Direct Determination of Absolute Radical Quantum Yields in Hydroxyl and Sulfate Radical-Based Treatment Processes.

The absolute radical quantum yield (Φ) is a critical parameter to evaluate the efficiency of radical-based processes in engineered water treatment. However, measuring Φ is fraught with challenges, as current quantification methods lack selectivity, specificity, and anti-interference capabilities, resulting in significant error propagation. Herein, we report a direct and reliable time-resolved technique to determine Φ at pH 7.0 for commonly used radical precursors in advanced oxidation processes. For H2O2 and peroxydisulfate (PDS), the values of Φ•OH and ΦSO4•- at 266 nm were measured to be 1.10 ± 0.01 and 1.46 ± 0.05, respectively. For peroxymonosulfate (PMS), we developed a new approach to determine Φ•OHPMS with terephthalic acid as a trap-and-trigger probe in the nonsteady state system. For the first time, the Φ•OHPMS value was measured to be 0.56 by the direct method, which is stoichiometrically equal to ΦSO4•-PMS (0.57 ± 0.02). Additionally, radical formation mechanisms were elucidated by density functional theory (DFT) calculations. The theoretical results showed that the highest occupied molecular orbitals of the radical precursors are O-O antibonding orbitals, facilitating the destabilization of the peroxy bond for radical formation. Electronic structures of these precursors were compared, aiming to rationalize the tendency of the Φ values we observed. Overall, this time-resolved technique with specific probes can be used as a reliable tool to determine Φ, serving as a scientific basis for the accurate performance evaluation of diverse radical-based treatment processes.

Overlooked Transformation of Nitrated Polycyclic Aromatic Hydrocarbons in Natural Waters: Role of Self-Photosensitization.

Photochemical transformation is an important process that involves trace organic contaminants (TrOCs) in sunlit surface waters. However, the environmental implications of their self-photosensitization pathway have been largely overlooked. Here, we selected 1-nitronaphthalene (1NN), a representative nitrated polycyclic aromatic hydrocarbon, to study the self-photosensitization process. We investigated the excited-state properties and relaxation kinetics of 1NN after sunlight absorption. The intrinsic decay rate constants of triplet (31NN*) and singlet (11NN*) excited states were estimated to be 1.5 × 106 and 2.5 × 108 s-1, respectively. Our results provided quantitative evidence for the environmental relevance of 31NN* in waters. Possible reactions of 31NN* with various water components were evaluated. With the reduction and oxidation potentials of -0.37 and 1.95 V, 31NN* can be either oxidized or reduced by dissolved organic matter isolates and surrogates. We also showed that hydroxyl (•OH) and sulfate (SO4•-) radicals can be generated via the 31NN*-induced oxidation of inorganic ions (OH- and SO42-, respectively). We further investigated the reaction kinetics of 31NN* and OH- forming •OH, an important photoinduced reactive intermediate, through complementary experimental and theoretical approaches. The rate constants for the reactions of 31NN* with OH- and 1NN with •OH were determined to be 4.22 × 107 and 3.95 ± 0.01 × 109 M-1 s-1, respectively. These findings yield new insights into self-photosensitization as a pathway for TrOC attenuation and provide more mechanistic details into their environmental fate.

Merits and Limitations of Radical vs. Nonradical Pathways in Persulfate-Based Advanced Oxidation Processes.

Urbanization and industrialization have exerted significant adverse effects on water quality, resulting in a growing need for reliable and eco-friendly treatment technologies. Persulfate (PS)-based advanced oxidation processes (AOPs) are emerging as viable technologies to treat challenging industrial wastewaters or remediate groundwater impacted by hazardous wastes. While the generated reactive species can degrade a variety of priority organic contaminants through radical and nonradical pathways, there is a lack of systematic and in-depth comparison of these pathways for practical implementation in different treatment scenarios. Our comparative analysis of reaction rate constants for radical vs. nonradical species indicates that radical-based AOPs may achieve high removal efficiency of organic contaminants with relatively short contact time. Nonradical AOPs feature advantages with minimal water matrix interference for complex wastewater treatments. Nonradical species (e.g., singlet oxygen, high-valent metals, and surface activated PS) preferentially react with contaminants bearing electron-donating groups, allowing enhancement of degradation efficiency of known target contaminants. For byproduct formation, analytical limitations and computational chemistry applications are also considered. Finally, we propose a holistically estimated electrical energy per order of reaction (EE/O) parameter and show significantly higher energy requirements for the nonradical pathways. Overall, these critical comparisons help prioritize basic research on PS-based AOPs and inform the merits and limitations of system-specific applications.

Corylin from Psoralea fructus (Psoralea corylifolia L.) protects against UV-induced skin aging by activating Nrf2 defense mechanisms.

Oxidative stress damage can lead to premature skin aging or age-related skin disorders. Therefore, strategies to improve oxidative stress-induced aging are needed to protect the skin and to treat skin diseases. This study aimed to determine whether the flavonoid corylin derived from Psoralea corylifolia can prevent UV-induced skin aging and if so, to explore the potential molecular mechanisms. We found that corylin potently blocked UV-induced skin photoaging in mice by reducing oxidative stress and increasing the nuclear expression of nuclear factor-erythroid factor 2-related factor 2 Nrf2. We also found that corylin stimulated Nrf2 translocation into the nucleus and increased the delivery of its target antioxidant genes together with Kelch-like ECH-associated protein 1 (Keap1) to dissociate Nrf2. These findings indicate that corylin could prevent skin aging by inhibiting oxidative stress via Keap1-Nrf2 in mouse cells. Thus, Nrf2 activation might be a therapeutic target for preventing skin aging or skin diseases caused by aging. Our findings also provided evidence that warrants the further investigation of plant ingredients to facilitate the discovery of novel therapies targeting skin aging.

Recent advances in the anti-aging effects of phytoestrogens on collagen, water content, and oxidative stress.

Skin undergoes degenerative changes as it ages, which include the loss of elasticity, reductions in the epidermal thickness and collagen content, elastic fiber degeneration, and increased wrinkling and dryness. Skin aging can be significantly delayed by the administration of estrogen. Estrogen deficiency following menopause results in atrophic skin changes and the acceleration of skin aging. Estrogen administration has positive effects on human skin by delaying or preventing skin aging manifestations, but the use of estrogen replacement is a risk factor for breast and uterine cancer. Phytoestrogens are a large family of plant-derived molecules possessing various degrees of estrogen-like activity; they exhibit agonist or antagonist estrogenic properties depending on the tissue. These molecules could be ideal candidates to combat skin aging and other detrimental effects of hypoestrogenism. In this paper, we review the effects of phytoestrogens on human skin and the mechanisms by which phytoestrogens can alleviate the changes due to aging.

Preliminary study on molecular mechanism of COVID-19 intervention by Polygonum cuspidatum through computer bioinformatics.

To explore the mechanism of action of Polygonum cuspidatum in intervening in coronavirus disease 2019 using a network pharmacology approach and to preliminarily elucidate its mechanism. The active ingredients and action targets of P cuspidatum were classified and summarized using computer virtual technology and molecular informatics methods. The active ingredients and relevant target information of P cuspidatum were identified using the TCM Systematic Pharmacology Database and Analysis Platform, the TCM Integrated Pharmacology Research Platform v2.0, and the SwissTarget database. The GENECARDS database was used to search for COVID-19 targets. The STRING database was analyzed and combined with Cytoscape 3.7.1 software to construct a protein interaction network map to screen the core targets. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was then performed. The core compound, polydatin, was selected and the core targets were analyzed by computer virtual docking using software such as discovery studio autodock tool. In vitro cell models were constructed to experimentally validate the activity of the core compound, polydatin. By computer screening, we identified 9 active ingredients and their corresponding 286 targets from P cuspidatum. A search of the GENECARDS database for COVID-19 yielded 303 core targets. By mapping the active ingredient targets to the disease targets, 27 overlapping targets could be extracted as potential targets for the treatment of COVID-19 with P cuspidatum. In addition, the enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathway on core targets showed that the coronavirus disease, MAPK signaling pathway, NF kappa B signaling pathway, and other signaling pathways were highly enriched. Combined with the degree-high target analysis in the protein interaction network, it was found to be mainly concentrated in the NF-kappaB (NF-κB) signaling pathway, indicating that the NF-κB signaling pathway may be an important pathway for P cuspidatum intervention. In vitro assays showed no effect of 0.1 to 10 µM polydatin on cell viability, but an inhibitory effect on the transcriptional activity of NF-κB-RE. Molecular docking showed stable covalent bonding of polydatin molecules with Il-1ß protein at residue leu-26, TNF protein ser-60, residue gly-121, and residue ile-258 of ICAM-1 protein, indicating a stable docking result. The treatment of COVID-19 with P cuspidatum is characterized by multi-component, multi-target, and multi-pathway, which can exert a complex network of regulatory effects through the interaction between different targets, providing a new idea and basis for further exploration of the mechanism of action of P cuspidatum in the treatment of COVID-19.

Environmental implications of superoxide radicals: From natural processes to engineering applications.

The roles of superoxide radical (O2•-) in the domains of physiological, physical, and material chemistry are becoming increasingly recognized. Although extensive efforts have been directed to understand O2•- functions in diverse aquatic systems, there is a lack of systematic and in-depth review for its kinetics and mechanisms in various environmental scenarios. This review aims to bridge this gap through discussion of O2•- generation pathways under both natural and controlled conditions. The merits and limitations of the generation and detection methods under various conditions are compared, with emphasis on different approaches for the determination of O2•--triggered reaction kinetics. We summarize the reaction rate constants of O2•- with organic contaminants covering a wide diversity of structures and reactivity. The comparison indicates that O2•- exhibits weak reactivity with most contaminants and lacks selectivity towards compounds with different functional groups, except with quinones which exhibit higher reactivity compared to non-quinones. Further, the reaction mechanisms, namely single electron transfer, nucleophilic substitution, hydrogen atom abstraction, and radical-adduct formation, are critically evaluated. Various environmental implications of O2•- are highlighted including maintenance of biogeochemical iron cycle, synthesis of nanoparticles for antibacterial purposes, desorption of contaminants from heterogeneous interfaces, and synergetic degradation of contaminants.

Protective effects and mechanisms of the Erzhi formula on glucocorticoid induced primary cortical neuron injury.

High concentrations of glucocorticoids (GC) can cross the blood-brain barrier into the brain parenchyma, triggering a stress state that can lead to a range of physiological changes. This study investigated whether Erzhi formula has neuroprotective effects against glucocorticoid damage by establishing a dexamethasone-induced primary cortical neuron injury model in vitro. The results showed that Erzhi formula could reduce dexamethasone-induced apoptosis in primary cultured cortical neurons and improve synaptic damage. Further, network pharmacological analysis revealed that Erzhi formula may exert antidepressant effects by multi-component, multi-target, and multi-pathway characteristics, in which Salidroside, Biochanin-A and other ingredients are key components, HSD11B1, NR3C1, and other proteins are key targets, and steroid metabolism may be a key process in its action. Moreover, our study found that the neuroprotective effect of Erzhi formula might be related to the 11ß-HSD1-GC/glucocorticoid receptor (GR) signaling pathway. The Erzhi formula could significantly inhibit the activity of 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) in vitro using homogeneous time-resolved fluorescence. In addition to providing evidence for the pharmacological effects of the Erzhi formula, the present study lays down the foundation for subsequent experiments.

Mechanistic and quantitative profiling of electro-Fenton process for wastewater treatment.

Electro-Fenton (EF) process represents an energy-efficient and scalable advanced oxidation technology (AOT) for micropollutants removal in wastewaters. However, mechanistic profiling and quantitation of contribution of each subprocess (i.e., adsorption at electrode, coagulation, radical oxidation, electrode oxidation/reduction, and H2O2 oxidation) to the overall degradation are substantially unclear, resulting in difficulty in tunability and optimization for different treatment scenarios. In this study, we investigated degradation kinetics of a target micropollutant in an EF system. The contribution of all possible subprocesses was elucidated by comparing the observed degradation rate in the EF system with the sum of the kinetics in each subprocess. The results indicated that the overall degradation can be attributed to the synergistic action of the above-mentioned subprocesses. The radical oxidation accounts for 87% elimination, followed by electrode reoxidation/reduction of 7.7%. These results not only advance the fundamental understanding of synergistic effect in EF system, but also open new possibilities to optimize these techniques for better scalability. In addition, the methodology in this study could potentially boost the in-depth exploration of subprocess contribution in other Fenton-like systems.

Implementation of laser flash photolysis for radical-induced reactions and environmental implications.

Confronted with the imperative crisis of water quality deterioration, the pursuit of state-of-the-art decontamination technologies for a sustainable future never stops. Fitting into the framework of suitability, advanced oxidation processes have been demonstrated as powerful technologies to produce highly reactive radicals for the degradation of toxic and refractory contaminants. Therefore, investigations on their radical-induced degradation have been the subject of scientistic and engineering interests for decades. To better understand the transient nature of these radical species and rapid degradation processes, laser flash photolysis (LFP) has been considered as a viable and powerful technique due to its high temporal resolution and rapid response. Although a number of studies exploited LFP for one (or one class of) specific reaction(s), reactions of many possible contaminants with radicals are largely unknown. Therefore, there is a pressing need to critically review its implementation for kinetic quantification and mechanism elucidation. Within this context, we introduce the development process and milestones of LFP with emphasis on compositions and operation principles. We then compare the specificity and suitability of different spectral modes for monitoring radicals and their decay kinetics. Radicals with high environmental relevance, namely hydroxyl radical, sulfate radical, and reactive chlorine species, are selected, and we discuss their generation, detection, and implications within the frame of LFP. Finally, we highlight remaining challenges and future perspectives. This review aims to advance our understandings of the implementation of LFP in radical-induced transient processes, and yield new insights for extrapolating this pump-probe technique to make significant strides in environmental implications.

Notoginsenoside R1 Regulates Ischemic Myocardial Lipid Metabolism by Activating the AKT/mTOR Signaling Pathway.

Ischemic heart diseases are responsible for more than one-third of all deaths worldwide. Radix notoginseng is widely used to treat ischemic heart disease in China and other Asian countries, and notoginsenoside R1 (NGR1) is its characteristic and large-amount ingredient. However, the potential molecular mechanisms of NGR1 in improving ischemic heart diseases are unclear. In this study, we combined pharmacological evaluation with network pharmacology, myocardial proteomics, and conventional molecular dynamics (MD) simulation to explore the cardio-protection mechanisms of NGR1. Our results revealed that NGR1 improved the echocardiographic, tissue pathological, and serum biochemical perturbations in myocardial ischemic rats. The network pharmacology studies indicated that NGR1 mainly regulated smooth muscle cell proliferation, vasculature development, and lipid metabolism signaling, especially in the PI3K/AKT pathway. Myocardial proteomics revealed that the function of NGR1 was focused on regulating metabolic and energy supply processes. The research combined reverse-docked targets with differential proteins and demonstrated that NGR1 modulated lipid metabolism in ischemic myocardia by interacting with mTOR and AKT. Conventional MD simulation was applied to investigate the influence of NGR1 on the structural stabilization of the mTOR and AKT complex. The results suggested that NGR1 can strengthen the affinity stabilization of mTOR and AKT. Our study first revealed that NGR1 enhanced the affinity stabilization of mTOR and AKT, thus promoting the activation of the AKT/mTOR pathway and improving lipid metabolic abnormity in myocardial ischemic rats.

An integration strategy combined progressive multivariate statistics with anticoagulant activity evaluation for screening anticoagulant quality markers in Chinese patent medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: The cardiovascular and cerebrovascular diseases affect human health globally. Naoxintong capsules (NXTs), a famous Chinese Patent Medicine, has been especially applied to treat cerebral infarction and coronary heart disease in clinical practice. The anticoagulant activity of this prescription plays an important role in this course of treatment. AIM OF THE STUDY: Thrombin and factor Xa (FXa) are two key targets considering the anticoagulant activity. The purpose of this investigation is to screen the quanlity markers as key thrombin and FXa inhibitors for the anticoagulant activity oriented quality control of Chinese patent medicine. MATERIALS AND METHODS: Simple multi-polar solvent extraction processes using various proportions of solvents were conducted and their thrombin/FXa inhibitory activities were evaluated in vitro. Bivariate correlation analysis (BCA), grey correlation analysis (GCA), and orthogonal partial least squares discriminate analysis (OPLS-DA) were adopted for screening the potential active markers related to the anticoagulant activity. The chemical structures of these active compounds were identified by UHPLC-Q-TOF-MS/MS and their thrombin/FXa inhibitory activity was determined. The molecular docking technology was applied to explore the interaction between the compounds and targets. The contribution of these anticoagulant active ingredients in NXT was also investigated. Last but not the least, the contents of these markers in NXT were determined by liquid chromatography-electrospray ionization tandem triple quadrupole mass spectrometry (HPLC-ESI-MS/MS) method. RESULTS: The results showed that the NXT extract exhibited great activity against thrombin and FXa, especially extracted by 75% methanol (v/v). Six marker compounds with potential anticoagulant activity were screened out. Therein, four of the active compounds owing thrombin inhibitory activity (paeoniflorin, lithospermic acid, salvianolic acid B, Z-ligustilide) and five of the active compounds owing FXa inhibitory activity (3,5-dicaffeoylquinic acid, rosmarinic acid, lithospermic acid, salvianolic acid B and Z-ligustilide). In addition, these active compounds accounted for a large proportion of thrombin/FXa inhibitory activity of NXTs. The binding energy also showed the strong interaction formed by close connection of the compounds to the residues of targets. CONCLUSIONS: The proposed integrated stategy could be an efficient strategy to screen potential thrombin/FXa inhibitors for the bioactivity related quanlity control of Chinese patent medicine.

Glycyrrhetinic acid regulates impaired macrophage autophagic flux in the treatment of non-alcoholic fatty liver disease.

Macrophages are involved in hepatocyte steatosis and necroinflammation and play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Impaired autophagy function (decreased autophagy or blocked autophagic flow) leads to cell damage and death and promotes NAFLD progression. The experimental and clinical research of glycyrrhetinic acid (GA) in the treatment of NAFLD has gradually attracted attention with clear pharmacological activities such as immune regulation, antiviral, antitumor, antioxidant, liver protection, and anti-inflammatory. However, the effects of GA on the STAT3-HIF-1α pathway and autophagy in macrophages are still unclear, and its mechanism of action in the treatment of NAFLD remains to be further elucidated. We constructed a NAFLD mouse model through a high-fat and high-sugar diet to investigate the therapeutic effects of GA. The results showed that GA reduced weight, improved the pathological changes and hepatic lipid deposition of liver, and abnormally elevated the levels of serum biochemical (AST, ALT, TG, T-CHO, LDL-C, and HDL-C) and inflammatory indexes (IL-1ß, IL-4, IL-6, MCP-1, and TNF-α) in NAFLD mice. Further examination revealed that GA ameliorates excessive hepatic macrophage infiltration and hepatocyte apoptosis. The results of the cell experiments further elaborated that GA modulated the PA-induced macrophage STAT3-HIF-1α pathway and ameliorated impaired autophagic flux (blockade of autophagosome-lysosome fusion) and overactivation of inflammation. Excessive hepatocyte apoptosis caused by the uncontrolled release of inflammatory cytokines was also suppressed by GA. Conclusion: This study demonstrated that GA could regulate the STAT3-HIF-1α pathway of macrophages, ameliorate the impaired autophagy flux, and reduce the excessive production of inflammatory cytokines to improve the excessive apoptosis of liver cells, thus playing a therapeutic role on NAFLD.

Dietary Supplements and Natural Products: An Update on Their Clinical Effectiveness and Molecular Mechanisms of Action During Accelerated Biological Aging.

Accelerated biological aging, which involves the gradual decline of organ or tissue functions and the distortion of physiological processes, underlies several human diseases. Away from the earlier free radical concept, telomere attrition, cellular senescence, proteostasis loss, mitochondrial dysfunction, stem cell exhaustion, and epigenetic and genomic alterations have emerged as biological hallmarks of aging. Moreover, nutrient-sensing metabolic pathways are critical to an organism's ability to sense and respond to nutrient levels. Pharmaceutical, genetic, and nutritional interventions reverting physiological declines by targeting nutrient-sensing metabolic pathways can promote healthy aging and increase lifespan. On this basis, biological aging hallmarks and nutrient-sensing dependent and independent pathways represent evolving drug targets for many age-linked diseases. Here, we discuss and update the scientific community on contemporary advances in how dietary supplements and natural products beneficially revert accelerated biological aging processes to retrograde human aging and age-dependent human diseases, both from the clinical and preclinical studies point-of-view. Overall, our review suggests that dietary/natural products increase healthspan-rather than lifespan-effectively minimizing the period of frailty at the end of life. However, real-world setting clinical trials and basic studies on dietary supplements and natural products are further required to decisively demonstrate whether dietary/natural products could promote human lifespan.

Abnormal bile acid metabolism is an important feature of gut microbiota and fecal metabolites in patients with slow transit constipation.

Destructions in the intestinal ecosystem are implicated with changes in slow transit constipation (STC), which is a kind of intractable constipation characterized by colonic motility disorder. In order to deepen the understanding of the structure of the STC gut microbiota and the relationship between the gut microbiota and fecal metabolites, we first used 16S rRNA amplicon sequencing to evaluate the gut microbiota in 30 STC patients and 30 healthy subjects. The α-diversity of the STC group was changed to a certain degree, and the ß-diversity was significantly different, which indicated that the composition of the gut microbiota of STC patients was inconsistent with healthy subjects. Among them, Bacteroides, Parabacteroides, Desulfovibrionaceae, and Ruminiclostridium were significantly upregulated, while Subdoligranulum was significantly downregulated. The metabolomics showed that different metabolites between the STC and the control group were involved in the process of bile acids and lipid metabolism, including taurocholate, taurochenodeoxycholate, taurine, deoxycholic acid, cyclohexylsulfamate, cholic acid, chenodeoxycholate, arachidonic acid, and 4-pyridoxic acid. We found that the colon histomorphology of STC patients was significantly disrupted, and TGR5 and FXR were significantly downregulated. The differences in metabolites were related to changes in the abundance of specific bacteria and patients' intestinal dysfunction. Analysis of the fecal genomics and metabolomics enabled separation of the STC from controls based on random forest model prediction [STC vs. control (14 gut microbiota and metabolite biomarkers)-Sensitivity: 1, Specificity: 0.877]. This study provided a perspective for the diagnosis and intervention of STC related with abnormal bile acid metabolism.

Modified Qing'e Formula protects against UV-induced skin oxidative damage via the activation of Nrf2/ARE defensive pathway.

Exposure to ultraviolet (UV) light triggers the rapid generation and accumulation of reactive oxygen species (ROS) in skin cells, which increases oxidative stress damage and leads to photoaging. Nuclear factor E2-related factor 2 (Nrf2) modulates the antioxidant defense of skin cells against environmental factors, especially ultraviolet radiation. Natural products that target Nrf2-regulated antioxidant reactions are promising candidates for anti-photoaging. The aim of this study was to investigate the protective effect of Modified Qing'e Formula (MQEF) on UV-induced skin oxidative damage and its molecular mechanisms. In this study, the photoaging models of human keratinocytes (HaCaT) and ICR mice were established by UV irradiation. In vitro models showed that MQEF displayed potent antioxidant activity, significantly increased cell viability and reduced apoptosis and excess ROS levels. Meanwhile, the knockdown of Nrf2 reversed the antioxidant and anti-apoptotic effects of MQEF. In vivo experiments indicated that MQEF could protect the skin against UV-exposed injury which manifested by water loss, sensitivity, tanning, wrinkling, and breakage of collagen and elastic fibers. The application of MQEF effectively increased the activity of antioxidant enzymes and reduced the content of malondialdehyde (MDA) in mice. In addition, MQEF was able to activate Nrf2 nuclear translocation in mouse skin tissue. In summary, MQEF may attenuate UV-induced photoaging by upregulating Nrf2 expression and enhancing antioxidant damage capacity. MQEF may be a potential candidate to prevent UV-induced photoaging by restoring redox homeostasis.

Natural products provide a new perspective for anti-complement treatment of severe COVID-19: a review.

Exaggerated immune response and cytokine storm are accounted for the severity of COVID-19, including organ dysfunction, especially progressive respiratory failure and generalized coagulopathy. Uncontrolled activation of complement contributes to acute and chronic inflammation, the generation of cytokine storm, intravascular coagulation and cell/tissue damage, which may be a favorable target for the treatment of multiple organ failure and reduction of mortality in critically ill patients with COVID-19. Cytokine storm suppression therapy can alleviate the symptoms of critically ill patients to some extent, but as a remedial etiological measure, its long-term efficacy is still questionable. Anti-complement therapy has undoubtedly become an important hotspot in the upstream regulation of cytokine storm. However, chemosynthetic complement inhibitors are expensive, and their drug resistance and long-term side effects require further investigation. New complement inhibitors with high efficiency and low toxicity can be obtained from natural products at low development cost. This paper puts forward some insights of the development of natural anti-complement products in traditional Chinese medicine, that may provide a bright perspective for suppressing cytokine storm in critically ill patients with COVID-19.

Anti-inflammatory activity of the Tongmai Yangxin pill in the treatment of coronary heart disease is associated with estrogen receptor and NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Tongmai Yangxin Pill (TMYX) is a patented traditional Chinese medicine originating from two classic prescriptions, Zhigancao Decoction and Shenmai Yin, which composed of 11 Chinese medicinal herbs: Rehmannia glutinosa (Gaertn.) DC., Spatholobus suberectus Dunn, Ophiopogon japonicus (Thunb.) Ker Gawl., Glycyrrhiza uralensis Fisch., Polygonum multiflorum Thunb., Equus asinus L., Schisandra chinensis (Turcz.) Baill., Codonopsis pilosula (Franch.) Nannf., Chinemys reevesii (Gray), Ziziphus jujuba Mill. and Cinnamomum cassia (L.) J.Presl (Committee of the Pharmacopoeia of PR China, 2015). TMYX has marketed in China for the treatment of chest pain, palpitation, angina, irregular heartbeat and coronary heart disease (CHD) for several decades. Previous studies have confirmed that TMYX can treat CHD by reducing inflammation, but the underlying pharmacological mechanism remains unclear. AIM OF THE STUDY: This study aimed to declare the underlying pharmacological mechanism of anti-inflammatory activity of TMYX in the treatment of CHD via clinical trial, microarray study, bioinformatics analysis and the vitro assays. MATERIALS AND METHODS: Eight CHD patients' serum biochemical indices including coagulation function, lipid metabolism, endothelial injury, metalloprotease, adhesion molecule, inflammatory mediator and homocysteine were measured to investigate the reduction of CHD risk by TMYX oral administration (40 pills/time, 2 times/day) for eight weeks. The expression profile chips and Ingenuity Pathway Analysis (IPA) were assessed to reveal the global transcriptional response and predict related functions, diseases and canonical pathways. The in vitro anti-inflammatory actions of TMYX were evaluated using oxidized low-density lipoprotein (100 µg/mL) induced murine RAW264.7 macrophage with an ethanol extract from TMYX (EETMYX) (25-100 µg/mL). RESULTS: TMYX treatment showed reduced levels of apolipoprotein B, endothelin 1, nuclear factor κB (NF-κB) and homocysteine in CHD patients. In contrast, the treatment increased the ratio of apolipoprotein A/apolipoprotein B. EETMYX restored cell morphology and suppressed the lipid deposition of the induced foam cells. EETMYX exerted anti-inflammatory effects by raising the mRNA and protein expression of Estrogen receptor 1 (ESR1), blocking the reduction of IκBa level and the phosphorylation of IKKα/ß, IκBα and NF-κB p65, accompanied by inhibiting MCP-1, TNF-α and IL-6 production, which were consistent with bioinformatics predictions. CONCLUSION: TMYX treatment improved the biochemical indices in CHD patients. EETMYX effectively attenuated macrophage foam cell formation and exhibited anti-inflammatory activity is associated with regulating ESR1 and NF-κB signaling pathway activity.

Mechanism of Action of Dengzhan Shengmai in Regulating Stroke from an Inflammatory Perspective: A Preliminary Analysis of Network Pharmacology.

Stroke is a complicated disease with an increasing incidence and a very high mortality rate. A classical Chinese herbal medicine, Dengzhan Shengmai (DZSM), has shown to have therapeutic effects on stroke; however, its chemical basis and molecular mechanism are still unclear. In this study, a systems biology approach was applicable to elucidate the underlying mechanism of action of DZSM on stroke. All the compounds were obtained from databases, and pendant-related targets were obtained from various data platforms, including the TCM Systematic Pharmacology (TCMSP) database, TCM Integrated Database (TCMIP), High Throughput Experimental Reference Database (HERB), Comparative Toxicogenomics Database (CTD), SwissTargetPredicition, and SymMap, The Human Gene Database (GENECARD) and Comparative Toxicogenomics Database (CTD) were used for stroke disease target data, followed by network pharmacology analysis to predict the potential effect of DZSM on stroke. Animal experiments were intended to validate the underlying mechanisms. A total of 846 chemical components were compiled for the targets of DZSM drug, and quercetin, kaempferol, and Wuweizisu C are the highest chemical components compiled from DZSM. Overlapping with 375 disease-specific targets and 149 core targets, the core targets include TNF, IL-6, ALB, and AKT1, which are shown to regulate the disease process from an anti-inflammatory perspective. 198 enrichment messages were obtained by KEGG enrichment analysis, and we believe that the role of the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, and IL-17 signaling pathway is more important. Based on rat experiments, we also demonstrated that DZSM could effectively modulate the inflammation level of brain infarct tissues and effectively alleviate behavioral characteristics. Grouped together, our study suggests that the combination of network pharmacology prediction and experimental validation can provide a useful tool to describe the molecular mechanisms of DZSM in Chinese medicine (TCM).

Network Pharmacology-Based Strategy to Investigate the Pharmacologic Mechanisms of Atractylodes macrocephala Koidz. for the Treatment of Chronic Gastritis.

Chronic gastritis (CG) is an inflammatory disease. Atractylodes macrocephala Koidz (AMK) is employed in traditional Chinese medicine (TCM) to treat various disorders. AMK can be efficacious against CG, but the active ingredients, drug targets, and its exact molecular mechanism are not known. We employed network pharmacology to analyze the active ingredients, drug targets, and key pathways of AMK in CG treatment. Seventy-seven AMK candidate ingredients were selected from four databases, and 27 active ingredients were selected for CG treatment. Twenty-five overlapping gene symbols related to CG and drugs were obtained from GeneCards and OMIM databases. A protein-protein interaction (PPI) network and TCM comprehensive network (Drug-Ingredients-Gene symbols-Disease network) were constructed, and 528 Gene Ontology (GO) terms and 26 pathways were obtained by analyses of enrichment of GO pathways and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. We suggest that the interleukin-17 signaling pathway, C-type lectin receptor signaling pathway, tumor necrosis factor signaling pathway, and AGE-RAGE signaling pathway in diabetic complications might serve as the key points and principal pathways for CG treatment. We also evaluated the reliability of some important active ingredients and targets by in vitro experiments. We showed that AMK probably influences the inflammatory response, amino acid synthesis, and energy metabolism when treating CG. This study provides novel insights for researchers to explore the mechanism of action of TCM systematically.