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Objective To explore the protective effect and mechanism of Jinyinqingre oral liquid on acute lung injury in-duced by lipopolysaccharide(LPS)in mice.Methods C57BL/6J mice were randomly divided into six groups according to the random number table method:blank control group,model control group,Jinyinqingre oral liquid low-dose group,Jinyinqingre oral liquid medium-dose group,Jinyinqingre oral liquid high-dose group,and dexamethasone group.Except for the blank control group,the other groups were injected with lipopolysac charide(LPS)(5 mg·kg-1)into the trachea to establish the acute lung injury model of mice,and the Jinyinqingre oral liquid low,medium,and high groups were continuously administered the drug by gavage for three days.After 24 h,lung tissue and bronchoalveolar lavage fluid(BALF)were collected from the six groups for follow-up detection.The pathological injury of lung tissue in each group was observed by HE staining.The total number of cells in BALF was detected.The to-tal protein content of BALF was detected by the BCA method.The contents of inflammatory cytokines TNF-α,IL-1β,IL-6,and IgM in BALF were detected by ELISA.The expression of NF-κB and NLRP3 proteins in lung tissues was detected by immunohistochemistry and Western blotting.Results Compared with model control group,Jinyinqingre oral liquid alleviated the pathological injury of lung tissue(P＜0.05),decreased the total cell count,total protein content and IgM expression in BALF(P＜0.01),and the expres-sion of inflammatory cytokines TNF-α,IL-6 and IL-1β in BALF was dreased(P＜0.05),the protein expressions of NF-κB and NL-RP3 in lung tissues was dreased(P＜0.05).Conclusion Jinyinqingre oral liquid attenuated the pathological injury,inflammatory exudation,and expression of inflammatory cytokines in LPS-induced lung injury in mice,and its mechanism may be through the reg-ulation of NF-κB/NLRP3 signaling pathway,providing a theoretical basis for its clinical application.

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OBJECTIVE To explore the protective effect and mechanism of Longshengzhi capsules on cerebral ischemia- reperfusion injury in rats. METHODS The model of middle cerebral artery occlusion （MCAO） was established by using the improved thread occlusion method. The experiment was divided into six groups： sham surgery group （only separating blood vessels without inserting thread plugs， given the same volume of normal saline）， model group （modeling， given the same volume of normal saline）， nimodipine group （positive control， modeling， dose of 20 mg/kg）， and low-dose， medium-dose， and high-dose groups of Longshengzhi capsules （modeling， doses of 0.72， 1.44 and 2.88 g/kg， respectively）， with 10 mice in each group. Each group was given corresponding medication solution/normal saline by gavage， once a day， for 7 consecutive days. One hour after the last administration， the Zea Longa scoring method was used to score the neurological deficits in each group of rats， and the ABC enzyme-linked immunosorbent assay was used to detect the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in rats； TTC staining was used to observe the volume of cerebral infarction in rats and calculate the cerebral infarction volume ratio. Hematoxylin eosin staining was used to observe the pathological changes in the brain tissue of rats. Immunohistochemical staining was used to detect the positive expression of NLRP3 protein in the brain tissue of rats. Real-time fluorescence quantitative PCR was used to detect mRNA relative expressions of Toll-like receptor 4 （TLR4） and nuclear factor-κB （NF-κB） in the brain tissue of rats. Western blot assay was adopted to detect the relative expressions of TLR4， NLRP3 and phosphorylated NF-κB （p-NF-κB） protein in the brain tissue of rats and its intracellular NF-κB protein. RESULTS Compared with the sham surgery group， the neural dysfunction score， serum levels of TNF-α and IL-6， cerebral infarction volume ratio， relative expression levels of NF-κB and TLR4 mRNA， as well as protein relative expressions of TLR4， NLRP3 and p-NF-κB in the brain tissue， and relative protein expression of intracellular NF-κB were increased significantly in the model group （P＜0.01）； the enlarged gap and significant edema were observed in cortical nerve cells of brain tissue in rats， with a large amount of inflammatory cell infiltration； the positive expression of NLRP3 protein in brain tissue of rats obviously increased. Compared with the model group， the levels of the above indicators in the medium-dose and high-dose groups of Longshengzhi capsules， as well as the Nimodipine group， were reversed to varying degrees， and most differences were statistically significant （P＜0.05 or P＜0.01）； the pathological morphology observation showed a significant improvement， and the positive expression of NLRP3 protein in the brain tissue of rats was obviously reduced. CONCLUSIONS Longshengzhi capsules may inhibit TLR4/NF-κB/NLRP3 signaling pathway and neuroinflammatory response， thereby achieving a protective effect against cerebral ischemia-reperfusion injury in rats.

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This paper aimed to study the effect of Erjing Pills on the improvement of neuroinflammation of rats with Alzheimer's di-sease(AD) induced by the combination of D-galactose and Aβ_(25-35) and its mechanism. SD rats were randomly divided into a sham group, a model control group, a positive drug group(donepezil, 1 mg·kg~(-1)), an Erjing Pills high-dose group(9.0 g·kg~(-1)), and an Erjing Pills low-dose group(4.5 g·kg~(-1)), with 14 rats each group. To establish the rat model of AD, Erjing Pills were intragastrically administrated to rats for 5 weeks after 2 weeks of D-galactose injection. D-galactose was intraperitoneally injected into rats for 3 weeks, and then Aβ_(25-35) was injected into the bilateral hippocampus. The new object recognition test was used to evaluate the learning and memory ability of rats after 4 weeks of intragastric administration. Tissues were acquired 24 h after the last administration. The immunofluorescence method was used to detect the activation of microglia in the brain tissue of rats. The positive expressions of Aβ_(1-42) and phosphory protein Tau~(404)(p-Tau~(404)) in the CA1 area of the hippocampus were detected by immunohistochemistry. The levels of inflammatory factors interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) in the brain tissue were determined by enzyme-linked immunosorbent assay(ELISA). Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)/nucleotide-binding oligomerization domain-like receptors 3(NLRP3) pathway-associated proteins in the brain tissue were determined by Western blot. The results showed that as compared with the sham group, the new object recognition index of rats in the model control group decreased significantly, the deposition of Aβ_(1-42) and p-Tau~(404) positive protein in the hippocampus increased significantly, and the levels of microglia activation increased significantly in the dentate gyrus. The levels of IL-1β, TNF-α, and IL-6 in the hippocampus of the model control group increased significantly, and the expression levels of TLR4, p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus increased significantly. Compared with the model control group, the Erjing Pill groups enhanced the new object recognition index of rats, decreased the deposition of Aβ_(1-42) and the expression of p-Tau~(404) positive protein in the hippocampus, inhibited the activation of microglia in the dentate gyrus, reduced the levels of inflammatory factors IL-1β, TNF-α, and IL-6 in the hippocampus, and down-regulated the expression levels of TLR4, p-NF-κB P65/NF-κB P65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus. In conclusion, Erjing Pills can improve the learning and memory ability of the rat model of AD presumably by improving the activation of microglia, reducing the expression levels of neuroinflammatory factors IL-1β, TNF-α, and IL-6, inhibiting the TLR4/NF-κB/NLRP3 neuroinflammation pathway, and decreasing hippocampal deposition of Aβ and expression of p-Tau, thereby restoring the hippocampal morphological structure.

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The present study aimed to investigate the inhibitory effect and mechanism of Isodon terricolous-medicated serum on lipopolysaccharide(LPS)-induced hepatic stellate cell(HSC) activation. LPS-induced HSCs were divided into a blank control group, an LPS model group, a colchicine-medicated serum group, an LPS + blank serum group, an I. terricolous-medicated serum group, a Toll-like receptor 4(TLR4) blocker group, and a TLR4 blocker + I. terricolous-medicated serum group. HSC proliferation was detected by methyl thiazolyl tetrazolium(MTT) assay. Enzyme-linked immunosorbent assay(ELISA) was used to measure type Ⅰ collagen(COL Ⅰ), COL Ⅲ, transforming growth factor-β1(TGF-β1), intercellular adhesion molecule-1(ICAM-1), α-smooth muscle actin(α-SMA), vascular cell adhesion molecule-1(VCAM-1), cysteinyl aspartate-specific proteinase-1(caspase-1), and monocyte chemotactic protein-1(MCP-1). Real-time PCR(RT-PCR) was used to detect mRNA expression of TLR4, IκBα, and NOD-like receptor thermal protein domain associated protein 3(NLRP3), nuclear factor-κB(NF-κB) p65, gasdermin D(GSDMD), and apoptosis-associated speck-like protein containing a CARD(ASC) in HSCs. Western blot(WB) was used to detect the protein levels of TLR4, p-IκBα, NF-κB p65, NLRP3, ASC, and GSDMD in HSCs. The results showed that I. terricolous-medicated serum could inhibit the proliferation activity of HSCs and inhibit the secretion of COL Ⅰ, COL Ⅲ, α-SMA, TGF-β1, caspase-1, MCP-1, VCAM-1, and ICAM-1 in HSCs. Compared with the LPS model group, the I. terricolous-medicated serum group, the colchicine-medicated serum group, and the TLR4 blocker group showed down-regulated expression of p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and up-regulated expression of IκBα. Compared with the TLR4 blocker group, the TLR4 blocker + I. terricolous-medicated serum group showed decreased expression of TLR4, p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and increased expression of IκBα. In conclusion, I. terricolous-medicated serum down-regulates HSC activation by inhibiting the TLR4/NF-κB/NLRP3 signaling pathway.

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{L-End}Objective To study the intervention effect of hydrogen on early inflammation in a rat silicosis model and its mechanism. {L-End}Methods Wistar rats of specific pathogen free were randomly divided into the control group, model group, tetrandrine group, hydrogen group and combined intervention group, with 10 rats in each group. The rats in the last four groups were treated with a dose of l.00 mL silica suspension with a mass concentration of 50.0 g/L by a one-time non-exposed tracheal method. The rats in the control group were given 0.9% sodium chloride solution in equal volume. After 24 hours of dust exposure, rats of the tetrandrine group were given 30 mg/kg body mass tetrandrine by gavage daily, rats of the hydrogen group were given 66.6% hydrogen inhalation continuously for four hours daily, rats of the combined intervention group were given the same interventions as the rats in the tetrandrine group and the hydrogen group, rats in the control group and model group were given 0.9% sodium chloride solution in equal volume by gavage. After 14 days of treatment, the lung coefficient of rats was determined, and lung histopathology was performed. The level of malondialdehyde in serum was detected by colorimetry. The level of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum were detected by enzyme-linked immunosorbent assay. The relative expression of nucleotide-binding oligomerization domain-like receptor thermal protein domain associated protein 3 (NLRP3), nuclear factor-κB (NF-κB) p65, NF-κB phosphorylated p65 (NF-κB p-p65), cysteinyl aspartate specific proteinase1 (Caspase1) and apoptosis-associated speck-like protein containing a CARD (ASC) in serum were detected in lung tissues by Western blot. The relative expression of NLRP3 and NF-κB p65 in lung tissues were detected by immunohistochemistry. {L-End}Results The result of pulmonary histopathology showed that the model group had obvious alveolar rupture and fusion, interstitial lymphocyte and macrophage infiltration, and alveolar wall thickening, collagen fibre deposition, and mild fibrotic hyperplasia, compared with the control group. The pathological outcomes of lung tissues in the three treated groups were alleviated compared with the model group, and the alveolar structure was more complete and the alveolar wall was thinner and the fewer collagen fibres in the rats of combined intervention group, compared with tetrandrine group and hydrogen group. The lung coefficient and Szapiel score of rats of the tetrandrine group, hydrogen group and combined intervention group were lower than those of the model group (all P<0.05). The levels of serum malondialdehyde, TNF-α and IL-1β in lung tissues, and the relative expression of NLRP3, NF-κB p65, NF-κB P-p65, Caspase1 and ASC in lung tissues increased in the model group, compared with the control group (all P<0.05). The indexes above decreased in the three treated groups than those in the model group (all P<0.05). The indexes above decreased in the combined intervention group than those in the tetrandrine group and hydrogen group (all P<0.05), except for the level of malondialdehyde in serum and the relative expression of NF-κB p-p65 in lung tissue. {L-End}Conclusion Hydrogen can intervene the early inflammation of silicosis through NF-κB/ NLRP3 signaling pathway.

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Aim To explore the mechanism of Polygonum capitatum(PC)in the treatment of Helicobacter Pylori associated gastritis(HAG). Methods The databases were used to identify the target of PC active compounds and HAG-related genes,and the intersection was taken to obtain the potential targets of PC treatment of HAG. The interaction network diagram of “drug-active compound-target-disease” and the protein-protein interaction(PPI)network of potential target protein interaction in HAG treated by PC were constructed by software Cytoscape 3.6.0. The important nodes in the network were screened by several topological indexes,and the GO and KEGG enrichment were analyzed by STRING database to obtain the potential signaling pathway of PC in the treatment of HAG. The binding ability of PC active components with key target proteins was observed by molecular docking method. On this basis,the related targets of PC in the treatment of HAG were verified in vivo and in vitro experiments. Results The PC active compounds and targets were identified through the database,and the “drug-active compound-target-disease” network diagram and the PPI network of potential target proteins were constructed. Combined with several topological indexes,the PPI network of potential target-protein interaction was analyzed,and 52 hub genes were screened. Further bioinformatics analysis and high-throughput sequencing revealed that PC exerted an effect on HAG through the Akt/NF-κB/NLRP3 pathway. Based on this,it was found that PC could reduce IL-18 and IL-1β in HAG GES-1 cells and HAG SD rats,up-regulate Akt and its phosphorylation level and reduce NF-κB expression,inhibit the activation of NLRP3 inflammatory body,so as to improve HAG inflammatory response. Conclusions PC could exert a therapeutic effect on HAG by activating Akt and its phosphorylation level,and inhibiting the expression of NF-κB and NLRP3 inflammasome related factors. This study provides a theoretical basis for explaining the mechanism of PC in the treatment of HAG.

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OBJECTIVES@#To study the protective effect of melatonin (Mel) against oxygen-induced retinopathy (OIR) in neonatal mice and the role of the HMGB1/NF-κB/NLRP3 axis.@*METHODS@#Neonatal C57BL/6J mice, aged 7 days, were randomly divided into a control group, a model group (OIR group), and a Mel treatment group (OIR+Mel group), with 9 mice in each group. The hyperoxia induction method was used to establish a model of OIR. Hematoxylin and eosin staining and retinal flat-mount preparation were used to observe retinal structure and neovascularization. Immunofluorescent staining was used to measure the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis and lymphocyte antigen 6G. Colorimetry was used to measure the activity of myeloperoxidase.@*RESULTS@#The OIR group had destruction of retinal structure with a large perfusion-free area and neovascularization, while the OIR+Mel group had improvement in destruction of retinal structure with reductions in neovascularization and perfusion-free area. Compared with the control group, the OIR group had significant increases in the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis, the expression of lymphocyte antigen 6G, and the activity of myeloperoxidase (P<0.05). Compared with the OIR group, the OIR+Mel group had significant reductions in the above indices (P<0.05). Compared with the control group, the OIR group had significant reductions in the expression of melatonin receptors in the retina (P<0.05). Compared with the OIR group, the OIR+Mel group had significant increases in the expression of melatonin receptors (P<0.05).@*CONCLUSIONS@#Mel can alleviate OIR-induced retinal damage in neonatal mice by inhibiting the HMGB1/NF-κB/NLRP3 axis and may exert an effect through the melatonin receptor pathway.

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Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.

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Lung and intestine combination therapy(LICT) is effective in the treatment of acute lung injury(ALI). In this study, the combination of Mahuang Decoction and Dachengqi Decoction(hereinafter referred to as the combination), a manifestation of LICT, was employed to explore the effect of nuclear factor kappaB(NF-κB)/nucleotide binding oligomerization domain-like receptors-3(NLRP3) pathway and alveolar macrophage activation on the lung inflammation in rats with ALI, for the purpose of elucidating the mechanism of LICT in treating ALI. After the modeling of ALI with limpolysaccharide(LPS, ip), rats were respectively given(ig) the combination at 10, 7.5, and 5 g·kg~(-1)(high-dose, medium-dose, and low-dose LICT groups, separately), once every 8 h for 3 times. Haematoxylin-eosin(HE) staining was used to observe the histopathological changes of lung tissue, followed by the scoring of inflammation. Immunohistochemistry was applied to detect alveolar macrophage activation, enzyme-linked immunosorbent assay(ELISA) was applied to detect the serum content of tumor necrosis factor-α(TNF-α) and interleukin-18(IL-18), Western blot was applied to detect the protein expression of phosphorylated-nuclear factor kappaB p65(p-NF-κB p65), nuclear factor kappaB p65(NF-κB p65), phosphorylated-inhibitor kappaB alpha(p-IκBα), inhibitor kappaB alpha(IκBα), and NLRP3 in lung tissue, and quantitative reverse transcription-PCR(qRT-PCR) was applied to detect the mRNA expression of TNF-α, IL-18, NLRP3, and NF-κB p65 in lung tissue. The results showed that LICT groups demonstrated lung injury relief, decrease in inflammation score, alleviation of alveolar macrophage activation, significant decline in serum content of inflammatory factors TNF-α and IL-18, and decrease of the protein expression of p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3, and mRNA expression of TNF-α, IL-18, NLRP3, and NF-κB p65 in lung tissue. In summary, LICT has definite therapeutic effect on ALI. The mechanism is that it inhibits alveolar macrophage activation by suppressing NF-κB/NLRP3 signaling pathway, thereby reducing the activation and release of inflammatory factors and finally inhibiting inflammation.

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This study investigated the differential mechanisms of Rehmanniae Radix and Rehmanniae Radix Praeparata in improving diabetes in mice through AMPK-mediated NF-κB/NLRP3 signaling pathway. The diabetic mouse model was established with high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days), after which the mice were randomly divided into model group, low-dose(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-dose(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, catalpol group(250 mg·kg~(-1)), 5-hydroxymethylfurfural(5-HMF) group(250 mg·kg~(-1)), metformin group(250 mg·kg~(-1)), with the normal group also set. The organ indexes of heart,liver, spleen, lung, kidney and pancreas were calculated after four weeks of administration. The pathological changes and fibrosis of pancreas, kidney and liver in mice were observed by hematoxylin-eosin(HE) staining and Masson staining. Western blot was used to determine the expression levels of Toll-like receptor-4(TLR4), nuclear factor-κB(NF-κB), Nod-like receptor protein 3(NLRP3),interleukin-1β(IL-1β), adenosine monophosphate-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK) in the pancreas, kidney and liver of mice. Compared with the model group, the administration groups witnessed significant decrease in the liver,spleen, kidney, pancreas and fat indexes of diabetic mice, and there was no significant difference in heart and lung indexes. The pathological states and fibrosis of pancreatic, kidney and liver tissues were significantly improved after administration. Additionally, the expression levels of TLR4, NF-κB and NLRP3 in pancreas, kidney and liver of diabetic mice were significantly lowered. The expression levels of p-AMPK/AMPK were enhanced significantly in kidney and liver of mice in Rehmanniae Radix group while in pancreas, kidney and liver in Rehmanniae Radix Praeparata group. This suggests that Rehmanniae Radix and Rehmanniae Radix Praeparata differ in the mechanism of regulating energy metabolism of multiple organs and thereby exerting anti-inflammatory effects to alleviate symptoms of diabetic mice.

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Objective:To investigate the possible mechanism of Xieheyin in alleviating obese polycystic ovary syndrome with insulin resistance（PCOS-IR）and reducing inflammatory response. Method:Ten of sixty SPF femlae C57BL/6J mice were randomly selected as the normal group，and the rest mice were given letrozole 0.002 g·kg^-1 combined with fecal suspension 2 g·kg^-1 for 28 consecutive days to establish model of PCOS-IR.The mice that were successfully modeled were randomized into the model group，metformin group（0.25 g·kg^-1），and low（10 g·kg^-1），medium（20 g·kg^-1），and high-dose（40 g·kg^-1）Xieheyin groups，and administered with the corresponding drugs by gavage，once a day，for four consecutive weeks. Except the normal control group， the mice in the other groups were continuously given fecal suspension combined with letrozole solution to maintain the model during the treatment. The mice were weighed once a week.Levels of fasting blood glucose （FBG） were detected by blood glucose test strips.And enzyme-linked immunosorbent assay （ELISA） method was used to detect serum testosterone（T），follicle stimulating hormone（FSH），luteinizing hormone（LH），fasting insulin（FINS）level，and LH/FSH and Homeostasis model assesment of insulin resistance （HOMA-IR） were calculated．The uterus and ovaries were weighed and fixed.Hematoxylin-eosin（HE）staining was used to observe ovarian tissue pathology morphology. Western blot was used to detect the expression levels of tight junction key molecular zonula occludens 1（ZO-1），occludin in colon tissues，and the expression levels of Toll-like receptor 4/nuclear factor kappa B/Nod-like receptor protein 3（TLR4/NF-<italic>κ</italic>B/NLRP3）signaling pathway and inflammation associated proteins cysteinyl aspartate specific proteinase-1（Caspase-1） and interleukin-1<italic>β</italic>（IL-1<italic>β</italic>） in colon tissues. Result:Compared with normal control group，the body weight of mice in the model control group increased significantly（<italic>P</italic><0.01）. Serum FINS，FBG，HOMA-IR，T，LH/FSH were significantly increased（<italic>P</italic><0.05，<italic>P</italic><0.01）. The uterine organ ratio were decreased significantly（<italic>P</italic><0.01），while the ovarian organ ratio were significantly increased（<italic>P</italic><0.01）. The number of atresia follicles and cystic dilatation follicles increased significantly，and the number of corpus luteum significantly decreased，the thickness of follicular granulosa cells also decreased，while the white membrane thickness of the ovary increased. Tight junction related ZO-1，occludin proteins in colon tissues were all decreased（<italic>P</italic><0.01）.The relative expression levels of inflammation-related protein IL-1<italic>β</italic>，Caspase-1 and TLR4/NF-<italic>κ</italic>B/NLRP3 target protein signaling pathway were significantly increased（<italic>P</italic><0.05）.Compared with model control group， the body weight of mice in the low，middle and high dose Xieheyin group decreased significantly（<italic>P</italic><0.01）. The serum T，LH/FSH，FINS，FBG，HOMA-IR were significantly decreased（<italic>P</italic><0.05，<italic>P</italic><0.01）. The uterine organ ratio were increased（<italic>P</italic><0.05），while the ovarian organ ratio were decreased（<italic>P</italic><0.05）. The number of cystic follicles decreased and corpus luteum increased，the thickness of follicular granulosa cells increased and be arranged normally，while the white membrane thickness of the ovary increased slightly. The expressions of ZO-1，occludin proteins were increased（<italic>P</italic><0.01）. The expression levels of IL-1<italic>β</italic>，Caspase-1 and TLR4/NF-<italic>κ</italic>B/NLRP3 target protein in the high dose group were significantly decreased（<italic>P</italic><0.01）. Conclusion:Xieheyin could activate intestinal TLR4/NF-<italic>κ</italic>B/NLRP3 signaling pathway，inhibit pro-inflammatory factor secretion，improve obesity and IR，which was correlated with rebuilding intestinal mucosal barrier and inhibiting intestinal inflammation．

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This study investigated the protective effect of total triterpenoids from Chaenomeles speciosa against Helicobacter pylori(Hp)-induced gastritis in mice and explored its possible mechanism. The chronic atrophic gastritis(CAG) model mice were randomly divided into four groups of model, total triterpenoids from C. speciosa(50 and 100 mg·kg~(-1)) and triple therapy, with C57 BL/6 J mice without Hp infection taken as the normal group. Mice in the treatment groups were given corresponding drugs once a day for 4 weeks. Then the following indexes were detected: the contents of reactive oxygen species(ROS), monocyte chemotactic protein 1(MCP-1), keratinocyte chemokines(KC), TNF-α, IL-1β, IL-6, IL-18, IL-4 and IL-10 in blood and gastric tissue, the activities and contents of LDH, MPO, SOD, GSH-Px, CAT and MDA in gastric tissue and the activities of β-glucuronidase, β-galactosidase, cathepsins B and D in blood, gastric tissue and lysosome. Besides, the mRNA expression levels of Toll-like receptor 4(TLR4), myeloid differentiation factor 88(MyD88), Bcl-2, Bcl-xl, Bax and Bad in gastric tissue were determined by quantitative real-time PCR. Western blot was employed to detect the protein expression levels of TLR4, MyD88, p-IKKβ, p-IκBα, NOD-like receptor 3(NLRP3), apoptosis-associated speck-like protein(ASC), pro-caspase-1, caspase-1, thioredoxin-interacting protein(TXNIP), pro-IL-1β, pro-IL-18, Bcl-2, Bcl-xl, Bax, Bad, cytochrome C, apoptotic protease-activating factor-1(Apaf-1), pro-caspase-9, pro-caspase-3, cleaved-caspase-9, cleaved-caspase-3, poly(ADP-ribose) polymerase 1(PARP-1), cleaved-PARP-1 and cytosol and nucleus NF-κB p65 in gastric tissue. The results indicated that the total triterpenoids from C. speciosa significantly suppressed Hp proliferation, alleviated the damage to gastric mucosa and improved lymphocyte infiltration and gland atrophy. They were also effective in reducing the activities of β-glucuronidase, β-galactosidase, cathepsins B and D in blood and gastric tissue, elevating the activities of β-glucuronidase and cathepsin D in lysosomal organelles, decreasing the contents of ROS, MCP-1, KC, TNF-α, IL-1β, IL-6, IL-18 in blood, MDA content and MPO and LDH activities in gastric tissue and increasing the contents of IL-4 and IL-10 in blood and activities of SOD, CAT and GSH-Px in gastric tissue. Other phenomena were also observed after the treatment with total triterpenoids from C. speciosa, including the down-regulation of the mRNA and protein expression levels of TLR4, MyD88, Bax and Bad, the protein expression levels of p-IKKβ, p-IκBα, NLRP3, ASC, pro-caspase-1, caspase-1, TXNIP, pro-IL-1β, pro-IL-18, cytochrome C, Apaf-1, cleaved-caspase-9, cleaved-caspase-3, cleaved-PARP-1 and nuclear NF-κB p65, reduction of p-IKKβ/IKKβ and p-IκBα/IκBα ratios and up-regulation of the mRNA and protein expression levels of Bcl-2 and Bcl-xl, up-regulation of pro-caspase-9, pro-caspace-3, cytosol NF-κB p65 protein expression levels and Bcl-2/Bax and Bcl-xl/Bad ratios in gastric tissue. These aforementioned results suggest that the total triterpenoids from C. speciosa have significant protective effects against CAG induced by Hp, and its mechanism may be related to enhancing the function of endogenous antioxidant system, suppressing the oxidative stress and inflammatory reaction induced by Hp, correcting lysosomal dysfunction and inflammatory activation of TLR4/NF-κB/NLRP3 inflammasome signaling pathway and thus inhibiting mitochondria-mediated apoptosis.

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