Search Results (121)

Toona sinensis (“Heiyouchun”) is a traditional Chinese woody vegetable, the leaves of which can also be processed into tea, known for its distinctive flavor and diverse bioactivities. However, the effects of leaf maturity and processing methods on its phytochemical composition and functional properties remain unclear. In this study, metabolomic analysis revealed 35 significantly different metabolites between tender and mature leaves, with higher concentrations of flavonoids, flavonoid glycosides, limonoids, and amino acids in tender leaves. Additionally, comparative analysis revealed that black tea fermentation preserves bioactive compounds more effectively than hot-air drying, particularly in tender leaves. In vitro activity assays showed that toon leaf tea extracts exhibited significant antioxidant and hypoglycemic effects, with black tea fermented tender leaves displaying the most potent bioactivity. Correlation analysis further confirmed a strong positive relationship between flavonoid/polyphenol content and bioactivity. These findings provide a theoretical foundation for optimizing processing techniques to enhance the functional properties of toon leaf tea. Full article

In normal conditions, neuroinflammation induces microglia and astrocyte activation to maintain brain homeostasis. However, excessive or prolonged neuroinflammation can inflict harmful damage on brain tissue. Numerous factors can trigger chronic neuroinflammation, ultimately leading to neurodegeneration. In this context, considering the pressing need for novel, natural approaches to mitigate neuroinflammatory damage, attention has turned to unconventional sources such as agricultural by-products. Citrus fruits are widely consumed globally, producing substantial waste, including peels, seeds, and pulp. Traditionally regarded as agricultural waste, these by-products are now recognized as valuable reservoirs of bioactive compounds, including flavonoids, carotenoids, terpenoids, and limonoids. Among these, citrus polyphenols—particularly flavanones like hesperidin, naringenin, and eriocitrin—have emerged as potent modulators of neuroinflammatory pathways through their multifaceted interactions with cellular antioxidant systems, pro-inflammatory signaling cascades, neurovascular integrity, and gut–brain axis dynamics. This review aims to characterize the key molecules present in citrus waste and synthesizes preclinical and clinical evidence to elucidate the biochemical mechanisms underlying neuroinflammation in neurodegenerative disorders. Full article

This study investigated the lethal and transgenerational effects of botanical and synthetic insecticides on the egg parasitoid Trichogramma atopovirilia, an important natural enemy of Spodoptera frugiperda in Brazil and beyond. The treatments were assessed for their impact on parasitism, emergence, sex ratio, and flight capacity of adults exposed to contaminated eggs. The botanical insecticide ESAM (ethanolic seed extract of Annona mucosa) significantly reduced the parasitism in the F₀ generation by 99.76%, categorizing it as toxic. Anosom^® [acetogenins (annonin as a major component)] and Azamax^® [limonoids (azadirachtin + 3-tigloilazadirachtol)] also caused substantial reductions (99.13% and 92.36%, respectively) in the parasitism rate. EFAMON (ethanolic leaf extract of Annona montana) reduced the parasitism by 62%, while the synthetic insecticide Premio^® (chlorantraniliprole) resulted in a 28.21% reduction. In the F₁ generation, emergence rates for EFAMON, Azamax^®, and Premio^® exceeded 70%, showing no significant differences from the negative control (82%), while Anosom^® resulted in a lower emergence rate of 61.39%. No significant effects were observed on sex ratio or parasitism in the F₁ and F₂ generations. Most adults reached high flight capacity (above 80%). These results indicate that while ESAM was toxic, the other treatments showed no transgenerational effects. Our findings contribute to understanding insecticide selectivity and highlight the importance of such studies for the sustainable management of S. frugiperda within integrated pest management programs. Full article

Conditions like diabetes mellitus (DM), cancer, infections, inflammation, cardiovascular diseases (CVDs), and gastrointestinal (GI) disorders continue to have a major global impact on mortality and morbidity. Medicinal plants have been used since ancient times in ethnomedicine (e.g., Ayurveda, Unani, Traditional Chinese Medicine, and European Traditional Medicine) for the treatment of a wide range of disorders. Plants are a rich source of diverse phytoconstituents with antidiabetic, anticancer, antimicrobial, antihypertensive, antioxidant, antihyperlipidemic, cardioprotective, immunomodulatory, and/or anti-inflammatory activities. This review focuses on the 35 plants most commonly reported for the treatment of these major disorders, with a particular emphasis on their traditional uses, phytoconstituent contents, pharmacological properties, and modes of action. Active phytomolecules with therapeutic potential include cucurbitane triterpenoids, diosgenin, and limonoids (azadiradione and gedunin), which exhibit antidiabetic properties, with cucurbitane triterpenoids specifically activating Glucose Transporter Type 4 (GLUT4) translocation. Capsaicin and curcumin demonstrate anticancer activity by deactivating NF-κB and arresting the cell cycle in the G2 phase. Antimicrobial activities have been observed for piperine, reserpine, berberine, dictamnine, chelerythrine, and allitridin, with the latter two triggering bacterial cell lysis. Quercetin, catechin, and genistein exhibit anti-inflammatory properties, with genistein specifically suppressing CD8+ cytotoxic T cell function. Ginsenoside Rg1 and ginsenoside Rg3 demonstrate potential for treating cardiovascular diseases, with ginsenoside Rg1 activating PPARα promoter, and the PI3K/Akt pathway. In contrast, ternatin, tannins, and quercitrin exhibit potential in gastrointestinal disorders, with quercitrin regulating arachidonic acid metabolism by suppressing cyclooxygenase (COX) and lipoxygenase activity. Further studies are warranted to fully investigate the clinical therapeutic benefits of these plants and their phytoconstituents, as well as to elucidate their underlying molecular mechanisms of action. Full article

Background/Objectives: Cutibacterium acnes (C. acnes), a bacterium residing in hair follicles, triggers acne by inducing monocyte-mediated inflammatory cytokine production. Gedunin, a limonoid derived from Azadirachta indica (commonly known as neem), is renowned for its antifungal, antimalarial, anticancer, anti-inflammatory, and neuroprotective effects. However, its role in mitigating C. acnes-induced skin inflammation remains unexplored. This study investigates the anti-inflammatory effects of gedunin on C. acnes-induced skin inflammation and elucidates the underlying mechanisms. Methods: The anti-inflammatory activity of gedunin was assessed using RAW 264.7 mouse macrophage cells and mouse bone-marrow-derived macrophages (BMDMs). Key inflammatory mediators, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and interleukin-6 (IL-6), were evaluated. Mechanistic studies focused on the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, along with the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. An in vivo acne model was employed to examine gedunin’s therapeutic efficacy. Results: Gedunin significantly reduced the expression of IL-1β, TNF-α, iNOS, COX-2, and IL-6 in RAW 264.7 cells. It inhibited NF-κB activation without affecting the MAPK pathways, including JNK/SAPK, ERK, and p38 MAPK. Gedunin also suppressed the activation of the NLRP3 inflammasome in BMDMs. In the mouse acne model, gedunin effectively alleviated C. acnes-induced inflammation, primarily by targeting NF-κB signaling. Conclusions: Gedunin demonstrates potential as a therapeutic agent for acne treatment by targeting key inflammatory pathways, particularly NF-κB signaling. This study highlights gedunin’s promise as an alternative approach to managing C. acnes-induced skin inflammation. Full article

Agro-industrial residues have transitions from being an environmental problem to being a cost-effective source of biopolymers and value-added chemicals. However, the efficient extraction of the desired products from these residues requires pretreatments. Fungal biorefinery is a fascinating approach for the biotransformation of raw materials into multiple products in a single batch. In this study, the ability of Trichoderma asperellum R to convert fruit scrap and green waste into value-added chemicals was tested in solid-state and in nonsterile conditions. A solid-state fermentation protocol for a tray bioreactor was developed using spawn as the inoculum for nonsterile substrates. T. asperellum R drove the fermentation of both substrates, shaping the metabolites that were enriched in the secondary plant metabolites. Strain R showed cellulase activity only when inoculated on fruit scraps, resulting in increased amounts of polysaccharides in the crude extract. This extract was also enriched in vanillic acid and limonoid, which are intriguing compounds due to the increasing interest in their potential as biological nitrification inhibitors or food additives. Finally, trimethoxybenzaldehyde, an interesting chemical building block, was identified in the extracts of the Trichoderma-guided fermentation. The overall results showed that the application of T. asperellum R has potential as a driver to facilitate the extraction of bioactive substances from nonsterile recalcitrant substrates. Full article

Phytochemical investigations of Melia azedarach fruits have led to the isolation of a novel tirucallane triterpenoid (1), four new limonoids (2–5), and four known limonoids (6–9). Their structures were clarified by comprehensive spectroscopic and spectrometric analyses. The anti-inflammatory activities of isolated compounds were assessed in vitro. Compound 2 exhibited the most potent anti-inflammatory effect, with an IC₅₀ value of 22.04 μM. Additionally, compound 2 attenuated LPS-induced reactive oxygen species (ROS) production and reduced the levels of inflammatory mediators IL-6 and TNF-α. A mechanistic study revealed that limonoid 2 suppresses the expression of iNOS and JAK2 and is implicated in the modulation of the NF-κB signaling cascade, which reveals its anti-inflammatory actions. Full article

Malaria remains one of the great killers in tropical regions of the world due to the transmission of the Plasmodium parasite by the bites of the female mosquito Anopheles. The resistance of this species to synthetic insecticides contributes to an increase in the incidence of malaria and therefore necessitates the development of new potent and eco-friendly insecticides. In this study, twelve previously reported limonoids from four Entandrophragma species collected in Cameroon have been computationally evaluated for their Anopheles gambiae AChE inhibitory activity. The docking procedure was carried out through Molecular Operating Environment 2019.01 (MOE), while the UCSF Chimera program was used to model the docking results based on interactions between proteins and ligands, and molecular dynamics trajectories were analyzed using the GROMACS 2021.1 tool. Entandrophragmin and encandollens B and C with docking scores ranging from −6.45 to −7.28 kcal/mol were the most promising hits compared to the reference azadirachtin (−6.22 kcal/mol) and were further evaluated for their mechanism of action. Subsequent evaluation classified encandollen C as the best candidate for the development of new potent eco-friendly insecticides based on its lower average RMSD and RMSF and its compactness over a 150 ns duration with acetylcholinesterase. Full article

Citrus fruits are widely grown, processed, and distributed in more than 140 countries, with annual global production exceeding 124.3 million metric tons. This substantial consumption generates significant organic waste, accounting for approximately 50–60% of the total fruit mass, primarily in the form of peel, pulp, and seeds. Often discarded or reused as animal feed, these wastes contribute to significant environmental pollution and economic losses. Therefore, the valorization of these by-products represents an important opportunity to mitigate these challenges and improve the sustainability of the Citrus-related industry. This review highlights Citrus seed waste concerning its invaluable bioactive compounds, including fatty acids, phenolic compounds, limonoids, dietary fibers, vitamins, and carotenoids. Chemical compositions of Citrus seed biowaste differ depending on a variety of factors, such as Citrus variety, fruit maturity, environmental conditions, waste storage conditions, and extraction methods. The extraction and purification of phytochemicals from Citrus seed biowaste are one of the major procedures for valorizing waste. The two types of effective extraction methods are traditional (conventional extraction) and innovative (green extraction). Furthermore, Citrus seeds have been demonstrated to exhibit several biological activities and health-promoting properties including antioxidative, anti-inflammatory, and anti-cancer activities. Therefore, these wastes are safe and beneficial compounds used in the production of functional foods, nutraceuticals, pharmaceuticals, and cosmetics. A conclusion can be reached by emphasizing the abundance of bioactive compounds in Citrus seed wastes, which makes them an excellent opportunity for increased environmental and economic utilization. Full article

Swietenia macrophylla fruit is a valuable and historically significant medicinal plant with anti-hypertension and anti-diabetes. We identified a toxic component, Febrifugin, from the edible part of the nut following zebrafish toxicity-guided isolation. Febrifugin is a mexicanolide-type limonoid compound. The toxic factor induced acute toxicity in zebrafish, including yolk sac edema and pericardial edema, reduced body length, decreased melanin deposition, and presented acute skeletal developmental issues. Further exploration of the acute toxicity mechanism through metabolomics revealed that Febrifugin caused significant changes in 13 metabolites in zebrafish larvae, which are involved in the pentose phosphate, tricarboxylic acid (TCA) cycle, and amino acid biosynthesis. The bioassay of oxidative stress capacity and qRT-PCR measurement showed that the compound significantly affected the h6pd gene in the pentose phosphate pathway and the mRNA expression of cs, idh3a, fh, and shda genes in the TCA cycle, leading to reactive oxygen species (ROS) accumulation and a notable decrease in glutathione (GSH) activity in zebrafish. These findings provide a basis for the rational use of S. macrophylla as a medicinal plant and raise awareness of the safety of medicinal plants. Full article

Plants of the Meliaceae family have long attracted researchers’ interest due to their various insecticidal activities, with triterpenes being the main active ingredients. In this paper, we discuss 93 triterpenoids with insecticidal activity from 37 insecticidal plant species of 15 genera (Munronia, Neobeguea, Pseudocedrela, Nymania, Quivisia, Ruagea, Dysoxylum, Soymida, Lansium, Sandoricum, Walsura, Trichilia, Swietenia, Turraea, and Xylocarpus) in the family Meliaceae. Among these genera, Trichilia deserves further research, with twelve species possessing insecticidal activity. The 93 insecticidal molecules included 27 ring-seco limonoids (comprising 1 ring A-seco group chemical, 1 ring B-seco group chemical, 5 ring D-seco group chemicals, 14 rings A,B-seco group chemicals, 5 rings B,D-seco group chemicals, and 1 rings A,B,D-seco group chemical), 22 ring-intact limonoids (comprising 5 cedrelone-class chemicals, 6 trichilin-class chemicals, 7 havanensin-class chemicals, 2 azadirone-class chemicals, 1 vilasinin-class chemical, and 1 other chemical), 33 2,30-linkage chemicals (comprising 25 mexicanolide-class chemicals and 8 phragmalin-class chemicals), 3 1,n-linkage-group chemicals, 3 onoceranoid-type triterpenoids, 2 apotirucallane-type terpenoids, 2 kokosanolide-type tetranortriterpenoids, and 1 cycloartane triterpene. In particular, 59 molecules showed antifeedant activity, 30 molecules exhibited poisonous effects, and 9 molecules possessed growth regulatory activity. Particularly, khayasin, beddomei lactone, 3β,24,25-trihydroxycycloartane, humilinolides A–E and methyl-2-hydroxy-3β-isobutyroxy-1-oxomeliac-8(30)-enate showed excellent insecticidal activities, which were comparable to that of azadirachtin and thus deserved more attention. Moreover, it was noteworthy that various chemicals (such as 12α-diacetoxywalsuranolide, 11β,12α-diacetoxycedrelone, 1α,7α,12α-triacetoxy-4α-carbomethoxy-11β-hydroxy-14β,15β-epoxyhavanensin, and 11-epi-21-hydroxytoonacilide, etc.) from Turraea showed excellent insecticidal activity. Specially, the insecticidal activity of khayasin from Neobeguea against the coconut leaf beetle were similar to that of rotenone. Therefore, it was a promising candidate insecticide for the control of the coconut leaf beetle. Full article

Obacunone, a natural triterpenoid, is an active component of the herbs Dictamnus dasycarpus Turcz. and Phellodendron amurense Rupr, and an indicator of the herbs’ quality. Owing to its multiple health benefits, several studies have investigated the multi-targeting potential action mechanisms of obacunone. To summarize recent developments on the pharmacological actions of obacunone and focus on the underlying molecular mechanisms and signaling networks, we searched PubMed, Europe PMC, Wiley Online Library, Web of Science, Google Scholar, Wanfang Medical Network, and China National Knowledge Infrastructure for articles published prior to March 2024. Existing research indicates obacunone has great potential to become a promising therapeutic option against tumors, fibrotic diseases, bone and cholesterol metabolism diseases, and infections of pathogenic microorganisms, among others. The paper contributes to providing up-to-date references for further research and clinical applications of obacunone. Full article

The insecticidal property of ring C-seco limonoids has been discovered empirically and the target protein identified, but, to date, the molecular mechanism of action has not been described at the atomic scale. We elucidate on computational grounds whether nine C-seco limonoids present sufficiently high affinity to bind specifically with the putative target enzyme of the insects (ecdysone 20-monooxygenase). To this end, 3D models of ligands and the receptor target were generated and their interaction energies estimated by docking simulations. As a proof of concept, the tetrahydro-isoquinolinyl propenamide derivative QHC is the reference ligand bound to aldosterone synthase in the complex with PDB entry 4ZGX. It served as the 3D template for target modeling via homology. QHC was successfully docked back to its crystal pose in a one-digit nanomolar range. The reported experimental binding affinities span over the nanomolar to lower micromolar range. All nine limonoids were found with strong affinities in the range of −9 < ΔG < −13 kcal/mol. The molt hormone ecdysone showed a comparable ΔG energy of −12 kcal/mol, whereas −11 kcal/mol was the back docking result for the liganded crystal 4ZGX. In conclusion, the nine C-seco limonoids were strong binders on theoretical grounds in an activity range between a ten-fold lower to a ten-fold higher concentration level than insecticide ecdysone with its known target receptor. The comparable or even stronger binding hints at ecdysone 20-monooxygenase as their target biomolecule. Our assumption, however, is in need of future experimental confirmation before conclusions with certainty can be drawn about the true molecular mechanism of action for the C-seco limonoids under scrutiny. Full article

Limonoids are extremely diversified in plants, with many categories of products bearing an intact, rearranged or fragmented oxygenated scaffold. A specific subgroup of fragmented or degraded limonoids derives from the tetranortriterpenoid prieurianin, initially isolated from the tree Trichilia prieuriana but also found in other plants of the Meliaceae family, including the more abundant species Aphanamixis polystachya. Prieurianin-type limonoids include about seventy compounds, among which are dregeanin and rohitukin. Prieurianin and analogs exhibit insecticidal, antimicrobial, antiadipogenic and/or antiparasitic properties but their mechanism of action remains ill-defined at present. Previous studies have shown that prieurianin, initially known as endosidin 1, stabilizes the actin cytoskeleton in plant and mammalian cells via the modulation of the architecture and dynamic of the actin network, most likely via interference with actin-binding proteins. A new mechanistic hypothesis is advanced here based on the recent discovery of the targeting of the chaperone protein Hsp47 by the fragmented limonoid fraxinellone. Molecular modeling suggested that prieurianin and, to a lesser extent dregeanin, can form very stable complexes with Hsp47 at the protein–collagen interface. Hsp-binding may account for the insecticidal action of the product. The present review draws up a new mechanistic portrait of prieurianin and provides an overview of the pharmacological properties of this atypical limonoid and its chemical family. Full article

Eight vilasinin-class limonoids, including the unusually chlorinated rubescins K–M (1–3), the 2,3-epoxylated rubescin N (4), and rubescins O–R (5–8), were newly isolated from Trichilia rubescens. The structures of the isolated compounds were determined through spectroscopic and spectrometric analyses, as well as ECD calculations. The natural occurrence of chlorinated limonoids 1–3 was confirmed by chemical methods and HPLC analysis of a roughly fractionated portion of the plant extract. Eight selected limonoids, including previously known and new compounds, were evaluated for antiproliferative activity against five human tumor cell lines. All tested limonoids, except 8, exhibited significant potency, with IC₅₀ values of <10 μM; in particular, limonoid 14 strongly inhibited tumor cell growth, with IC₅₀ values of 0.54–2.06 μM against all tumor cell lines, including multi-drug-resistant cells. Full article