity against P. falciparum and L. donovani. This novel antiplasmodial and antileishmanial chemical scaffold qualifies as a promising starting point for further medicinal chemistry-driven development of a dually active agent against two major infectious diseases affecting humans in Africa.

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.

Antimalarial ceramicines Q-T from Chisocheton ceramicus.

Ceramicines are a series of limonoids that were isolated from the bark of Malaysian Chisocheton ceramicus (Meliaceae) and were known to show various biological activity. Four new limonoids, ceramicines Q-T (1-4) were isolated from the barks of C. ceramicus, and their structures were determined on the basis of the 1D and 2D NMR analyses in combination with calculated 13C chemical shift data. Ceramicines Q-T (1-4) were established to be new limonoids with a cyclopentanone[α]phenanthren ring system with a ß-furyl ring at C-17, and without a tetrahydrofuran ring like ceramicine B, which is characteristic of known ceramicines. Ceramicine R (2) exhibited potent antimalarial activity against Plasmodium falciparum 3D7 strain with IC50 value of 2.8 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.

Ultra-high performance liquid chromatography Q-Orbitrap MS/MS-based profiling and quantification of limonoids in Meliaceae plants.

Meliaceae plants have been extensively used in agriculture, folklore, and traditional medicine. They are the major storehouses for structurally diverse limonoids (meliacins) possessing various bioactivities like antifeedant, insecticidal, antimicrobial, etc. However accurate detection of these tetranortriterpenes from the vast pool of metabolites in plant tissue extracts or biological sample is a crucial challenge. Though the mass spectrum (MS) provides the molecular mass and the corresponding elemental composition, it cannot be relied precisely. The exact identification of a specific metabolite demands the MS/MS spectrum containing the signature product ions. In the present study, we have developed the UHPLC Q-Orbitrap-based method for identification, quantification, and characterization of limonoids in different plant tissue extracts requiring minimum plant material. Using this method, we carried out the limonoid profiling in different tissue extracts of sixteen Meliaceae plants and the identification of limonoids was performed by comparing the retention time (RT), ESI-( +)-MS spectrum, and HCD-MS/MS of the purified fifteen limonoids used as reference standards. Our results revealed that early intermediates of the limonoid biosynthetic pathway such as azadiradione, epoxyazadiradione, and gedunin occurred more commonly in Meliaceae plants. The MS/MS spectrum library of the fifteen limonoids generated in this study can be utilized for identification of these limonoids in other plant tissue extracts, botanical fertilizers, agrochemical formulations, and bio pesticides.

The Genus Walsura: A Rich Resource of Bioactive Limonoids, Triterpenoids, and Other Types of Compounds.

Medicinal plants of the genus Walsura (family Meliaceae) are native to tropical zones of a number of Asian countries, and have been used in systems of folk medicine. Several original research articles on Walsura species are available, but an overview highlighting the phytochemical and biological aspects of the compounds isolated to date is so far absent. Since the 1970s, phytochemical investigations on the genus Walsura have been undertaken, and more than 220 compounds from ten species have been identified. Natural products from Walsura species that have received the most attention are limonoids (114 compounds) and triterpenoids (72 compounds). Walsura limonoids have been characterized structurally as having diverse skeletons and more than 100 such compounds are new to the literature, while dammaranes, tirucallanes, and apotirucallanes are the main triterpenoid types from this genus. Other Walsura constituents comprise sesquiterpenoids, flavonoids, sterols, lignans, xanthones, and anthraquinones. Walsura species constituents have also been studied in natural product drug discovery screening programs. Many in vitro biological and some in vivo pharmacological investigations have been carried out on Walsura species isolated compounds. Walsura components display properties such as cancer cell cytotoxicity, antimicrobial, antidiabetes, anti-inflammatory, antioxidant, antifeedant, antifertility, ichthyotoxic, and neuroprotection activities.

Identification of limonoids from Walsura yunnanensis and evaluation of their cytotoxicity against cancer cell lines.

Three new limonoids, walsurauias A-C (1-3), along with four known ones, were isolated from the leaves and twigs of Walsura yunnanensis C. Y. Wu. Their structures were determined on the basis of comprehensive spectroscopic data analysis. The new limonoids were screened for their cytotoxic activity (IC50 0.81-5.73 µM) against four human cancer cell lines, including A549, HepG2, HCT116 p21KO and CNE-2. And α,ß-unsaturated ketone moieties in rings A and B are essential for their cytotoxic activity. Selected compounds were further investigated. Compounds 1-3 effectively induced G2/M cell cycle arrest and apoptosis in a dose-dependent manner in cancer cells. In addition, compounds 1-3 inhibited the colony formation and compounds 2 and 3 suppressed the migration of cancer cells.

Walsogynes H-O from Walsura chrysogyne.

Eight new limonoids, walsogynes H-O (1-8) were isolated from the barks of Walsura chrysogyne, and their structures were determined on the basis of the 1D and 2D NMR data. Walsogynes H-M (1-6) and O (8) were concluded to be 11,12-seco limonoids with a dodecahydro-1H-naphtho[1,8-bc:3,4-c']difuran skeleton, and walsogyne N (7) to be 11,12-seco limonoid sharing a unique dodecahydronaphtho[1,8-bc:5,4-b'c']difuran skeleton. Walsogynes H-O (1-8) exhibited potent antimalarial activity against Plasmodium falciparum 3D7 strain with IC50 value of 2.5, 2.6, 1.6, 2.5, 1.5, 2.6, 2.1, and 1.1 µM, respectively.

Insecticidal and Feeding Deterrent Effects of Kaempferia galanga L. and Amomum subulatum on Pieris rapae L. Larva.

<b>Background and Objective:</b> <i>Pieris rapae</i> L., is one of the most widespread and destructive pests of cruciferous plants. At present, synthetic chemical insecticide is still the main approach to control this pest despite several disadvantages to human health and the wildlife environment as well as biological resistance. To search for plants having insecticidal activity, the biological effects of two medicinal plants <i>Kaempferia galanga</i> L. and <i>Amomum subulatum </i>on <i>Pieris rapae</i> L., were investigated. <b>Materials and Methods:</b> The methanol extracts of dry rhizomes and fruits of <i>Kaempferia galanga</i> L. and <i>Amomum subulatum </i>were used to determine the mortality, feeding and oviposition deterrence of larvae and adult of <i>Pieris rapae</i> L. <b>Results:</b> <i>Kaempferia galanga</i> L. and <i>Amomum subulatum</i> exhibited insecticidal activity against <i>Pieris rapae</i> L., with LC₅₀ values of 2.11 and 11.80% (w/v), respectively. In the antifeedant test, <i>Kaempferia galanga</i> L., extract showed no significant difference with the control at the low concentration (0.5 and 1%). Whereas, with a concentration of 0.5%, <i>Amomum subulatum</i> extract demonstrated a high antifeedant effect on <i>Pieris rapae</i> L., larvae. In addition, plants treated with these two extracts reduced eggs laid by <i>Pieris rapae</i> L., in field conditions showing the oviposition deterrent properties. <b>Conclusion:</b> These results indicated that <i>Kaempferia galanga</i> L. and <i>Amomum subulatum </i>extracts have insecticidal substances against <i>Pieris rapae </i>L., which can be used for developing effective pesticides or/and oviposition deterrents for integrated pest management.

Contribution of Meliaceous plants in furnishing lead compounds for antiplasmodial and insecticidal drug development.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria remains one of the greatest threats to human life especially in the tropical and sub-tropical regions where it claims hundreds of thousands of lives of young children every year. Meliaceae represent a large family of trees and shrubs, which are widely used in African traditional medicine for the treatment of several ailments including fever due to malaria. The in vitro and in vivo antiplasmodial as well as insecticidal investigations of their extracts or isolated compounds have led to promising results but to the best of our knowledge, no specific review on the traditional uses, phytochemistry of the antiplasmodial, insecticidal and cytotoxic lead compounds and extracts of Meliaceae plants has been compiled. AIMS: To review the literature up to 2021 on the Meliaceae family with antiplasmodial, insecticidal and cytotoxic activity. MATERIALS AND METHODS: A number of online libraries including PubMed, Scifinder, Google Scholar and Web of Science were used in searching for information on antiplasmodial metabolites from Meliaceous plants. The keywords Meliaceae, malaria, Plasmodium, Anopheles and antiplasmodial were used to monitor and refine our search without language restriction. RESULTS: The phytochemical investigations of genera of the family Meliaceae led to the isolation and characterization of a wide range of structural diversity of compounds, 124 of which have been evaluated for their antiplasmodial potency against 11 chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum strains. A total of 45 compounds were reported with promising insecticidal potentials against two efficient vector species, Anopheles stephensi Liston and A. gambiae Giles. Limonoids were the most abundant (51.6%) reported compounds and they exhibited the most promising antiplasmodial activity such as gedunin (3) which demonstrated an activity equal to quinine or azadirachtin (1) displaying promising larvicidal, pupicidal and adulticidal effects on different larval instars of A. stephensi with almost 100% larval mortality at 1 ppm concentration. CONCLUSION: Studies performed so far on Meliaceae plants have reported compounds with significant antiplasmodial and insecticidal activity, lending support to the use of species of this family in folk medicine, for the treatment of malaria. Moreover, results qualified several of these species as important sources of compounds for the development of eco-friendly pesticides to control mosquito vectors. However, more in vitro, in vivo and full ADMET studies are still required to provide additional data that could guide in developing novel drugs and insecticides.

Bioassay-guided isolation of vilasinin-type limonoids and phenyl alkene from the leaves of Trichilia gilgiana and their antiplasmodial activities.

Bioassay-guided fractionation of the CH2Cl2-MeOH (1:1) leaves extract of Trichilia gilgiana, yielded two new vilasinin-type limonoids named gilgianin A (1) and gilgianin B (2), one new phenyl alkene derivative designated as gilgialkene A (3), along with six known compounds: rubescin H (4), TS3 (5), trichirubine A (6), sitosteryl-6'-O-undecanoate-ß-D-glucoside (7), scopoletin (8), and octadecane-2-one (9). Their structures were elucidated based on spectroscopic analysis and comparison with literature data. Compounds 5 and 6 exhibited the highest antiplasmodial activity with IC50 values of 1.14 and 1.32 µM respectively. Moreover, compound 5 was very cytotoxic with CC50 value of 0.88 µM, compared to compound 6, which was not cytotoxic (CC50 > 10 µg/mL). Compounds 1 (IC50 = 9.84 µM), 2 (IC50 = 11.04 µM) and 4 (IC50 = 10.71 µM) presented good antiplasmodial activity while also exhibiting significant cytotoxicity, with CC50 values ranging from of 14.45 to 29.7 µM.[Formula: see text].

Exploring the therapeutic nature of limonoids and triterpenoids against SARS-CoV-2 by targeting nsp13, nsp14, and nsp15 through molecular docking and dynamics simulations.

BACKGROUND AND AIM: The ongoing global pandemic due to SARS-CoV-2 caused a medical emergency. Since December 2019, the COVID-19 disease is spread across the globe through physical contact and respiratory droplets. Coronavirus caused a severe effect on the human immune system where some of the non-structural proteins (nsp) are involved in virus-mediated immune response and pathogenesis. To suppress the viral RNA replication mechanism and immune-mediated responses, we aimed to identify limonoids and triterpenoids as antagonists by targeting helicases (nsp13), exonuclease (nsp14), and endoribonuclease (nsp15) of SARS-CoV-2 as therapeutic proteins. EXPERIMENTAL PROCEDURE: In silico molecular docking and drug-likeness of a library of 369 phytochemicals from limonoids and triterpenoids were performed to screen the potential hits that binds effectively at the active site of the proteins target. In addition, the molecular dynamics simulations of the proteins and their complexes with the potential hits were performed for 100 ns by using GROMACS. RESULTS AND CONCLUSION: The potential compounds 26-deoxyactein and 25-O-anhydrocimigenol 3-O-beta-d-xylopyranoside posing strong interactions with a minimum binding energy of -10.1 and -9.5 kcal/mol, respectively and sustained close contact with nsp13 for 100 ns. The nsp14 replication fork activity was hindered by the tomentosolic acid, timosaponin A-I, and shizukaol A with the binding affinity score of -9.2, -9.2, and -9.0 kcal/mol, respectively. The nsp15 endoribonuclease catalytic residues were inhibited potentially by limonin, 25-O-anhydrocimigenol 3-O-alpha-l-arabinopyranoside, and asperagenin posing strong binding affinity scores of -9.0, -8.8, and -8.7 kcal/mol, respectively. Computationally predicted potential phytochemicals for SARS-CoV-2 are known to possess various medicinal properties.

Limonoids and unsaturated fatty acids present in Melia toosendan increase ceramide production in keratinocytes.

The skin barrier prevents moisture evaporation and the entry of foreign substances such as allergens. Ceramides are one of the most important factors for maintaining skin barrier function. Melia toosendan is a plant of the Meliaceae family, and its fruit extracts have been used in Traditional Chinese Medicine as analgesics and anthelmintics; however, its ability to increase ceramide levels has not been reported. In this study, we screened for compounds present in M. toosendan fruit extracts that increase ceramide levels in the skin. We fractionated the extracts based on their activity to identify the active components. Nimbolinins, limonoids such as toosendanin, and hydroxylated unsaturated fatty acids were found to be the major active components. The structure-activity relationship of toosendanin derivatives indicated that the sites around R4 and R5 contributed to the activity. To the best of our knowledge, this is the first report showing that limonoids promote ceramide production in skin cells. Therefore, M. toosendan fruit extracts may be used to develop products for improving the skin barrier function.

Evaluation of Pomelo Seed Extracts as Natural Antioxidant, Antibacterial, Herbicidal Agents, and Their Functional Components.

Pomelo seeds (PS) are important by-product of pomelo fruits (Citrus grandis Osbeck). The value-added utilization of PS remains highly challenged. This study aimed to investigate the utilization potential of PS as natural antioxidant, antibacterial, herbicidal agents, and their functional components. The ethanolic extract (EE) of PS and its four fractions as PEE (petroleum ether extract), AcOEtE (ethyl acetate extract), BTE (butanol extract), and WE (water extract), were prepared and biologically evaluated. BTE exhibited the best antioxidant activity among all these extracts, in both ABTS (2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) and FRAP (ferric reducing antioxidant power) assays. AcOEtE was superior to other extracts in herbicidal assay against both Festuca elata Keng (IC50 of 0.48 mg mL-1 ) and Amaranthus retroflexus L. (IC50 of 0.94 mg mL-1 ). Meanwhile, both AcOEtE and BTE demonstrated inhibitory effects against Bacillus subtilis, Escherichia coli, and Xanthomonas citri subsp. citri, with MIC ranging 2.5-5.0 mg mL-1 . Furthermore, the primary chemical components involving naringin, deacetylnomilin, limonin, nomilin, and obacunone, were quantified in all these extracts. PCA (principal component analysis) suggested that naringin might highly contribute to the antioxidant activity of PS, and the herbicidal activity should be ascribed to limonoids. This study successfully identified AcOEtE and BTE as naturally occurring antioxidant, antibacterial, and herbicidal agents, showing application potential in food and cosmetics industries, and organic farming agriculture.