Potential Utilization of Phenolic Acid Compounds as Anti-Inflammatory Agents through TNF-α Convertase Inhibition Mechanisms: A Network Pharmacology, Docking, and Molecular Dynamics Approach.

Inflammation is a dysregulated immune response characterized by an excessive release of proinflammatory mediators, such as cytokines and prostanoids, leading to tissue damage and various pathological conditions. Natural compounds, notably phenolic acid phytocompounds from plants, have recently garnered substantial interest as potential therapeutic agents to bolster well-being and combat inflammation recently. Based on previous research, the precise molecular mechanism underlying the anti-inflammatory activity of phenolic acids remains elusive. Therefore, this study aimed to predict the molecular mechanisms underpinning the anti-inflammatory properties of selected phenolic acid phytocompounds through comprehensive network pharmacology, molecular docking, and dynamic simulations. Network pharmacology analysis successfully identified TNF-α convertase as a potential target for anti-inflammatory purposes. Among tested compounds, chlorogenic acid (-6.90 kcal/mol), rosmarinic acid (-6.82 kcal/mol), and ellagic acid (-5.46 kcal/mol) exhibited the strongest binding affinity toward TNF-α convertase. Furthermore, phenolic acid compounds demonstrated molecular binding poses similar to those of the native ligand, indicating their potential as inhibitors of TNF-α convertase. This study provides valuable insights into the molecular mechanisms that drive the anti-inflammatory effects of phenolic compounds, particularly through the suppression of TNF-α production via TNF-α convertase inhibition, thus reinforcing their anti-inflammatory attributes.

Ulvan/Silver nanoparticle hydrogel films for burn wound dressing.

Ulvan is a polysaccharide from green algae that shows good hydrogel film dressing characteristics. Silver nanoparticles (AgNP) can be incorporated into the hydrogel film to improve antibacterial properties and provide a potential burn treatment. In this study, we developed a novel hydrogel film wound dressing composed of ulvan and silver nanoparticles. Two concentrations (0.5 mM and 1 mM) of silver nitrate were used to produce ulvan-silver nanoparticles hydrogel film (UHF-AgNP0.5 and UHF-AgNP1), respectively. The physicochemical characteristics of the hydrogel films were evaluated, including particle size, zeta potential, Fourier transform infrared (FTIR), X-ray diffractometry (XRD), scanning electron microscope and energy-dispersive X-ray (SEM-EDX). Furthermore, the in vitro antimicrobial activity, and second-degree burn wound healing test were evaluated. The UHF-AgNP0.5 showed the highest antimicrobial activity compared to UHF-AgNP1 and UHF film. Meanwhile, an in vivo study using Wistar rats induced second-degree burns showed that UHF-AgNP0.5 significantly accelerated the healing process by regulating the inflammatory process, increasing re-epithelialization, and improving the vascularization process. Ulvan-silver nanoparticle hydrogel films have the ability to accelerate the healing of second-degree burns and are potential candidates for wound dressings.

In silico screening of potential compounds from begonia genus as 3CL protease (3Cl pro) SARS-CoV-2 inhibitors.

Background: The emergence of Coronavirus disease (COVID-19) has been declared a pandemic and made a medical emergency worldwide. Various attempts have been made, including optimizing effective treatments against the disease or developing a vaccine. Since the SARS-CoV-2 protease crystal structure has been discovered, searching for its inhibitors by in silico technique becomes possible. Objective: This study aims to virtually screen the potential of phytoconstituents from the Begonia genus as 3Cl pro-SARS-CoV- 2 inhibitors, based on its crucial role in viral replication, hence making these proteases "promising" for the anti-SARS-CoV-2 target. Methods: In silico screening was carried out by molecular docking on the web-based program DockThor and validated by a retrospective method. Predictive binding affinity (Dock Score) was used for scoring the compounds. Further molecular dynamics on Desmond was performed to assess the complex stability. Results: Virtual screening protocol was valid with the area under curve value 0.913. Molecular docking revealed only ß-sitosterol- 3-O-ß-D-glucopyranoside with a lower docking score of - 9.712 kcal/mol than positive control of indinavir. The molecular dynamic study showed that the compound was stable for the first 30 ns simulations time with Root Mean Square Deviation <3 Å, despite minor fluctuations observed at the end of simulation times. Root Mean Square Fluctuation of catalytic sites HIS41 and CYS145 was 0.756 Å and 0.773 Å, respectively. Conclusions: This result suggests that ß-sitosterol-3-O-ß-Dglucopyranoside might be a prospective metabolite compound that can be developed as anti-SARS-CoV-2.

Molecular Docking and Molecular Dynamics Studies of Antidiabetic Phenolic Compound Isolated from Leaf Extract of Englerophytum magalismontanum (Sond.) T.D.Penn.

Englerophytum magalismontanum, a medicinal plant with ethnopharmacology use, has a dearth of information regarding its antidiabetic properties. This study evaluated the crude methanol leaf extract of E. magalismontanum and its fractions for total phenolic content, antioxidant activity, and digestive enzymes (α-amylase and α-glucosidase) inhibitory activity using standard methods. The total phenolic content (56.53 ± 1.94 mg GAE/g dry extract) and DPPH Trolox antioxidant equivalent (TAE) (1.51 ± 0.66 µg/mL) of the methanol fraction were the highest among the fractions. The IC50 values of the methanol fraction against α-amylase (10.76 ± 1.33 µg/mL) and α-glucosidase (12.25 ± 1.05 µg/mL) activities were also high. Being the most active, the methanol fraction was subjected to bio-assay guided column chromatography-based enzyme inhibition to obtain a pure compound. The phenolic compound isolated and identified as naringenin inhibited α-amylase and α-glucosidase with IC50 of 5.81 ± 2.14 µg/mL and 4.77 ± 2.99 µg/mL, respectively. This is the first study to isolate naringenin from E. magalismontanum extract. The molecular docking and molecular dynamics studies demonstrated naringenin as a promising lead compound in comparison to acarbose for the treatment of diabetes through the inhibition of α-glucosidase activity.

Development and Characterization of Ulvan Polysaccharides-Based Hydrogel Films for Potential Wound Dressing Applications.

BACKGROUND: Ulvan is a natural polymer and type of sulfated polysaccharides from green seaweed that could have potential as a candidate for wound dressing material based on the support of its biopolymer characteristics such as antioxidant and antimicrobial activities. OBJECTIVE: In this study, we developed and prepared three different hydrogel films to explore the potency of ulvan for wound dressing application. METHODS: Ulvan hydrogel films were prepared by the facile method through ionic crosslinking with boric acid and added glycerol as a plasticizer. The films were evaluated in regard to swelling degree, water vapor transmission (WVTR), Fourier transform infrared (FTIR), powder x-ray diffractometry (P-XRD), scanning electron microscopy (SEM), mechanical properties, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), antimicrobial, and antioxidant activity. RESULTS: The hydrogel films showed that the different concentration of ulvan in the formula affects the characteristics of the hydrogel film. The higher the concentration of ulvan in UHF, the higher the value of viscosity (201±13.45 to 689±62.23 cps for UHF5 to UHF10), swelling degree (82% to 130% for UHF5 to UHF10 at 1 h), moisture content (24%±1.94% to 18.4%±0.51 for UHF5 to UHF10), and the WVTR were obtained in the range 1856-2590g/m2/24h. Meanwhile, the SEM showed porous hydrogel film. Besides, all hydrogel films can reduce hydroxyl radicals and inhibit gram-positive and negative bacteria (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Streptococcus epidermidis). CONCLUSION: The swelling behavior and WVTR of these films are great and could have potential as a wound dressing biomaterial, supported by their antimicrobial and antioxidant properties.

GC-MS, LC-MS/MS, Docking and Molecular Dynamics Approaches to Identify Potential SARS-CoV-2 3-Chymotrypsin-Like Protease Inhibitors from Zingiber officinale Roscoe.

This study aims to identify and isolate the secondary metabolites of Zingiber officinale using GC-MS, preparative TLC, and LC-MS/MS methods, to evaluate the inhibitory potency on SARS-CoV-2 3 chymotrypsin-like protease enzyme, as well as to study the molecular interaction and stability by using docking and molecular dynamics simulations. GC-MS analysis suggested for the isolation of terpenoids compounds as major compounds on methanol extract of pseudostems and rhizomes. Isolation and LC-MS/MS analysis identified 5-hydro-7, 8, 2'-trimethoxyflavanone (9), (E)-hexadecyl-ferulate (1), isocyperol (2), N-isobutyl-(2E,4E)-octadecadienamide (3), and nootkatone (4) from the rhizome extract, as well as from the leaves extract with the absence of 9. Three known steroid compounds, i.e., spinasterone (7), spinasterol (8), and 24-methylcholesta-7-en-3ß-on (6), were further identified from the pseudostem extract. Molecular docking showed that steroids compounds 7, 8, and 6 have lower predictive binding energies (MMGBSA) than other metabolites with binding energy of -87.91, -78.11, and -68.80 kcal/mole, respectively. Further characterization on the single isolated compound by NMR showed that 6 was identified and possessed 75% inhibitory activity on SARS-CoV-2 3CL protease enzyme that was slightly different with the positive control GC376 (77%). MD simulations showed the complex stability with compound 6 during 100 ns simulation time.

Antioxidant and antiviral potency of Begonia medicinalis fractions.

OBJECTIVES: This study aims to evaluate the antioxidant and antiviral potency of n-hexane, ethyl acetate and, water fractions of Begonia medicinalis Ardi & D.C.Thomas as well as to identify the chemical constituents. METHODS: Assays for antioxidant and antiviral activity (HIV-1) were carried out on MT-4 cells infected with HIV using the DPPH method and the determination of the cytopathic effect. Meanwhile, GC-MS was used to identify the chemical compounds. RESULTS: The determination of antioxidants showed that all fractions possessed potent activity with the IC50 ranging from 2.61 to 8.26 µg/mL. From the antiviral activity of MT-4 cells infected by HIV, the n-hexane fraction of B. medicinalis showed the most potency with the IC50 of 0.04 ± 0.05 µg/mL. It has less cytotoxicity (11.08 ± 4.60 µg/mL) affording the high selectivity index of 238.80. Furthermore, GC-MS analysis of n-hexane fraction found the major compound of carboxylic acid derivate with the area percentage of 76.4% and the presence of phenolic compounds (8.38%). Meanwhile, in water fraction, terpenoids were found in a higher concentration (10.05%) than others. CONCLUSIONS: Therefore, this study supports the application of B. medicinalis as a herbal medicine for antioxidant and antiviral.

A Comprehensive Review on Ulvan Based Hydrogel and Its Biomedical Applications.

Ulvan is a natural sulfated polysaccharide obtained from marine green algae composed of 3-sulfated rhamnoglucuronan as the main component. It has a unique chemical structure that rich of L-rhamnosa, D-glucuronic acid, and L-iduronic acid. Ulvan has a similar structure to glycosaminoglycans (GAGs) in mammals including chondroitin sulfate, dermatan sulfate, and heparan sulfate that has broad range applications for many years. Here, we provide an overview of ulvan based hydrogels for biomedical applications. Hydrogels are one of ulvan advances in polymer science for application in drug delivery, tissue engineering, and wound healing. This review presented an overview about functional information of ulvan based hydrogels and the promising potential in biomedicals collected from published papers in Scopus, PubMed, and Google Scholar. Other important aspects concerning properties, hydrogel-forming mechanisms, and ulvan based hydrogel developments were reported as well. As conclusion, ulvan showed interesting properties in forming hydrogels and promising advances in biomedical applications.

Antiviral screening on Alpinia eremochlamys, Etlingera flexuosa, and Etlingera acanthoides extracts against HIV-infected MT-4 cells.

Alpinia eremochlamys K. Schum, Etlingera flexuosa A.D. Poulsen, and Etlingera acanthoides A.D. Poulsen are endemic Zingiberaceae plants from Central Sulawesi, Indonesia. This study is the first report on screening the potential antiviral activity of ethanol extracts of the leaves, pseudostems, and rhizomes parts on HIV-infected MT-4 cells and identifying chemical constituents by GC-MS. The plants were extracted by the maceration method using 96% ethanol as a solvent. The antiviral activity was measured using Viral-ToxGlo colorimetric method and using the extracts at concentrations ranging from 7.8 to 1000 µg/mL. GC-MS was used to identify the secondary metabolites of potential extracts. The results showed that ethanol extract of E. acanthoides rhizome was the most potent antiviral activity (IC50 of 1.74 ± 2.46 µg/mL) and less toxic on lymphocyte (MT-4) cells (CC50 of 204.90 ± 106.35 µg/mL), affording the highest value of selectivity index (SI) of 117.76. A. eremochlamys rhizomes also showed promising antiviral activity with IC50 of 64.18 ± 2.58 µg/mL and no toxicity on MT-4 cells affording a high SI value 19.05. Preliminary GC-MS identification showed the presence of terpenoids and fatty acids as major compounds. Zerumbone, ar-turmerone, caryophyllene, and caryophyllene oxide were also detected. Chemical constituents identified by GC-MS might be responsible for the antiviral activity of extracts, suggesting further isolation and antiviral testing of the purified compounds.

A new steroid glycoside from Begonia sp.: cytotoxic activity and docking studies.

Chemical investigation on the ethyl acetate extract of the aerial parts of Begonia sp. afforded a new steroid glycoside, 9(11)α,16(17)α-dioxirane-20,25-dihydroxy-ß-sitosterol-3-O-ß-glucopyranoside (1) along with a known steroidal glycoside, ß-sitosterol-3-O-ß-D-glucopyranoside (2). The Chemical structures were elucidated by 1D and 2D NMR and mass spectroscopic analysis. Cytotoxicity against four different cancer cell lines (HeLa, T47D, WiDr and Vero) was assessed. Compound 1 was more potent and selective against breast cancer cell line (T47D) than other cell lines with an IC50 value of 0.16 µg/mL. Further docking study of 1 exhibited the preference of molecule to bind in the epidermal growth factor receptor tyrosine kinase (EGFR-TK) binding pockets with docking scores of -97.8800 (PLANTS) and -3.56 kcal/mol (AutoDock 4.2.6).

Docking Study on Anti-HIV-1 Activity of Secondary Metabolites from Zingiberaceae Plants.

INTRODUCTION: Human immunodeficiency virus type-1 (HIV-1) that causes acquired immunodeficiency syndrome (AIDS) has become a worldwide health problem today. There are approximately 30 anti-HIV-1 drugs that have been used in the treatment of AIDS. However, effective anti HIV-1 agents with less side affect and high inhibition potency are still in demand. OBJECTIVE: The objective of this study was to identify the potential compounds from Zingiberaceae plants that might be active as anti-HIV-1 by molecular docking. MATERIALS AND METHODS: Molecular docking simulation was performed by using AutoDock 4.2 on Linux operation system. Docking protocol was validated by using root mean square deviation (RMSD) value using redocking and cross-docking methods. The reported metabolites from Zingiberaceae plants were docked on HIV-1 protease, integrase, and reverse transcriptase protein enzymes. RESULTS: The docking result showed that the genera of Zingiber, Etlingera, Alpinia, Hedychium, and Boesenbergia have potential metabolites that inhibit HIV protease, integrase, and reverse transcriptase enzymes by possessing lower docking energy than native ligand of amprenavir, raltegravir, and nevirapine. Among the metabolites, noralpindenoside B and alpindenoside A from Alpinia densespicata inhibited protease enzymes with the lowest docking energy of -18.02 and -17.90 kcal/mol, respectively. Meanwhile, panduratin E from Boesenbergia pandurata Roxb. and 5α,8α-epidioxyergosta-6,22-dien-3ß-ol from Etlingera elatior showed the lowest docking energy on integrase protein with docking energy of -11.97 and -11.41 kcal/mol, respectively. Pahangensin A from Alpinia pahangensis Ridley showed the lowest docking energy on reverse transcriptase enzyme with docking energy of -13.76 kcal/mol. CONCLUSION: The docking molecular study has identified the possible potential compounds from Zingiberaceae plants that might be used for anti-HIV-1 treatment. So, this study suggested further isolation and purification of the predicted compounds.

A review of steroids from Sarcophyton species.

This review reports the structural diversity of steroids from Sarcophyton species based on literature from the beginning of marine steroid research until now. There are 65 compounds studied from eight species. Most of them are polyhydroxy-type steroids of C-27-C-31 carbon skeleton. Their biological activities are highly diverse ranging from cytotoxic, antibacterial, antifungal, antiviral, anti-inflammatory, antidiabetic to antiosteoporosis properties.

The role of new eudesmane-type sesquiterpenoid and known eudesmane derivatives from the red alga Laurencia obtusa as potential antifungal-antitumour agents.

A new eudesmane sesquiterpenoid, eudesma-4(15),7-diene-5,11-diol (1) along with the known trinor-sesquiterene, teuhetenone (2), and a seco-eudesmane sesquiterpene, chabrolidione B (3), have been isolated from the Red Sea red alga Laurencia obtusa. The chemical structures were elucidated on the basis of extensive spectroscopic analysis. The antifungal and cytotoxic activities of the isolated metabolites were tested against several fungi, yeast and human mammary carcinoma cell line (MCF-7). Compounds 1 and 3 showed a much better activity [minimum inhibitory concentration (MIC): 2.9 µM] than that of amphotericin B (MIC: 4.6 µM). Interestingly, compound 2, the least active antifungal compound, retained the high anticancer activity against MCF-7 (22 µM) in comparison with cisplatin (59 µM), which was determined by employing lactate dehydrogenase assay. Compounds 1-3 are recorded here for the first time from algal flora. The chemotaxonomic importance of the isolated metabolites was discussed.