Aspergillus ochraceus: Metabolites,Bioactivities, Biosynthesis,and Biotechnological Potential

Fungus continues to attract great attention as a promising pool of biometabolites. Aspergillus ochraceus Wilh (Aspergillaceae) has established its capacity to biosynthesize a myriad of metabolites belonging to different chemical classes, such as isocoumarins, pyrazines, sterols, indole alkaloids, diketopiperazines, polyketides, peptides, quinones, polyketides, and sesquiterpenoids, revealing various bioactivities that are antimicrobial, cytotoxic, antiviral, anti-inflammatory, insecticidal, and neuroprotective. Additionally, A. ochraceus produces a variety of enzymes that could have variable industrial and biotechnological applications. From 1965 until June 2022, 165 metabolites were reported from A. ochraceus isolated from different sources. In this review, the formerly separated metabolites from A. ochraceus, including their bioactivities and biosynthesis, in addition, the industrial and biotechnological potential of A. ochraceus are highlighted.     

Identification of anti-Parkinson's Disease Lead Compounds from Aspergillus ochraceus Targeting Adenosin Receptors A2A

Two novel alkaloids compounds together with fifteen know metabolites were identified from Aspergillus ochraceus. The stereochemistry features of the new molecules were determined via HRESIMS, NMR, ECD, and XRD analyses. Amongst these, compounds two compounds exhibited potential efficacy as anti-Parkinson's disease with the EC₅₀ values of 2.30 and 2.45 μM , respectively. ADMET prediction showed that these compounds owned favorable drug-like characteristics and safe toxicity scores towards CNS drugs. Virtual screening analyses manifested that the compounds exhibited not only robust and reliable interactions to adenosine receptors A_2A, but also higher binding selectivity to A_2A receptors than to A₁ and A₃ receptors. Molecular dynamics simulation demonstrated the reliability of molecular docking results and the stability of the complexes obtained with the novel compounds and A_2A receptors in natural environments. It is the first time that anti-PD lead compounds have been identified from Aspergillus ochraceus and targeting adenosine A_2A receptors.     

Effects of Different Opioid Drugs on Oxidative Status and Proteasome Activity in SH-SY5Y Cells

Opioids are the most effective drugs used for the management of moderate to severe pain; however, their chronic use is often associated with numerous adverse effects. Some results indicate the involvement of oxidative stress as well as of proteasome function in the development of some opioid-related side effects including analgesic tolerance, opioid-induced hyperalgesia (OIH) and dependence. Based on the evidence, this study investigated the impact of morphine, buprenorphine or tapentadol on intracellular reactive oxygen species levels (ROS), superoxide dismutase activity/gene expression, as well as β2 and β5 subunit proteasome activity/biosynthesis in SH-SY5Y cells. Results showed that tested opioids differently altered ROS production and SOD activity/biosynthesis. Indeed, the increase in ROS production and the reduction in SOD function elicited by morphine were not shared by the other opioids. Moreover, tested drugs produced distinct changes in β2(trypsin-like) and β5(chymotrypsin-like) proteasome activity and biosynthesis. In fact, while prolonged morphine exposure significantly increased the proteolytic activity of both subunits and β5 mRNA levels, buprenorphine and tapentadol either reduced or did not alter these parameters. These results, showing different actions of the selected opioid drugs on the investigated parameters, suggest that a low µ receptor intrinsic efficacy could be related to a smaller oxidative stress and proteasome activation and could be useful to shed more light on the role of the investigated cellular processes in the occurrence of these opioid drug side effects.     

ACTH(6–9)PGP Peptide Protects SH-SY5Y Cells from H2O2, tert-Butyl Hydroperoxide,and Cyanide Cytotoxicity via Stimulation of Proliferation and Induction of Prosurvival-Related Genes

Stabilized melanocortin analog peptide ACTH(6–9)PGP (HFRWPGP) possesses a wide range of neuroprotective activities. However, its mechanism of action remains poorly understood. In this paper, we present a study of the proproliferative and cytoprotective activity of the adrenocorticotropic hormone fragment 6–9 (HFRW) linked with the peptide prolyine–glycyl–proline on the SH-SY5Y cells in the model of oxidative stress-related toxicity. The peptide dose-dependently protected cells from H₂O₂, tert-butyl hydroperoxide, and KCN and demonstrated proproliferative activity. The mechanism of its action was the modulation of proliferation-related NF-κB genes and stimulation of prosurvival NRF2-gene-related pathway, as well as a decrease in apoptosis.     

Optimization of Fermentation Process of Pomegranate Peel and Schisandra Chinensis and the Biological Activities of Fermentation Broth: Antioxidant Activity and Protective Effect Against H2O2-induced Oxidative Damage in HaCaT Cells

In this study, the lactobacillus fermentation process of pomegranate (Punica granatum L.) peel and Schisandra chinensis (Turcz.) Baill (PP&SC) was optimized by using the response surface method (RSM) coupled with a Box-Behnken design. The optimum fermentation condition with the maximal yield of ellagic acid (99.49 ± 0.47 mg/g) was as follows: 1:1 (w:w) ratio of pomegranate peel to Schisandra chinensis, 1% (v:v) of strains with a 1:1 (v:v) ratio of Lactobacillus Plantarum to Streptococcus Thermophilus, a 37 °C fermentation temperature, 33 h of fermentation time, 1:20 (g:mL) of a solid–liquid ratio and 3 g/100 mL of a glucose dosage. Under these conditions, the achieved fermentation broth (FB) showed stronger free radical scavenging abilities than the water extract (WE) against the ABTS⁺, DPPH, OH⁻ and O₂⁻ radicals. The cytotoxicity and the protective effect of FB on the intracellular ROS level in HaCaT cells were further detected by the Cell Counting Kit-8 (CCK-8) assay. The results showed that FB had no significant cytotoxicity toward HaCaT cells when its content was no more than 8 mg/mL. The FB with a concentration of 8 mg/mL had a good protective effect against oxidative damage, which can effectively reduce the ROS level to 125.94% ± 13.46% (p < 0.001) compared with 294.49% ± 11.54% of the control group in H₂O₂-damaged HaCaT cells. The outstanding antioxidant ability and protective effect against H₂O₂-induced oxidative damage in HaCaT cells promote the potential for the FB of PP&SC as a functional raw material of cosmetics.     

Protective Effects of Jujubosides on 6-OHDA-Induced Neurotoxicity in SH-SY5Y and SK-N-SH Cells

6-hydroxydopamine (6-OHDA) is used to induce oxidative damage in neuronal cells, which can serve as an experimental model of Parkinson’s disease (PD). Jujuboside A and B confer free radical scavenging effects but have never been examined for their neuroprotective effects, especially in PD; therefore, in this study, we aimed to investigate the feasibility of jujubosides as protectors of neurons against 6-OHDA and the underlying mechanisms. 6-OHDA-induced neurotoxicity in the human neuronal cell lines SH-SY5Y and SK-N-SH, was used to evaluate the protective effects of jujubosides. These findings indicated that jujuboside A and B were both capable of rescuing the 6-OHDA-induced loss of cell viability, activation of apoptosis, elevation of reactive oxygen species, and downregulation of the expression levels of superoxide dismutase, catalase, and glutathione peroxidase. In addition, jujuboside A and B can reverse a 6-OHDA-elevated Bax/Bcl-2 ratio, downregulate phosphorylated PI3K and AKT, and activate caspase-3, -7, and -9. These findings showed that jujubosides were capable of protecting both SH-SY5Y and SK-N-SH neuronal cells from 6-OHDA-induced toxicity via the rebalancing of the redox system, together with the resetting of the PI3K/AKT apoptotic signaling cascade. In conclusion, jujuboside may be a potential drug for PD prevention.     

Preparation of Antioxidant Protein Hydrolysates from Pleurotus geesteranus and Their Protective Effects on H2O2 Oxidative Damaged PC12 Cells

Pleurotus geesteranus is a promising source of bioactive compounds. However, knowledge of the antioxidant behaviors of P. geesteranus protein hydrolysates (PGPHs) is limited. In this study, PGPHs were prepared with papain, alcalase, flavourzyme, pepsin, and pancreatin, respectively. The antioxidant properties and cytoprotective effects against oxidative stress of PGPHs were investigated using different chemical assays and H₂O₂ damaged PC12 cells, respectively. The results showed that PGPHs exhibited superior antioxidant activity. Especially, hydrolysate generated by alcalase displayed the strongest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (91.62%), 2,2-azino-bis (3-ethylbenzothia zoline-6-sulfonic acid) (ABTS) radical scavenging activity (90.53%), ferric reducing antioxidant power, and metal ion-chelating activity (82.16%). Analysis of amino acid composition revealed that this hydrolysate was rich in hydrophobic, negatively charged, and aromatic amino acids, contributing to its superior antioxidant properties. Additionally, alcalase hydrolysate showed cytoprotective effects on H₂O₂-induced oxidative stress in PC12 cells via diminishing intracellular reactive oxygen species (ROS) accumulation by stimulating antioxidant enzyme activities. Taken together, alcalase hydrolysate of P. geesteranus protein can be used as beneficial ingredients with antioxidant properties and protective effects against ROS-mediated oxidative stress.     

Polyphenolic Extracts from Spent Coffee Grounds Prevent H2O2-Induced Oxidative Stress in Centropomus viridis Brain Cells

Oxidative stress in aquatic organisms might suppress the immune system and propagate infectious diseases. This study aimed to investigate the protective effect of polyphenolic extracts from spent coffee grounds (SCG) against oxidative stress, induced by H₂O₂, in C. viridis brain cells, through an in vitro model. Hydrophilic extracts from SCG are rich in quinic, ferulic and caffeic acids and showed antioxidant capacity in DPPH, ORAC and FRAP assays. Furthermore, pretreatment of C. viridis brain cells with the polyphenolic extracts from SCG (230 and 460 µg/mL) for 24 h prior to 100 µM H₂O₂ exposure (1 h) significantly increased antioxidant enzymes activity (superoxide dismutase and catalase) and reduced lipid peroxidation (measured by MDA levels). These results suggest that polyphenols found in SCG extracts exert an antioxidative protective effect against oxidative stress in C. viridis brain cells by stimulating the activity of SOD and CAT.     

New naphthopyrones from marine-derived fungus Aspergillus niger 2HL-M-8 and their in vitro antiproliferative activity

A new cytotoxic dimeric naphthopyrone, aurasperone H (1), together with eight related known polyketides (2–9) was isolated from a marine-derived fungus Aspergillus niger 2HL-M-8. The structure of new compound 1 was elucidated on the basis of its spectroscopic data (1D, 2D NMR and CD). Compound 1 exhibited moderate inhibitory activity against the human lung adenocarcinoma A549 and the human leukaemia HL-60 cell lines. Compound 5 displayed significant in vitro antiproliferative activity against HL-60 cell line with an IC₅₀ value of 0.8 μM.     

Optimization of Ultrasound-Assisted Cellulase Extraction from Nymphaea hybrid Flower and Biological Activities: Antioxidant Activity,Protective Effect against ROS Oxidative Damage in HaCaT Cells and Inhibition of Melanin Production in B16 Cells

In this study, ultrasonic-assisted cellulase extraction (UCE) was applied to extract flavonoids and polyphenols from the Nymphaea hybrid flower. The extraction conditions were optimized using the response surface method (RSM) coupled with a Box-Behnken design. The crude extract of Nymphaea hybrid (NHE) was further purified using AB-8 macroporous resins, and the purified extract (NHEP) was characterized by FTIR and HPLC. In vitro activity determination by chemical method showed that NHEP displayed strong free radical scavenging abilities against the DPPH and ABTS radicals, good reduction power, and hyaluronidase inhibition. The cell viability by CCK-8 assays showed that NHEP had no significant cytotoxicity for B16 and HaCaT cells when the concentration was below 100 μg/mL and 120 μg/mL, respectively. NHEP with a concentration of 20–160 μg/mL can more effectively reduce the ROS level in H₂O₂ damaged HaCaT cells compared with 10 μg/mL of VC. The 40 μg/mL of NHEP had similar activity against intracellular melanin production in the B16 melanoma cells compared with 20 μg/mL Kojic acid. Good activities of antioxidation, whitening and protective effect against H₂O₂-induced oxidative damage promote the potential for NHEP as a functional raw material in the field of cosmetics and medicine.     

A Comprehensive In Silico Study of New Metabolites from Heteroxenia fuscescens with SARS-CoV-2 Inhibitory Activity

Chemical investigation of the total extract of the Egyptian soft coral Heteroxenia fuscescens, led to the isolation of eight compounds, including two new metabolites, sesquiterpene fusceterpene A (1) and a sterol fuscesterol A (4), along with six known compounds. The structures of 1–8 were elucidated via intensive studies of their 1D, 2D-NMR, and HR-MS analyses, as well as a comparison of their spectral data with those mentioned in the literature. Subsequent comprehensive in-silico-based investigations against almost all viral proteins, including those of the new variants, e.g., Omicron, revealed the most probable target for these isolated compounds, which was found to be M^pro. Additionally, the dynamic modes of interaction of the putatively active compounds were highlighted, depending on 50-ns-long MDS. In conclusion, the structural information provided in the current investigation highlights the antiviral potential of H. fuscescens metabolites with 3β,5α,6β-trihydroxy steroids with different nuclei against SARS-CoV-2, including newly widespread variants.     

Influence of 40 Hz and 100 Hz Vibration on SH-SY5Y Cells Growth and Differentiation—A Preliminary Study

(1) Background: A novel bioreactor platform of neuronal cell cultures using low-magnitude, low-frequency (LMLF) vibrational stimulation was designed to discover vibration influence and mimic the dynamic environment of the in vivo state. To better understand the impact of 40 Hz and 100 Hz vibration on cell differentiation, we join biotechnology and advanced medical technology to design the nano-vibration system. The influence of vibration on the development of nervous tissue on the selected cell line SH-SY5Y (experimental research model in Alzheimer’s and Parkinson’s) was investigated. (2) Methods: The vibration stimulation of cell differentiation and elongation of their neuritis were monitored. We measured how vibrations affect the morphology and differentiation of nerve cells in vitro. (3) Results: The highest average length of neurites was observed in response to the 40 Hz vibration on the collagen surface in the differentiating medium, but cells response did not increase with vibration frequency. Also, vibrations at a frequency of 40 Hz or 100 Hz did not affect the average density of neurites. 100 Hz vibration increased the neurites density significantly with time for cultures on collagen and non-collagen surfaces. The exposure of neuronal cells to 40 Hz and 100 Hz vibration enhanced cell differentiation. The 40 Hz vibration has the best impact on neuronal-like cell growth and differentiation. (4) Conclusions: The data demonstrated that exposure to neuronal cells to 40 Hz and 100 Hz vibration enhanced cell differentiation and proliferation. This positive impact of vibration can be used in tissue engineering and regenerative medicine. It is planned to optimize the processes and study its molecular mechanisms concerning carrying out the research.     

Microperoxidase-11 Modified Electrode and Its Electrocatalytic Activity on the Reduction of O2 and H2O2

Microperoxidase-11(MP-11) was immobilized on the surface of a silanized glass carbon electrode by means of the covalent bond with glutaraldehyde.The measurements of cyclic voltammetry demonstrated that the formal redox potential of immobilized MP-11 was -170mV.which is significantly more positive than that of MP-11 in a solution or immobilized on the surface of electrodes prepared with other methods.This MP-11 modified electrode showed a good electrocatalytic activity and stability for the reduction of oxygen and hydrogen peroxide.     

H_2O_2氧化N_2生成N_2O和H_2O机理的研究

采用量子化学计算方法研究了Ｈ２Ｏ２ 氧化Ｎ２ 生成Ｎ２Ｏ 和Ｈ２Ｏ 的机理．结果发现, Ｈ２Ｏ２ 氧化Ｎ２ 先通过１ 个四元环过渡态形成中间体Ｈ２Ｎ２Ｏ２ 分子,Ｈ２Ｎ２Ｏ２ 再通过一个五元环过渡态形成Ｎ２Ｏ和Ｈ２Ｏ．根据计算得到的每步反应的活化能,得知Ｈ２Ｏ２ 氧化Ｎ２ 生成中间体Ｈ２Ｎ２Ｏ２ 分子是整个反应的控制步骤．     

New Aquapentachlorochromate(III) Compounds: K2[CrCl5(H2O)] and (NH4)2[CrCl5(H2O)]

Synthesis and crystal structures of two new compounds, K₂[CrCl₅(H₂O)] ( I ) and (NH₄)₂[CrCl₅(H₂O)] ( II ) are reported. Both compounds were prepared from chromium(VI) salts by two different methods and reaction pathways of these syntheses are suggested. The crystal structures of these two aquapentachlorochromates(III) have been determined from three dimensional X‐ray data collected at low temperature, 173 K. The two structures are isomorphous and their unit cell dimensions are quite similar. They are orthorhombic, space groups Pnma, with Z = 4. Both structures are composed of [CrCl₅(H₂O)]^2? units held together by the counterion framework. The coordination around the chromium ion deviates from a regular octahedron due to the shorter equatorial chromium‐oxygen bond.     

Synthesis,Crystal Structure and Antitumor Activity of a New Coordination Polymer [Cd（C（14）H（10）N3O5）2（C5H5N）2]n

A new cadmium coordination polymer,[Cd(C14H10N3O5)2(C5H5N)2]n,has been synthesized by the reaction of 2-hydroxy-N'-(4-nitrobenzoyl)benzohydraizide with cadmium acetate in pyridine and ethanol mixture solution.Its molecular structure was characterized by elemental analysis,IR spectra and X-ray crystal structure determination.Crystal data for this compound:tetragonal,space group I41/a,Mr=871.10,a=16.960(6),b=16.960(6),c=28.612(6) ,V= 8230(4)3,Z=8,Dc=1.406 g·m-3 and F(000)=3536.the final R=0.0326,wR=0.0847 for 2682 observed reflections with I 2σ(I) and R=0.0460,wR=0.0896 for all reflections.In the molecular structure of the complex,the cadmium atoms are coordinated to four N and two O atoms forming a slightly distorted octahedral geometry.The intermolecular hydrogen bonds link the neighboring molecules to form a coordination polymer which was then evaluated for its anti-tumor activities against two kinds of cell lines (K562 and BGC) by MTT method.A preliminary bioactivity study indicates that the complex has distinct inhibitory effect on K562 cell lines.     

Antioxidant Activity of Acanthopanax senticosus Flavonoids in H2O2-Induced RAW 264.7 Cells and DSS-Induced Colitis in Mice

The redox reaction is a normal process of biological metabolism in the body that leads to the production of free radicals. Under conditions such as pathogenic infection, stress, and drug exposure, free radicals can exceed normal levels, causing protein denaturation, DNA damage, and the oxidation of the cell membrane, which, in turn, causes inflammation. Acanthopanax senticosus (A. senticosus) flavonoids are the main bioactive ingredients with antioxidant function. H₂O₂-treated RAW 264.7 cells and DSS-induced colitis in mice were used to evaluate the antioxidant properties of A. senticosus flavonoids. The results show that A. senticosus flavonoids can significantly downregulate the levels of ROS and MDA in H₂O₂-treated RAW 264.7 cells and increase the levels of CAT, SOD, and GPx. A. senticosus flavonoids can also increase the body weights of DSS-induced colitis mice, increase the DAI index, and ameliorate the shortening of the colon. ELISA experiments confirmed that A. senticosus flavonoids could reduce the level of MDA in the mouse serum and increase the levels of SOD, CAT, and GPx. Histopathology showed that the tissue pathological changes in the A. senticosus flavonoid group were significantly lower than those in the DSS group. The Western blot experiments showed that the antioxidant capacity of A. senticosus flavonoids was accomplished through the Nrf2 pathway. In conclusion, A. senticosus flavonoids can relieve oxidative stress in vivo and in vitro and protect cells or tissues from oxidative damage.     

ZnFe2O4中阳离子分布对苯酚H2O2羟化制苯二酚催化活性的影响

具有尖晶石结构的铁酸盐是苯酚H2O2羟化合成苯二酚的有效催化剂.分别用共沉淀和水热法制备了ZnFe2O4,并用Mossbauer,XRD和ESR等方法予以表征.发现不同方法制备的ZnFe2O4中阳离子在四面体和八面体位置的分布不同,认为阳离子分布影响了催化活性.     

Monitoring H2O2 on the Surface of Single Cells with Liquid Crystal Elastomer Microspheres

Live‐imaging of signaling molecules released from living cells is a fundamental challenge in life sciences. Herein, we synthesized liquid crystal elastomer microspheres functionalized with horse‐radish peroxidase (LCEM‐HRP), which can be immobilized directly on the cell membrane to monitor real‐time release of H₂O₂ at the single‐cell level. LCEM‐HRP could report H₂O₂ through a concentric‐to‐radial (C‐R) transfiguration, which is due to the deprotonation of LCEM‐HRP and the break of inter or intra‐chain hydrogen bonding in LCEM‐HRP caused by HRP‐catalyzed reduction of H₂O₂. The level of transfiguration of LCEM‐HRP revealed the different amounts of H₂O₂ released from cells. The estimated detection sensitivity was ≈2.2×10^?7 μm for 10 min of detection time. The cell lines and cell–cell heterogeneity was explored from different configurations. LCEM‐HRP presents a new approach for in situ real‐time imaging of H₂O₂ release from living cells and can be the basis for seeking more advanced chemical probes for imaging of various signaling molecules in the cellular microenvironment.