Cimicifuga heracleifolia kom. Attenuates ulcerative colitis through the PI3K/AKT/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Cimicifuga heracleifolia Kom. (C. heracleifolia) has demonstrated efficacy in treating gastrointestinal disorders, including splenasthenic diarrhea. Ulcerative colitis (UC), a chronic inflammatory bowel disease, shares similarities with splenasthenic diarrhea. However, the pharmacological effects of C. heracleifolia on UC and the underlying mechanisms remain unexplored. AIM OF THE STUDY: The present study investigates the therapeutic potential and mechanisms of C. heracleifolia in UC. METHODS: Initially, network pharmacology analysis, encompassing ingredient screening, target prediction, protein-protein interaction (PPI) network analysis, and enrichment analysis, was employed to predict the mechanisms of C. heracleifolia. The findings were further validated using transcriptomics and functional assays in a dextran sulfate sodium (DSS)-induced UC model. Additionally, bioactive compounds were identified through surface plasmon resonance (SPR) analysis, molecular docking, and cell-based assays. RESULTS: A total of 52 ingredients of C. heracleifolia were screened, and 32 key targets were identified within a PPI network comprising 285 potential therapeutic targets. Enrichment analysis indicated that the anti-UC effects of C. heracleifolia are mediated through immune response modulation and the inhibition of inflammatory signaling pathways. In vivo experiments showed that C. heracleifolia mitigated histological damage in the colon, reduced the expression of phosphorylated Akt1, nuclear factor-kappa B (NF-κB) p65, and inhibitor of Kappa B kinase α/ß (IKKα/ß), suppressed the content of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and enhanced the expression of tight junction proteins. Moreover, cimigenoside, caffeic acid, and methyl caffeate were identified as the bioactive constituents responsible for the UC treatment effects of C. heracleifolia. CONCLUSIONS: In summary, this study is the first to demonstrate that C. heracleifolia exerts therapeutic effects on UC by enhancing the intestinal mucosal barrier and inhibiting the phosphatidylinositol 3-kinase (PI3K)/AKT/NF-κB signaling pathway. These findings offer valuable insights into the clinical application of C. heracleifolia for UC management.

Tryptophan Metabolism Disorder-Triggered Diseases, Mechanisms, and Therapeutic Strategies: A Scientometric Review.

BACKGROUND: Tryptophan is widely present in foods such as peanuts, milk, and bananas, playing a crucial role in maintaining metabolic homeostasis in health and disease. Tryptophan metabolism is involved in the development and progression of immune, nervous, and digestive system diseases. Although some excellent reviews on tryptophan metabolism exist, there has been no systematic scientometric study as of yet. METHODS: This review provides and summarizes research hotspots and potential future directions by analyzing annual publications, topics, keywords, and highly cited papers sourced from Web of Science spanning 1964 to 2022. RESULTS: This review provides a scientometric overview of tryptophan metabolism disorder-triggered diseases, mechanisms, and therapeutic strategies. CONCLUSIONS: The gut microbiota regulates gut permeability, inflammation, and host immunity by directly converting tryptophan to indole and its derivatives. Gut microbial metabolites regulate tryptophan metabolism by activating specific receptors or enzymes. Additionally, the kynurenine (KYN) pathway, activated by indoleamine-2, 3-dioxygenase (IDO) and tryptophan 2, 3-dioxygenase, affects the migration and invasion of glioma cells and the development of COVID-19 and depression. The research and development of IDO inhibitors help to improve the effectiveness of immunotherapy. Tryptophan metabolites as potential markers are used for disease therapy, guiding clinical decision-making. Tryptophan metabolites serve as targets to provide a new promising strategy for neuroprotective/neurotoxic imbalance affecting brain structure and function. In summary, this review provides valuable guidance for the basic research and clinical application of tryptophan metabolism.

Biomedical potentials of alginate via physical, chemical, and biological modifications.

Alginate is a linear polysaccharide with a modifiable structure and abundant functional groups, offers immense potential for tailoring diverse alginate-based materials to meet the demands of biomedical applications. Given the advancements in modification techniques, it is significant to analyze and summarize the modification of alginate by physical, chemical and biological methods. These approaches provide plentiful information on the preparation, characterization and application of alginate-based materials. Physical modification generally involves blending and physical crosslinking, while chemical modification relies on chemical reactions, mainly including acylation, sulfation, phosphorylation, carbodiimide coupling, nucleophilic substitution, graft copolymerization, terminal modification, and degradation. Chemical modified alginate contains chemically crosslinked alginate, grafted alginate and oligo-alginate. Biological modification associated with various enzymes to realize the hydrolysis or grafting. These diverse modifications hold great promise in fully harnessing the potential of alginate for its burgeoning biomedical applications in the future. In summary, this review provides a comprehensive discussion and summary of different modification methods applied to improve the properties of alginate while expanding its biomedical potentials.

Advances and future perspectives of intranasal drug delivery: A scientometric review.

Intranasal drug delivery is as a noninvasive and efficient approach extensively utilized for treating the local, central nervous system, and systemic diseases. Despite numerous reviews delving into the application of intranasal drug delivery across biomedical fields, a comprehensive analysis of advancements and future perspectives remains elusive. This review elucidates the research progress of intranasal drug delivery through a scientometric analysis. It scrutinizes several challenges to bolster research in this domain, encompassing a thorough exploration of entry and elimination mechanisms specific to intranasal delivery, the identification of drugs compatible with the nasal cavity, the selection of dosage forms to surmount limited drug-loading capacity and poor solubility, and the identification of diseases amenable to the intranasal delivery strategy. Overall, this review furnishes a perspective aimed at galvanizing future research and development concerning intranasal drug delivery.

Pulmonary administration of tetrandrine loaded Zinc-Alginate nanogels attenuates pulmonary fibrosis in rats.

Pulmonary fibrosis is a chronic and progressive disease, current systemic administration is not fully effective with many side effects, such as gastrointestinal and liver injury. The pulmonary delivery system for pulmonary fibrosis may contribute to maximize therapeutic benefit. Natural compounds might have prominence as potential drug candidates, but the low bioavailabilities affect their clinical use. Tetrandrine is a natural alkaloid with good anti-inflammatory, antifibrogenetic and antioxidant effects, and it is used as a clinical therapeutic drug for the treatment of silicosis in China. In the present study, we explore a new strategy of pulmonary delivery system to improve low solubility and pesticide effect of tetrandrine. Tetrandrine was loaded into alginate nanogels by reverse microemulsion method. The release behavior of tetrandrine reached zero-order kinetics release and the maximum free radical clearance rates reached up to 90%. The pulmonary fibrosis rats were treated with tetrandrine nanogels by using ultrasonic atomizing inhalation. Tetrandrine nanogels decreased the development and progression of fibrosis by reducing inflammation response and bating the deposition of extra cellular matrix. In conclusion, ultrasonic atomizing inhalation of tetrandrine nanogels provided a new therapeutic strategy for pulmonary fibrosis.

Enhanced antidepressant effects of BDNF-quercetin alginate nanogels for depression therapy.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) with neuronic development and function is a promising therapeutic agent for treating depressive disorder, according to the neurotrophin hypothesis. However, the delivery of BDNF into the brain is not easy as these large protein molecules cannot efficiently cross the blood-brain barrier (BBB) and easily suffer oxidative damage in vivo. Therefore, the quercetin-based alginate nanogels (quercetin nanogels) loaded with BDNF have been developed, which could efficiently bypass the BBB via the nose-to-brain pathway and protect BDNF from oxidative damage, providing an effective route for the therapy of depressive disorders by intranasal delivery. RESULTS: Quercetin nanogels exhibited uniform size distribution, excellent biocompatibility, and potent antioxidant and anti-inflammatory activities. Quercetin nanogels in the thermosensitive gel achieved sustained and controlled release of BDNF with non-Fick's diffusion, exhibited rapid brain distribution, and achieved nearly 50-fold enhanced bioavailability compared to oral quercetin. Quercetin nanogels as a therapeutic drug delivery carrier exerted antidepressant effects on reserpine-induced rats, effectively delivered BDNF to reverse despair behavior in stress-induced mice, and exhibited antidepressant effects on chronic mild unpredictable stimulation (CUMS) rats. These antidepressant effects of BDNF-Quercetin nanogels for CUMS rats are associated with the regulation of the glutamatergic system, PI3K-Akt, and BDNF-TrkB signaling pathway. CONCLUSIONS: In this study, we provide a promising strategy for brain delivery of BDNF for treating depressive disorders, effectively achieved through combining quercetin nanogels and intranasal administration.

A self-healing hydrogel wound dressing based on oxidized Bletilla striata polysaccharide and cationic gelatin for skin trauma treatment.

Skin trauma presents significant treatment challenges in clinical settings. Hydrogels made from naturally-derived polysaccharide have demonstrated great potential in wound healing. Here, a novel in-situ crosslinked self-healing hydrogel was prepared using oxidized Bletilla striata polysaccharide (BSP) and cationic gelatin via a Schiff-base reaction without the need for any chemical crosslinkers. Similar to the natural extracellular matrix, the BSP-gelatin hydrogel (BG-gel) exhibited typical viscoelastic characteristics. The rheological properties, mechanical behavior, porous structure, and degradation performance of BG-gel could be adjusted by changing the aldehyde group content of BSP. Importantly, the hydrogel showed superior hemostatic performance in mouse tail amputation and rat liver incision models. It significantly facilitated wound healing by promoting hair follicles regeneration, blood vessels repair, collagen deposition, and inducing skin tissue remodeling via increased CD31 expression in a full-thickness skin wound rat model. This multifunctional hydrogel holds potential as a wound dressing for skin trauma, offering both hemostasis and expedited healing.

Therapeutic role of curcumin in adult neurogenesis for management of psychiatric and neurological disorders: a scientometric study to an in-depth review.

Aberrant neurogenesis is a major factor in psychiatric and neurological disorders that have significantly attracted the attention of neuroscientists. Curcumin is a primary constituent of curcuminoid that exerts several positive pharmacological effects on aberrant neurogenesis. First, it is important to understand the different processes of neurogenesis, and whether their dysfunction promotes etiology as well as the development of many psychiatric and neurological disorders; then investigate mechanisms by which curcumin affects neurogenesis as an active participant in pathophysiological events. Based on scientometric studies and additional extensive research, we explore the mechanisms by which curcumin regulates adult neurogenesis and in turn affects psychiatric diseases, i.e., depression and neurological disorders among them traumatic brain injury (TBI), stroke, Alzheimer's disease (AD), Gulf War Illness (GWI) and Fragile X syndrome (FXS). This review aims to elucidate the therapeutic effects and mechanisms of curcumin on adult neurogenesis in various psychiatric and neurological disorders. Specifically, we discuss the regulatory role of curcumin in different activities of neural stem cells (NSCs), including proliferation, differentiation, and migration of NSCs. This is geared toward providing novel application prospects of curcumin in treating psychiatric and neurological disorders by regulating adult neurogenesis.

Antioxidant Activities of Natural Polysaccharides and Their Derivatives for Biomedical and Medicinal Applications.

Many chronic diseases such as Alzheimer's disease, diabetes, and cardiovascular diseases are closely related to in vivo oxidative stress caused by excessive reactive oxygen species (ROS). Natural polysaccharides, as a kind of biomacromolecule with good biocompatibility, have been widely used in biomedical and medicinal applications due to their superior antioxidant properties. In this review, scientometric analysis of the highly cited papers in the Web of Science (WOS) database finds that antioxidant activity is the most widely studied and popular among pharmacological effects of natural polysaccharides. The antioxidant mechanisms of natural polysaccharides mainly contain the regulation of signal transduction pathways, the activation of enzymes, and the scavenging of free radicals. We continuously discuss the antioxidant activities of natural polysaccharides and their derivatives. At the same time, we summarize their applications in the field of pharmaceutics/drug delivery, tissue engineering, and antimicrobial food additives/packaging materials. Overall, this review provides up-to-date information for the further development and application of natural polysaccharides with antioxidant activities.

A Review of Non-Invasive Drug Delivery through Respiratory Routes.

With rapid and non-invasive characteristics, the respiratory route of administration has drawn significant attention compared with the limitations of conventional routes. Respiratory delivery can bypass the physiological barrier to achieve local and systemic disease treatment. A scientometric analysis and review were used to analyze how respiratory delivery can contribute to local and systemic therapy. The literature data obtained from the Web of Science Core Collection database showed an increasing worldwide tendency toward respiratory delivery from 1998 to 2020. Keywords analysis suggested that nasal and pulmonary drug delivery are the leading research topics in respiratory delivery. Based on the results of scientometric analysis, the research hotspots mainly included therapy for central nervous systems (CNS) disorders (Parkinson's disease, Alzheimer's disease, depression, glioblastoma, and epilepsy), tracheal and bronchial or lung diseases (chronic obstructive pulmonary disease, asthma, acute lung injury or respiratory distress syndrome, lung cancer, and idiopathic pulmonary fibrosis), and systemic diseases (diabetes and COVID-19). The study of advanced preparations contained nano drug delivery systems of the respiratory route, drug delivery barriers investigation (blood-brain barrier, BBB), and chitosan-based biomaterials for respiratory delivery. These results provided researchers with future research directions related to respiratory delivery.

Dan-Lou tablets reduces inflammatory response via suppression of the MyD88/p38 MAPK/NF-κB signaling pathway in RAW 264.7 macrophages induced by ox-LDL.

ETHNOPHARMACOLOGICAL EVIDENCE: The anti-inflammatory effect of Dan-Lou tablets (DLT) have been reported; however, the signaling pathways involved and their role in foam cell formation remains unclear. AIM OF THE STUDY: The purpose of this study was to determine the molecular target and mechanism of DLT in the treatment of coronary heart disease (CHD), and investigate the role of DLT in inhibiting foam cell formation and the anti-inflammatory effects of RAW 264.7 macrophages. MATERIALS AND METHODS: This study explored and elucidated the main active components, therapeutic targets, and pharmacological mechanisms of DLT treatment for CHD using network pharmacology. Secondly, the accuracy of the interaction of key active compounds with key proteins was verified by molecular docking analysis. Eight chemical compositions were determined from the ethanol extract of DLT (EEDL) by high-performance liquid chromatography. Finally, this study used EEDL intervention with oxidized low-density lipoprotein (ox-LDL) to induce RAW264.7 macrophages to verify the results of network pharmacology. RESULTS: According to network pharmacological analysis, 269 common targets of DLT and CHD were obtained from an online database, and 24 key targets were obtained from further analysis. GO enrichment and KEGG analyses were performed, mainly involving the cAMP, cGMP-PKG, MAPK, and NF-κB signaling pathways, and vascular smooth muscle contraction. Molecular docking showed that the active components in DLT docked well with MyD88, NF-κB, and p38 MAPK. The eight compounds from the EEDL have been identified as gallic acid, salvianolic acid, puerarin, daidzein, paeoniflorin, salvianolic acid B, cryptotanshinone, and tanshinone IIA with concentrations of 4.62, 4.76, 23.73, 34.24, 14.59, 21.69, 0.34, and 0.47 µg/mg, respectively. Further in vitro experiments showed that the levels of MyD88 and p-p38 MAPK in RAW 264.7 macrophages induced by ox-LDL increased noticeably. Stimulating the NF-κB signaling pathway increased the release of pro-flammatory factors (TNF-α and IL-1ß) and strengthened the inflammatory response (P < 0.05 or P < 0.01), while the levels of MyD88, p38 MAPK, NF-κB, TNF-α, and IL-1ß decreased after EEDL treatment (P < 0.05 or P < 0.01). CONCLUSION: The study demonstrated that the anti-inflammatory activity of the DLT intervention of ox-LDL-induced RAW 264.7 macrophages may involve the MyD88/p38 MAPK/NF-κB signaling pathway.

A novel inhalable quercetin-alginate nanogel as a promising therapy for acute lung injury.

BACKGROUND: Acute lung injury (ALI), a severe health-threatening disease, has a risk of causing chronic pulmonary fibrosis. Informative and powerful evidence suggests that inflammation and oxidative stress play a central role in the pathogenesis of ALI. Quercetin is well recognized for its excellent antioxidant and anti-inflammatory properties, which showed great potential for ALI treatment. However, the application of quercetin is often hindered by its low solubility and bioavailability. Therefore, to overcome these challenges, an inhalable quercetin-alginate nanogel (QU-Nanogel) was fabricated, and by this special "material-drug" structure, the solubility and bioavailability of quercetin were significantly enhanced, which could further increase the activity of quercetin and provide a promising therapy for ALI. RESULTS: QU-Nanogel is a novel alginate and quercetin based "material-drug" structural inhalable nanogel, in which quercetin was stabilized by hydrogen bonding to obtain a "co-construct" water-soluble nanogel system, showing antioxidant and anti-inflammatory properties. QU-Nanogel has an even distribution in size of less than 100 nm and good biocompatibility, which shows a stronger protective and antioxidant effect in vitro. Tissue distribution results provided evidence that the QU-Nanogel by ultrasonic aerosol inhalation is a feasible approach to targeted pulmonary drug delivery. Moreover, QU-Nanogel was remarkably reversed ALI rats by relieving oxidative stress damage and acting the down-regulation effects of mRNA and protein expression of inflammation cytokines via ultrasonic aerosol inhalation administration. CONCLUSIONS: In the ALI rat model, this novel nanogel showed an excellent therapeutic effect by ultrasonic aerosol inhalation administration by protecting and reducing pulmonary inflammation, thereby preventing subsequent pulmonary fibrosis. This work demonstrates that this inhalable QU-Nanogel may function as a promising drug delivery strategy in treating ALI.

Current Research Trends in Cytokine Storm: A Scientometric Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is currently rampant worldwide, resulting in unpredictable harm to humans. High blood levels of cytokines and chemokines have been marked in patients with COVID-19 infection, leading to cytokine storm syndrome. Cytokine storms are violent inflammatory immune responses that reveal the devastating effect of immune dysregulation and the critical role of an effective host immune response. METHODS: Scientometric analysis summarizes the literature on cytokine storms in recent decades and provides a valuable and timely approach to tracking the development of new trends. This review summarizes the pathogenesis and treatment of diseases associated with cytokine storms comprehensively based on scientometric analysis. RESULTS: Field distribution, knowledge structure, and research topic evolution correlated with cytokine storms are revealed, and the occurrence, development, and treatment of disease relevant to cytokine storms are illustrated. CONCLUSION: Cytokine storms can be induced by pathogens and iatrogenic causes and can also occur in the context of autoimmune diseases and monogenic diseases as well. These reveal the multidisciplinary nature of cytokine storms and remind the complexity of the pathophysiological features, clinical presentation, and management. Overall, this scientometric study provides a macroscopic presentation and further direction for researchers who focus on cytokine storms.

Systematic identification of the interventional mechanism of Qingfei Xiaoyan Wan (QFXYW) in treatment of the cytokine storm in acute lung injury using transcriptomics-based system pharmacological analyses.

CONTEXT: Acute lung injury (ALI) is a complex, severe inflammation disease with high mortality, and there is no specific and effective treatment for ALI. Qingfei Xiaoyan Wan (QFXYW) has been widely used to treat lung-related diseases for centuries. OBJECTIVE: This study evaluates the potential effects and elucidates the therapeutic mechanism of QFXYW against LPS induced ALI in mice. MATERIALS AND METHODS: BALB/c Mice in each group were first orally administered medicines (0.9% saline solution for the control group, 0.5 mg/kg Dexamethasone, or 1.3, 2.6, 5.2 g/kg QFXYW), after 4 h, the groups were injected LPS (1.0 mg/kg) to induce ALI, then the same medicines were administered repeatedly. The transcriptomics-based system pharmacological analyses were applied to screen the hub genes, RT-PCR, ELISA, and protein array assay was applied to verify the predicted hub genes and key pathways. RESULTS: QFXYW significantly decreased the number of leukocytes from (6.34 ± 0.51) × 105/mL to (4.01 ± 0.11) × 105/mL, accompanied by the neutrophil from (1.41 ± 0.19) × 105/mL to (0.77 ± 0.10) × 105/mL in bronchoalveolar lavage fluid (BALF). Based on Degree of node connection (Degree) and BottleNeck (BN), important parameters of network topology, the protein-protein interaction (PPI) network screened hub genes, including IL-6, TNF-α, CCL2, TLR2, CXCL1, and MMP-9. The results of RT-PCR, ELISA, and protein chip assay revealed that QFXYW could effectively inhibit ALI via multiple key targets and the cytokine-cytokine signalling pathway. CONCLUSIONS: This study showed that QFXYW decreased the number of leukocytes and neutrophils by attenuating inflammatory response, which provides an important basis for the use of QFXYW in the treatment of ALI.

ROS-responsive thioketal-linked alginate/chitosan carriers for irritable bowel syndrome with diarrhea therapy.

A colon-specific carrier that can protect drugs from the destruction in the gastrointestinal tract is critical for treating irritable bowel syndrome with diarrhea (IBS-D). In this study, chitosan was cross-linked by the thioketal (TK) bond to serve as a ROS-sensitive core of microspheres. Then the chitosan core was coated with an alginate shell. The alginate/chitosan microspheres can protect puerarin against the destruction and elimination in the gastrointestinal tract and release puerarin at the lesion sites in large quantities. The microspheres were characterized using differential scanning calorimetry, Fourier-transform infrared spectroscopy, and scanning electron microscopy. The swelling study showed that microspheres would shrink in an acidic environment. The in vitro release analysis indicated that little puerarin was released at gastric pH but burst release was observed in simulated colonic fluid containing H2O2. Fluorescent tracer revealed that the fluorescence of microspheres lasted up to 30 h in the colon, which was beneficial to prolong the action time between puerarin and colon. The in vivo studies indicated that puerarin-loaded microspheres are more effective in the treatment of IBS-D than free puerarin. Altogether, the ROS-responsive alginate/chitosan microspheres may be a promising strategy for IBS-D.

Alginate nanogels-based thermosensitive hydrogel to improve antidepressant-like effects of albiflorin via intranasal delivery.

Depression is a primary public health problem. However, current antidepressants work slowly, and together with side effects. Herein, the alginate nanogels were constructed to load albiflorin (albiflorin nanogels), which further formed albiflorin nanogel loaded self-assembled thermosensitive hydrogel system (albiflorin-NGSTH) and were used to improve its antidepressant effects. The nanogel showed a nano-scaled particle size and stronger antioxidant activity. Rheological studies showed that albiflorin-NGSTH had a sol-gel transition at approximately 28 °C. Albiflorin-NGSTH quickly entered the brain by intranasal delivery, and had a continuously release for albiflorin. Preliminary results of mice behavioral despair tests found that albiflorin-NGSTH had no effects on independent exploratory behavior and anxiety of the mice, and significantly decreased immobility duration of the mice in tail suspension test (TST). Moreover, the intranasally administrated albiflorin-NGSTH at a low dose improved depressive behavior, decreased levels of proinflammatory cytokines, and repaired neuronal damage of chronic unpredictable mild stress (CUMS) rats, which indicated an excellent potential for depression therapy. The treatment of albiflorin-NGSTH on depressive disorder was achieved by regulating signal pathway related to depression. Therefore, albiflorin-NGSTH has an excellent potential for clinical application in intranasal drug delivery systems.

Targeting hippocampal phospholipid and tryptophan metabolism for antidepressant-like effects of albiflorin.

BACKGROUND: Current antidepressant therapy remains unsatisfactory due to its delayed clinical onset of action and the heterogeneity of depression. Targeting disturbed neurometabolic pathways could provide a novel therapeutic approach for the treatment of depression. Albiflorin is a phytomedicine isolated from the root of Peony (Paeonia albiflora Pall) with excellent clinical tolerance. Until now, the antidepressant-like activities of albiflorin in different subtypes of depression and its effects on neurometabolism are unknown. PURPOSE: The objective of this study was to investigate the rapid antidepressant-like effects of albiflorin in three common animal models of depression and elucidate the pharmaco-metabolic mechanisms of its action using a multi-omics approach. RESULTS: We found that albiflorin produces rapid antidepressant-like effects in chronic unpredictable mild stress (CUMS), olfactory bulbectomy (OBX), and lipopolysaccharide (LPS)-induced murine models of depression. Using a system-wide approach combining metabolomics, lipidomics, and transcriptomics, we showed that the therapeutic effects of albiflorin are highly associated with the rapid restoration of a set of common metabolic abnormities in the hippocampus across all three depression models, including phospholipid and tryptophan metabolism. Further mechanistic analysis revealed that albiflorin normalized the metabolic dysregulation in phospholipid metabolism by suppressing hippocampal cytosolic phospholipases A2 (cPLA2). Additionally, inhibition of cPLA2 overexpression by albiflorin corrects abnormal kynurenine pathway of tryptophan metabolism via the cPLA2-protein kinase B (Akt1)-indoleamine 2,3-dioxygenase 1(IDO1) regulatory loop and directs tryptophan catabolism towards more hippocampal serotonin biosynthesis. CONCLUSION: Our study contributed to a better understanding of the homogeneity in the metabolic mechanisms of depression and established a proof-of-concept for rapid treatment of depression through targeting dysregulated neurometabolic pathways.

Integration of transcriptomics and system pharmacology to reveal the therapeutic mechanism underlying Qingfei Xiaoyan Wan to treat allergic asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Asthma is a chronic inflammatory disease, characterized by airway inflammation, hyperresponsiveness, and bronchial smooth muscle contraction. Qingfei Xiaoyan Wan (QFXYW), a traditional Chinese formula, has been shown to exert anti-asthma effects and immune response in multiple diseases. AIM OF THIS STUDY: In this study, we evaluated the therapeutic mechanism of QFXYW in the suppression of allergic asthma by integrating of transcriptomics and system pharmacology. MATERIALS AND METHODS: BALB/c mice were sensitized with ovalbumin (OVA) to establish the allergic asthma model, and its success was confirmed with behavioral observations. Lung histopathological analysis, inflammatory pathology scores, transcription factors were used to evaluate the effects of QFXYW on allergic asthma. The therapeutic mechanism of QFXYW in treating allergic asthma through integrated transcriptomics and system pharmacology was then determined: hub genes were screened out by topological analysis and functional enrichment analysis were performed to identify key signaling pathway. Subsequently, quantitative RP-PCR and protein array were performed to detect the mRNA of hub genes and to predict the key pathway in OVA-induced allergic asthma, respectively. RESULTS: Our results demonstrated that QFXYW could significantly attenuate inflammatory cell infiltration, mucus secretion, and epithelial damage. The transcriptomics analysis found the six hub genes with the highest values- CXCL10, CXCL2, CXCL1, IL-6, CCL-5, and CCL-4 were screened out. Functional enrichment analysis showed that the differentially expressed genes (DEGs) were mainly enriched in the inflammatory response and cytokine signaling pathway. Moreover, the quantitative RT-PCR verification experiment found the CXCL2 and CXCL1 were significantly suppressed after treatment with QFXYW. The results of protein array showed that QFXYW inhibited the multi-cytokines of OVA-induced allergic asthma via cytokine signaling pathway. CONCLUSIONS: QFXYW may have mediated OVA-induced allergic asthma mainly through the hub genes CXCL2, CXCL1, and the cytokine signaling pathway. This finding will offer a novel strategy to explore effective and safe mechanism of Traditional Chinese Medicine (TCM) formula to treat allergic asthma.

Intranasal co-delivery of berberine and evodiamine by self-assembled thermosensitive in-situ hydrogels for improving depressive disorder.

The orally administrated antidepressants not only caused side effects such as dizziness, diarrhea, and drug resistance, but also worked slowly. Therefore, new antidepressants and preparations derived from natural medicines play an important role in the study of antidepressant drugs. It was reported that the two components of Zuojin pill, berberine (BBR) and evodiamine (EVO), were used in combination to improve depressive disorder. In our study, a self-assembled thermosensitive in-situ hydrogel was prepared to achieve sustained co-delivery of BBR and EVO. The preparation process of hydrogel consists of two steps, namely, the inclusion of the drugs and thermosensitive self-assembly of the hydrogel. In vitro experimental results indicated that the prepared hydrogel showed a good thermosensitive property under physiological temperature. The hydrogel had a slow and controlled release behavior for BBR and EVO, according with first-order equation. In vivo experimental results indicated that compared to intragastric administration of drug solution, the intranasal administration of hydrogel increased bioavailability of BBR and EVO, approximately 135 and 112 folds, respectively. The hydrogel at a low dose significantly reversed behavioral despair of the mice, improved depressive symptom of rats, and treated depressive disorder by regulating the abnormal levels of monoamine neurotransmitters (including 5-hydroxytryptamine, noradrenalin and dopamine) metabolism and related metabolic pathways such as purine, citrate cycle, scorbate and aldarate, butanoate, vitamin B6, and pyrimidine metabolism. Therefore, as a drug co-delivery system, the intranasally administrated hydrogels with a good release and high bioavailability provides a non-invasive therapeutic strategy for the clinical treatment of depression, which attains antidepressant effects by regulation of the monoamine neurotransmitters metabolism and related metabolic pathways.

Puerarin from Pueraria lobata alleviates the symptoms of irritable bowel syndrome-diarrhea.

As a functional bowel disorder, irritable bowel syndrome (IBS), especially IBS-diarrhea (IBS-D), affects approximately 9-20% of the population worldwide. Classical treatments for IBS usually result in some side effects and intestinal microbial disorders, which inhibit the clinical effects. Natural edible medicines with beneficial effects and few side effects have received more attention in recent years. Puerarin is the main active ingredient in pueraria and has been used in China to treat splenasthenic diarrhea and as a natural food in folk medicine for hundreds of years. However, there have been no reports of using puerarin in the treatment of IBS-D, and the underlying mechanism is also still unclear. In this study, a comprehensive model that could reflect the symptoms of IBS-D was established by combining neonatal maternal separation (NMS) and adult colonic acetic acid stimulation (ACAAS) in rats. The results showed that puerarin could reverse the abdominal pain and diarrhea in IBS-D rats. The therapeutic effect was realized by regulating the richness of the gut microbiota to maintain the stabilization of the intestinal micro-ecology. Furthermore, the possible mechanism might be related to the activity of the hypothalamic-pituitary-adrenal (HPA) axis by the suppressed expression of corticotropin-releasing hormone receptor (CRF) 1. At the same time, intestinal function was improved by enhancing the proliferation of colonic epithelial cells by upregulating the expression of p-ERK/ERK and by repairing the colonic mucus barrier by upregulating occludin expression. All these results suggest that puerarin could exert excellent therapeutic effects on IBS-D.