Apoptosis in Alzheimer’s disease: insight into the signaling pathways and therapeutic avenues

IKZF3 modulates cerebral ischemia/reperfusion injury by inhibiting neuroinflammation.

Purpose 2019 Coronavirus disease (COVID-19) is endangering health of populations worldwide. Latest research has proved that Lianhua Qingwen granules (LHQW) can reduce tissue damage caused by inflammatory reactions and relieve patients’ clinical symptoms. However, the mechanism of LHQW treats COVID-19 is currently lacking. Therefore, we employed computer simulations to investigate the mechanism of LHQW treats COVID-19 by modulating inflammatory response. Methods We employed bioinformatics to screen active ingredients in LHQW and intersection gene targets. PPI, GO and KEGG was used to analyze relationship of intersection gene targets. Molecular dynamics simulations validated the binding stability of active ingredients and target proteins. Binding free energy, radius of gyration and the solvent accessible surface area were analyzed by supercomputer platform. Results COVID-19 had 4628 gene targets, LHQW had 1409 gene targets, intersection gene targets were 415. Bioinformatics analysis showed that intersection targets were closely related to inflammation and immunomodulatory. Molecular docking suggested that active ingredients (including: licopyranocoumarin, Glycyrol and 3-3-Oxopropanoic acid) in LHQW played a role in treating COVID-19 by acting on CSF2, CXCL8, CCR5, NLRP3, IFNG and TNF. Molecular dynamics was used to prove the binding stability of active ingredients and protein targets. Conclusion The mechanism of active ingredients in LHQW treats COVID-19 was investigated by computer simulations. We found that active ingredients in LHQW not only reduce cell damage and tissue destruction by inhibiting the inflammatory response through CSF2, CXCL8, CCR5 and IFNG, but also regulate cell survival and growth through NLRP3 and TNF thereby reducing apoptosis. Graphical Abstract The mechanisms analysis of Lianhua Qingwen granules (LHQW) treats COVID-19.

https://www.frontiersin.org/articles/10.3389/fcimb.2022.1044770/pdf

Molecular docking and molecular dynamics study Lianhua Qingwen granules (LHQW) treats COVID-19 by inhibiting inflammatory response and regulating cell survival

Background Idiopathic sudden hearing loss (ISHL) is characterized by sudden unexplainable and unilateral hearing loss as a clinically emergent symptom. The use of the herb Erlongjiaonang (ELJN) in traditional Chinese medicine is known to effectively control and cure ISHL. This study explored the underlying molecular mechanisms using network pharmacology and molecular docking analyses. Method The Traditional Chinese Medicine System Pharmacological database and the Swiss Target Prediction database were searched for the identification of ELJN constituents and potential gene targets, respectively, while ISHL-related gene abnormality was assessed using the Online Mendelian Inheritance in Man and Gene Card databases. The interaction of ELJN gene targets with ISHL genes was obtained after these databases were cross-screened, and a drug component–intersecting target network was constructed, and the gene ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes, and protein–protein interaction networks were analyzed. Cytoscape software tools were used to map the active components–crossover target–signaling pathway network and screened targets were then validated by establishing molecular docking with the corresponding components. Result Erlongjiaonang contains 85 components and 250 corresponding gene targets, while ISHL has 714 disease-related targets, resulting in 66 cross-targets. The bioinformatical analyses revealed these 66 cross-targets, including isorhamnetin and formononetin on NOS3 expression, baicalein on AKT1 activity, and kaempferol and quercetin on NOS3 and AKT1 activity, as potential ELJN-induced anti-ISHL targets. Conclusion This study uncovered potential ELJN gene targets and molecular signaling pathways in the control of ISHL, providing a molecular basis for further investigation of the anti-ISHL activity of ELJN.

Potential molecular mechanisms of Erlongjiaonang action in idiopathic sudden hearing loss: A network pharmacology and molecular docking analyses

Huoluo Xiaoling Pellet promotes microglia M2 polarization through increasing MCPIP1 expression for ischemia stroke alleviation.

Background: Drug resistance is the major cause of increasing mortality in prostate cancer (PCa). Therefore, it an urgent to develop more effective therapeutic agents for PCa treatment. Xihuang pills (XHP) have been recorded as the efficient anti-tumor formula in ancient Chinese medical literature, which has been utilized in several types of cancers nowadays. However, the effect protective role of XHP on the PCa and its underlying mechanisms are still unclear. Methods: The active ingredients of XHP were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and BATMAN-TCM. The potential targets of PCa were acquired from the Gene Cards and OMIM databases. R language and Perl language program were utilized to clarify the interaction between the PCa-related targets and the potential targets of XHP. The potential targets of XHP for prostate cancer were gathered from the Gene ontology and KEGG pathway. Furthermore, cell proliferation assays were verified by PC3 and LNCaP cells. The efficacy and potential mechanism tests were confirmed by the PCa PC3 cells and mice subcutaneous transplantation. The effects of PI3K/Akt/mTOR-related proteins on proliferation, apoptosis, and cell cycle of PCa cells were measured by the Cell Counting Kit-8(CCK8), TUNEL assay, real-time quantitative reverse transcription PCR (QRT-PCR), and Western Blotting, respectively. Results: The active components of four traditional Chinese medicines in XHP were searched on the TCMSP and Batman TCM database. The biological active components of XHP were obtained as OB ≥30% and DL ≥0.18. The analysis of gene ontology and KEGG pathway identified the PI3K/Akt/mTOR signaling pathway as the XHP-associated pathway. Collectively, the results of in vitro and in vivo experiments showed that XHP had the effect of inhibiting on the proliferation of PC3 and LNCaP cells. XHP promoted the apoptosis and restrained the cell cycle and invasion of the PC3 cells and subcutaneous transplantation. Meanwhile, the suppression of XHP on the level of expression of PI3K, Akt, and mTOR-pathway-related pathway proteins has been identified in a dose-dependent manner. Conclusion: PI3K/Akt/mTOR pathway-related pathway proteins were confirmed as the potential XHP-associated targets for PCa. XHP can suppress the proliferation of prostate cancer via inhibitions of the PI3K/Akt/mTOR pathway.

/pdf/exploring-the-pharmacological-mechanisms-of-xihuang-pills-2j8dfab0.pdf

Exploring the Pharmacological Mechanisms of Xihuang Pills Against Prostate Cancer via Integrating Network Pharmacology and Experimental Validation In Vitro and In Vivo

Background Chlorogenic acid (CGA) is a polyphenolic compound with antioxidant and anti-inflammatory properties. CGA has been shown to improve neuroinflammation. This study is aimed at elucidating the exact mechanism by which CGA reduces neuroinflammation. Methods Oxygen and glucose deprivation (OGD) was utilized to treat BV2 microglia and HT-22 hippocampal neurons to engineer an in vitro model of hypoxic ischemia reperfusion. The levels of inflammatory factors (IL-1β, IL-6, TNF-α, IL-4, and IL-10) and oxidative stress factors (MDA, SOD, and GSH-PX) in microglia were determined by ELISA kits. The neuron proliferation was assessed by CCK-8 assay, and LDH kit was used to determine LDH release in neurons. The fluorescent dye DCF-DA was employed to measure ROS levels in neurons. Correlation of MIR497HG, miR-29b-3p, and SIRT1/NF-κB in neurons and microglia was determined by qRT-PCR. Expressions of inflammatory proteins (COX2, iNOS), oxidative stress pathways (Nrf2, HO-1), and apoptosis-related proteins (Bcl-2, Bax, caspase3, caspase8, and caspase9) in microglia or neurons were determined by western blot. The interactions between MIR497HG and miR-29b-3p, as well as between miR-29b-3p and SIRT1, were determined by dual luciferase assay and RIP assay. Results CGA attenuated OGD-mediated inflammation and oxidative stress in microglia and inhibited microglia-mediated neuronal apoptosis. CGA increased the levels of MIR497HG and SIRT1 and suppressed the levels of miR-29b-3p in BV2 and HT-22 cells. MIR497HG knockdown, miR-29b-3p upregulation, and SIRT1 inhibition inhibited CGA-mediated anti-inflammatory and neuronal protective functions. There is a targeting correlation between MIR497HG, miR-29b-3p, and Sirt1. MIR497HG sponges miR-29b-3p to regulate SIRT1 expression in an indirect manner. Conclusion CGA upregulates MIR497HG to curb miR-29b-3p expression, hence initiating the SIRT1/NF-κB signaling pathway and repressing OGD-elicited inflammation, oxidative stress, and neuron apoptosis.

/pdf/chlorogenic-acid-prevents-microglia-induced-neuronal-3j781af3.pdf

Chlorogenic Acid Prevents Microglia-Induced Neuronal Apoptosis and Oxidative Stress under Hypoxia-Ischemia Environment by Regulating the MIR497HG/miR-29b-3p/SIRT1 Axis

Abstract Context Chlorogenic acid (CGA) has good antioxidant effects, but its explicit mechanism in cerebral ischaemia-reperfusion injury is still uncertain. Objective We studied the effect of CGA in human brain microvascular endothelial cells (HBMECs) under OGD/R damage. Materials and methods HBMECs in 4 groups were treated with oxygen-glucose deprivation/re-oxygenation (OGD/R) (4 + 24 h), normal no CGA treatment and different concentrations (20, 40 or 80 μM) of CGA. Male C57BL/6J mice were classified as sham, middle cerebral artery occlusion (MCAO), and MCAO + CGA (30 mg/kg/day) groups. Mice in the sham group were not subjected to MCAO. Cell viability, apoptosis, angiogenesis and related protein levels were investigated by CCK-8, flow cytometry, TUNEL staining, tube formation and western blot assays. Infarct volume of brain tissues was analyzed by TTC staining. Results CGA curbed apoptosis (from 32.87% to 13.12% in flow cytometry; from 34.46% to 17.8% in TUNEL assay) but accelerated cell angiogenesis of HBMECs with OGD/R treatment. Moreover, CGA augmented activation of the PI3K-Akt signalling (p-PI3K/PI3K level, from 0.39 to 0.49; p-Akt/Akt level, from 0.52 to 0.81), and the effect of CGA on apoptosis and angiogenesis was abolished by an inhibitor of PI3K-Akt signalling. Furthermore, CGA attenuated infarct (from 41.26% to 22.21%) and apoptosis and promoted angiogenesis and activation of the PI3K/Akt signalling in MCAO-induced mice. Conclusions CGA effectively repressed apoptosis and promoted angiogenesis in OGD/R-treated HBMECs and MCAO-treated mice by modulating PI3K-Akt signalling. Our research provides a theoretical basis for the use of CGA in the treatment of ischaemic stroke.

https://www.tandfonline.com/doi/pdf/10.1080/13880209.2022.2110599?needAccess=true

Chlorogenic acid promotes angiogenesis and attenuates apoptosis following cerebral ischaemia-reperfusion injury by regulating the PI3K-Akt signalling

The invention relates to a traditional Chinese medicine combination for treating chronic prostatitis and a preparation method thereof. Raw materials of the traditional Chinese medicine combination include yam rhizome, grassleaf sweetflag rhizome, lycopus herb, barbed skullcap herb, spreading hedyotis herb and cowherb seed. The preparation method includes: weighing the raw materials according to a proportion, using water of 6-12 times in weight to decoct for 1-3 times, 1-3h per time; mixing medicine liquid, and filtering; taking filtrate for centrifuging, and collecting supernate; concentrating the supernate to be extract to obtain the traditional Chinese medicine combination; or further concentrating the supernate, drying, and smashing the supernate to be extract powder to obtain the traditional Chinese medicine combination. Experiments show that the traditional Chinese medicine combination can be used for treating chronic prostatitis and is better than the prior art in effect.

Qun-fang Lin

Papers

Exploring the Pharmacological Mechanisms of Xihuang Pills Against Prostate Cancer via Integrating Network Pharmacology and Experimental Validation In Vitro and In Vivo

Chlorogenic Acid Prevents Microglia-Induced Neuronal Apoptosis and Oxidative Stress under Hypoxia-Ischemia Environment by Regulating the MIR497HG/miR-29b-3p/SIRT1 Axis

Chlorogenic acid promotes angiogenesis and attenuates apoptosis following cerebral ischaemia-reperfusion injury by regulating the PI3K-Akt signalling

Traditional Chinese medicine combination for treating chronic prostatitis and preparation method thereof