Mechanism Of Bioactivity Research Articles

The structural characteristics of Crassostrea gigas peptide-zinc complexes and the bioactive mechanism of their enhanced zinc absorption

Zinc is an essential mineral for human health, and its deficiency can lead to various health issues. Oysters (Crassostrea gigas) are known to be a rich source of protein-bound zinc. Oyster peptides were complexed with zinc sulfate (ZnSO4) to be oyster peptide-zinc chelates (OPZs) that offer potential as a valuable zinc supplement. The complexation of zinc with oyster peptides induces conformational changes in the peptides, altering their overall spatial arrangement. This could potentially impact their functions and properties. OPZs have demonstrated enhanced physical and gastrointestinal stability, as they are resistant to digestion by pepsin and trypsin. The research has shown that OPZs can modulate the expression of key proteins involved in zinc binding (MT1), peptide transport (PePT1), and zinc transport (ZIP4 and ZnT1) in enterocytes. By regulating the proteins expression, OPZs have the potential to affect zinc absorption and homeostasis. Furthermore, OPZs have been found to enhance zinc absorption through dual pathways compared to the single pathway of inorganic zinc. Additionally, they have the potential to improve zinc bioaccessibility and bioavailability, meaning they can make zinc more easily absorbed by the body and readily available for use.

Integrated serum metabolomics and network pharmacology analysis on the bioactive metabolites and mechanism exploration of Bufei huoxue capsule on chronic obstructive pulmonary disease rats

Ethnopharmacological relevanceBufei Huoxue capsule (BHC) as a classic Chinese patent medicine formula, has the efficacy of tonifying the lungs and activating the blood. It has been extensively used in China for the treatment of chronic obstructive pulmonary disease (COPD) clinically. However, its mechanism is still unclear, which hampers the applications of BHC in treating COPD. Aim of the studyThe purpose of the present study was to demonstrate the protective efficacy and mechanism of BHC on COPD model rats by integrating serum metabolomics analysis and network pharmacology study. Materials and methodsA COPD rat model was established by cigarette fumigation combined with lipopolysaccharide (LPS) airway drip for 90 consecutive days. After oral administration for 30 days, the rats were placed in the body tracing box of the EMKA Small Animal Noninvasive Lung Function Test System to determine lung function related indexes. Histopathological alteration was observed by H&E staining and Masson staining. The serum levels of inflammatory cytokine, matrix metalloprotein 9, and laminin were determined by ELISA kits. Oxidative stress levels were tested by biochemical methods. UHPLC-Q-TOF/MS analysis of serum metabolomics and network pharmacology were performed to reveal the bioactive metabolites, key components and pathways for BHC treating COPD. WB and ELISA kits were used to verify the effects of BHC on key pathway. ResultsBHC could improve lung function, immunity, lung histopathological changes and collagen deposition in COPD model rats. It also could significantly reduce inflammatory response in vivo, regulate oxidative stress level, reduce laminin content, and regulate protease-antiprotease balance. Metabolomics analysis found 46 biomarkers of COPD, of which BHC significantly improved the levels of 23 differential metabolites including arachidonic acid, leukotriene B4 and prostaglandin E2. Combined with the results of network pharmacology, the components of BHC, such as calycosin, oxypaeoniflora, (S)-bavachin and neobavaisoflavone could play therapeutic roles through the arachidonic acid pathway. In addition, the results of WB and ELISA indicated that BHC could suppress the expressions of COX2 and 5-LOX in lung tissues and inhibit the generation of AA and its metabolites in serum samples. Regulation of arachidonic acid metabolic pathway may be the crucial mechanism for BHC treating COPD. ConclusionsIn summary, the studies indicated that BHC exhibited the protective effect on COPD model rats by anti-inflammatory and anti-oxidative properties through arachidonic acid metabolism pathway. This study provided beneficial support for the applications of BHC in treating COPD.

Biological Activity and Sterilization Mechanism of Marine Fungi-derived Aromatic Butenolide Asperbutenolide A Against Staphylococcus aureus.

Marine fungi represent a huge untapped resource of natural products. The bio-activity of a new asperbutenolide A from marine fungus Aspergillus terreus was not well known. In the present study, the minimum inhibitory concentration (MIC) and RNA-Sequencing were used to analyze the bio-activity and sterilization mechanism of asperbutenolide A against clinical pathogenic microbes. The results showed that the MICs of asperbutenolide A against methicillin-resistant Staphylococcus aureus (MRSA) were 4.0-8.0 μg/mL. The asperbutenolide A present poor bio-activity against with candida. The sterilization mechanism of asperbutenolide A against MRSA showed that there were 1426 differentially-expressed genes (DEGs) between the groups of MRSA treated with asperbutenolide A and negative control. Gene Ontology (GO) classification analysis indicated that the DEGs were mainly involved in cellular process, metabolic process, cellular anatomical entity, binding, catalytic activity, etc. Kyoto Encyclopedia of Genes and Genomes (KEGG) classification analysis showed that these DEGs were mainly enriched in amino acid metabolism, carbohydrate metabolism, membrane transport, etc. Moreover, qRT-PCR showed similar trends in the expressions of argF, ureA, glmS and opuCA with the RNA-Sequencing. These results indicated that asperbutenolide A was with ideal bio-activity against with MRSA and could be as a new antibacterial agent.

Qing Xia Jie Yi Formula granules alleviated acute pancreatitis through inhibition of M1 macrophage polarization by suppressing glycolysis

Ethnopharmacological relevanceHerbal formulas from Traditional Chinese Medicine are common and well-established practice for treating acute pancreatitis (AP) patients. However, little is known about their bioactive ingredients and mechanisms, such as their targets and pathways to inhibit inflammation. Aim of the studyThis study aimed to evaluate the effect of Qing Xia Jie Yi Formula (QXJYF) granules on AP and discuss the molecular mechanisms involved. Materials and methodsMajor compounds in QXJYF granules were identified using UPLC-quadrupole-Orbitrap mass spectrometry (UPLC-Q-Orbitrap MS). The effect of QXJYF granules on experimental AP models both in vitro and in vivo, and detailed mechanisms were clarified. Two AP models were induced in mice by intraperitoneally injections of caerulein or L-arginine, and QXJYF granules were used to treat AP mice in vivo. Histological evaluation of pancreas and lung, serum amylase and lipase levels, serum inflammatory cytokines, inflammatory cell infiltration and macrophage phenotype were assessed. Bone marrow derived macrophages (BMDMs) were cultured and treated with QXJYF granules in vitro. BMDM phenotype and glycolysis levels were measured. Lastly, clinical effect of QXJYF granules on AP patients was verified. Predicted severe AP (pSAP) patients eligible for inclusion were assessed for enrollment. ResultsNine major compounds were identified in QXJYF granules. Data showed that QXJYF granules significantly alleviated AP severity both in caerulein and L-arginine-induced AP models in vivo, pancreatic injury and inflammatory cell infiltration, systematic inflammation, lung injury and inflammatory cell infiltration were all improved after QXJYF treatment. QXJYF granules significantly reduced M1 macrophages during AP both in vivo and in vitro; besides, the mRNA expression levels of M1 genes such as inos, Tnfα, Il1β and Il6 were significantly lower after QXJYF treatment in M1 macrophages. Mechanistically, we found that HK2, PFKFB3, PKM, LDHα levels were increased in M1 macrophages, but significantly decreased after QXJYF treatment. Clinical data indicated that QXJYF granules could significantly reduce CRP levels and shorten the duration of organ failure, thereby reducing the incidence of SAP and preventing pSAP patients from progressing to SAP. ConclusionQXJYF granules alleviated AP through the inhibition of M1 macrophage polarization by suppressing glycolysis.

Antioxidative, Metabolic and Vascular Medicinal Potentials of Natural Products in the Non-Edible Wastes of Fruits Belonging to the Citrus and Prunus Genera: A Review.

Diabetes mellitus and related metabolic and vascular impairments are notable health problems. Fruits and vegetables contain phenolics that are beneficial to metabolic and oxidative health and useful in preventing associated disease. Scientific evidence has shown that some bioactive phenolics are more abundant in the non-edible parts (especially the peels) of many fruits than in their respective edible tissues. Fruits belonging to the Citrus and Prunus genera are commonly consumed worldwide, including in South Africa, and their non-edible wastes (peel and seed) have been shown to have antioxidative, metabolic and vascular pharmacological potentials and medicinal phytochemistry. It is therefore imperative to evaluate the pharmacological actions and phytochemical properties of the non-edible wastes of these fruits and understand how they could potentially be of medicinal relevance in oxidative, metabolic and vascular diseases, including diabetes, oxidative stress, obesity, hypertension and related cardiovascular impairments. In the absence of a previous review that has concomitantly presented the medicinal potentials of fruits wastes from both genera, this review presents a critical analysis of previous and recent perspectives on the medicinal potential of the non-edible wastes from the selected Citrus and Prunus fruits in metabolic, vascular and oxidative health. This review further exposes the medicinal phytochemistry, while elucidating the underlying mechanisms through the fruit wastes potentiates their therapeutic effects. A literature search was carried out on "PubMed" to identify peer-reviewed published (mostly 2015 and beyond) studies reporting the antidiabetic, antioxidative, antihypertensive, anti-hyperlipidemic and anti-inflammatory properties of the non-edible parts of the selected fruits. The data of the selected studies were analyzed to understand the bioactive mechanisms, bioactive principles and toxicological profiles. The wastes (seed and peel) of the selected fruits had antioxidant, anti-obesogenic, antihypertensive, anti-inflammatory, antidiabetic and tissue protective potentials. Some phenolic acids and terpenes, as well as flavonoids and glycosides such as narirutin, nobiletin, hesperidin, naringin, naringenin, quercetin, rutin, diosmin, etc., were the possible bioactive principles. The peel and seed of the selected fruits belonging to the Citrus and Prunus genera are potential sources of bioactive compounds that could be of medicinal relevance for improving oxidative, metabolic and vascular health. However, there is a need for appropriate toxicological studies.

Revisiting Nitroaromatic Drugs: Mechanisms of Bioactivation, Metabolism and Toxicity and Methods to Synthesize Nitroaromatic Fragments

Nitroaromatic drugs represent an important class of therapeutic agents, endowed with different pharmacological properties such as antibacterial, antiprotozoal, anti-Parkinson, anticancer, etc. However, the nitroheterocycle and nitroarene fragments are considered potentially toxic, with reports of mutagenicity and genotoxicity. The bioreduction process of the nitro group plays a central role in the antimicrobial and toxicological mechanism of action of nitroaromatic drugs. This article will review the nitroaromatic drugs approved by the Food and Drug Administration (FDA) in the last 30 years, the mechanisms of bioactivation, metabolism and toxicity and, finally, it will revisit the main methodologies for obtaining the nitroaromatic fragment from aromatic nitration reaction and oxidation of arylamines and/or heteroarylamines.

A plasma-3D print combined in vitro platform with implications for reliable materiobiological screening.

Materiobiology is an emerging field focused on the physiochemical properties of biomaterials concerning biological outcomes which includes but is not limited to the biological responses and bioactivity of surface-modified biomaterials. Herein, we report a novel in vitro characterization platform for characterizing nanoparticle surface-modified 3D printed PLA scaffolds. We have introduced innovative design parameters that were practical for ubiquitous in vitro assays like those utilizing 96 and 24-well plates. Subsequently, gold and silica nanoparticles were deposited using two low-temperature plasma-assisted processes namely plasma electroless reduction (PER) and dusty plasma on 3D scaffolds. Materiobiological testing began with nanoparticle surface modification optimization on 96 well plate design 3D scaffolds. We have employed 3D laser confocal imaging and scanning electron microscopy to study the deposition of nanoparticles. It was found that the formation and distribution of the nanoparticles were time-dependent. In vitro assays were performed utilizing an osteosarcoma (MG-63) cell as a model. These cells were grown on both 96 and 24 well plate design 3D scaffolds. Subsequently, we performed different in vitro assays such as cell viability, and fluorescence staining of cytoskeletal actin and DNA incorporation. The actin cytoskeleton staining showed more homogeneity in the cell monolayer growing on the gold nanoparticle-modified 3D scaffolds than the control 3D PLA scaffold. Furthermore, the mineralization and protein adsorption experiments conducted on 96 well plate design scaffolds have shown enhanced mineralization and bovine serum albumin adsorption for the gold nanoparticle-modified scaffolds compared to the control scaffolds. Taken together, this study reports the efficacy of this new in vitro platform in conducting more reliable and efficient materiobiology studies. It is also worth mentioning that this platform has significant futuristic potential for developing as a high throughput screening platform. Such platforms could have a significant impact on the systematic study of biocompatibility and bioactive mechanisms of nanoparticle-modified 3D-printed scaffolds for tissue engineering. It would also provide unique ways to investigate mechanisms of biological responses and subsequent bioactive mechanisms for implantable biomaterials. Moreover, this platform can derive more consistent and reliable in vitro results which can improve the success rate of further in vivo experiments.

Bioactive components and potential mechanisms of Biqi Capsule in the treatment of osteoarthritis: based on chondroprotective and anti-inflammatory activity.

Cartilage damage and synovial inflammation are vital pathological changes in osteoarthritis (OA). Biqi Capsule, a traditional Chinese medicine formula used for the clinical treatment of arthritis in China, yields advantages in attenuating OA progression. The drawback here is that the bioactive components and pharmacological mechanisms by which Biqi Capsule exerts its anti-inflammatory and chondroprotective effects have yet to be fully clarified. For in vivo studies, a papain-induced OA rat model was established to explore the pharmacological effects and potential mechanisms of Biqi Capsule against OA. Biqi Capsule alleviated articular cartilage degeneration and chondrocyte damage in OA rats and inhibited the phosphorylation of NF-κB and the expression of pro-inflammatory cytokines in synovial tissue. Network pharmacology analysis suggested that the primary biological processes regulated by Biqi Capsule are inflammation and oxidative stress, and the critical pathway regulated is the PI3K/AKT signaling pathway. The result of this analysis was later verified on SW1353 cells. The in vitro studies demonstrated that Glycyrrhizic Acid and Liquiritin in Biqi Capsule attenuated H2O2-stimulated SW1353 chondrocyte damage via activation of PI3K/AKT/mTOR pathway. Moreover, Biqi Capsule alleviated inflammatory responses in LPS-stimulated RAW264.7 macrophages via the NF-κB/IL-6 pathway. These observations were suggested to have been facilitated by Brucine, Liquiritin, Salvianolic Acid B, Glycyrrhizic Acid, Cryptotanshinone, and Tanshinone ⅡA. Put together, this study partially clarifies the pharmacological mechanisms and the bioactive components of Biqi capsules against OA and suggests that it is a promising therapeutic option for the treatment of OA. Chemical compounds studied in this article. Strychnine (Pubchem CID:441071); Brucine (Pubchem CID:442021); Liquiritin (Pubchem CID:503737); Salvianolic Acid B (Pubchem CID:6451084); Glycyrrhizic Acid (Pubchem CID:14982); Cryptotanshinone (Pubchem CID:160254); Tanshinone ⅡA (Pubchem CID:164676).

Consumption of carotenoid-rich Momordica cochinchinensis (Gac) aril improves glycemic control in type 2 diabetic mice partially through taste receptor type 1 mediated glucagon-like peptide 1 secretion.

Incretin-based therapies are widely used to improve glycemic control and β cell dysfunction in the treatment of type 2 diabetes. Momordica cochinchinensis (Gac fruit), a nutritious melon cultivated in many regions, has underexplored health benefits, particular its edible aril. This study comprehensively investigates the stimulatory effect of Gac aril on glucagon-like peptide 1 (GLP-1) secretion, identifies the responsible active constituents, and explores the underlying mechanisms related to its anti-diabetic effects. GLP-1-secreting STC-1 intestinal L cells were used to assess bioactivity and molecular mechanisms. Additionally, the in vivo anti-diabetic effects of Gac aril consumption were evaluated using type 2 diabetic mice induced by a high fat diet and streptozotocin injection, with or without GLP-1 receptor expression. The results demonstrated that Gac pulp and aril stimulated GLP-1 secretion, while Gac seeds did not. β-Carotene, a major constituent of Gac aril, was identified as the key mediator of GLP-1 secretion via sweet taste receptor-mediated signaling in STC-1 cells. Dietary intake of Gac aril significantly improved fasting blood glucose, glucose tolerance, insulin sensitivity, β-cell function, and hemoglobin A1c in type 2 diabetic mice. GLP-1 levels increased 2-fold, and decreased levels of ghrelin and adiponectin were restored. The anti-diabetic effects were partially diminished in GLP-1 receptor knockout mice, suggesting Gac aril's effects are mediated, in part, through GLP-1. In conclusion, Gac aril consumption may provide health benefits for managing type 2 diabetes, partially by enhancing endogenous GLP-1 levels.

Protective effect of MP-40 mitigates BDL-induced hepatic fibrosis by inhibiting the NLRP3-mediated pyroptosis.

Hepatic fibrosis and its associated consequences continue to pose a substantial global health challenge. Developing novel approaches to hepatic fibrosis management and prevention is critically necessary. Radix Paeoniae Alba (RPA) is widely used in Traditional Chinese Medicine (TCM) to treat various diseases. Our earlier research found that a bioactive component of RPA had a dose-dependent effect on anti-allergic asthma. RPA reduces allergic asthma by slowing the hepatic wind, according to "Treatise on Febrile Diseases". However, this bioactive fraction's pharmacological effects and mechanisms on the liver are unknown. This study examined the bioactive fraction MP-40, the methanol extract of RPA (MRPA), on bile duct ligation (BDL) for its anti-hepatic fibrosis activity and potential mechanisms. First, the effectiveness of MP-40 in treating BDL-induced hepatic fibrosis in mice and rats was evaluated through survival rates, ALT, AST HYP, and pathological changes. Molecular assays were performed using in vitro cultures of HSC-T6 activation. The expression of α-SMA and Collagen I evaluated fibro-tropic factors with HSC activation. Furthermore, the levels of pyroptosis were assessed by examining the expression of the pyroptosis-related proteins, including NLRP3, Cleaved Caspase-1, GSDMD-N, and 1L-1β. Additionally, the effective constituents of MP-40 were identified by extraction, separation, and identification. Finally, PF and TGG, as the delegate compounds of MP-40, were tested to confirm their inhibition effects on HSC-T6 activation. The findings demonstrated that MP-40 and MRPA could lower ALT, AST, and HYP levels, boost survival rates, and reduce liver damage in BDL mice and rats. Furthermore, MP-40 outperforms MRPA. MP-40 was proven to drastically diminish fibrotic α-SMA and Collagen I. The expression of pyroptosis-related proteins NLRP3, Cleaved Caspase-1, TGF-β1, GSDMD-N, and 1L-1β decreased. MP-40 inhibited the synthesis of pyroptosis-related proteins more effectively than MCC950 (an NLRP3-specific inhibitor). Monoterpene glycosides and tannins were shown to be the most potent MP-40 components. Finally, the delegate compounds MP-40, PF, and TGG were shown to have substantial inhibitory effects on HSC-T6 activation. The results proved that MP-40 alleviates BDL-induced cholestatic hepatic fibrosis by inhibiting NLRP3-mediated pyroptosis. PF and TGG play a role in treating BDL-induced cholestatic hepatic fibrosis in MP-40.

Network pharmacology-based dissection of the bioactive compounds and pharmacological mechanisms of yiqi fumai lyophilized injection for the treatment of heart failure

Objective: Yiqi Fumai Lyophilized Injection (YQFM), a Chinese medicine injection, has been widely used for the treatment of cardiovascular diseases, especially heart failure (HF). However, bioactive compounds and underlying mechanisms of YQFM in treating HF remain poorly understood. Materials and Methods: Network pharmacology was employed to investigate the bioactive compounds and mechanisms of YQFM. A compound-target network was constructed to screen bioactive compounds based on contribution index calculation. Then, an adriamycin-induced HF rat model was established to evaluate the cardio-protective effects of YQFM by hematoxylin and eosin staining and enzyme-linked immunosorbent assays. Results: Network pharmacology indicated that YQFM may alleviate HF through 36 compounds and 109 targets. Particularly, ginsenosides Rb1, Rg1, Re, Rf, Rb2, Rh1, schisandrin, and ginsenoside Rc were indicated as the top contributors of YQFM in treating HF. YQFM was predicted to act on multiple targets such as vascular endothelial growth factor A, interleukin-2 (IL-2), IL-6, and IL-1β, as well as to regulate signaling pathways such as hypoxia-inducible factor 1, tumor necrosis factor, VEGF, and PI3K-Akt. The pharmacological study suggested that YQFM could attenuate cardiac injury and up-regulate plasma concentrations of VEGFR-1 and NO in HF rats. Ginsenoside Rb1, as the major contributor from network pharmacology analysis, also showed a cardioprotective effect and up-regulation of VEGFR-1 in plasma. Conclusions: Ginsenosides and schisandrin were predicted as the most important contributors to the cardioprotective effect of YQMF. Ginsenoside Rb1 was proved to alleviate HF and increase the plasma concentration of VEGFR-1.

Bioactive components and mechanisms of Pu-erh tea in improving levodopa metabolism in rats through COMT inhibition.

Catechol-O-methyltransferase (COMT) plays a central role in the metabolic inactivation of endogenous neurotransmitters and xenobiotic drugs and hormones having catecholic structures. Its inhibitors are used in clinical practice to treat Parkinson's disease. In this study, a fluorescence-based visualization inhibitor screening method was developed to assess the inhibition activity on COMT both in vitro and in living cells. Following the screening of 94 natural products, Pu-erh tea extract exhibited the most potent inhibitory effect on COMT with an IC50 value of 0.34 μg mL-1. In vivo experiments revealed that Pu-erh tea extract substantially hindered COMT-mediated levodopa metabolism in rats, resulting in a significant increase in levodopa levels and a notable decrease in 3-O-methyldopa in plasma. Subsequently, the chemical components of Pu-erh tea were analyzed using UHPLC-Q-Exactive Orbitrap HRMS, identifying 24 major components. Among them, epigallocatechin gallate, gallocatechin gallate, epicatechin gallate, and catechin gallate exhibited potent inhibition of COMT activity with IC50 values from 93.7 nM to 125.8 nM and were the main bioactive constituents in Pu-erh tea responsible for its COMT inhibition effect. Inhibition kinetics analyses and docking simulations revealed that these compounds competitively inhibit COMT-mediated O-methylation at the catechol site. Overall, this study not only explained how Pu-erh tea catechins inhibit COMT, suggesting Pu-erh tea as a potential dietary intervention for Parkinson's disease, but also introduced a new strategy for discovering COMT inhibitors more effectively.

A Deep Insight into Chemistry and Pharmacology of Genus Angelica.: An Up-to-date Systematic Review

Introduction: Healthcare providers globally need plant-derived bioactive compounds for the treatment of ailments. The present systematic review article emphasizes the chemistry and pharmacology parts of various Angelica species, family Apiaceae. The species of Angelica genus, native to the Indian Himalayan, are beneficial for several therapeutic and edible purposes. Aromatherapy uses essential oils obtained from various species of the Angelica genus. The population of various Angelica species is declining quickly due to premature destructive harvesting. The traditional medicinal system involves Angelica glauca Edgew and other Angelica species to treat respiratory, Central Nervous System (CNS) disorders and many more ailments. Method: An extensive literature survey on the chemistry and pharmacological aspects of various Angelica species, including A. glauca, secondary metabolites, mechanism behind various pharmacological activities, and marketed products of plants of Genus Angelica was conducted using scientific databases. The search terms Angelica species, botanical description, wild Angelica, important phytoconstituents and their pharmacological responses, plant parts used, and the molecular mechanism behind observed prominent activities were used for data collection. In total, 92 publications were included from year 1983 to 2023. Articles focusing on other than Angelica species and other than the English language were excluded from the study. Also, the papers with no full-text availability were excluded from the present study. Species of the Angelica genus have been known for a wide range of biological activities, including antioxidant, anti-inflammatory, antimicrobial and immunotoxic. Result: The present paper highlights the secondary metabolites present in the Angelica species and their scientific uses. Ancient Ayurvedic treatise claims several other pharmacological activities, but scientific validation of some indications, including the exact mechanism of action, is underway. : Ancient Ayurvedic treatise claims several other pharmacological activities, but scientific validation of some indications, including the exact mechanism of action, is underway. Conclusion: This review compiles 30 years of data on Angelica species related to their phytochemistry, pharmacology, molecular mechanisms of bioactivity, recent advancements and possible future scope of applied and translational research.

Analysis of color stability and degree of conversion of different types of resin composites.

Resin composites containing surface pre-reacted glass (S-PRG) have been introduced to reduce demineralization and improve remineralization of the tooth structure. However, water diffusion within the material is necessary for its action, which can impair its overall physicomechanical properties over time, including color stability. This study aimed to evaluate the color stability and related degree of conversion (DC) of four resin composites. Discs (6 x 4 mm, n = 5/group) of microhybrid (MH), nanofilled (NF), nanohybrid (NH), and S-PRG-based nanohybrid (S-PRG-NH) composites with two opacities (A2/A2E and A2O/A2D) were prepared. Color (CIELab and CIEDE2000) was evaluated with a spectrophotometer after aging in grape juice (2 x 10 min/10mL/7days). The DC was analyzed by using Fourier transform infrared spectroscopy before and after light-curing. Data were statistically analyzed by using two-way analysis of variance and post-hoc least significant difference tests (p<0.05). In the color stability analysis, the interaction between filler type and opacity was significant (CIELab, p = 0.0015; CIEDE2000, p = 0.0026). NH presented the highest color stability, which did not differ from that of MH. The greatest color alteration was observed for S-PRG-NH. S-PRG fillers also influenced DC (p < 0.05). The nanohybrid resin composite presented favorable overall performance, which is likely related to its more stable organic content. Notwithstanding the benefits of using S-PRG-based nanohybrid resins, mostly in aesthetic procedures, professionals should consider the susceptibility of such resins to color alteration, probably due to the water-based bioactive mechanism of action.

Investigating the potential hub genes and mechanisms of Artemisia annua L. against breast cancer based on network pharmacology and molecular docking

Artemisia annua L. has been revealed to possess antitumor effect in various human cancers. However, the mechanism of A. annua treating breast cancer (BRCA) has not been clearly elucidated. In present study, the bioactive compounds and mechanism of A. annua in the treatment of BRCA were explored based on network pharmacology and molecular docking. TCMSP database was used to predict the active components and components targets of A. annua. The targets of BRCA were collected through TTD, GeneCards, OMIM, PharmGKB and DisGeNET database. The analysis of GO and KEGG enrichment was conducted for intersection targets. Protein–Protein interaction (PPI) network was constructed using the STRING online database. Candidate core targets were screened using the gene expression analysis and survival analysis. Molecular docking analysis was conducted to verify whether the bioactive compounds had a definite affinity with candidate core targets. Finally, MTT and RT-qPCR experiments of MCF-7 cells and MDA-MB-231 cells were carried out to verify the results of network pharmacology.The quercetin, luteolin, kaempferol were selected as hub compounds of A. annua against BRCA. After the conduction of topological analysis, survival analysis, and gene expression analysis for the potential targets of A. annua against BRCA, 4 candidate hub targets (BICR5, CCNA2, E2F1 and FOS) were identified. Molecular docking results demonstrated that 3 hub components of A. annua had strong binding efficiency with the 4 candidate hub targets. The enrichment analysis of KEGG pathway revealed that A. annua exerted anti-BRCA effects via p53 signaling pathway, etc. After treated with total flavonoids of A. annua (ATF) for 48 h, mRNA expression levels of BICR5, CCNA2, E2F1 and FOS were significantly down-regulated in both MCF-7 cells and MDA-MB-231 cells. The present study reveals the mechanism of A. annua against BRCA through multiple targets, multiple ingredients and multiple signal pathways, and provides more references for its clinical application.

Integrative pharmacology reveals the mechanisms of Erzhi pills, A traditional Chinese formulation, stimulating melanogenesis

Ethnopharmacological relevanceErzhi pills (EZP), a traditional Chinese medicine formula prescribed for the treatment of vitiligo, has shown promising efficacy. However, the oral bioactive components and mechanisms underlying the promotion of melanogenesis by EZP remain unclear. Aim of the studyThis study aimed to investigate the pharmacological basis and mechanism of EZP in promoting melanogenesis. Materials and methodsUHPLC-TOF-MS analysis was used to identify absorbed phytochemicals in serum after oral administration of EZP. Network pharmacology methods were used to predict potential targets and pathways involved in the melanogenic activity of EZP, resulting in the construction of a “compound-target-pathway” network. Zebrafish and B16F10 cells were used to evaluate the effects of EZP on tyrosinase activity and melanin content. Western blot and ELISA analyses were used to validate the effects of EZP on melanogenesis-related proteins, including MITF, TYR, CREB, p-CREB, and cAMP. ResultsUHPLC-TOF-MS analysis identified 36 compounds derived from EZP in serum samples. Network pharmacology predictions revealed 89 target proteins associated with the identified compounds and closely related to vitiligo. GO and KEGG analyses indicated the involvement of the cAMP/PKA signaling pathway in the promotion of melanogenesis by EZP. Experimental results showed that EZP increased tyrosinase activity and melanin content in zebrafish and B16F10 cells without inducing toxicity. Western blot and ELISA results suggested that the melanogenic effect of EZP may be related to the activation of the cAMP/PKA signaling pathway. These results confirm the feasibility of combining serum pharmacological and network pharmacological approaches. ConclusionsEZP have the potential to increase tyrosinase activity and melanin content in zebrafish and cells possibly through activation of the cAMP/PKA pathway.

Glycosaminoglycans' Ability to Promote Wound Healing: From Native Living Macromolecules to Artificial Biomaterials.

Glycosaminoglycans (GAGs) are important for the occurrence of signaling molecules and maintenance of microenvironment within the extracellular matrix (ECM) in living tissues. GAGs and GAG-based biomaterial approaches have been widely explored to promote in situ tissue regeneration and repair by regulating the wound microenvironment, accelerating re-epithelialization, and controlling ECM remodeling. However, most approaches remain unacceptable for clinical applications. To improve insights into material design and clinical translational applications, this review highlights the innate roles and bioactive mechanisms of native GAGs during in situ wound healing and presents common GAG-based biomaterials and the adaptability of application scenarios in facilitating wound healing. Furthermore, challenges before the widespread commercialization of GAG-based biomaterials are shared, to ensure that future designed and constructed GAG-based artificial biomaterials are more likely to recapitulate the unique and tissue-specific profile of native GAG expression in human tissues. This review provides a more explicit and clear selection guide for researchers designing biomimetic materials, which will resemble or exceed their natural counterparts in certain functions, thereby suiting for specific environments or therapeutic goals.

Traditional Chinese medicines treat ischemic stroke and their main bioactive constituents and mechanisms.

Ischemic stroke (IS) remains one of the leading causes of death and disability in humans. Unfortunately, none of the treatments effectively provide functional benefits to patients with IS, although many do so by targeting different aspects of the ischemic cascade response. The advantages of traditional Chinese medicine (TCM) in preventing and treating IS are obvious in terms of early treatment and global coordination. The efficacy of TCM and its bioactive constituents has been scientifically proven over the past decades. Based on clinical trials, this article provides a review of commonly used TCM patent medicines and herbal decoctions indicated for IS. In addition, this paper also reviews the mechanisms of bioactive constituents in TCM for the treatment of IS in recent years, both domestically and internationally. A comprehensive review of preclinical and clinical studies will hopefully provide new ideas to address the threat of IS.

Bioactivities and Mechanisms of Action of Diphyllin and Its Derivatives: A Comprehensive Systematic Review.

Natural products are treasure houses for modern drug discovery. Diphyllin is a natural arylnaphthalene lignan lactone isolated from the leaf of Astilboides tabularis. Studies have found that it possesses plenty of bioactivity characteristics. In this paper, we reviewed the structure, bioactivity, and mechanism of action of diphyllin and its derivatives. The references were obtained from PubMed, Web of Science, and Science Direct databases up to August 2023. Papers without a bio-evaluation were excluded. Diphyllin and its derivatives have demonstrated V-ATPase inhibition, anti-tumor, anti-virus, anti-biofilm, anti-inflammatory, and anti-oxidant activities. The most studied activities of diphyllin and its derivatives are V-ATPase inhibition, anti-tumor activities, and anti-virus activities. Furthermore, V-ATPase inhibition activity is the mechanism of many bioactivities, including anti-tumor, anti-virus, and anti-inflammatory activities. We also found that the galactosylated modification of diphyllin is a common phenomenon in plants, and therefore, galactosylated modification is applied by researchers in the laboratory to obtain more excellent diphyllin derivatives. This review will provide useful information for the development of diphyllin-based anti-tumor and anti-virus compounds.

Ethanol extract of Verbena officinalis alleviates MCAO-induced ischaemic stroke by inhibiting IL17A pathway-regulated neuroinflammation

BackgroundThe prevention and treatment of ischaemic stroke is a worldwide challenge, and effective clinical treatment strategies are lacking. Studies have demonstrated the efficacy of Verbena officinalis in managing cerebrovascular disorders. However, the neuroprotective bioactive components and mechanisms remain unclear. PurposeTo investigate the pharmacological combinatorial components and mechanism underlying the anti-ischemic stroke effect of the ethanol extract of Verbena officinalis (VO Ex). Study design and methodsThe components of VO Ex were identified by HPLC. A middle cerebral artery occlusion (MCAO) induced brain injury model was used to assess the therapeutic effect of VO Ex. The activity of the chemical components of VO Ex was evaluated using a primary astrocyte injury model induced by oxygen-glucose deprivation/reperfusion (OGD/R). RNA sequencing was used to reveal the potential targets of VO Ex against cerebral ischemia–reperfusion injury (CIRI), and the results were verified by qRT-PCR and western blotting. The key components and target binding ability were predicted by molecular docking. Finally, the mechanism of combinatorial components was verified by experiments. ResultsThe HPLC results indicated that the main ingredients of VO Ex were hastatoside, verbenalin, acteoside, luteolin, apigenin and hispidulin. In vivo experiments showed that VO Ex improved MCAO-induced acute cerebral ischemic injury. Transcriptomic data and biological experiments suggested that VO Ex exerted therapeutic effects through IL17A signalling pathways. The in vitro experiments indicated that verbenalin, acteoside, luteolin, apigenin and hispidulin exhibited neuroprotective activities. The novel formula of VALAH, derived from the aforementioned active ingredients, exhibited superior efficacy compared to each individual component. Molecular docking and mechanistic studies have confirmed that VALAH functions in the treatment of ischaemic stroke by suppressing the activation of the IL17A signalling pathway. ConclusionThis work is the first to reveal that VO Ex effectively inhibits the IL17A signaling pathway and mitigates neuroinflammation following ischemic stroke. Moreover, we identified the novel formula VALAH as the bioactive combinatorial components for VO Ex. Further research suggests that the activity of VALAH is associated with IL17A-mediated regulation of neuroinflammation. This finding provides new insights into the efficacious components and mechanisms of traditional Chinese medicine.