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Helicobacter pylori (H. pylori) plays an important role in chronic atrophic gastritis (CAG). Interestingly, Shaoyao Gancao decoction (SGD), a traditional Chinese analgesic prescription, has the efficacy of relaxing spasms and relieving pain. Here, we aimed to identify whether SGD alleviates CAG and the underlying mechanism. A CAG mouse model was developed using H. pylori colonization and a high-salt diet. Histological staining was used to study the histopathological damage changes, and RT-qPCR assays the production of inflammatory responses in the gastric mucosa of mice. H. pylori and a high-salt diet induced gastric mucosal damage and apoptosis of gastric mucosal epithelial cells in mice, eliciting a significant inflammatory response. Treatment with SGD alleviated CAG-induced gastric mucosal damage, reduced apoptosis of gastric mucosal epithelial cells, and inhibited the inflammatory response. Bioinformatics was then used to construct the pharmacological network of SGD to explore its potential targets. SGD inhibited inflammatory response in mice with CAG by suppressing the expression of MAOB. Overexpression of MAOB impaired the therapeutic effect of SGD on inflammation in mice with CAG. Collectively, our findings indicated that SGD has the potential to alleviate CAG via downregulating MAOB. [ABSTRACT FROM AUTHOR]

Background: Dental caries is a dynamic, multifactorial disease that destroys teeth and can affect anyone's quality of life because it can cause tooth loss and make chewing difficult. Dental caries involves various factors, such as Streptococcus mutans and host factors. Currently, adjuvant therapies, such as curcumin, have emerged, but how they work has not been adequately described. Therefore, this work aims to identify the molecular mechanism of curcumin in caries and Streptococcus mutans. Methods: We obtained differentially expressed genes from a GEO dataset, and curcumin targets were obtained from other databases. The common targets were analyzed according to gene ontology enrichment, key genes were obtained, and binding to curcumin was verified by molecular docking. Results: Our analysis showed that curcumin presents 134 therapeutic targets in caries. According to the gene ontology analysis, these targets are mainly involved in apoptosis and inflammation. There are seven key proteins involved in the action of curcumin on caries: MAPK1, BCL2, KRAS, CXCL8, TGFB1, MMP9, and IL1B, all of which spontaneously bind curcumin. In addition, curcumin affects metabolic pathways related to lipid, purine, and pyrimidine metabolism in Streptococcus mutans. Conclusions: Curcumin affects both host carious processes and Streptococcus mutans. [ABSTRACT FROM AUTHOR]

Cancer is a major disease that threatens human health all over the world. Intervention and prevention in premalignant processes are successful ways to prevent cancer from striking. On the other hand, the marine ecosystem is a treasure storehouse of promising bioactive metabolites. The use of such marine products can be optimized by selecting a suitable nanocarrier. Therefore, epi-obtusane, previously isolated from Aplysia oculifera, was investigated for its potential anticancer effects toward cervical cancer through a series of in vitro assays in HeLa cells using the MTT assay method. Additionally, the sesquiterpene was encapsulated within a liposomal formulation (size = 130.8 ± 50.3, PDI = 0.462, zeta potential −12.3 ± 2.3), and the antiproliferative potential of epi-obtusane was investigated against the human cervical cancer cell line HeLa before and after encapsulation with liposomes. Epi-obtusane exhibited a potent effect against the HeLa cell line, while the formulated molecule with liposomes increased the in vitro antiproliferative activity. Additionally, cell cycle arrest analysis, as well as the apoptosis assay, performed via FITC-Annexin-V/propidium iodide double staining (flow cytofluorimetry), were carried out. The pharmacological network enabled us to deliver further insights into the mechanism of epi-obtusane, suggesting that STAT3 might be targeted by the compound. Moreover, molecular docking showed a comparable binding score of the isolated compound towards the STAT3 SH2 domain. The targets possess an anticancer effect through the endometrial cancer pathway, regulation of DNA templated transcription, and nitric oxide synthase, as mentioned by the KEGG and ShinyGo 7.1 databases. [ABSTRACT FROM AUTHOR]

Background: Dental caries is a dynamic, multifactorial disease that destroys teeth and can affect anyone’s quality of life because it can cause tooth loss and make chewing difficult. Dental caries involves various factors, such as Streptococcus mutans and host factors. Currently, adjuvant therapies, such as curcumin, have emerged, but how they work has not been adequately described. Therefore, this work aims to identify the molecular mechanism of curcumin in caries and Streptococcus mutans. Methods: We obtained differentially expressed genes from a GEO dataset, and curcumin targets were obtained from other databases. The common targets were analyzed according to gene ontology enrichment, key genes were obtained, and binding to curcumin was verified by molecular docking. Results: Our analysis showed that curcumin presents 134 therapeutic targets in caries. According to the gene ontology analysis, these targets are mainly involved in apoptosis and inflammation. There are seven key proteins involved in the action of curcumin on caries: MAPK1, BCL2, KRAS, CXCL8, TGFB1, MMP9, and IL1B, all of which spontaneously bind curcumin. In addition, curcumin affects metabolic pathways related to lipid, purine, and pyrimidine metabolism in Streptococcus mutans. Conclusions: Curcumin affects both host carious processes and Streptococcus mutans.

Abelmoschus esculentus Linn. (okra, F. Malvaceae) is a fruit widely consumed all over the world. In our study, the anti-Alzheimer's potential of A. esculentus was evaluated. An in vitro DPPH free radical assay on A. esculentus seed's total extract and AChE inhibition potential screening indicated a significant anti-Alzheimer's activity of the extract, which was confirmed through an in vivo study in an aluminum-intoxicated rat model. Additionally, in vivo results demonstrated significant improvement in Alzheimer's rats, which was confirmed by improving T-maze, beam balance tests, lower serum levels of AChE, norepinephrine, glycated end products, IL-6, and MDA. The levels of dopamine, BDNF, GSH, and TAC returned to normal values during the study. Moreover, histological investigations of brain tissue revealed that the destruction in collagen fiber nearly returns back to the normal pattern. Metabolomic analysis of the ethanolic extract of A. esculentus seeds via LC–HR-ESI-MS dereplicated ten compounds. A network pharmacology study displayed the relation between identified compounds and 136 genes, among which 84 genes related to Alzheimer's disorders, and focused on AChE, APP, BACE1, MAPT and TNF genes with interactions to all Alzheimer's disorders. Consequently, the results revealed in our study grant potential dietary elements for the management of Alzheimer's disorders. [ABSTRACT FROM AUTHOR]

Cancer is a major disease that threatens human health all over the world. Intervention and prevention in premalignant processes are successful ways to prevent cancer from striking. On the other hand, the marine ecosystem is a treasure storehouse of promising bioactive metabolites. The use of such marine products can be optimized by selecting a suitable nanocarrier. Therefore, epi-obtusane, previously isolated from Aplysia oculifera, was investigated for its potential anticancer effects toward cervical cancer through a series of in vitro assays in HeLa cells using the MTT assay method. Additionally, the sesquiterpene was encapsulated within a liposomal formulation (size = 130.8 ± 50.3, PDI = 0.462, zeta potential −12.3 ± 2.3), and the antiproliferative potential of epi-obtusane was investigated against the human cervical cancer cell line HeLa before and after encapsulation with liposomes. Epi-obtusane exhibited a potent effect against the HeLa cell line, while the formulated molecule with liposomes increased the in vitro antiproliferative activity. Additionally, cell cycle arrest analysis, as well as the apoptosis assay, performed via FITC-Annexin-V/propidium iodide double staining (flow cytofluorimetry), were carried out. The pharmacological network enabled us to deliver further insights into the mechanism of epi-obtusane, suggesting that STAT3 might be targeted by the compound. Moreover, molecular docking showed a comparable binding score of the isolated compound towards the STAT3 SH2 domain. The targets possess an anticancer effect through the endometrial cancer pathway, regulation of DNA templated transcription, and nitric oxide synthase, as mentioned by the KEGG and ShinyGo 7.1 databases.

Background: Depression, a widespread mental disorder, presents significant risks to both physical and mental health due to its high rates of recurrence and suicide. Currently, single-target antidepressants typically alleviate depressive symptoms or delay the progression of depression rather than cure it. Ginsenoside Rg1 is one of the main ginsenosides found in Panax ginseng roots. It improves depressive symptoms through various mechanisms, suggesting its potential as a treatment for depression., Materials and Methods: We evaluated preclinical studies to comprehensively discuss the antidepressant mechanism of ginsenoside Rg1 and review its toxicity and medicinal value. Additionally, pharmacological network and molecular docking analyses were performed to further validate the antidepressant effects of ginsenoside Rg1., Results: The antidepressant mechanism of ginsenoside Rg1 may involve various pharmacological mechanisms and pathways, such as inhibiting neuroinflammation and over-activation of microglia, preserving nerve synapse structure, promoting neurogenesis, regulating monoamine neurotransmitter levels, inhibiting hyperfunction of the hypothalamic-pituitary-adrenal axis, and combatting antioxidative stress. Moreover, ginsenoside Rg1 preserves astrocyte gap junction function by regulating connexin43 protein biosynthesis and degradation, contributing to its antidepressant effect. Pharmacological network and molecular docking studies identified five targets (AKT1, STAT3, EGFR, PPARG, and HSP90AA1) as potential molecular regulatory sites of ginsenoside Rg1., Conclusions: Ginsenoside Rg1 may exert its antidepressant effects via various pharmacological mechanisms. In addition, multicenter clinical case-control and molecular targeted studies are required to confirm both the clinical efficacy of ginsenoside Rg1 and its potential direct targets., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Abelmoschus esculentus Linn. (okra, F. Malvaceae) is a fruit widely consumed all over the world. In our study, the anti-Alzheimer’s potential of A. esculentus was evaluated. An in vitro DPPH free radical assay on A. esculentus seed’s total extract and AChE inhibition potential screening indicated a significant anti-Alzheimer’s activity of the extract, which was confirmed through an in vivo study in an aluminum-intoxicated rat model. Additionally, in vivo results demonstrated significant improvement in Alzheimer’s rats, which was confirmed by improving T-maze, beam balance tests, lower serum levels of AChE, norepinephrine, glycated end products, IL-6, and MDA. The levels of dopamine, BDNF, GSH, and TAC returned to normal values during the study. Moreover, histological investigations of brain tissue revealed that the destruction in collagen fiber nearly returns back to the normal pattern. Metabolomic analysis of the ethanolic extract of A. esculentus seeds via LC–HR-ESI-MS dereplicated ten compounds. A network pharmacology study displayed the relation between identified compounds and 136 genes, among which 84 genes related to Alzheimer’s disorders, and focused on AChE, APP, BACE1, MAPT and TNF genes with interactions to all Alzheimer’s disorders. Consequently, the results revealed in our study grant potential dietary elements for the management of Alzheimer’s disorders.

Context Kai-Xin-San (KXS) has been used to treat Alzheimer’s disease (AD) for thousands of years. However, no quantitative data regarding AD treatment using KXS are available. Moreover, its active compounds and mechanism of action for the treatment of AD remain largely unclear. Objectives To evaluate the efficacy and the potential pharmacological mechanisms of KXS in AD treatment. Materials and methods A systematic collection of KXS experiments was conducted from PubMed, Web of Science, Embase, CNKI, VIP, and Wanfang Data up to February, 2020. Review Manager 5 software was used for meta-analysis. In network pharmacology, components of KXS were screened, AD-related genes were then identified and the ‘component-target-pathway’ network constructed. Molecular docking was finally employed for in silico simulation matching between representative KXS compounds and their target genes. Results Meta-analysis revealed that KXS improves the cognitive benefits in AD models by reducing the time of escape latency (SMD = −16.84) as well as increasing the number of cross-platform (SMD = 2.56) and proportion of time in the target quadrant (SMD = 7.52). Network pharmacology identified 25 KXS active compounds and 44 genes targets. DRD2, MAOA, ACHE, ADRA2A and CHRM2 were core target proteins. Besides, 22 potential pathways of KXS were identified, like cholinergic synapses, the cGMP/PKG pathway and calcium signalling. Molecular docking showed that stigmasterol, aposcopolamine and inermin can closely bind three targets (ACHE, ADRA2A and CHRM2). Discussion and conclusion These findings suggest that KXS exerts effect on AD through multi-target, multi-component and multi-pathway mechanism. Future studies may explore the active components of KXS.

Helicobacter pylori (H. pylori) plays an important role in chronic atrophic gastritis (CAG). Interestingly, Shaoyao Gancao decoction (SGD), a traditional Chinese analgesic prescription, has the efficacy of relaxing spasms and relieving pain. Here, we aimed to identify whether SGD alleviates CAG and the underlying mechanism. A CAG mouse model was developed using H. pylori colonization and a high-salt diet. Histological staining was used to study the histopathological damage changes, and RT-qPCR assays the production of inflammatory responses in the gastric mucosa of mice. H. pylori and a high-salt diet induced gastric mucosal damage and apoptosis of gastric mucosal epithelial cells in mice, eliciting a significant inflammatory response. Treatment with SGD alleviated CAG-induced gastric mucosal damage, reduced apoptosis of gastric mucosal epithelial cells, and inhibited the inflammatory response. Bioinformatics was then used to construct the pharmacological network of SGD to explore its potential targets. SGD inhibited inflammatory response in mice with CAG by suppressing the expression of MAOB. Overexpression of MAOB impaired the therapeutic effect of SGD on inflammation in mice with CAG. Collectively, our findings indicated that SGD has the potential to alleviate CAG via downregulating MAOB.

Kai-Xin-San (KXS) has been used to treat Alzheimer's disease (AD) for thousands of years. However, no quantitative data regarding AD treatment using KXS are available. Moreover, its active compounds and mechanism of action for the treatment of AD remain largely unclear. To evaluate the efficacy and the potential pharmacological mechanisms of KXS in AD treatment. A systematic collection of KXS experiments was conducted from PubMed, Web of Science, Embase, CNKI, VIP, and Wanfang Data up to February, 2020. Review Manager 5 software was used for meta-analysis. In network pharmacology, components of KXS were screened, AD-related genes were then identified and the 'component-target-pathway' network constructed. Molecular docking was finally employed for in silico simulation matching between representative KXS compounds and their target genes. Meta-analysis revealed that KXS improves the cognitive benefits in AD models by reducing the time of escape latency (SMD = −16.84) as well as increasing the number of cross-platform (SMD = 2.56) and proportion of time in the target quadrant (SMD = 7.52). Network pharmacology identified 25 KXS active compounds and 44 genes targets. DRD2, MAOA, ACHE, ADRA2A and CHRM2 were core target proteins. Besides, 22 potential pathways of KXS were identified, like cholinergic synapses, the cGMP/PKG pathway and calcium signalling. Molecular docking showed that stigmasterol, aposcopolamine and inermin can closely bind three targets (ACHE, ADRA2A and CHRM2). These findings suggest that KXS exerts effect on AD through multi-target, multi-component and multi-pathway mechanism. Future studies may explore the active components of KXS. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is the most frequent cancer in the female population worldwide. Although there are treatments available, they are ineffective and cause adverse effects. 6-gingerol is an active component in ginger with anticancer activity. This research aims to discover the mechanism by which 6-gingerol act as an anticancer agent on CC through a pharmacological network using bioinformatics databases. From MalaCard, Swiss Target Prediction, Comparative Toxicogenomics Database, and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, we obtained the target genes for 6-gingerol and CC and matched them. We got 26 genes and analyzed them in ShinyGO-0.76.3 and DAVID-Bioinformatics Resources. Then, we generated a protein-protein interaction network in Cytoscape and obtained 12 hub genes. Hub genes were analyzed in Gene Expression Profiling Interactive Analysis and TISIDB. In addition, molecular docking studies were performed between target proteins with 6-gingerol using SwissDock database. Finally, molecular dynamics studies for three proteins with the lowest interaction energy were implemented using Gromacs software. According to gene ontology results, 6-gingerol is involved in processes of apoptosis, cell cycle, and protein kinase complexes, affecting mitochondria and pathways related to HPV infection. CTNNB1 gene was negatively correlated with CD8+ infiltration but was not associated with a higher survival rate. Furthermore, the molecular docking study showed that 6-gingerol has a high binding to proteins, and the molecular dynamics showed a stable interaction of 6-gingerol to AKT1, CCNB1, and CTNNB1 proteins. Conclusion, our work helps to understand the anticancer activity of 6-gingerol in CC that should be studied experimentally.Communicated by Ramaswamy H. Sarma.

Introduction: The nuclear transcription factor PPARγ, which can modulate cell growth via proliferation and apoptosis-related mechanisms, is a promising target in cancer therapy. This study aims to focus on PPARγ as the target and use virtual screening to find hits., Methods: A set of 5,677 flavonoid compounds were filtered by subjecting them to descriptor-based drug-likeness and ADMET strategies to discover drug-like compounds. The candidates' modes of binding to PPARγ were then evaluated using docking and MD simulation. PharmMapper was used to identify the potential targets of selected hits. The pharmacological network was constructed based on the GO and KEGG pathway analysis., Results: In primary screening, 3,057 compounds met various drug-likeness criteria and docked well as partial agonists in the PPARγ-LBD. Five compounds (euchrenone b 1 , kaempferol-7-Orhamnoside, vincetoxicoside B, morusin, and karanjin) were selected with the use of ADMET profiles for further MD simulation investigation. Based on the PharmMapper findings, 52 proteins were then submitted to GO and KEGG enrichment analysis. As expected by GO and KEGG pathway enrichment studies, core targets were enriched in the PI3K-Akt signaling pathway (p < 0.01), indicating that certain chemicals may be involved in cancer processes., Conclusion: Our results suggested that the selected compounds might have sufficient drug-likeness, pharmacokinetics, and in silico bioactivity by acting as PPARγ partial agonists. Although much work remains to illuminate extensive cancer therapeutic/ chemopreventive efficacy of flavonoids in vivo, in silico methodology of our cheminformatics research may be able to provide additional data regarding the efficacy and safety of potential candidates for therapeutic targets., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The aim of this study was to predict the target genes and pathways of Rhizoma alismatis (RA) in the treatment of gastric cancer (GC) by an bioinformatics analysis., Methods: The Traditional Chinese Medicine System Pharmacology database was used to obtain the chemical components and target genes of RA. GC-related genes were downloaded from GeneCard website. GO and KEGG enrichment analyses were used to detect the potential mechanisms of RA targets. Hub genes were identified by protein-protein interaction (PPI) network and then verified by quantitative real-time polymerase chain reaction (qRT-PCR) analysis., Results: Our analyses identified 34 target genes that contribute to the development of GC. GO analysis showed that the biological functions of the target genes mainly included activation of receptors, including the nuclear receptor, steroid hormone receptor, acetylcholine receptor, G-protein coupled serotonin receptor, serotonin receptor and others. According to KEGG analysis, we found that insulin resistance, galactose metabolism, adipocytokine signaling pathway, breast cancer pathway, and cholinergic synapse were the top 5 pathways involving RA target genes. qRT-PCR and immunohistochemical analysis indicated that RA had significant effects on the expression of hub genes, including MYC, CASP3, SP1, MAPK8, PPARG, FOS, and SLC2A1., Conclusions: Our study revealed the multi-component, multi-target, and multi-mechanisms of RA on GC, which suggest novel therapeutics for GC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tcr-21-1041). The authors have no conflicts of interest to declare., (2021 Translational Cancer Research. All rights reserved.)