Marine Natural Compounds Research Articles

Synthesis of Marine (-)-Pelorol and Future Perspectives.

Meroterpenoid-type marine natural compounds have attracted an increasing amount of attention due to their peculiar chemical structures and their potential for the development of therapeutically important probes. Within this group of substances pelorol stands out; it is a natural compound isolated from marine organisms with a unique structure and an interesting biological profile. In this article, we summarize and highlight the most interesting aspects of the synthetic procedures towards this compound, which have two common key steps. The first is the coupling of a drimanyl derivative with a compound derived from an arene. The second is a Friedel-Crafts cyclization which forms the C ring of the natural product. Despite the synthetic advances achieved so far, we consider that a more efficient synthetic procedures could be carried out, since their synthetic routes are difficult to scale up due to numerous reaction steps and the limitations imposed by the use of some reagents. In this article, we present a new and versatile retrosynthetic analysis of (-)-pelorol and analogs, which is highly desirable for their easy preparation and subsequent broad study of their biological activities. This is a retrosynthetic route that could improve those reported in the literature in terms of cost-effectiveness.

Marine natural compounds as potential CBP bromodomain inhibitors for treating cancer: an in-silico approach using molecular docking, ADMET, molecular dynamics simulations and MM-PBSA binding free energy calculations.

The online version contains supplementary material available at 10.1007/s40203-024-00258-5.

Identification of Novel PBP2B Protein Inhibitors against Streptococcus pneumoniae in Marine Natural Products using an In-Silico Approach

Background: The aim of this research is to identify marine natural compounds derived from green, red, and brown algae that might possibly inhibit the Penicillin-Binding Proteins (PBPs) protein, which is responsible for the development of antibiotic resistance in Streptococcus pneumoniae (mutated resistant 5204-PBP2B strain). We obtained this by using virtual screening and molecular docking. In AutoDock Vina and the Schrodinger suite software, we screened a library of marine natural chemicals and discovered four intriguing candidates that had strong binding affinities to the active region of the PBPs protein. Based on our findings, four naturally occurring marine chemicals show great promise as new inhibitors of S. pneumoniae 5204-PBP2B protein. These discoveries reveal important new information on the potential application of marine natural products as a source of new drugs to combat antibiotic resistance in Streptococcus pneumoniae and other bacterial infections. Methods: The 3318 compounds in the Comprehensive Marine Natural Products Database (CMNPD) derived from green algae (293 compounds), brown algae (1212 compounds) and red algae (1813 compounds) were taken into consideration for this study. Through virtual screening and molecular docking investigations, we found the optimum compounds for the Penicillin-Binding Proteins (PBPs) protein in Streptococcus pneumoniae. Utilizing AutoDock Vina and Schrodinger Suite software, the 5204-PBP2B protein selected for this investigation was examined. The structure and binding interaction have been displayed using PyMOL software. Results: Through virtual screening and molecular docking investigations for the 5204-PBP2B protein in Streptococcus pneumoniae, we were able to identify four marine natural products that are present in brown algae from the Comprehensive Marine Natural Products Database. Conclusion: The study has indicated that the main cause of bacterial resistance to antibiotics is 5204-PBP2B in S. pneumoniae. This study's methodology has been shown to be effective in identifying four strong inhibitors of the CMNPD. In this work, potent molecules from CMNPD compounds were screened using the 3D structure of mutated resistant 5204 strain, named 5204- PBP2B (PDB ID: 2WAE) of S. pneumoniae. Out of 3318 compounds that showed strong interactions with PBP2B, docking studies revealed that four of the compounds were inhibitory for the protein and could be used to treat PBP2B. These four marine products were selected as a result of our earlier research on Klebsiella pneumonia’s New Delhi metallo-β-lactamase-1 (NDM-1) protein. This study thus reveals the importance of marine natural products for improving the drug development process, as well as the ability of four marine products generated from brown algae to inhibit both the NDM-1 protein of Klebsiella pneumoniae and the 5204-PBP2B protein in Streptococcus pneumoniae. It is also possible to expand this approach by investigating how different receptor inhibitors interact in a lab setting. Potential inhibitors can be discovered by evaluating the biological activity of the drugs and applying virtual screening and molecular docking techniques.

The therapeutic potential and application of marine alkaloids in treating breast cancer

Breast cancer is a major threat to women’s health worldwide. Although the 5-year survival rate is relatively high, treating recurrent and metastatic breast cancer remains challenging. Existing anticancer drugs are often accompanied by adverse reactions; thus, there is an urgent need to explore safer and more effective treatment options. Marine natural compounds, especially alkaloids, are considered to be a potential treasure trove of new anticancer drugs due to their unique chemical structure and wide range of biological activities. A variety of marine alkaloids against breast cancer, including ecteinascidins, halichondrins, manzamines, and trabectedins, have opened new avenues for breast cancer treatment by employing multiple mechanisms, such as inducing cell apoptosis and autophagy, blocking cell cycle, inhibiting angiogenesis, targeting oncogene pathways, and inhibiting metastasis and invasion. Currently, Yondelis (trabectedin) has completed phase II clinical trials in patients with breast cancer and has shown certain efficacy. However, the clinical application of marine alkaloids still needs further research and development. This article deeply explores the mechanism of action of marine alkaloids against breast cancer and anticipates their clinical application prospects. With the deepening of research and the advancement of development, marine alkaloids are expected to bring new breakthroughs in breast cancer treatment.

Exploring Dimethylsulfoniopropionate as a potential treatment for Alzheimer's disease: A study using the 3 × Tg-AD mouse model

BackgroundAlzheimer's disease (AD), the most common neurodegenerative disorder, affects a broad spectrum of aging populations. AD is characterized by pathological amyloid-β (Aβ) plaques and neurofibrillary tangles, leading to neural degeneration and cognitive decline. The lack of effective treatments for AD highlights the urgent need for novel therapeutic agents, particularly in the early stages. Dimethylsulfoniopropionate (DMSP) is a natural marine compound with antioxidant and neuroprotective properties. However, studies on the efficacy of DMSP in the treatment of AD and its associated mechanisms are limited. PurposeThis study aimed to explore the therapeutic effects and mechanisms of action of DMSP as an AD treatment using a preclinical 3 × Tg-AD mouse model. MethodsThe research involved administering DMSP (7 μg/mL and 11 μg/mL in drinking water) to four-month-old 3 × Tg-AD mice consecutively for three months. The Y-maze test, novel object recognition test, and Morris water maze test were used to assess memory and learning ability. The relative expression levels and distribution of proteins relevant to Aβ and tau pathology, synapses, and glial cells were analyzed using western blotting and immunofluorescence assays. Additionally, proteomic and bioinformatics approaches were used to explore the potential targets of DMSP treatment. ResultsDMSP-treated AD mice showed significantly enhanced cognitive function, suggesting that DMSP mitigates memory and learning impairments in AD. Moreover, DMSP diminished the abnormal accumulation of Aβ and phosphorylated tau in both the cortex and hippocampus, which are crucial hallmarks of AD pathology. In addition to its neuroprotective properties, DMSP restored synaptic density and the expression of synaptic and neuronal proteins, which are essential for proper brain function. DMSP displayed anti-inflammatory properties, as evidenced by its ability to suppress inflammatory astrocytes and maintain microglial homeostasis. Notably, DMSP facilitated the maturation of oligodendrocytes (OLs) from oligodendrocyte progenitor cells (OPCs), a critical process in the development of the brain myelination architecture. Proteomic analysis revealed that DMSP positively influenced biological processes crucial for oligodendrocyte development, myelination, and axonal ensheathment, which are often compromised in patients with AD. Protein validation and brain tissue staining supported the role of DMSP in preserving myelin enrichment and sheath integrity. These therapeutic effects were largely attributed to the enhanced expression of myelin-associated glycoprotein (Mag) and tetraspanin Cd9. ConclusionOverall, our findings highlight DMSP as a promising novel therapeutic candidate for AD, offering multifaceted benefits in cognitive and memory enhancement, reduction of Aβ and tau pathology, neuronal synapse protection, anti-inflammatory effects, and myelin sheath restoration as an innovative target compared to other studies. In addition to being a potentially effective treatment for AD, DMSP may also have the potential to address other neurodegenerative diseases that are closely associated with myelin impairment.

Chemical versus Natural Biocide Compounds - Minireview on Antifouling Coatings

Marine biofouling is an old problem, known and studied for centuries, since the beginning of navigation. The accumulation of marine biofouling begins on the submerged portion of an ocean-going vessel or on any installation (equipments, pipes, platforms, etc.) within minutes of contact with seawater. Over time, this accumulation increases the ship's resistance, leading to increases in the physical resistance of the ship in the water, with negative consequences on fuel consumption and greenhouse gas emissions, high maintenance costs (due to corrosion), and a negative impact on the marine environment (due to the release of toic bioactive compounds into the environment and the transfer of invasive species). These environmental issues were identified and recognized by the IMO, which in the early 1990s, through the Marine Environment Protection Committee (MEPC), adopted a resolution recommending that member governments adopt measures to eliminate TBT-based antifouling paints. These recommendations have led to the identification, development, and application of new antifouling technologies that could provide the maritime industry with a significant potential opportunity with an innovative, cost-effective, and efficient approach to the effects of marine biofouling. Our study aimed to make a small incursion in time, through the specialized literature on methods used to combat marine fouling, to highlight new research approaches to the identification and use of natural biocides to replace chemical ones. The targeting of research directions towards the identification of the most environmentally friendly antifouling compounds, in particular natural marine compounds, has been a focus of international researchers in recent years. To achieve this goal, going back to nature is currently the best option, as it could provide us with very effective models for research and development of antifouling coatings. In the development and modeling of new antifouling paints, the influence of the physical-chemical parameters of seawater (pH, salinity, temperature) on the chemical components (active groups) of the biocides used should not be ignored. The aim of this study is to highlight the importance of developing new antifouling paint technologies using biodegradable, non-toic, and environmentally friendly compounds according to international legislation. In recent years there has been an increasing emphasis in research studies on the combination of natural biocides (obtained through the valorization of marine wastes) with natural or synthetic hydrogels whose action is to minimize the attachment of marine fouling.

AS1041, a novel derivative of marine natural compound Aspergiolide A, induces senescence of leukemia cells via oxidative stress-induced DNA damage and BCR-ABL degradation

Chronic myelogenous leukemia (CML) is characterized by the constitutive activation of BCR-ABL tyrosine kinase. Imatinib was approved for CML therapy, however, BCR-ABL-dependent drug resistance, especially BCR-ABL-T315I mutation, restricts its clinical application. In this study, we reported anthraquinone lactone AS1041, a synthesized derivative of marine natural compound Aspergiolide A, showed anti-leukemia effect in vitro and in vivo by promoting cell senescence. Mechanistic study revealed the pro-senescence effect of AS1041 was dependent on oxidative stress-induced DNA damage, and the resultant activation of P53/P21 and P16INK4a/Rb. Also, AS1041 promoted ubiquitin proteasome system (UPS)-mediated BCR-ABL degradation, which also contributed to AS1041-induced senescence. In vivo, AS1041-induced senescence promoted tumor growth inhibition. In summary, the in vitro and in vivo antitumor effect of AS1041 suggests it can serve as a pro-senescence agent for alternative antileukemia therapy and imatinib-resistant cancer therapy by enhancing cellular oxidative stress and BCR-ABL degradation.

Exploring marine algae-derived phycocyanin nanoparticles as a safe and effective adjuvant for sunscreen systems

BackgroundUV radiation (UV) exposure risks skin damage and cancer due to DNA damage and oxidative stress. Synthetic chemical sunscreens that protect against UV radiation can have health and environmental concerns. This study explores phycocyanin (PC), a marine algae-derived natural photoprotective compound, and its crosslinked nanoparticles (PCNP) as safe and effective adjuvants for sunscreen systems.MethodsPCNP was synthesized via genipin-crosslinking. PC and PCNP biocompatibility were assessed on mouse embryonic fibroblast cells. ABTS evaluated antioxidant activity, and the UV absorption capacity of PC and PCNP were analyzed. PCNP skin permeability was tested in vitro and in vivo. Gel formulations with PCNP were examined for UV absorption effects.ResultsPCNP showed good biocompatibility, maintaining cell viability above 90% across concentrations. Both PC and PCNP demonstrated concentration-dependent antioxidant activity, efficiently scavenging free radicals. PCNP exhibited enhanced UV absorption in the UVB range compared to PC alone. Skin permeation studies displayed limited PCNP penetration through skin layers. In vivo, absorption assessments indicated PCNP localized mainly in the stratum corneum. PCNP-containing gels displayed improved UV absorption compared to gels without PCNP.ConclusionThis study showcases PCNP’s potential as a natural and safe adjuvant for sunscreen with enhanced UV protection capabilities. PCNP preserved antioxidant activity, displayed limited skin penetration, and enhanced UV absorption. The findings suggest PCNP’s promise as a viable alternative to synthetic sunscreen agents, delivering effective photoprotection while minimizing health and environmental concerns.

An in vitro anticancerous and antioxidant potentials of the brown seaweed Sargassum polycystum C. Agardh

Discovering new therapeutic agents for cancer treatment remains a significant issue in the search for a cure as, cancer is the preeminent reason of death worldwide. The majority of compounds used as chemotherapeutic medications to treat cancer have been found and isolated in plants for their synthetic derivatives. Biomaterials made from marine algae are crucial components of several medications used for the treatment of cancer and other diseases, due to their diverse bioactivities. The goal of the current study was to assess the marine algae Sargassum polycystum antioxidant capacity and anticancer efficacy against the A549 cell line. The antioxidants are crucial for preventing oxidative stress-related damage (OS). OS has been linked to the pathogenesis of several illnesses, including cancer, diabetes, and heart disease. Marine algae-derived natural compounds shield cells by reducing the effects of oxidative stress. From the algal extract DPPH radical scavenging activity in a concentration–dependent manner with maximum scavenging activity (IC50 value = 27.7±1.3µg/ml) was carried out. The in vitro anticancerous activity against the A549 Lung cancer cell line revealed that the IC50 value of Sargassum polycystum was 13±1.5 µg/ml. Thus we can deduce that the secondary metabolites from marine algae can advance with a substantial range of anti-cancerous medicaments.

Exploration of comprehensive marine natural products database against dengue viral non-structural protein 1 using high-throughput computational studies

Dengue virus (DENV) non-structural protein 1 (NS1) is a versatile quasi-protein essential for the multiplication of the virus. This study applied high-throughput virtual screening (HTVS) and molecular dynamics (MD) simulation to detect the potential marine natural compounds against the NS1 of DENV. The structure of the NS1 protein was retrieved from Protein Data Bank with (PDB ID: 4O6B). Missing residues were added using modeler software. Molecular operating environment (MOE) programme was used to prepare the protein before docking. Virtual screening was performed on PyRx software to identify natural compounds retrieved from Comprehensive Marine Natural Products Database (CMNPD) against the NS1 protein, and best-docked compounds were examined by molecular docking and molecular dynamic (MD) simulation. Out of 31,561 marine compounds, the top 10 compounds showed docking scores lesser than −8.0 kcal/mol. One of the best hit compounds, CMNPD6802, was further analyzed using MD simulation study at 100 nanoseconds and Molecular Mechanics with Generalized Born and Surface Area Solvation (MM/GBSA). Based on its total binding energy, determined using the MM/GBSA approach, CMNPD6802 was ranked first. Its pharmacokinetic properties concerning the target protein NS1 were also evaluated. The results of the MD simulation showed that CMNPD6802 remained in close contact with the protein throughout the activation period, mapped using principal component analysis. These findings suggest that CMNPD6802 could serve as an NS1 inhibitor and may be a potential candidate for treating DENV infections. Communicated by Ramaswamy H. Sarma

The Marine Natural Compound Dragmacidin D Selectively Induces Apoptosis in Triple-Negative Breast Cancer Spheroids.

Cancer cells grown in 3D spheroid cultures are considered more predictive for clinical efficacy. The marine natural product dragmacidin D induces apoptosis in MDA-MB-231 and MDA-MB-468 triple-negative breast cancer (TNBC) spheroids within 24 h of treatment while showing no cytotoxicity against the same cells grown in monolayers and treated for 72 h. The IC50 for cytotoxicity based on caspase 3/7 cleavage in the spheroid assay was 8 ± 1 µM in MDA-MB-231 cells and 16 ± 0.6 µM in MDA-MB-468 cells at 24 h. No cytotoxicity was seen at all in 2D, even at the highest concentration tested. Thus, the IC50 for cytotoxicity in the MTT assay (2D) in these cells was found to be >75 µM at 72 h. Dragmacidin D exhibited synergy when used in conjunction with paclitaxel, a current treatment for TNBC. Studies into the signaling changes using a reverse-phase protein array showed that treatment with dragmacidin D caused significant decreases in histones. Differential protein expression was used to hypothesize that its potential mechanism of action involves acting as a protein synthesis inhibitor or a ribonucleotide reductase inhibitor. Further testing is necessary to validate this hypothesis. Dragmacidin D also caused a slight decrease in an invasion assay in the MDA-MB-231 cells, although this failed to be statistically significant. Dragmacidin D shows intriguing selectivity for spheroids and has the potential to be a treatment option for triple-negative breast cancer, which merits further research into understanding this activity.

Marine-Derived Compounds for CDK5 Inhibition in Cancer: Integrating Multi-Stage Virtual Screening, MM/GBSA Analysis and Molecular Dynamics Investigations.

Cyclin-dependent kinase 5 (CDK5) plays a crucial role in various biological processes, including immune response, insulin secretion regulation, apoptosis, DNA (deoxyribonucleic acid) damage response, epithelial-mesenchymal transition (EMT), cell migration and invasion, angiogenesis, and myogenesis. Overactivation of CDK5 is associated with the initiation and progression of cancer. Inhibiting CDK5 has shown potential in suppressing cancer development. Despite advancements in CDK5-targeted inhibitor research, the range of compounds available for clinical and preclinical trials remains limited. The marine environment has emerged as a prolific source of diverse natural products with noteworthy biological activities, including anti-cancer properties. In this study, we screened a library of 47,450 marine natural compounds from the comprehensive marine natural product database (CMNPD) to assess their binding affinity with CDK5. Marine compounds demonstrating superior binding affinity compared to a reference compound were identified through high-throughput virtual screening, standard precision and extra-precision Glide docking modes. Refinement of the selected molecules involved evaluating molecular mechanics-generalized born surface area (MM/GBSA) free binding energy. The three most promising compounds, (excoecariphenol B, excoecariphenol A, and zyzzyanone B), along with the reference, exhibiting favorable binding characteristics were chosen for molecular dynamics (MD) simulations for 200 nanoseconds. These compounds demonstrated interaction stability with the target during MD simulations. The marine compounds identified in this study hold potential as effective CDK5 inhibitors and warrant subsequent experimental validation.

Rhizochalinin Exhibits Anticancer Activity and Synergizes with EGFR Inhibitors in Glioblastoma In Vitro Models.

Rhizochalinin (Rhiz) is a recently discovered cytotoxic sphingolipid synthesized from the marine natural compound rhizochalin. Previously, Rhiz demonstrated high in vitro and in vivo efficacy in various cancer models. Here, we report Rhiz to be highly active in human glioblastoma cell lines as well as in patient-derived glioma-stem like neurosphere models. Rhiz counteracted glioblastoma cell proliferation by inducing apoptosis, G2/M-phase cell cycle arrest, and inhibition of autophagy. Proteomic profiling followed by bioinformatic analysis suggested suppression of the Akt pathway as one of the major biological effects of Rhiz. Suppression of Akt as well as IGF-1R and MEK1/2 kinase was confirmed in Rhiz-treated GBM cells. In addition, Rhiz pretreatment resulted in a more pronounced inhibitory effect of γ-irradiation on the growth of patient-derived glioma-spheres, an effect to which the Akt inhibition may also contribute decisively. In contrast, EGFR upregulation, observed in all GBM neurospheres under Rhiz treatment, was postulated to be a possible sign of incipient resistance. In line with this, combinational therapy with EGFR-targeted tyrosine kinase inhibitors synergistically increased the efficacy of Rhiz resulting in dramatic inhibition of GBM cell viability as well as a significant reduction of neurosphere size in the case of combination with lapatinib. Preliminary in vitro data generated using a parallel artificial membrane permeability (PAMPA) assay suggested that Rhiz cannot cross the blood brain barrier and therefore alternative drug delivery methods should be used in the further in vivo studies. In conclusion, Rhiz is a promising new candidate for the treatment of human glioblastoma, which should be further developed in combination with EGFR inhibitors.

Marine Natural Compound (Neviotin A) Displays Anticancer Efficacy by Triggering Transcriptomic Alterations and Cell Death in MCF-7 Cells.

We investigated the anticancer mechanism of a chloroform extract of marine sponge (Haliclona fascigera) (sample C) in human breast adenocarcinoma (MCF-7) cells. Viability analysis using MTT and neutral red uptake (NRU) assays showed that sample C exposure decreased the proliferation of cells. Flow cytometric data exhibited reactive oxygen species (ROS), nitric oxide (NO), dysfunction of mitochondrial potential, and apoptosis in sample C-treated MCF-7 cells. A qPCR array of sample C-treated MCF-7 cells showed crosstalk between different pathways of apoptosis, especially BIRC5, BCL2L2, and TNFRSF1A genes. Immunofluorescence analysis affirmed the localization of p53, bax, bcl2, MAPKPK2, PARP-1, and caspase-3 proteins in exposed cells. Bioassay-guided fractionation of sample C revealed Neviotin A as the most active compound triggering maximum cell death in MCF-7, indicating its pharmacological potency for the development of a drug for the treatment of human breast cancer.

Integrated multi-omics analyses reveal Jorunnamycin A as a novel suppressor for muscle-invasive bladder cancer by targeting FASN and TOP1

BackgroundBladder cancer is a urological carcinoma with high incidence, among which muscle invasive bladder cancer (MIBC) is a malignant carcinoma with high mortality. There is an urgent need to develop new drugs with low toxicity and high efficiency for MIBC because existing medication has defects, such as high toxicity, poor efficacy, and side effects. Jorunnamycin A (JorA), a natural marine compound, has been found to have a high efficiency anticancer effect, but its anticancer function and mechanism on bladder cancer have not been studied.MethodsTo examine the anticancer effect of JorA on MIBC, Cell Counting Kit 8, EdU staining, and colony formation analyses were performed. Moreover, a xenograft mouse model was used to verify the anticancer effect in vivo. To investigate the pharmacological mechanism of JorA, high-throughput quantitative proteomics, transcriptomics, RT-qPCR, western blotting, immunofluorescence staining, flow cytometry, pulldown assays, and molecular docking were performed.ResultsJorA inhibited the proliferation of MIBC cells, and the IC50 of T24 and UM-UC-3 was 0.054 and 0.084 μM, respectively. JorA-induced significantly changed proteins were enriched in “cancer-related pathways” and “EGFR-related signaling pathways”, which mainly manifested by inhibiting cell proliferation and promoting cell apoptosis. Specifically, JorA dampened the DNA synthesis rate, induced phosphatidylserine eversion, and inhibited cell migration. Furthermore, it was discovered that fatty acid synthase (FASN) and topoisomerase 1 (TOP1) are the JorA interaction proteins. Using DockThor software, the 3D docking structures of JorA binding to FASN and TOP1 were obtained (the binding affinities were − 8.153 and − 7.264 kcal/mol, respectively).ConclusionsThe marine compound JorA was discovered to have a specific inhibitory effect on MIBC, and its potential pharmacological mechanism was revealed for the first time. This discovery makes an important contribution to the development of new high efficiency and low toxicity drugs for bladder cancer therapy.Graphical

Hydrogen/Deuterium Exchange in Ambrox Could Improve the Long-Term Scent and Shelf Life of Perfumes

Ambrox is a marine natural compound with a delicious ambergris-type scent widely used in fine perfumery. The increase in the long-term scent and shelf life of perfumes has become a paramount endeavor in the fragrance industry. To the best of our knowledge, the exchange of hydrogen by deuterium to decrease the volatility of the constituents of a perfume has not yet been investigated. In this article, we propose this new use of deuteration to synthesize deuterated ambrox in order to decrease its volatility and improve the long-term scent and extend the shelf-life of perfumes.

Discovery of a natural small-molecule AMP-activated kinase activator that alleviates nonalcoholic steatohepatitis

Non-alcoholic steatohepatitis (NASH) is a primary cause of cirrhosis and hepatocellular carcinoma. Unfortunately, there is no approved drug treatment for NASH. AMP-activated kinase (AMPK) is an important metabolic sensor and whole-body regulator. It has been proposed that AMPK activators could be used for treating metabolic diseases such as obesity, type 2 diabetes and NASH. In this study, we screened a marine natural compound library by monitoring AMPK activity and found a potent AMPK activator, candidusin A (CHNQD-0803). Further studies showed that CHNQD-0803 directly binds recombinant AMPK with a KD value of 4.728 × 10–8 M and activates AMPK at both molecular and intracellular levels. We then investigated the roles and mechanisms of CHNQD-0803 in PA-induced fat deposition, LPS-stimulated inflammation, TGF-β-induced fibrosis cell models and the MCD-induced mouse model of NASH. The results showed that CHNQD-0803 inhibited the expression of adipogenesis genes and reduced fat deposition, negatively regulated the NF-κB-TNFα inflammatory axis to suppress inflammation, and ameliorated liver injury and fibrosis. These data indicate that CHNQD-0803 as an AMPK activator is a novel potential therapeutic candidate for NASH treatment.

Computational Characterization of Xyloketal B with Human C-Reactive Protein For Management of Kawasaki Disease (KD)

The most common underlying cause of acquired cardiovascular disease in developed countries is Kawasaki disease (KD), a systemic vasculitis. The most serious and common consequence of KD is the growth of coronary artery involvement, however therapy with intravenous gammaglobulin can minimized this issue. There are various limitations of using intravenous gammaglobulin which further make researchers to look for alternative medicine. It has been found that marine natural products and compounds from natural sources are having cardioprotective nature. The present research aims at filling the gap with computational analysis to explore the target ability y of Xyloketal B on human C-Reactive Protein having vital role in Kawasaki disease. It has been found that the marine compound has the ability to inhibit CRP with considerable negative biding energy of-8.47Kcal/mol. The present stdy may aid researchers to explore new invention having the potential for enzymatic and chemical modification of the molecule for the management of KD. Patients having a history of coronary artery disease, involvement are encouraged to have long-term follow-up.

In silico analysis of marine natural product for protein arginine methyltransferase 5(PRMT5) inhibitors based on pharmacophore and molecular docking

Over the past few decades, various inhibitors of PRMT5 have been developed because of its involvement in a variety of tumor development processes. As of now, no drugs targeting PRMT5 have been approved, and multiple drugs entering clinical trials have proven to have side effects. In this study, PRMT5 was used to perform virtual screening of 52119 marine natural compounds by combining various methods. We constructed 20 pharmacophore models based on multiple ligands. The best pharmacophore model AARR_2 was selected by analyzing the statistical parameters of the pharmacophore model and the binding characteristics of the ligand active site, and then 3552 compounds were screened out. Compared with the positive compound, 46 compounds were selected based on the molecular docking fraction and docking mode analysis. Then, 3D-QSAR was used to analyze the relationship between structure and activity of the compounds. Then, in addition to marine compounds 36404, 36405 and 14436, we selected compound 46 (the positive control compound) and used the CLC-Pred online Web server to predict their cytotoxicity to human cell lines, making cell experiments possible. Finally, we conducted the prediction of ADMET in order to better promote clinical trials. After comprehensive judgment, we screened out the marine natural compounds 36404 and 36405 as candidates for PRMT5 substrate competitive inhibitors. Communicated by Ramaswamy H. Sarma

Antinociceptive Effects of Aaptamine, a Sponge Component, on Peripheral Neuropathy in Rats

Aaptamine, a natural marine compound isolated from the sea sponge, has various biological activities, including delta-opioid agonist properties. However, the effects of aaptamine in neuropathic pain remain unclear. In the present study, we used a chronic constriction injury (CCI)-induced peripheral neuropathic rat model to explore the analgesic effects of intrathecal aaptamine administration. We also investigated cellular angiogenesis and lactate dehydrogenase A (LDHA) expression in the ipsilateral lumbar spinal cord after aaptamine administration in CCI rats by immunohistofluorescence. The results showed that aaptamine alleviates CCI-induced nociceptive sensitization, allodynia, and hyperalgesia. Moreover, aaptamine significantly downregulated CCI-induced vascular endothelial growth factor (VEGF), cluster of differentiation 31 (CD31), and LDHA expression in the spinal cord. Double immunofluorescent staining showed that the spinal VEGF and LDHA majorly expressed on astrocytes and neurons, respectively, in CCI rats and inhibited by aaptamine. Collectively, our results indicate aaptamine's potential as an analgesic agent for neuropathic pain. Furthermore, inhibition of astrocyte-derived angiogenesis and neuronal LDHA expression might be beneficial in neuropathy.