Millmerranones G, a meroterpene isolated from a mangrove-derived fungus Aspergillus sp. GXIMD 03004.

One new meroterpene derivative, millmerranones G (1), and three known analogues (2-4) were identified from the mangrove-derived fungus Aspergillus sp. GXIMD 03004, which was isolated from the leaves of mangrove Acanthus ilicifolius L. collected from Beibu Gulf in China. The structure of 1 was characterised by a comprehensive interpretation of the NMR spectroscopic and HRESIMS data. The absolute configuration for 1 was established using experimental and calculated ECD data. The anti-Vibrio activities of all compounds were evaluated, the result showed that compounds 1 and 2 has weak activity against Vibrio harveyi.

Mauritone A, a new polyketide from a fungal-bacterial symbiont Aspergillus spelaeus GXIMD 04541/Sphingomonas echinoides GXIMD 04532.

A new polyketide, mauritone A (1) with six known polyketides curvulone B (2), curvularin (3), 12-oxocurvularin (4), (10E,15S)-10,11-dehydrocurvularin (5), (11R,15S)-11-hydroxycurvularin (6), and (11S,15S)-11-hydroxycurvularin (7) were isolated from the fungal-bacterial symbiont Aspergillus spelaeus GXIMD 04541/Sphingomonas echinoides GXIMD 04532 derived from Mauritia arabica. Their structures were elucidated by extensive spectral analysis. All compounds (1-7) were evaluated for their anti-inflammatory effects. The inhibitory effects of 4, 5, and 7 on nitric oxide (NO) production were found to be significant, with IC50 values of 5.5 ± 0.26, 2.0 ± 0.31, and 8.3 ± 0.62 µM, respectively, surpassing that of the positive control quercetin (10.6 ± 0.64 µM). Compounds 3 and 6 exhibited moderate inhibition of NO, with IC50 values of 18.6 ± 0.53 and 12.7 ± 0.45 µM, respectively.

Avellanin A Has an Antiproliferative Effect on TP-Induced RWPE-1 Cells via the PI3K-Akt Signalling Pathway.

Cyclic pentapeptide compounds have garnered much attention as a drug discovery resource. This study focused on the characterization and anti-benign prostatic hyperplasia (BPH) properties of avellanin A from Aspergillus fumigatus fungus in marine sediment samples collected in the Beibu Gulf of Guangxi Province in China. The antiproliferative effect and molecular mechanism of avellanin A were explored in testosterone propionate (TP)-induced RWPE-1 cells. The transcriptome results showed that avellanin A significantly blocked the ECM-receptor interaction and suppressed the downstream PI3K-Akt signalling pathway. Molecular docking revealed that avellanin A has a good affinity for the cathepsin L protein, which is involved in the terminal degradation of extracellular matrix components. Subsequently, qRT-PCR analysis revealed that the expression of the genes COL1A1, COL1A2, COL5A2, COL6A3, MMP2, MMP9, ITGA2, and ITGB3 was significantly downregulated after avellanin A intervention. The Western blot results also confirmed that it not only reduced ITGB3 and FAK/p-FAK protein expression but also inhibited PI3K/p-PI3K and Akt/p-Akt protein expression in the PI3K-Akt signalling pathway. Furthermore, avellanin A downregulated Cyclin D1 protein expression and upregulated Bax, p21WAF1/Cip1, and p53 proapoptotic protein expression in TP-induced RWPE-1 cells, leading to cell cycle arrest and inhibition of cell proliferation. The results of this study support the use of avellanin A as a potential new drug for the treatment of BPH.

New Cyclic Pentapeptides from the Mangrove-Derived Aspergillus fumigatus GXIMD 03099.

Four new cyclic pentapeptides, avellanins D-G (1-4), together with four known compounds (5-8), were isolated from a mangrove-derived Aspergillus fumigatus GXIMD 03099 fungus from Acanthus ilicifolius L. Their structures were elucidated by analysis of HRESIMS, NMR, and ESI-MS/MS data. Their absolute configurations were determined by X-ray diffraction analysis and Marfey's method. Compounds 1-8 were screened for insecticidal and antibacterial activities. Compound 2 showed insecticidal activity against newly hatched larvae of Culex quinquefasciatus with an LC50 value of 86.6 µM; compound 4 had weak activity against Vibrio harveyi with an MIC value of 5.85 µM.

Discovery of Anti-Hypercholesterolemia Agents Targeting LXRα from Marine Microorganism-Derived Natural Products.

A strategy integrating in silico molecular docking with LXRα and phenotypic assays was adopted to discover anti-hypercholesterolemia agents in a small library containing 205 marine microorganism-derived natural products, collected by our group in recent years. Two fumitremorgin derivatives, 12R,13S-dihydroxyfumitremorgin C (1) and tryprostatin A (3), were identified as potential LXRα agonists, by real-time qPCR and Western blot (WB) analysis, together with a surface plasmon resonance (SPR) assay. The anti-hypercholesterolemic effects of 1 and 3, together with their mechanisms, were investigated in depth using different cell and mouse models, among which the study of LXRα is of crucial importance. Compound 1 or 3 exhibited the capacity to effectively reverse excessive lipid accumulation in a hepatic steatosis cell model and significantly reduce liver damage and blood cholesterol levels in high cholesterol diet (HCD)-fed wild-type mice, whereas those beneficial effects were completely nullified in HCD-fed LXRα-knockout mice. Furthermore, 1 and 3 outperformed common LXRα agonists by suppressing the expression of sterol regulatory element-binding protein 1 (SREBP1) in HCD-fed mice, mitigating lipotoxicity. Thus, this study highlights the discovery of two marine microorganism-derived anti-hypercholesterolemia agents targeting LXRα.

New Alkaloids and Steroids from Hydranth of Goniopora columna Corals and Their Inhibiting Lung Cancer Cell Activities.

A new alkaloids, aplysingoniopora A (1), and new configuration pregnane type steroid compound, 9,17-α-pregn-1,4,20-en-3-one (2), and two known pregnane type steroid compounds (3 and 4) were isolated from hydranth of Goniopora columna corals. The compounds structures and absolute configurations were determined by extensive spectroscopic analysis, MS data, single-crystal X-ray diffraction analysis and quantum chemical calculation. The anticancer effect of the compounds were explored in human non-small-cell lung cancer (NSCLC) A549 cell lines. As the results, the compound 3 and 4 induces toxicity and has proliferation inhibitory effects on A549 cells (IC50=58.99 µM and 58.77 µM, respectively) in vitro.

New Polyene Macrolide Compounds from Mangrove-Derived Strain Streptomyces hiroshimensis GXIMD 06359: Isolation, Antifungal Activity, and Mechanism against Talaromyces marneffei.

Mangrove-derived actinomycetes represent a rich source of novel bioactive natural products in drug discovery. In this study, four new polyene macrolide antibiotics antifungalmycin B-E (1-4), along with seven known analogs (5-11), were isolated from the fermentation broth of the mangrove strain Streptomyces hiroshimensis GXIMD 06359. All compounds from this strain were purified using semi-preparative HPLC and Sephadex LH-20 gel filtration while following an antifungal activity-guided fractionation. Their structures were elucidated through spectroscopic techniques including UV, HR-ESI-MS, and NMR. These compounds exhibited broad-spectrum antifungal activity against Talaromyces marneffei with minimum inhibitory concentration (MIC) values being in the range of 2-128 µg/mL except compound 2. This is the first report of polyene derivatives produced by S. hiroshimensis as bioactive compounds against T. marneffei. In vitro studies showed that compound 1 exerted a significantly stronger antifungal activity against T. marneffei than other new compounds, and the antifungal mechanism of compound 1 may be related to the disrupted cell membrane, which causes mitochondrial dysfunction, resulting in leakage of intracellular biological components, and subsequently, cell death. Taken together, this study provides a basis for compound 1 preventing and controlling talaromycosis.

Sonneralignan A, a new lignan from the fruit of mangrove Sonneratia apetala.

A new lignan, sonneralignan A (1), along with two known lignan compounds, (+)-lariciresinol-9-O-ß-D-glucopyranoside (2) and (-)isolariciresinol-9-O-ß-D-glucopyranoside (3) were isolated from the n-butanol extract of the mangrove Sonneratia apetala fruit. The structures of the compounds were elucidated on the basis of extensive spectral analysis. The evaluation of activity showed that compound 1 exhibited significant anti-aging activity, which extended the mean lifespan of Caenorhabditis elegans by up to 19.13% (p < 0.05) and 55.29% (p < 0.01) under normal and heat stress cultivation conditions, respectively. Molecular docking studies showed that compound 1 was bound to the DNA binding domain of DAF-16 and promoted the conformation of DAF-16, thus strengthening the interaction between the DAF-16 and related DNA. TRP-252, SER-250 and SER-249 of the binding region might be the key amino residues during the interaction.

Proteomic Identification of Plasma Components in Tachypleus tridentatus and Their Effects on the Longitudinal Bone Growth Rate in Rats.

Tachypleus tridentatus (T. tridentatus) is a marine animal and traditional Chinese medicine. T. tridentatus plasma is a valuable resource for important medical and health-based functions. In this experiment, in order to evaluate the effect and mechanism of T. tridentatus plasma with respect to the promotion of bone tissue growth in rats, the processes of ultrafiltration and mass spectrometry were first used to separate and identify the components of T. tridentatus plasma. Then, a comparison of the effects of the T. tridentatus plasma samples, which each possessed different molecular weights, regarding the growth of the long bones of rats was conducted. Finally, transcriptomics, proteomics, and bioinformatics were all used to analyze the biological functions and related signaling pathways of the T. tridentatus plasma in order to promote rat bone growth. The results showed that the contents of amino acid residues in peptides are related to the growth promotion that was contained in the 10-30 kDa plasma group. Moreover, the T. tridentatus plasma samples were found to be higher in this respect than those in the whole plasma group. In addition, the 10-30 kDa plasma group could significantly promote bone growth activity in rats. The proteomic analysis showed that the proteins that were differentially expressed in the 10-30 kDa plasma group were mainly enriched in the PI3K-AKT signal pathway. Our study suggested that the T. tridentatus plasma possesses promising potential for the purposes of clinical use, whereby it can serve the role of a growth-promoting agent.

Stappia sediminis sp. nov., isolated from rhizosphere soil of coastal herb Zoysia matrella within the Beibu Gulf.

A bacterial isolate (BGMRC 2046T) was isolated from the rhizosphere soil of Zoysia matrella collected from the Beibu Gulf of China. The results of a polyphasic taxonomic study revealed that this strain belongs to a member of the genus Stappia with the characteristics of Gram-stain-negative, catalase- and oxidase-positive, motile, short rod-shaped. The strain grew at 20-37 °C (optimal, 28 °C), pH 6.0-9.0 (optimal, pH 7.0), and 1-7% (w/v) optimal, NaCl (1-3%). A phylogenetic evaluation based on 16S rRNA gene sequence analysis revealed that this strain fall into the family Stappiaceae, being most closely related to Stappia indica CGMCC 1A01226T (95.8% sequence similarity), Stappia stellulata DSM 5886T (95.1%), and Stappia taiwanensis DSM 23284T (94.4%). The major cellular fatty acid, respiratory quinone and polar lipids were all detected from new species (BGMRC 2046T), that shows the chemical characteristics of BGMRC 2046T. The major polar lipids were two unidentified ninhydrin positive phospholipids, four unidentified phospholipids, and one unidentified lipid. Genome sequencing revealed a genome size of 4.78 Mbp and a G + C content of 60.8%. Pairwise comparison of the genomes of the new strain BGMRC 2046T and the three most closely related strains resulted in gANI values was lower than 75% and a digital DNA-DNA hybridization values was lower than 24%. The strain possessed genes encoding choline uptake and conversion to betaine gene clusters. The results of the polyphasic taxonomic study showed that strain BGMRC 2046T represents a new species of the genus Stappia. The name Stappia sediminis sp. nov. is proposed for the species with the type strain BGMRC 2046T (= KCTC52115T = CGMCC1.17425T).

Characterization of the Aminosugar Biosynthetic and Regulatory Genes of Vicenistatin in Monodonata labio-Associated Streptomyces parvus SCSIO Mla-L010.

Vicenistatin (1) is a potent polyketide antitumor antibiotic composed of a 20-membered macrolactam core appended to a unique aminosugar, vicenisamine. In this study, vicenistatin was isolated and its biosynthetic gene cluster identified from Monodonata labio-associated Streptomyces parvus SCSIO Mla-L010. A set of five genes, vicC, vicD, vicE, vicF, and vicG, was confirmed to be involved in the biosynthesis of the aminosugar by gene inactivations. VicG was characterized as an N-methyltransferase that catalyzes the methylation of the 4'-amino group in the last step of the aminosugar biosynthetic pathway; the N-demethyl intermediate 4'-N-demethylvicenistatin (2) was isolated from the ΔvicG mutant strain. In addition, vicR1 was characterized as a positive pathway-specific regulatory gene. Notably, N-demethyl compound 2 was found to exert impressive antibacterial activities, with MIC values spanning 0.06-4 µg/mL, against a panel of Gram-positive bacteria including methicillin-resistant Staphylococcus aureus, Gram-negative Helicobacter pylori, and mycobacterium Mycobacterium smegmatis and the fungal pathogen Candida albicans. Compound 2 was also found to display reduced cytotoxicities relative to vicenistatin, especially against noncancerous human cell lines.

Sonneradon A Extends Lifespan of Caenorhabditis elegans by Modulating Mitochondrial and IIS Signaling Pathways.

Aging is related to the lowered overall functioning and increased risk for various age-related diseases in humans. Sonneradon A (SDA), a new compound first extracted from the edible fruits of mangrove Sonneratia apetala, showed remarkable antiaging activity. However, the role of SDA in antiaging remains unclear. In this article, we studied the function of SDA in antiaging by using the animal model Caenorhabditis elegans. Results showed that SDA inhibited production of reactive oxygen species (ROS) by 53%, and reduced the accumulation of aging markers such as lipids and lipofuscins. Moreover, SDA also enhanced the innate immune response to Pseudomonas aeruginosa infection. Genetic analysis of a series of mutants showed that SDA extended the lifespan of the mutants of eat-2 and glp-1. Together, this effect may be related to the enhanced resistance to oxidative stress via mitochondrial and insulin/insulin-like growth factor-1 signaling (IIS) pathways. The results of this study provided new evidence for an antiaging effect of SDA in C. elegans, as well as insights into the implication of antiaging activity of SDA in higher organisms.

Pararhizobium mangrovi sp. nov., Isolated From Aegiceras corniculatum Stem.

A novel Gram-stain-negative, catalase- and oxidase-positive, motile, short rod-shaped bacterium designated BGMRC 6574T was isolated from stems of Aegiceras corniculatum collected from Hainan province, China. The strain grew at 25-37 °C (optimal at 28 °C), pH 5.0-10.0 (pH 7.0), and 3-8% (w/v) NaCl (3%). Based on the 16S rRNA phylogenetic analysis, the strain was closely related to Pararhizobium haloflavum MCCC 1K03228T (96.45% sequence similarity). The novel strain showed an average nucleotide identity value and a digital DNA-DNA hybridization of 72.62 and 27.1%, respectively, to P. haloflavum MCCC 1K03228T based on draft genome sequences. The G+C content of the genomic DNA was 64.7 mol%. The major respiratory quinone was Q-10. The strain possessed genes putatively encoding choline uptake and conversion to betaine gene clusters. The extract significantly delayed the lifespan of Caenorhabditis elegans compared to the control (P < 0.05). The major polar lipids were phosphatidylcholine, seven unidentified phospholipids, three unidentified ninhydrin-positive phospholipids, and two unidentified lipids. The major cellular fatty acid was C19:0 cyclo ω8c. The results of a polyphasic taxonomic study showed that strain BGMRC 6574T represents a new species of the genus Pararhizobium, and it was named Pararhizobium mangrovi sp. nov. The type strain is BGMRC 6574T (=KCTC 72636T = CGMCC 1.16783).

New 24-Membered Macrolactins Isolated from Marine Bacteria Bacillus siamensis as Potent Fungal Inhibitors against Sugarcane Smut.

Sugarcane smut, caused by Sporisorium scitamineum, is one of the most devastating fungal diseases affecting sugarcane worldwide. To develop a potent sugarcane smut fungicide, secondary metabolites of marine-derived Bacillus siamensis were isolated and screened for inhibitory activities, which led to the discovery of five new 24-membered macrolactins, bamemacrolactins A-E (1-5), with 3 being the most potent inhibitor. The antifungal mechanism of 3 was studied by assessing its effects on mycelial morphology and the cell wall. Differential proteomics were used to analyze proteins in S. scitamineum upon treatment with bamemacrolactin C and to elucidate its antifungal mechanism. A total of 533 differentially expressed proteins were found. After the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, eight target proteins were selected, and their functions were discussed. Six of the eight proteins were reported as antifungal targets. The target proteins are involved in the oxidative phosphorylation pathway. Therefore, the potent inhibition of S. scitamineum by compound 3 is most likely through oxidative phosphorylation and targeting a series of enzymes.

Martelella alba sp. nov., isolated from mangrove rhizosphere soil within the Beibu Gulf.

Strain BGMRC 2036T was isolated from rhizosphere soil of Bruguiear gymnorrhiza collected from the Beibu Gulf of China. Optimum growth occurred at 28 °C, pH 7.0, and under the conditions of 3-5% (w/v) NaCl. The phylogenetic comparisons of 16S rRNA gene sequences displayed that strain BGMRC 2036T was closely related to Martelella limonii NBRC109441T (96.6% sequence similarity), M. mediterranea CGMCC 1.12224T (96.5%), M. lutilitoris GH2-6T (96.5%), M. radicis BM5-7T (96.2%), and M. mangrove BM9-1T (95.9%), M. suaedae NBRC109440T (95.8%). The phylogenomic tree based on the up-to-date bacterial core gene set indicated that the strain BGMRC 2036T form a clade formed with members of the genera Martelella. The major polar lipids include phosphatidylmethylethanolamine, phosphatidylglycerol, phosphatidylcholine, phosphotidylinositol, two unidentified phospholipids, and three unidentified ninhydrin positive phospholipids. The major respiratory quinone is Q-10, which is similar to those of genera Martelella. The main cellular fatty acids are C18:1 ω7c, C16:0, and C12:0 aldehyde. Genome sequencing revealed a genome size of 4.99 Mbp and a G + C content of 62.3 mol%. Pairwise comparison of the genomes of the new strain BGMRC 2036T and the three reference strains M. endophytica YC 6887T, M. mediterranea CGMCC 1.12224T, and M. mangrovi USBA-857 indicated that gANI value was lower than 81% and a digital DNA-DNA hybridization value was lower than 27%. The strain BGMRC 2036T possessed genes putatively encoding riboflavin synthesis and flavodoxin A polyphasic taxonomic study suggested that strain BGMRC 2036T represented a novel species belonging to the genus Martelella, and it was named Martelella alba sp. nov. The type strain is BGMRC 2036T (=KCTC 52121T =NBRC 111908T).

Bruguierivorax albus gen. nov. sp. nov. Isolated from Mangrove Sediment and Proposal of Bruguierivoracaceae fam. nov.

A novel Gram-negative, motile, aerobic rod-shaped bacterium designated BGMRC 2031T was isolated from mangrove sediment collected from Guangxi Province, China. Optimal growth occurred at 28 °C and pH 7.0-8.0 in the presence of 1% (w/v) NaCl. Alignment based on 16S rRNA gene sequences indicated that strain BGMRC 2031T is most closely related to Sodalis praecaptivus HS1T (95.6%, sequence similarity), followed by Biostraticola tofi DSM 19580T (95.5%), Sodalis glossinidius DSM 16929T (95.4%), and Brenneria goodwinii FRB141T (94.9%) sequence similarity. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain BGMRC 2031T formed a distinct branch in a robust cluster and revealed that strain BGMRC 2031T, genera Biostraticola and Sodalis, formed a novel family-level clade in the order Enterobacterales. The novel strain showed an average nucleotide similarity of 74.7%, 74.2%, and 73.1% for S. praecaptivus HS1T, S. glossinidius DSM 16929T, and B. tofi DSM 19580T, respectively. The genomes of the BGMRC 2031T shared the presence of a riboflavin synthesis gene cluster. The menaquinones of strain BGMRC 2031T were MK-8 and Q-8, which were similar to those of genus Biostraticola. The major fatty acids (> 10%) were C16:0 (19.9%), summed feature 2 (iso-C16:1 and/or C14:0 3-OH, 18.10%), summed feature 3 (C16:1 ω7c and/or C16:1 ω6c, 15.3%), C12:0 (13.9%), C17:0 cyclo (11.4%), and C14:0 (10.4%). The main polar lipids were phosphatidyl methylethanolamine, phosphatidyl glycerol, diphosphatidyl glycerol, phosphatidyl inositol, one unidentified phospholipid, and one unknown polar lipid. The G+C content of strain BGMRC 2031T was 55.4%. Strain BGMRC 2031T could extend the mean lifespan and maximum lifespan of Caenorhabditis elegans by 4.5% and 12.5%, respectively. Overall, the results of this study indicate that BGMRC 2031T is a novel species in a new genus, for which the name Bruguierivorax albus gen. nov. sp. nov. is proposed, and the type of strain is designated as BGMRC 2031T (= NBRC 111907T = KCTC 52119T). In addition, a novel family, Bruguierivoracaceae fam. nov., is proposed to accommodate the genera Bruguierivorax, Biostraticola, and Sodalis.

Marinoid J, a phenylglycoside from Avicennia marina fruit, ameliorates cognitive impairment in rat vascular dementia: a quantitative iTRAQ proteomic study.

CONTEXT: Fruit of Avicennia marina (Forsk.) Vierh. (Acanthaceae) is used as a Chinese herb. Studies have found that it contains marinoid J, a novel phenylethanoid glycoside (PG) compound, but its neuroprotective functions are largely unknown. OBJECTIVE: This study evaluated the effects of marinoid J on vascular dementia (VD) and determined its potential mechanisms of action. MATERIALS AND METHODS: The VD model was established by the ligation of the bilateral common carotid artery in Sprague-Dawley rats, who received daily intragastrically administration of saline, marinoid J (125 or 500 mg/kg body weight/d), or oxiracetam (250 mg/kg body weight/d) for 14 days (20 rats in each group). The Morris water maze (MWM) was used to evaluate cognitive performance. The hippocampus was subjected to histological and proteomic analyses. RESULTS: Marinoid J shortened the escape latency of VD rats (31.07 ± 3.74 s, p < 0.05). It also decreased malondialdehyde (MDA) (27.53%) and nitric oxide (NO) (20.41%) while increasing superoxide dismutase (SOD) (11.26%) and glutathione peroxidase (GSH-Px) (20.38%) content in hippocampus tissues. Proteomic analysis revealed 45 differentially expressed proteins (DEPs) in marinoid J-treated VD rats, which included angiotensin-converting enzyme (ACE), keratin 18 (KRT18), cluster of differentiation 34 (CD34), and synaptotagmin II (SYT2). CONCLUSIONS: Marinoid J played a role in protecting hippocampal neurons by regulating a set of proteins that influence oxidative stress and apoptosis, this effect may thereby alleviate the symptoms of VD rats. Thus, pharmacological manipulation of marinoid J may offer a novel opportunity for VD treatment.

Rapid improvement in the macrolactins production of Bacillus sp. combining atmospheric room temperature plasma with the specific growth rate index.

Macrolactins (MLNs) have attracted considerable attention due to their antibacterial and antiviral properties. Here, the MLN production of Bacillus sp. strain IMDGX0108 was improved using a breeding strategy of atmospheric room temperature plasma (ARTP) technique. Combining with a selection procedure based on the colony morphology and specific growth rate index (SGRI), two genetically stable mutants A29 and A72 were identified. The MLN production of A29 and A72 was 35.2% and 52.8% greater than that of the parent strain, respectively. The best-performing mutant A72 was subjected to RNA-sequence analysis. Five pathways were significantly enriched, and fatty acid bioprocesses might play an important role in improving the production of MLNs. The combined strategy developed herein (i.e., ARTP mutation plus an efficient screening procedure) might be an appropriate method by which to obtain strains overproducing MLNs.

Compounds from the fruits of mangrove Sonneratia apetala: Isolation, molecular docking and antiaging effects using a Caenorhabditis elegans model.

The chemical investigation of the fruits of a mangrove Sonneratia apetala collected from the Beibu Gulf led to the isolation of four new compounds, sonneradons A-D (1-4), as well as 18 known compounds (5-22). The structures of the new compounds were elucidated based on extensive spectroscopic analysis, and the structures of the known compounds were established by comparison of their spectroscopic data with those of related metabolites. The antiaging activities of all isolates were evaluated using the nematode Caenorhabditis elegans as a model organism. The results showed that 10 compounds could protect C. elegans by extending its lifespan. Compound 1 possessed the most potent effect in the anti-heat stress assay and significantly attenuated aging-related decreases in the pumping and bending of the nematodes in the healthspan assay. Molecular docking studies suggested that compound 1 was bound to the DNA binding domain of HSF-1 and promoted the conformation of HSF-1, thus strengthening the interaction between the HSF-1 and related DNA. GLN49, ASN-74, and LYS-80 of the binding region might be the key amino residues during the interaction.

Apoptosis effect of Aegiceras corniculatum on human colorectal cancer via activation of FoxO signaling pathway.

Aegiceras corniculatum (L.) Blanco is known to exhibit anticancer effects against different types of cancer; however, to the best of our knowledge, the anticancer activity and underlying mechanisms of action of A. corniculatum leaf extract on colorectal cancer have not been elucidated. In the present study, colony-forming assay, western blot analysis, flow cytometry, and a xenograft model were used to investigate the effects of an n-butanol extract of A. corniculatum leaves (NACL) on colorectal cancer in vitro and in vivo. The results showed that NACL inhibits the viability and proliferation of colorectal cancer cells in a dose-dependent manner. Besides, NACL also induces cell apoptosis and cell cycle arrest by activating Forkhead box proteins and controlling the cell cycle checkpoint pathways, which are associated with the caspase-dependent mitochondrial apoptotic cascades and Bcl-2 family proteins. More importantly, the tumour sizes in HT-29 xenograft nude mice decreased after treatment with NACL in vivo. These findings indicate that A. corniculatum leaf extracts have potent anticancer activities across different colorectal and other solid tumour cell lines, via regulation of the cell cycle and apoptosis; thus, it has the potential to be developed as an anticancer agent to enhance clinical standards of care for patients with colorectal cancer.