Food Allergens of Plant and Animal Origin: Classification, Characteristics, and Properties.

Food allergy is an adverse immune response to specific foods that can be either IgE-mediated or non-IgE mediated. The causes of IgE-mediated food allergy are multifactorial and involve genetic, dietary, and environmental factors. The prevalence of food allergy has increased over the last few decades, especially in urbanized, industrialized, and Westernized countries, and the epithelial barrier hypothesis has been recently suggested as a possible explanation for this increase. Food allergens of plant and animal origin are classified into a few families and superfamilies that are widely distributed and conserved. While it is known that food allergens share common properties, such as stability to enzymes and solubility, they also exhibit differential properties, and exceptions to the common characteristics exist. In recent years, novel characteristics of food allergens have been proposed based on their immunological properties and their ability to act as adjuvants or enhancers of the immune system.This chapter provides an overview of the current knowledge of food allergy, covering their prevalence, classification of food allergens from plant and animal origins, and recent advancements in the characterization of the properties of these allergens.

Evaluation of the Suppressive Capacity of Regulatory T Cells in Food Allergy Research.

Regulatory T cells (Treg) exert a crucial role in the suppression of exacerbated T helper (Th) cell responses, including those of type 2 Th (Th2) cells, and in the maintenance of tolerance to environmental antigens and food allergens. The functional capacity of Tregs to suppress Th2 responses has been studied through activation and immunosuppression assays using cells from mice and humans. The immunosuppression assay is an essential in vitro tool that allows the evaluation of the Treg capacity to limit the proliferation and expansion of conventional T cells. This approach enables the determination of the suppressive ability of different Treg subsets. In this chapter, we describe a basic and well-established immunosuppression protocol for human and murine Treg that has been widely applied in food allergy research.

1D-, 2D-Gel Electrophoresis, Immunoblotting, and Enzyme-Linked Immunosorbent Assay (ELISA) for the Study of Food Allergens.

Protein-based methods have been fundamental for the study of food allergens, not only from a mechanistic and diagnostic point of view, but especially with respect to allergen management and food safety. In this chapter, four individual protocols are suggested, relying on one-dimensional, two-dimensional gel electrophoresis, immunoblotting, and enzyme-linked immunosorbent assay (ELISA). The particularities of the proposed protocols are focused on previous research targeting specific allergenic foods, with cow's milk proteins as case studies. Data on the importance of protein extraction and the use of different animal-raised antibodies and/or sera of food-allergic patients are also critically discussed within method development and optimization. The protocols herein described are successful examples applied to the study of cow's milk allergens in complex matrices, although they can be easily developed and optimized for any food allergen or allergenic food.

Animal Models in the Study of Food Allergens: Long-Term Maintenance of Allergic Reactivity in Mouse Models of Food Allergy.

Multiple mouse models have been used to characterize mechanisms of allergic sensitization and anaphylaxis and are widely used for preclinical development of novel therapeutics. However, the majority of published works with mouse models of food allergy have very short intervals between the time of sensitization and the end of the study, and the duration of maintenance of reactivity has not been widely reported. This chapter focuses on two of the most commonly used mouse models with sensitization to peanut or ovalbumin, with the focus on the long-term durability of sensitization to allow for longer therapeutic protocols and assessment of sustained unresponsiveness.

A Mouse Model of Shrimp Allergy with Cross-Reactivity to Crab and Lobster.

Food allergies are a growing public health problem with recent estimates of 10% of the US population affected by this immunologic disease. The quality of life is greatly impaired in food allergic individuals and their caregivers due to constant vigilance and fear of accidental exposure. Shellfish allergies are of particular concern because their prevalence has increased over the past 15 years, now affecting an estimated 3% of the adult population and 1.3% of children in the USA. Additionally, they are rarely outgrown, can result in fatal reactions, and there are no FDA-approved therapies for shellfish allergies. Reactions to one type of shellfish, crustaceans (shrimp, lobster, and crab), can be especially severe. The major crustacean allergens are highly conserved across species, resulting in high cross-reactivity of IgE between shrimp, lobster, and crab in allergic individuals. To develop novel therapies for shellfish allergies, preclinical mouse models are required. In this chapter, we present detailed methodology to induce shrimp allergy in CC027 mice. Once sensitized, mice produce shrimp-specific IgE, that is cross-reactive with lobster and crab, and experience anaphylaxis upon shrimp challenge. This model can be used to further investigate mechanisms of sensitization and preclinical testing of therapies.

Visual and rapid detection of escolar (Lepidocybium flavobrunneum) using loop mediated isothermal amplification in conjunction with a specific molecular beacon probe.

Species adulteration has become a main reason for the unexpected exposure to escolar, which is often related with the gastrointestinal disease called keriorrhea. Sensitive and accurate identification of escolar is required to protect consumers from commercial and health frauds. The present study established a visual and rapid method for escolar detection using LAMP (loop-mediated isothermal amplification) in conjunction with a MB (molecular beacon) probe. The visual MB-LAMP assay demonstrated high specificity and superb sensitivity (1 pg DNA) for escolar and low to 0.1 % (w/w) simulated adulteration could be detected within 25 min. Additionally, method validation on commercial products highlighted the umbrella term of white tuna for escolar on Chinese market. All these results indicated that the MB-LAMP method is a useful tool for rapid, sensitive and convenient detection of escolar and can also be used as a point-of-care molecular diagnostic technique since it does not require the expensive equipment.

Antidepressant effect of Perilla frutescens essential oil through monoamine neurotransmitters and BDNF/TrkB signal pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine posits that affect-mind ill-being is the primary cause of depression, with Qi movement stagnation as its pathogenesis. As such, clinical treatment for depression should prioritize regulating Qi and relieving depressive symptoms. The pharmacological properties of traditional Chinese medicine indicate that Perilla frutescens may have potential therapeutic effects on depression and other neuropsychiatric diseases due to its ability to regulate Qi and alleviate depressive symptoms. Although previous studies have reported the antidepressant effects of Perilla frutescens, the mechanism underlying PFEO inhalation-mediated antidepressant effect remains unclear. AIM OF THE STUDY: The aim of this investigation is to elucidate the antidepressant mechanisms of PFEO by examining its effects on monoamine neurotransmitters and the BDNF/TrkB signaling pathway. MATERIALS AND METHODS: The CUMS rat model of depression was established, and the depressive state of the animals was assessed through sucrose preference and forced swim tests. ELISA assays were conducted to determine monoamine neurotransmitter levels in the hippocampus and cerebral cortex of rats. Immunohistochemistry, western blotting, and RT-PCR experiments were employed to investigate the BDNF/TrkB signaling pathway's regulation of depression via PFEO inhalation. RESULTS: It has been observed that inhalation administration of PFEO can significantly enhance the preference for sugar water in CUMS rats and reduce their immobility time during forced swimming. Additionally, there was an increase in the levels of monoamine transmitters in both the hippocampus and cerebral cortex of these rats. Furthermore, there was an upregulation in the expression levels of BDNF and TrkB positive cells as well as BDNF and TrkB proteins within both regions, along with increased BDNF mRNA and TrkB mRNA expression levels. CONCLUSION: The antidepressant effect of PFEO via inhalation administration is speculated to be mediated through the monoamine neurotransmitters and BDNF/TrkB signaling pathway.

Ameliorative effect of scopolamine-induced cognitive dysfunction by Fufangmuniziqi formula: The roles of alkaloids, saponins, and flavonoids.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufangmuniziqi formula (FFMN), a traditional Uyghur medicine used in China, is derived from an ancient Uyghur medical book and consists of 13 herbs. The herbs of FFMN, such as Peganum harmala L., Glycyrrhiza uralensis Fisch., and Nigella glandulifera, have been demonstrated to have acetylcholinesterase (AChE) inhibitory, anti-neuroinflammatory, or antioxidant effects. Therefore, FFMN may have a good anti-Alzheimer's disease (AD) effect, but its specific action and mechanism need to be further proven. AIM OF THE STUDY: This study aims to investigate the anti-AD effects of FFMN and the role played by alkaloids, flavonoids, and saponins in anti-AD. MATERIALS AND METHODS: The alkaloids, flavonoids, and saponins fractions of FFMN were prepared by macroporous resin chromatography. The absorbed ingredients in the drug-containing serum were identified by UPLC⁃Q⁃TOF⁃MS. An AD mouse model was established by intraperitoneal injection of scopolamine (SCO). The role of different fractions of FFMN in the anti-AD process was examined by Morris water maze (MWM), in-vitro cell, and AChE inhibition assay. RESULTS: A total of 20 ingredients were identified in the serum samples collected after oral administration of FFMN, and seven compounds were selected as candidate active compounds. MWM experiments showed that different fractions of FFMN could significantly improve SCO-induced learning memory impairment in mice. The alkaloids fraction (ALK) regulated cholinergic function by inhibiting AChE activity, activating choline acetyltransferase activity, and protein expression. Flavonoids and saponins were more potent than the ALK in downregulating pro-inflammatory factors or inflammatory mediators, such as TNF-α, MPO, and nitric oxide. Western blot results further confirmed that flavonoids and saponins attenuated neuroinflammation by inhibiting the phosphorylation of IκB and NF-κB p65. This result was also verified by in-vitro cellular assays. FFMN enhanced antioxidant defense by increasing the activity of superoxide dismutase and reducing the production of MDA. Combined with cellular experiments, flavonoids and saponins were proven more protective against oxidative damage. CONCLUSION: FFMN improved cognitive and memory impairment in the SCO-induced AD mouse model. ALK mainly enhanced the function of the cholinergic system. Flavonoid and saponin fractions mainly attenuated neuroinflammation and oxidative stress by modulating the NF-κB pathway. All these findings strongly suggested that the combination of alkaloid, flavonoid, and saponin fractions derived from FFMN is a promising anti-AD agent that deserves further development.

Longdan Xiegan decoction ameliorates vulvovaginal candidiasis by inhibiting the NLRP3 inflammasome via the Toll-like receptor /MyD88 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Longdan Xiegan decoction (LXD) is a standardized herbal prescription originally documented in the "Medical Formula Collection" by the eminent physician Wang Ang during the Qing dynasty. It has been used extensively to treat vulvovaginal candidiasis (VVC). However, despite its effectiveness, the mechanism of action remains unknown. AIM OF THE STUDY: To elucidate the mechanism by which LXD relieves VVC via the Toll-like receptor/MyD88 pathway and activation of the NLRP3 inflammasome. MATERIALS AND METHODS: Female Kunming mice (n = 96) were randomly divided into six groups: control, VVC model, LXD (10/20/40 mL/kg), and positive drug fluconazole. Mice were vaginally administered Candida albicans (C. albicans) solution (20 µL; 1 × 108 colony-forming units/mL), suspended for 5 min, and observed daily for changes in their condition. Continuous dilution was used to determine the number of colony-forming units. Gram, periodic acid-Schiff, Papanicolaou, and hematoxylin and eosin staining were used to determine the extent of infection. Enzyme-linked immunosorbent assay(ELISA) was used to determine the levels of proinflammatory cytokines IL-1ß and IL-18. TLR2, TLR4, MyD88, NF-κB, NLRP3, ASC, and caspase-1 protein expression were determined using western blotting. RESULTS: C. albicans infection destroyed the integrity of the vaginal mucosa, increased fungal burden and the influx of neutrophils into the vaginal cavity, and promoted the secretion of proinflammatory cytokines. C. albicans stimulated the expression of TLR2, TLR4, MyD88, NF-κB, NLRP3, ASC, and caspase-1 in vaginal tissue. Fungal burden, hyphal formation, and C. albicans adhesion were reduced in the 20 and 40 mL/kg LXD groups. Hematoxylin and eosin staining showed that inflammation was reduced and the stratum corneum had recovered in the 20 and 40 mL/kg LXD groups. LXD (20 and 40 mL/kg) significantly reduced IL-1ß, IL-18 levels and the number of neutrophils in vaginal lavage and decreased TLR2, TLR4, MyD88, NF-κB, NLRP3, ASC, and caspase-1 expression. CONCLUSIONS: This study systematically demonstrated the therapeutic effect of LXD on protein expression and pathological conditions in VVC mice. The results showed that LXD could eliminate the invasion of vaginal hyphae in mice, reduce the recruitment of neutrophils, and reduce the expression of TLR/MyD88 pathway-related proteins and NLRP3 inflammasome. The above results clearly indicate that LXD may profoundly regulate NLRP3 inflammasome through the TLR/MyD88 pathway and play a therapeutic role in VVC.

Qinzhizhudan formula dampens inflammation in microglia polarization of vascular dementia rats by blocking MyD88/NF-κB signaling pathway: Through integrating network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Qinzhizhudan Formula (QZZD) is composed of Scutellaria baicalensis Georgi (Huang Qin) extract, Gardenia jasminoides (Zhizi) extract and Suis Fellis Pulvis (Zhudanfen) (ratio of 4:5:6). This formula is optimized from Qingkailing (QKL) injection. Regarding brain injury, QZZD is protective. However, the mechanism by which QZZD treats vascular dementia (VD) has not been elucidated. AIM OF THE STUDY: To ascertain QZZD's effect on the treatment of VD and further investigate the molecular mechanisms. MATERIALS AND METHODS: In this study, we screened the possible components and targets of QZZD against VD and microglia polarization using network pharmacology (NP), then an animal model of bilateral common carotid artery ligation method (2VO) was induced. Afterward, The Morris water maze was employed to evaluate cognitive ability, and pathological alterations in the CA1 area of the hippocampus were detected using HE and Nissl staining. To confirm the affect of QZZD on VD and its molecular mechanism, the contents of inflammatory factors IL-1ß, TNF-α, IL-4, and IL-10 were performed to detect by ELISA, the phenotype polarization of microglia cells was detected by immunofluorescence staining, and the expressions of MyD88, p-IκBα and p-NF-κB p65 in brain tissue were detected by western blot. RESULTS: A total of 112 active compounds and 363 common targets of QZZD, microglia polarization, and VD were identified, according to the NP analysis. 38 hub targets were screened out from the PPI network. GO analysis and KEGG pathway analysis showed that QZZD may regulate microglia polarization through anti-inflammatory mechanism such as Toll-like receptor signaling pathway and NF-κB signaling pathway. The further results showed that QZZD can alleviate the memory impairment induced by 2VO. QZZD profoundly rescued brain hippocampus neuronal damage and increased the number of neurons. These advantageous outcomes were linked to the control of microglia polarization. QZZD decreased M1 phenotypic marker expression while increasing M2 phenotypic marker expression. QZZD may controll the polarization of the M1 microglia by blocking the core part of Toll-like receptor signaling pathway, that is the MyD88/NF-κB signaling pathway, which reduced the neurotoxic effects of the microglia. CONCLUSION: Here, we explored the anti-VD microglial polarization characteristic of QZZD for the first time and clarified its mechanisms. These findings will provide valuable clues for the discovery of anti-VD agents.

Astragalus saponins protect against extrahepatic and intrahepatic cholestatic liver fibrosis models by activation of farnesoid X receptor.

ETHNOPHARMACOLOGICAL RELEVANCE: Cholestatic Liver Fibrosis (CLF) is a hepatobiliary disease that typically arises as a late-stage complication of cholestasis, which can have multiple underlying causes. There are no satisfactory chemical or biological drugs for CLF. Total Astragalus saponins (TAS) are considered to be the main active constituents of the traditional Chinese herb Astragali Radix (AR), which has the obvious improvement effects for treating CLF. However, the mechanism of anti-CLF effects of TAS is still unclear. AIM OF THE STUDY: The present study was undertaken to investigate the therapeutic effects of TAS against bile duct ligation (BDL) and 3, 5-diethoxycarbonyl-1,4-dihydroxychollidine (DDC) -induced CLF models and to reveal the potential mechanism to support its clinic use with scientific evidence. MATERIALS AND METHODS: In this study, BDL-induced CLF rats were treated with TAS (20 mg/kg, 40 mg/kg) and DDC-induced CLF mice were treated with 56 mg/kg TAS. The therapeutic effects of TAS on extrahepatic and intrahepatic CLF models were evaluated by serum biochemical analysis, liver histopathology and hydroxyproline (Hyp). Thirty-nine individual bile acids (BAs) in serum and liver were quantified by using UHPLC-Q-Exactive Orbitrap HRMS. qRT-PCR, Western blot and immunohistochemistry analysis were used to measure the expression of liver fibrosis and ductular reaction markers, inflammatory factors and BAs related metabolic transporters, along with nuclear receptor farnesoid X receptor (FXR). RESULTS: The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBiL), direct bilirubin (DBiL) and contents of liver Hyp were dose-dependently improved after treatment for TAS in BDL and DDC- induced CLF models. And the increased levels of ALT and AST were significantly improved by total extract from Astragali radix (ASE) in BDL model. The liver fibrosis and ductular reaction markers, α-smooth muscle actin (α-SMA) and cytokeratin 19 (CK19), were significantly ameliorated in TAS group. And the liver expression of inflammatory factors: interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin 1ß (IL-1ß) were significantly decreased after TAS treatment. In addition, TAS significantly ameliorated taurine-conjugated BAs (tau-BAs) levels, particularly α-TMCA, ß-TMCA and TCA contents in serum and liver, which correlated with induced expressions of hepatic FXR and BAs secretion transporters. Furthermore, TAS significantly improved short heterodimer partner (SHP), cholesterol 7α-hydroxylase (Cyp7a1), Na+ taurocholate cotransport peptide (NTCP) and bile-salt export pump (BSEP) mRNA and protein expression. CONCLUSIONS: TAS exerted a hepatoprotective effect against CLF by ameliorating liver injury, inflammation and restoring the altered tau-BAs metabolism to produce a positive regulatory effect on FXR-related receptors and transporters.

Qinlian hongqu decoction ameliorates hyperlipidemia via the IRE1-α/IKKB-ß/NF-κb signaling pathway: Network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Qinlian Hongqu decoction (QLHQD) is a traditional Chinese medicine (TCM) formula. It has previously been found to mitigate hyperlipidemia, although its mechanism requires further clarification. AIM OF THE STUDY: This study explored QLHQD's mechanism in treating hyperlipidemia based on network pharmacology and experimental validation. MATERIALS AND METHODS: The components of QLHQD were analyzed by means of ultrahigh performanceliquid chromatography-quadrupole/orbitrapmass spectrometry (UHPLC-Q-Orbitrap-HRMS) and the targets of hyperlipidemia were predicted using the Swiss ADME, GeneCards, OMIM, DrugBank, TTD, and PharmGKB databases. A drug-component-target-disease network was constructed using Cytoscape v3.7.1. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were performed using the Bioinformatics platform. Based on the KEGG results, the non-alcoholic fatty liver disease signaling pathways were selected for experimental validation in an animal model. RESULTS: We identified 34 components of QLHQD, 94 targets of hyperlipidemia, and 18 lipid metabolism-related pathways from the KEGG analysis. The results of the animal experiment revealed that QLHQD alleviated lipid metabolism disorders, obesity, insulin resistance, and inflammation in rats with hyperlipidemia induced by high-fat diets. Additionally, it reduced the expression of IRE1-α, TRAF2, IKKB-ß, and NF-κB proteins in the liver of hyperlipidemic rats. CONCLUSION: QLHQD is able to significantly mitigate hyperlipidemia induced via high-fat diets in rats. The mechanism of action in this regard might involve regulating the IRE1-α/IKKB-ß/NF-κB signaling pathway in the liver, thereby attenuating inflammatory responses and insulin resistance.

Therapeutic potential of elema-1,3,7(11),8-tetraen-8,12-lactam from Curcuma wenyujin on diabetic retinopathy via anti-inflammatory and anti-angiogenic pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, the causes of diabetic retinopathy (DR) are blood stasis and heat. Curcuma wenyujin Y. H. Chen & C. Ling and its extracts have the effects of promoting blood circulation to remove blood stasis, clearing the heart, and cooling the blood, and have been used in the treatment of DR. Elema-1,3,7 (11),8-tetraen-8,12-lactam (Ele), an N-containing sesquiterpene isolated from this plant. However, the anti-inflammatory and anti-angiogenic effects of Ele and its therapeutic potential in DR are still unknown. AIM OF THE STUDY: To evaluate the anti-inflammatory and anti-angiogenic effects of Ele and its therapeutic potential in DR. MATERIALS AND METHODS: In vitro, anti-inflammatory and anti-angiogenic effects were assessed using TNF-α or VEGF-stimulated HUVECs. Protein expression was analyzed using Western blotting. ICAM-1 and TNF-α mRNA expressions were analyzed using real-time quantitative RT-PCR. The therapeutic potential in DR was assessed using both animal models of STZ-induced diabetes and oxygen-induced retinopathy. The retinal vascular permeability was measured using Evans blue, and the quantitation of retinal leukostasis using FITC-coupled Con A. The retinal neovascular tufts were analyzed using fluorescein angiography and counting pre-retinal vascular lumens. RESULTS: Ele inhibited NF-κB pathway, and ICAM-1, TNF-α mRNA expression in TNF-α- stimulated HUVECs. It also inhibits the multistep process of angiogenesis by inhibiting the phosphorylation of VEGFR2 and its downstream signaling kinases Src, Erk1/2, Akt, and mTOR in VEGF-stimulated HUVECs. Intravitreal injection of Ele can significantly reduce retinal microvascular leakage, leukostasis, and expression of ICAM-1, TNF-α in diabetic rats and inhibits oxygen-induced retinal neovascularization and VEGFR2 phosphorylation in OIR mice. CONCLUSIONS: Ele has anti-inflammatory and anti-angiogenic effects through inhibiting NF-κB and VEGFR2 signaling pathways, and it may be a potential drug candidate for DR.

Integration of network pharmacology and proteomics to elucidate the mechanism and targets of traditional Chinese medicine Biyuan Tongqiao granule against allergic rhinitis in an ovalbumin-induced mice model.

ETHNOPHARMACOLOGICAL RELEVANCE: Biyuan Tongqiao granule (BYTQ) is a traditional Chinese medicine that has been used in China to clinically treat patients with allergic rhinitis (AR), yet its underlying mechanism and targets remains unclear. AIM OF THE STUDY: The study aimed to investigate the potential mechanism of BYTQ against AR using the ovalbumin (OVA) -induced AR mice model. Integrating network pharmacology and proteomics to investigate possible targets of BYTQ for AR. MATERIALS AND METHODS: The compounds in BYTQ were analyzed using UHPLC-ESI-QE-Orbitrap-MS. The OVA/Al(OH)3 were used to induce the AR mice model. The nasal symptoms, histopathology, immune subsets, inflammatory factors, and differentially expressed proteins were examined. Proteomics analysis elucidated the potential mechanisms of BYTQ to improve AR, which was further validated by Western blot (WB) assay. The compounds and potential targets of BYTQ were systematically elucidated by integrating network pharmacology and proteomics analysis to explore the mechanism. The binding affinity between key potential targets and corresponding compounds was then validated using molecular docking. Molecular docking results were verified by a western blotting and cellular thermal shift assay (CETSA). RESULTS: A total of 58 compounds were identified from BYTQ. BYTQ significantly suppressed AR symptoms by inhibiting the release of OVA-specific immunoglobulin E (IgE) and histamine, improving the pathological injury of nasal mucosal tissue, and regulating the proportions of lymphocytes to maintain immune balance. Proteomics analysis showed that the cell adhesion factors and focal adhesion pathway might be potential mechanism of BYTQ against AR. The levels of E-selectin, vascular endothelial cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) proteins in the nasal mucosal tissue were significantly downregulated in the BYTQ-H group compared to the AR group. Integrating network pharmacology and proteomics analysis identified that SRC, PIK3R1, HSP90AA1, GRB2, AKT1, MAPK3, MAPK1, TP53, PIK3CA, and STAT3 may be potential protein targets for BYTQ to treat AR. Molecular docking analysis indicated that the active compounds of BYTQ could bind tightly to these key targets. In addition, BYTQ could inhibit OVA-induced phosphorylation levels of PI3K, AKT1, STAT3 and ERK1/2. The CETSA data suggested that BYTQ could improve the heat stability of PI3K, AKT1, STAT3 and ERK1/2. CONCLUSIONS: BYTQ suppresses E-selectin and VCAM-1 and ICAM1 expression by regulating PI3K/AKT and STAT3/MAPK signaling pathways, thus alleviating inflammation in AR mice. BYTQ is the aggressive treatment for AR.

Traditional Chinese Medicine: A promising strategy to regulate the imbalance of bacterial flora, impaired intestinal barrier and immune function attributed to ulcerative colitis through intestinal microecology.

ETHNOPHARMACOLOGICAL RELEVANCE: Globally, plant materials are widely used as an additional and alternative therapy for the treating of diverse diseases. Ulcerative colitis (UC) is a chronic, recurrent and nonspecific inflammation of the bowel, referred to as "modern intractable disease" according to the World Health Organization. With the continuous development of theoretical research in Traditional Chinese Medicine (TCM) and the advantages of TCM in terms of low side effects, TCM has shown great progress in the research of treating UC. AIM OF THIS REVIEW: This review aimed to explore the correlation between intestinal microbiota and UC, summarize research advances in TCM for treating UC, and discuss the mechanism of action of TCM remedies in regulating intestinal microbiota and repairing damaged intestinal barrier, which will provide a theoretical basis for future studies to elucidate the mechanism of TCM remedies based on gut microbiota and provide novel ideas for the clinical treatment of UC. METHODS: We have collected and collated relevant articles from different scientific databases in recent years on the use of TCM in treating UC in relation to intestinal microecology. Based on the available studies, the therapeutic effects of TCM are analysed and the correlation between the pathogenesis of UC and intestinal microecology is explored. RESULTS: TCM is used to further protect the intestinal epithelium and tight junctions, regulate immunity and intestinal flora by regulating intestinal microecology, thereby achieving the effect of treating UC. Additionally, TCM remedies can effectively increase the abundance of beneficial bacteria that produce short-chain fatty acids, decrease the abundance of pathogenic bacteria, restore the balance of intestinal microbiota, and indirectly alleviate intestinal mucosal immune barrier dysfunction and promote the repair of damaged colorectal mucosa. CONCLUSION: Intestinal microbiota is closely related to UC pathogenesis. The alleviation of intestinal dysbiosis can be a potential novel therapeutic strategy for UC. TCM remedies can exert protective and therapeutic effects on UC through various mechanisms. Although intestinal microbiota can aid in the identification of different TCM syndromes types, further studies are needed using modern medical technology. This will improve the clinical therapeutic efficacy of TCM remedies in UC and promote the application of precision medicine.

Antipyretic and antinociceptive effects of methanolic extract of C. iria L. tuber.

ETHNOPHARMACOLOGICAL RELEVANCE: Cyperus iria L. is a sedge belongs to Cyperaceae family. Tuber of this plant is traditionally used in fever. AIM OF THE STUDY: This study aimed to verify the effectiveness of this plant part against fever. Additionally, antinociceptive effect of the plant was evaluated. MATERIALS AND METHODS: Antipyretic effect was evaluated by yeast induced hyperthermia experiment. Antinociceptive effect was determined by acetic acid induced writhing test and hot plate test. Four different doses of plant extract were used in mice model. RESULTS: Extract at dose of 400 mg/kg.bw produced greater effect than paracetamol; reduction of elevated mice body temperature was observed by 2.6 °F and 4.2 °F after 4 h by paracetamol and 400 mg/kg.bw extract respectively. In acetic acid writhing test, extract at 400 mg/kg.bw and diclofenac were found to have equivalent effects producing percentage inhibition of writhing of 67.68% and 68.29% respectively. In hot plat test, significant reduction in latency was also observed after administration of plant extracts. Mean percent maximal effect was 83.55% and 67.26% for ketorolac and extract (400 mg/kg.bw) respectively. CONCLUSION: Our study endorsed the traditional use of C. iria tuber in fever with possible antinociceptive effects.

Network pharmacology and transcriptomics to determine Danggui Yifei Decoction mechanism of action for the treatment of chronic lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Several children with pneumonia (especially severe cases) have symptoms of cough and expectoration during the recovery stage after standard symptomatic treatment, which eventually results in chronic lung injury. Danggui yifei Decoction (DGYFD), a traditional Chinese formula, has shown clinical promise for the treatment of chronic lung injury during the recovery stage of pneumonia, however, its mechanism of action is yet to be deciphered. AIM OF THIS STUDY: To investigate the therapeutic mechanism of DGYFD for the treatment of chronic lung injury by integrating network pharmacology and transcriptomics. MATERIALS AND METHODS: BALB/c mice were used to establish the chronic lung injury mouse model by intratracheal instillation of lipopolysaccharide (LPS). Pathological analysis of lung tissue, lung injury histological score, lung index, protein levels in bronchoalveolar lavage fluid (BALF), immunohistochemical staining, blood rheology, inflammatory cytokines, and oxidative stress levels were used to evaluate the pharmacological effects of DGYFD. Chemical components of DGYFD were identified using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Integrated network pharmacology together with transcriptomics was used to predict potential biological targets. Western blot analysis was used to verify the results. RESULTS: In this study, we demonstrated that DGYFD could improve lung injury pathological changes, decreases lung index, down-regulate NO and IL-6 levels, and regulate blood rheology. In addition, DGYFD was able to reduce the protein levels in BALF, up-regulate the expression levels of occludin and ZO-1, improve the ultrastructure of lung tissues, and reverse the imbalance of AT I and AT II cells to repair the alveolar-capillary permeability barrier. Twenty-nine active ingredients of DGYFD and 389 potential targets were identified by UPLC-MS/MS and network pharmacology, and 64 differentially expressed genes (DEGs) were identified using transcriptomics. GO and KEGG analysis revealed that the MAPK pathway may be the molecular target. Further, we found that DGYFD inhibits phosphorylation levels of p38 MAPK and JNK in chronic lung injury mouse models. CONCLUSIONS: DGYFD could regulate the imbalance between the excessive release of inflammatory cytokines and oxidative stress, repair the alveolar-capillary permeability barrier and improve the pathological changes during chronic lung injury by regulating the MAPK signaling pathway.

Integrated proteomics and metabolomics reveals metabolism disorders in the α-syn mice and potential therapeutic effect of Acanthopanax senticosus extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: Acanthopanax senticosus (Rupr.et.Maxim.)Harms(AS) is an extract of Eleutherococcus senticocus Maxim(Rupr.et.Maxim.). In modern medical interpretation, Acanthopanax senticosus can be used to treat Parkinson's disease, and a large number of modern pharmacological and clinical studies also support this application. Our study demonstrated that AS extracts can increase the activity of various antioxidant enzymes and improve the symptoms of Parkinson's disease in mice. AIM OF THE STUDY: The current study looked at the protective effect of Acanthopanax senticosus extracts(ASE) in preventing PD. METHODS AND MATERIALS: First, the α-syn-overexpressing mice were chosen as suitable models for Parkinson's disease in vivo. HE staining was used to observe the pathological changes in the substantia nigra. Meanwhile, TH expression in substantia nigra was analyzed by immunohistochemistry. Behavioral and biochemical tests evaluated neuroprotective effects of ASE on PD mice. Subsequently, combined with proteomics and metabolomics analysis, the changes in brain proteins and metabolites in mice treated with ASE for PD were studied. Finally, Western blot was used to detect metabolome-related and proteomic proteins in the brain tissue of α-syn mice. RESULTS: Forty-nine common differentially expressed proteins were screened by proteomics analysis, among which 28 were significantly up-regulated,and 21 were significantly down-regulated. Metabolomics analysis showed that twenty-five potentially important metabolites were involved in the therapeutic effect of ASE on PD. Most of the different proteins and metabolites were considered to be enriched in a variety of species in metabolic pathways, including glutathione metabolism and alanine aspartate and glutamate metabolism and other pathways, which means that ASE may have molecular mechanisms to ameliorate PD dysfunction. In addition, we found that decreases in glutathione and glutathione disulfide levels may play a critical role in these systemic changes and warrant further investigation. In the glutathione metabolic pathway, ASE also acts on GPX4, GCLC and GCLM. CONCLUSIONS: ASE can effectively relieve behavioral symptoms of α-syn mice and relieve oxidative stress in brain tissue. These findings suggest that ASE offers a potential solution to target these pathways for the treatment of PD.

Xiao-Ban-Xia decoction mitigates cisplatin-induced emesis via restoring PINK1/Parkin mediated mitophagy deficiency in a rat pica model.

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese anti-emetic formula, Xiao-Ban-Xia decoction (XBXD) was recorded in Golden Chamber, and has promising anti-emetic effect on chemotherapy-induced nausea and vomiting (CINV). AIM OF THE STUDY: This study aimed to determine whether the underlying mechanism of XBXD against CINV is correlated to the restoration of cisplatin-induced PINK1/Parkin mediated mitophagy deficiency and mitigation of gastrointestinal inflammation. MATERIALS AND METHODS: The rat pica model was established by intraperitoneal injection of cisplatin 6 mg/kg. The daily kaolin consumption, food intake and body weight were recorded every 24 h. The pathological damage of gastric antrum and ileum were observed by hematoxylin-eosin staining. The levels of serum reactive oxygen species (ROS), interleukin-1ß (IL-1ß) and interleukin-1ß (IL-18) were detected by ELISA. The expression of microtubule-associated protein 1 light chain 3 (LC3) in gastric antrum and ileum was detected by Immunofluorescence staining. The levels of LC3II, P62/SQSTM1, PTEN-induced putative protein kinases (PINK1), E3 ubiquitin ligase (Parkin), AMP-dependent protein kinases (AMPK), phosphorylated AMPK (p-AMPK), nuclear factor erythroid 2-related factor (Nrf2) and kelch like ECH Associated Protein 1 (Keap1) in gastric antrum and ileum were assayed by western blotting. RESULTS: At 24 h and 72 h following cisplatin challenge, XBXD inhibited cisplatin-induced elevation of kaolin consumption, and improved the daily food intake and body weight loss in rats. Cisplatin-induced gastrointestinal histopathological damages were alleviated, and serum levels of ROS, IL-1ß and IL-18 increases were mitigated following XBXD treatments. In gastric antrum and ileum, XBXD activated AMPK-Nrf2 signaling pathway and restored cisplatin-induced PINK1/Parkin mediated mitophagy deficiency. CONCLUSIONS: XBXD significantly ameliorated CINV in a cisplatin-induced rat pica model. The underlying anti-emetic mechanism of XBXD might be related to the activation of AMPK-Nrf2 signaling pathway and the restoration of cisplatin-induced PINK1/Parkin-mediated mitophagy deficiency in the gastrointestinal tract.

Hepatoprotective efficacy and interventional mechanism of JianPi LiShi YangGan formula in acute-on-chronic liver failure.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute-on-chronic liver failure (ACLF) progresses rapidly with a high short-term death rate. Although JianPi LiShi YangGan formula (YGF) has been used to treat ACLF by managing inflammatory responses and reducing endotoxemia, hepatocyte injury, and mortality, the underlying mechanisms remain unclear. AIM OF THE STUDY: This study aims to investigate the potential mechanisms underlying the efficacy and protective benefits of YGF in mice with ACLF. MATERIALS AND METHODS: YGF composition was determined using high-performance liquid chromatography coupled with mass spectrometry. We constructed a mouse model of ACLF using carbon tetrachloride, lipopolysaccharide (LPS), and D-galactosamine (D-Gal), as well as an in vitro model of D-Gal/LPS-induced hepatocyte injury. The therapeutic effects of YGF in ACLF mice were verified using hematoxylin-eosin, Sirius red, and Masson staining, and by measuring serum alanine transaminase (ALT), aspartate transaminase (AST), and inflammatory cytokine levels. Mitochondrial damage in hepatocytes was evaluated using electron microscopy, while superoxide anion levels in liver tissue were investigated using dihydroethidium. Transcriptome analysis, immunohistochemistry, western blotting, and immunofluorescence assays were performed to explore the mechanisms underlying the ameliorative effects of YGF against ACLF. RESULTS: In mice with ACLF, YGF therapy partially decreased serum inflammatory cytokine levels, as well as hepatocyte injury and liver fibrosis. The livers of ACLF mice treated with YGF exhibited decreased mitochondrial damage and reactive oxygen species generation, as well as a decreased number of M1 macrophages and increased number of M2 macrophages. Transcriptome analysis revealed that YGF may regulate biological processes such as autophagy, mitophagy, and PI3K/AKT signaling. In ACLF mice, YGF promoted mitophagy and inhibited PI3K/AKT/mTOR pathway activation in hepatocytes. Meanwhile, the autophagy inhibitor 3M-A reduced the capacity of YGF to induce autophagy and protect against hepatocyte injury in vitro. In contrast, the PI3K agonist 740 Y-P suppressed the ability of YGF to control PI3K/AKT/mTOR pathway activation and induce autophagy. CONCLUSIONS: Together, our findings suggest that YGF mediates autophagy, tight junctions, cytokine generation, and other biological processes. In addition, YGF inhibits hepatic inflammatory responses and ameliorates hepatocyte injury in mice with ACLF. Mechanistically, YGF can promote mitophagy to ameliorate acute-on-chronic liver failure by inhibiting the PI3K/AKT/mTOR pathway.