Special Issue-"Natural Products That Might Change Society".

This Special Issue of Molecules gathers eight research papers and two review articles covering the isolation, identification, and biological activity of selected natural products, with the aim of discovering potential candidates that could change society and improve human health [...].

Anti-phototoxicity and anti-melanogenesis activities of eelgrass Zostera marina and its phenolic constituents.

The eelgrass Zostera marina L. has several economic roles, from its earlier usage in the insulation industry to protecting the earth from global warming. In this study, we aimed to discover the cosmetic potential of Z. marina. A methanolic extract of Z. marina showed anti-phototoxicity and anti-melanogenesis activity with an IC50 of 17.5 µM, followed by a phytochemical analysis of its phenolic constituents. Ten compounds (1-10) were isolated by several chromatographic techniques and identified by means of nuclear magnetic resonance spectroscopy (NMR) as well as high-resolution mass spectrometry (HR/MS). The identified compounds are caffeic acid (1), 3,4-dihydroxybenzoic acid (protocatechuic acid) (2), luteolin (3), diosmetin (4), 4-coumaroyl-4'-hydroxyl phenyllactic acid (5), rosmarinic acid (6), caffeoyl-4'-hydroxy-phenyllactic acid (isorinic acid) (7), apigenin 7-O-ß-D-glucopyranoside (8), luteolin 7-O-ß-D-glucopyranoside (9), and luteolin 7-sulfate (10). This is the first report to identify compounds 5 and 7 from the family Zosteraceae. The isolated compounds were assessed for their anti-aging abilities and were found to exhibit good anti-phototoxicity and anti-melanogenesis activities by increasing the viability of UVB-irradiated HaCaT cells by 6% to 34% and by inhibiting melanin synthesis in B16 melanoma cells by 44% to 65%.

Novel inhibitory effect of black chokeberry (Aronia melanocarpa) from selected eight berries extracts on advanced glycation end-products formation and corresponding mechanism study.

Numerous health hazards have been connected to advanced glycation end products (AGEs). In this investigation, using reaction models including BSA-fructose, BSA- methylglyoxal (MGO), and BSA-glyoxal (GO), we examined the anti-glycation potential of eight different berry species on AGEs formation. Our results indicate that black chokeberry (Aronia melanocarpa) exhibited the highest inhibitory effects, with IC50 values of 0.35 ± 0.02, 0.45 ± 0.03, and 0.48 ± 0.11 mg/mL, respectively. Furthermore, our findings suggest that black chokeberry inhibits AGE formation by binding to BSA, which alleviates the conformation alteration, prevents protein cross-linking, and traps reactive α-dicarbonyls to form adducts. Notably, three major polyphenols, including cyanidin-3-O-galactoside, cyanidin-3-O-arabinoside, and procyanidin B2 from black chokeberry, showed remarkably inhibitory effect on MGO/GO capture, and new adducts formation was verified through LC-MS/MS analysis. In summary, our research provides a theoretical basis for the use of berries, particularly black chokeberry, as natural functional food components with potential anti-glycation effects.

Cytotoxicity evaluation of phytochemicals from stingless bee (Tetragonula biroi) propolis.

Three prenylated flavonoids (1-3) were isolated from Tetragonula biroi propolis. The structures of the isolated compounds were characterized by NMR, IR, and UV spectroscopic and mass spectrometric analyses. The cytotoxicity activity of the crude extracts, fractions and the isolated compounds were established against four cell lines such as Caco-2, HeLa, MCF-7, and OVK-18. Among the tested compounds, compound 1 showed cytotoxicity activity against MCF-7 cell lines, whereas compound 2 showed good activity against Caco-2 and OVK-18 cell lines with IC50 values of 14.73 and 14.44, respectively. Moreover, compound 3 exhibited strong activity against OVK-18 cell lines. These findings contribute to the phytochemical understanding of the T. biroi propolis, and their cytotoxicity effects for future pharmaceutical purposes.

Long term administration of loquat leaves and their major component, ursolic acid, attenuated endogenous amyloid-ß burden and memory impairment.

Loquat (Eriobotrya japonica) leaves contain many bioactive components such as ursolic acid (UA) and amygdalin. We investigated the effects of loquat leaf powder and methanol extract in human neuroglioma H4 cells stably expressing the Swedish-type APP695 (APPNL-H4 cells) and C57BL/6 J mice. Surprisingly, the extract greatly enhanced cellular amyloid-beta peptide (Aß) 42 productions in APPNL-H4 cells. Administration of leaf powder increased Aß42 levels after 3 months and decreased levels after 12 months compared to control mice. Leaf powder had no effect on working memory after 3 months, but improved working memory after 12 months. Administration of UA decreased Aß42 and P-tau levels and improved working memory after 12 months, similar to the administration of leave powder for 12 months. Amygdalin enhanced cellular Aß42 production in APPNL-H4 cells, which was the same as the extract. Three-month administration of amygdalin increased Aß42 levels slightly but did not significantly increase them, which is similar to the trend observed with the administration of leaf powder for 3 months. UA was likely the main compound contained in loquat leaves responsible for the decrease in intracerebral Aß42 and P-tau levels. Also, amygdalin might be one of the compounds responsible for the transiently increased intracerebral Aß42 levels.

A reverse micelle-mediated dispersive liquid-liquid microextraction coupled to high-performance liquid chromatography for the simultaneous determination of agomelatine and venlafaxine in pharmaceuticals and human plasma.

An eco-friendly dispersive liquid-liquid microextraction mediated with a reverse micelle and coupled to an HPLC-DAD was developed for the simultaneous determination of venlafaxine and agomelatine in dosage forms and human plasma. All the parameters affecting the extraction efficiencies of both drugs were investigated and optimized. Under the optimal conditions, an effective analytes' preconcentration with enrichment factors (EFs) up to 72 was achieved. The linearity of the method was established over the concentration range of 0.50-70.0 and 3.0-100.0 ng/mL for venlafaxine and agomelatine, respectively with good correlation coefficients > 0.998. The method exhibited low detection limits in the range of 0.15-0.89 ng/mL and excellent precisions expressed in %RSD < 3% with average recoveries between 95.0 to 101.0%. The proposed method was employed to analyze the targeted analytes in dosage forms and human plasma samples with favorable characteristics like excellent enrichment, high sensitivity, great accuracy, and high precision. Finally, the greenness of the developed method was assessed using three distinct metric tools, confirming the greenness of the proposed method. The findings of this research could have more general implications for the extraction of other analytes from various matrices.

Identification and immunological characterization of PLA2G2A and cell death-associated molecular clusters in idiopathic pulmonary fibrosis.

AIMS: Idiopathic pulmonary fibrosis (IPF) is a severe pulmonary interstitial pneumonia. Our study focuses on the role of PLA2 enzyme in the IPF to explore a more effective diagnosis and treatment mechanism of IPF. MAIN METHODS: Transcriptome data of IPF from GEO database and bleomycin-induced pulmonary fibrosis mice were analyzed to identify PLA2 enzyme and their metabolite, lysophosphatidylcholines 18:0, in IPF. Based on PLA2G2A and PLA2G2D / PLA2G2A-associated cell death genes (PCDs), the consensus clustering analysis was used to identify the subtypes of IPF and the correlation between PLA2G2A and prognosis was analyzed. The machine learning (ML) models and artificial neural network (ANN) model was used to validate the diagnostic accuracy of PLA2s and PCDs in diagnosing IPF. The gene and protein expression of NLRP3, GSDMD, and CASP-1 was estimated in recombinant PLA2G2A protein induced MLE-12 cells. KEY FINDINGS: The expression of PLA2G2D, PLA2G2A, and LPC18 significantly changed in IPF. Furtherly, PLA2G2A has a significant correlation with poor patient prognosis, which could predict the 2 or 3-years mortality rates of IPF. Two subtypes of IPF patients, identified based on PCDs, showed significant different immunoinfiltration. Recombinant PLA2G2A protein could induce the pyrotosis in the MLE-12 cell. The generalized linear model and ANN model of PLA2s or PCDs accurate diagnosis IPF. SIGNIFICANCE: PLA2G2A is the most robustly associated gene with IPF among the PLA2s, which demonstrates a potential in diagnosing and prognostic value in IPF, and provides a foundation for further understanding and breakthroughs in IPF diagnosis and treatment.

Studies on the Nonalkaloidal Secondary Metabolites of Hippeastrum vittatum (L'Her.) Herb. Bulbs.

Sixteen chemically varied metabolites were isolated from the bulbs of Hippeastrum vittatum (L'Her.) Herb., including eight flavonoids [3'-methyl isoliquiritigenin (2), 7-hydroxyflavan (8), 7-hydroxyflavanone (9), 7-hydroxyflavan-3-ol (10), 7-methoxy-3',4'-methylenedioxyflavan-3-ol (11), 7-hydroxy-3',4'-methylenedioxy flavan (12), 2',4'-dihydroxy-3'-methyl-3,4-methylenedioxychalcone (13), and isoliquiritigenin (14)], four acetophenones [2,6-dimethoxy-4-hydroxyacetophenone (3), 2,4-dihydroxyacetophenone (4), 2,4-dihydroxy-6-methoxy-3-methylacetophenone (6), and 2,4,6-trimethoxyacetophenone (7)], two alkaloids [lycorine (1) and narciprimine (15)], one phenol derivative [p-nitrophenol (5)], and one steroid [ß-sitosterol 3-O-ß-glucopyranoside (16)]. Their structures were elucidated by combining one- and two-dimensional NMR and ESI-MS techniques and by comparison with the reported literature data and some authentic samples. Except for lycorine (1), the isolated metabolites were obtained herein for the first time from Hippeastrum plants, among which compound 13 was identified as a new chalcone derivative. Additionally, the total phenolic and flavonoid contents of the total ethanol extract and different fractions of the bulbs were determined by the Folin-Ciocalteu and aluminum chloride colorimetric methods, respectively, whereas their antioxidant potential was compared using the phosphomolybdenum and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assays. Finally, the binding affinities of compounds 1-16 to some key target proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), namely, main protease (Mpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp), were screened and compared using molecular docking analysis. The possible chemotaxonomic significance of the identified metabolites was also discussed.

The application of biosurfactant-producing bacteria immobilized in PVA/SA/bentonite bio-composite for hydrocarbon-contaminated soil bioremediation.

Oil spills that contaminate the environment can harm the surrounding ecosystem. The oil contains petroleum hydrocarbon which is toxic to the environment hence it needs to be removed. The use of bacteria as remediation media was modified by immobilizing into a matrix hence the bacteria can survive in harsh conditions. In this research, the ability of biosurfactant-producing bacteria (Pseudomonas aeruginosa, Bacillus subtilis, and Ralstonia pickettii) immobilized in the PVA/SA/bentonite matrix was tested in remediation on oil-contaminated soil. The immobilized beads filled with bacteria were added to the original soil sample, as well as washed soil. The beads were characterized by using FTIR and SEM. Based on FTIR analysis, the PVA/SA/bentonite@bacteria beads had similar functional groups compared to each other. SEM analysis showed that the beads had non-smooth structure, while the bacteria were spread outside and agglomerated. Furthermore, GC-MS analysis results showed that immobilized B. subtilis and R. pickettii completely degraded tetratriacontane and heneicosane, respectively. Meanwhile, after soil washing pre-treatment, immobilized bacteria could completely degrade octadecane (P. aeruginosa and R. pickettii) and tetratriacontane (P. aeruginosa and B. subtilis). Based on those results, immobilized bacteria could degrade oil compounds. The degradation result was influenced by the enzymes produced, the ability of the bacteria, the suitability of the test media, and the matrix used. Therefore, this study can be a reference for further soil remediation using eco-friendly methods.

Vanilla pompona Leaves and Stems as New Sources of Bioactive Compounds: The Therapeutic Potential for Skin Senescence.

A large variety of natural plants are widely produced and utilised because of their remarkable pharmacological effects. In this study, two phenolic glycosides were isolated for the first time from Vanilla pompona Schiede (Orchidaceae) from Kyushu, Japan: bis [4-(ß-D - O-glucopyranosyloxy)-benzyl] (S)-2-isopropylmalate (1: ) and bis 4-[ß-D-O-glucopyranosyloxy)-benzyl]-(2R,3S)-2-isopropyl tartrate (2: ). We have discovered that the crude extract of V. pompona leaves and stems and its two phenolic glycosides (compounds 1:  - 2: ) are highly effective in reversing skin senescence. V. pompona and compounds 1:  - 2: were found to promote the synthesis of collagen, hyaluronic acid, and elastin in skin fibroblasts in a normal skin cell model; in a replicative senescence model, V. pompona and compounds 1:  - 2: significantly reduced the ageing phenotype in skin fibroblasts. These compounds also demonstrated a significant protective effect in a UV-induced photo-senescence model; the possible mechanisms of this effect were investigated in this study. To the best of our knowledge, this study is the first to develop V. pompona leaves and stems as new sources of bioactive compounds and to examine their therapeutic potential for skin senescence. The development potential of V. pompona leaves and stems for use in the cosmetics, cosmeceutical, and pharmaceutical industries remains to be investigated.

Phytochemical, ethnomedicinal uses and pharmacological profile of Juncus decipiens (Buchenau) Nakai (common rush).

Juncus decipiens is a member of the Juncaceae family and has culinary, medicinal, and decorative properties. It is also used in traditional Chinese Medicines for many years that promotes diuresis for strangury and clears out heart fire. This species has recently gained medicinal attention as a source of phenanthrenes, phenolic compounds, glycerides, flavonoids, and cycloartane triterpenes. This plant was also shown to be active, and researchers explored its antioxidant, anti-inflammatory, antialgal, antibacterial, and psychological behaviour-boosting properties. Preliminary research suggests that this species might be used for skin protection and brain disorders if proper clinical trials are conducted. The ethnomedicinal, phytochemistry, biological potencies, dangers, and scopes of Juncus decipiens have been examined in this respect.

Deacylated Derivative of Hericenone C Treated by Lipase Shows Enhanced Neuroprotective Properties Compared to Its Parent Compound.

Hericium erinaceus, a mushroom species commonly known as Yamabushitake in Japan, is known to have a stimulatory effect on neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Hericenone C, a meroterpenoid with palmitic acid as the fatty acid side chain, is reported to be one such stimulant. However, according to the structure of the compound, the fatty acid side chain seems highly susceptible to lipase decomposition, under in vivo metabolic conditions. To study this phenomenon, hericenone C from the ethanol extract of the fruiting body was subjected to lipase enzyme treatment and observed for changes in the chemical structure. The compound formed after the lipase enzyme digestion was isolated and identified using LC-QTOF-MS combined with 1H-NMR analysis. It was found to be a derivative of hericenone C without its fatty acid side chain and was named deacylhericenone. Interestingly, a comparative investigation of the neuroprotective properties of hericenone C and deacylhericenone showed that the BDNF mRNA expression in human astrocytoma cells (1321N1) and the protection against H2O2-induced oxidative stress was considerably higher in the case of deacylhericenone. These findings suggest that the stronger bioactive form of the hericenone C compound is in fact deacylhericenone.

Identification of telomere-related genes associated with aging-related molecular clusters and the construction of a diagnostic model in Alzheimer's disease based on a bioinformatic analysis.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease that is strongly associated with aging. Telomeres are DNA sequences that protect chromosomes from damage and shorten with age. Telomere-related genes (TRGs) may play a role in AD's pathogenesis. OBJECTIVES: To identify TRGs related to aging clusters in AD patients, explore their immunological characteristics, and build a TRG-based prediction model for AD and AD subtypes. METHODS: We analyzed the gene expression profiles of 97 AD samples from the GSE132903 dataset, using aging-related genes (ARGs) as clustering variables. We also assessed immune-cell infiltration in each cluster. We performed a weighted gene co-expression network analysis to identify cluster-specific differentially expressed TRGs. We compared four machine-learning models (random forest, generalized linear model [GLM], gradient boosting model, and support vector machine) for predicting AD and AD subtypes based on TRGs and validated TRGs by conducting an artificial neural network (ANN) analysis and a nomogram model. RESULTS: We identified two aging clusters in AD patients with distinct immunological features: Cluster A had higher immune scores than Cluster B. Cluster A and the immune system are intimately associated, and this association could affect immunological function and result in AD via the digestive system. The GLM predicted AD and AD subtypes most accurately and was validated by the ANN analysis and nomogram model. CONCLUSION: Our analyses revealed novel TRGs associated with aging clusters in AD patients and their immunological characteristics. We also developed a promising prediction model based on TRGs for assessing AD risk.

New benzaldehyde derivatives from the fruiting bodies of Hericium erinaceus with cytotoxic activity.

Four new natural compounds named hericenone O (1), hericenone P (2), hericenone Q (3), and hericenone R (4), two of them were reported synthetically (3-4), together with eleven known compounds were isolated from the fruiting bodies of Hericium erinaceus. The chemical structures of the isolated compounds were elucidated by using NMR analysis and mass spectrometry, as well as comparisons with the reported data in the literature. The bioactivity evaluation revealed that hericenone Q showed significant cytotoxic activity against Hep-G2 with IC50 values of 23.89 µM, and against HCT-116 with IC50 values of 65.64 µM.

Oligomeric Proanthocyanidin Complex from Avocado Seed as A Promising α-glucosidase Inhibitor: Characteristics and Mechanisms.

Although considered an abundant source of agricultural by-products, avocado (Persea americana Mill.) seed, with several biological activities and bioactive components, might become a promising resource for phytopharmaceutical development. In this study, through bioassay-guided isolation of the main α-glucosidase inhibitors in avocado seed, we discovered the major α-glucosidase inhibitor to be avocado seed oligomeric proanthocyanidin complex (ASOPC). Thiolysis and UPLC-DAD-HRESIMS showed the presence of A- and B-type procyanidins, and B-type propelargonidin with (epi)afzelechin as extension unit. Mean degree of polymerization (mDP) of ASOPC was calculated as 7.3 ± 1. Furthermore, ASOPC appeared to be a strong, reversible, competitive inhibitor of α-glucosidase, with IC50 value of 0.1 µg/mL, which was significantly lower than Acarbose (IC50 = 75.6 µg/mL), indicated that ASOPC is a potential natural α-glucosidase inhibitor. These findings would contribute to the direction of utilizing avocado seed bioactive components with the possibility to be used as natural anti-diabetic agents.

Investigation of pulmonary toxicity evaluation on mice exposed to polystyrene nanoplastics: The potential protective role of the antioxidant N-acetylcysteine.

Accumulating evidences show that the hazardous substance atmospheric nanoplastics increase the respiratory risk of individuals, but the inside toxicity mechanisms to lung tissue remain unclear. This study aims at investigating the potential mechanisms of inhaled cationic polystyrene nanoplastics (amine-polystyrene nanoplastics, APS-NPs)-induced pulmonary toxicity on mice. In vivo, the mice intratracheal administrated with APS-NPs suspension (5 mg/kg) were found inflammatory infiltrates in lung tissues through histopathology analysis. Furthermore, transcriptome analysis demonstrated that 1821 differentially expressed mRNA between APS group and control group were dominantly associated with 288 known KEGG pathways, indicating that APS-NPs might cause early inflammatory responses in lung tissue by activating the NLRP3/capase-1/IL-1ß signaling pathway. Moreover, in vitro results also showed that NLRP3 inflammasome could be activated to induce pyroptosis in MLE-12 cells after exposure to APS-NPs. And, MH-S cells after exposure to APS-NPs exhibited increased Irg1 proteins, leading to the increasing generation of ROS and inflammatory factors (e.g., tnf-α, il-6, il-1ß). In conclusion, these results revealed that Irg1/NF-κB/NLRP3/Caspase-1 signaling pathway was activated significantly after exposing to APS-NPs, leading to pulmonary toxicity on mice. Intriguingly, prior administration of the clinical antioxidant N-acetylcysteine (NAC) could serve as a possible candidate for the prevention and treatment of pulmonary toxicity induced by APS-NPs. The study contributes to a better understanding of the potential risks of environmental nanoplastics to humans and its improvement measure.

Antioxidant, anti-inflammatory and anti-acne activities of stingless bee (Tetragonula biroi) propolis.

We collected stingless bee propolis Tetragonula biroi in order to find materials for medicine and cosmetics applications from tropical rainforest resources. Even though this bee has some biological functions including a cancer cell line, hair growth promotion, asthma remedy, α-glucosidase enzyme inhibition, and antiviral action, the investigation on anti-acne has not been reported yet. This study was to focus on propolis Tetragonula biroi extracts and leads us to isolate active compounds for antioxidant, anti-inflammatory, and anti-acne. We used methanol to obtain the extract from this propolis and assayed it with antioxidants, anti-inflammation, and anti-acne. The extract showed strong activity in antioxidants by DPPH radical scavenging activity (82.31% in 6.25 µg/ml). Via a column chromatography and Reveleris PREP purification system, we isolated 3'-O-methyldiplacone, nymphaeol A, and 5,7,3',4'-tetrahydroxy-6-geranyl flavonol. These compounds showed potential biological activity with IC50 for antioxidant 6.33, 15.49, 17.32 µM; and antiinflammatory 121.54, 121.20, 117.31 µM. The isolated compounds showed anti-acne properties with properties 0.00, 14.11, and 13.78 mm for the inhibition zone (at a concentration of 1 µg/well), respectively. The results indicated that the propolis extract of Tetragonula biroi has the potential to be developed as a cosmetic agent; however, further work needs to be done to clarify its application.

Miniaturized ternary deep eutectic solvent-based matrix solid-phase dispersion: A green sample preparation method for the determination of chlorophenols in river sediment.

New ternary deep eutectic solvents were prepared and applied as efficient green dispersing solvents in miniaturized matrix solid-phase dispersion to extract chlorophenols from river sediments for the first time. High-performance liquid chromatography coupled with a photodiode array detector was used to analyze the target analytes. The significant factors affecting the extraction were optimized as follows: dispersant (100 mg), sample (100 mg), ternary eutectic solvents (150 µl), grinding for 1 min, 450 µl of acetonitrile as the elution solvent, and vortex mixing for 20 s. Under the optimal conditions, the method exhibited excellent linearity (correlation coefficient > 0.9980), low limits of detection between 1.039-2.478 µg/g, and extraction recoveries between 93.9% and 99.2%. Furthermore, the method demonstrated excellent precision in the intra- and inter-day analysis with a relative standard deviation below 6%. When compared to conventional extraction techniques, the miniaturized matrix solid-phase dispersion considerably reduced samples and solvent usag, offering important environmental benefits. The green profile of the method was assessed using the complementary green analytical procedure index tool confirming its eco-friendship. The technique was finally employed to evaluate sediment samples from three distinct locations along the Zuibaiji River, indicating its applicability for monitoring environmental samples.

Specneuzhenide improves bleomycin-induced pulmonary fibrosis in mice via AMPK-dependent reduction of PD-L1.

BACKGROUND: Pulmonary fibrosis (PF) is an escalating global health issue, characterized by rising rates of morbidity and mortality annually. Consequently, further investigation of potential damage mechanisms and potential preventive strategies for PF are warranted. Specnuezhenide (SPN), a prominent secoiridoid compound derived from Ligustrum lucidum Ait, exhibits anti-inflammatory and anti-oxidative capacities, indicating the potential therapeutic actions on PF. However, the underlying mechanisms of SPN on PF remain unclear. PURPOSE: This work was aimed at investigating the protective actions of SPN on PF and the potential mechanism. METHODS: In vivo, mice were administrated with bleomycin (BLM) to establish PF model. PF mice were treated with SPN (45/90 mg/kg) by gavage. In vitro, we employed TGF-ß1 (10 ng/mL)-induced MLE-12 and PLFs cells, which then were treated with SPN (5, 10, 20 µM). DARTS assay, biofilm interference experiment and molecular docking were performed to investigate the molecular target of SPN. RESULTS: In vivo, we found SPN treatment improved survival rate, alleviated pathological changes through reducing BLM-induced extracellular matrix (ECM) deposition, as well as BLM-induced epithelial-mesenchymal transition (EMT). In vitro, SPN inhibited EMT and lung fibroblast transdifferentiation. Mechanistically, SPN activated the AMPK protein to decrease the abnormally high level of PD-L1. Furthermore, the compound C, known as an AMPK inhibitor, exhibited a significant hindrance to the inhibition of SPN on TGF-ß1-caused fibroblast transdifferentiation and proliferation. This outcome could be attributed to the fact that compound C could eliminate the inhibitory effects of SPN on PD-L1 expression. Interestingly, DARTS assay, biofilm interference experiment and molecular docking results all indicated that SPN could bind to AMPK, which suggested that SPN might be a potential agonist targeting AMPK protein. CONCLUSION: Altogether, the results in our work illustrated that SPN promoted AMPK-dependent reduction of PD-L1 protein, contributing to the inhibition of fibrosis progression. Thus, SPN may represent a potential AMPK agonist for PF treatment.

Screening of Selected Stingless Bee Honey Varieties for ACE2-Spike Protein-Binding Inhibition Activity: A Potential Preventive Medicine Against SARS-Cov-2 Infection.

The broader objective of this study is to identify natural materials that might inhibit the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We have focused on stingless bee honey, which has a unique taste that is both sweet and sour and sometimes bitter. We screened 12 samples of honey from 11 species of stingless bees using an angiotensin-converting enzyme 2 (ACE2)-spike protein-binding assay and phytochemical analysis. Ten of the samples showed inhibition above 50% in this assay system. Most of the honey contained tannins, alkaloids, flavonoids, triterpenoids, carotenoids and carbohydrates. Our findings in this in vitro study showed that honey from stingless bees may have a potent effect against SARS-CoV-2 infection by inhibiting the ACE2-spike protein-binding.