Croton stipulaceus Kunth, a native Mexican medicinal plant with antioxidant and anti-inflammatory activities / Croton stipulaceus Kunth, planta medicinal mexicana con actividad antioxidante y antiinflamatoria

Leaves of Croton stipulaceuswere extracted (EHex, ECHCl3and EEtOH extracts) to assesstheir antioxidant potential, anti-inflammatory activity in murine models and acute toxicity. EEtOH showed the highest effect in DPPH (37.80% inhibition), FRAP (1065.00 ± 55.30 µmolFe2+) and total polyphenols (231.24 ± 9.05 meq AG/gM). EHex was the most active, ~ 50% inhibition of TPA-induced ear edema; while EEtOH (dose of 2 mg/ear) showed the highest inhibition in the chronic model (97% inhibition), and inhibited MPO activity (48%). In carrageenan-induced edema, ECHCl3(dose 500 mg/kg) was the most active. None of the extracts showed acute toxicity (LD50) at 2 g/kg (p.o.). This work is the first report that supports the traditional use of C. stipulaceusas an anti-inflammatory.

De las hojas de Croton stipulaceusse obtuvieron diferentes extractos (EHex, ECHCl3y EEtOH) evaluando el potencial antioxidante y la actividad antiinflamatoria en modelos murinos y la toxicidad aguda. El EEtOH mostró mayor efecto en DPPH (37.80% inhibición), FRAP (1065.00 ± 55.30 µmolFe2+) y polifenolestotales (231.24 ± 9.05 meq AG/gM). El EHex fue el más activo, cercano al 50% de inhibición del edema auricular inducido con TPA; mientras que el EEtOH (dosis de 2 mg/oreja) mostró la mayor inhibición en el modelo crónico (97% inhibición), e inhibió la actividad de la MPO (48%). En el edema inducido con carragenina, el ECHCl3(dosis 500 mg/kg) fue el más activo. Ninguno de los extractos mostró una toxicidad aguda (DL50) mayor a 2 g/kg (p.o). Este trabajo es el primer reporte que sustenta el uso tradicional de C. stipulaceuscomo antiinflamatorio.

Dietary supplementation with integral chia and flax flours ameliorates systemic inflammation / La suplementación dietaria con harinas integrales de chia y lino tiene efectos antiinflamatorios sistémicos

Abstract Introduction : Chia and flax seeds are rich in alpha-linolenic acid (ALA), which is bioconverted into the active derivatives eicosapentaenoic (EPA) and doco sahexaenoic (DHA) having multiple beneficial effects. However, there is limited knowledge about the anti-inflammatory effects of chia and flax integral flours diets rich in ALA. Objective : The study aimed to evaluate the anti-inflammatory effect of dietary supplementation with integral chia and flax flours in a murine model of LPS-induced systemic inflammation. Methods : Balb/c mice were distributed into three groups: diet A (control), diet B (supplemented with inte gral chia flour), and diet C (supplemented with integral flax flour). Nutritional, hematological, and biochemical determinations were performed. ALA, EPA, and DHA were assessed by GC-MS in the liver, brain, cardiac and skeletal muscles. NF-kB immunoassays were per formed in kidney, liver, and peritoneal macrophages, respectively. The phagocytic capacity was determined in peritoneal macrophages and the expression of the pro- and anti-inflammatory cytokines was assessed by RT-qPCR in the kidney, liver, and spleen. Results : Diets B and C exhibited optimal nutritional adequacy and caused increased levels of ALA, EPA, and DHA in critical tissues compared to the control. The phagocytic capacity of murine peritoneal macrophages (p< 0.01) and IL-10 transcription increased, whereas the expression of NF-κB, IL-1β, IL-6, and TNF-α decreased in animals fed both experimental diets. Conclusions : This work contributes to the current knowledge of the anti-inflammatory effects of chia and flax integral flours rich in ALA and reinforces the health advantages of their consumption.

Resumen Introducción : Las semillas de chía y lino son ricas en ácido alfa-linolénico (ALA), sus derivados activos eico sapentaenoico (EPA) y docosahexaenoico (DHA) ejercen probados efectos beneficiosos. Existe un conocimiento limitado sobre los efectos protectores de ambas semillas bajo la forma de harinas integrales, siendo de particular interés el efecto antiinflamatorio. Objetivo : El objetivo de este trabajo fue evaluar el efecto antiinflamatorio de la suplementación dietaria con harinas integrales de semillas de chía y lino en un modelo murino de inflamación sistémica inducido por LPS. Métodos : Ratones de la cepa Balb/c fueron distribui dos en tres grupos: dieta A (control), dieta B (suplemen tada con harina integral de chía) y dieta C (suplementa da con harina integral de lino). Se efecturaron determi naciones nutricionales, hematológicas y bioquímicas. El contenido de ALA, EPA y DHA en hígado, cerebro, corazón y músculo esquelético se determinó por cromatografía GC-MS. Se realizó la inmunodetección de NF-kB en macrófagos peritoneales, riñón e hígado. Se determinó la capacidad fagocítica de macrófagos peritoneales y se evaluó la expresión de citoquinas pro y antiinflamatorias por RT-qPCR en riñón, hígado y bazo. Resultados : Las dietas B y C mostraron una adecua ción nutricional óptima y generaron niveles elevados de ALA, EPA y DHA en tejidos críticos. La capacidad fagocítica de los macrófagos peritoneales (p< 0.01) y la transcripción de IL-10 aumentó, mientras que la expre sión de NF-κB, IL-1β, IL-6 y TNF-α disminuyó en animales de los grupos B y C. Conclusiones : Este trabajo contribuye al conocimien to actual de los efectos antiinflamatorios de ambas hari nas integrales y refuerza los beneficios de su consumo.

Drugs and natural products for the treatment of COVID-19 during 2020, the first year of the pandemic / Fármacos y productos naturales para el tratamiento de la COVID-19 durante 2020, el primer año de la pandemia

Abstract This work aimed to show which treatments showed efficacy against coronavirus disease 2019 (COVID-19); therefore, the results of 37 clinical trials started in 2020 and completed in 2021 are reviewed and discussed here. These were selected from databases, excluding vaccines, computational studies, in silico, in vitro, and those with hyperimmune sera from recovered patients. We found 34 drugs, one vitamin, and one herbal remedy with pharmacological activity against symptomatic COVID-19. They reduced mortality, disease progression, or recovery time. For each treatment, the identifier and type of trial, the severity of the disease, the sponsor, the country where the trial was conducted, and the trial results are presented. The drugs were classified according to their mechanism of action. Several drugs that reduced mortality also reduced inflammation in the most severe cases. These include some that are not considered anti-inflammatory, such as Aviptadil, pyridostigmine bromide, anakinra, imatinib, baricitinib, and bevacizumab, as well as the combination of ivermectin, aspirin, dexamethasone, and enoxaparin. Nigella sativa seeds with honey have also been reported to have therapeutic activity. On the other hand, tofacitinib, novaferon with ritonavir, and lopinavir were also effective, as well as in combination with antiviral therapies such as danoprevir with ritonavir. The natural products colchicine and Vitamin D3 were only effective in patients with mild-to-moderate COVID-19, as was hydroxychloroquine. Drug repositioning has been the main tool in the search for effective therapies by expanding the pharmacological options available to patients.

Resumen El objetivo del presente trabajo fue conocer qué tratamientos mostraron efectividad contra COVID-19, para lo cual se revisan y discuten los resultados de 37 estudios clínicos iniciados durante 2020 y concluidos en 2021. Estos fueron seleccionados de bases de datos, excluyendo vacunas, estudios computacionales, in silico, in vitro y con sueros hiperinmunes de pacientes recuperados. Se documentaron 34 fármacos, una vitamina y un remedio herbolario, con actividad farmacológica ante COVID-19 sintomático. Estos redujeron la mortalidad, el progreso de la enfermedad, o el tiempo de recuperación. Para cada tratamiento se presenta identificador y tipo de estudio, la gravedad de la enfermedad, patrocinador, país donde se realizó, así como sus resultados. Los fármacos se clasificaron de acuerdo con su mecanismo de acción. Varios fármacos que redujeron la mortalidad también disminuyeron la inflamación en los casos más graves. Esto incluyendo algunos no considerados antiinflamatorios, como el aviptadil, el bromuro de piridostigmina, el anakinra, el imatinib, el baricitinib y el bevacizumab, así como la combinación de ivermectina, aspirina, dexametasona y enoxaparina. También se reportaron con actividad terapéutica las semillas de Nigella sativa con miel. Además, resultaron efectivos el tofacitinib, el novaferón con ritonavir y lopinavir, así como los antivirales en terapias combinadas como el danoprevir con ritonavir. Los productos naturales colchicina y vitamina D3, solo tuvieron actividad en los pacientes en estado leve a moderado de la COVID-19, así como la hidroxicloroquina. El reposicionamiento de fármacos fue la principal herramienta para buscar terapias efectivas ampliando las opciones farmacológicas accesibles a los pacientes.

Effect of Lactobacillus crispatus on Female Reproductive Tract Health and Its Antibacterial and Anti-inflammatory Mechanisms / 中山大学学报(医学科学版)

Lactobacilli are important colonizing bacteria in female reproductive tract， among which Lactobacillus crispatus is closely associated with reproductive tract health and plays a crucial role in maintaining the vaginal microbiota balance. A decrease in the abundance of Lactobacillus crispatus may be correlated with various female reproductive tract diseases， such as bacterial vaginosis and vulvovaginal candidiasis， and it can even lead to adverse pregnancy outcomes such as infertility and embryo arrest. This article provides an overview of the basic characteristics of Lactobacillus crispatus， relationship between the decrease of its quantity and reproductive tract diseases， its ability to inhibit pathogenic bacteria such as Candida albicans and Chlamydia trachomatis， and the anti-inflammatory effects of Lactobacillus crispatus. The aim is to provide references for the use of Lactobacillus crispatus in vaginal therapeutics.

Effect of Curcumin on Promoting Skin Wound Healing in Diabetes Mice / 医药导报

Objective To study the effect of curcumin on wound healing in diabetic mice.Methods The effect of curcumin on fibroblast activity was examined by the MTT assay,and the ROS detection kit was used to detect the effect of curcumin on the hydrogen peroxide-induced scavenging effect of reactive oxygen species(ROS)in fibroblasts.Q-PCR was used to detect the effects of curcumin on the mRNA expression of inflammatory factors CD86,CD206,IL-6 and ARG1 in lipopolysaccharide-induced RAW 264.7macrophage.The wound model of diabetes was established by intraperitoneal injection of streptozotocin.Hematoxylin-eosin(HE)and Masson staining were used to evaluate wound healing and histomorphological changes,and immunofluorescence staining was used to determine skin tissue α-smooth muscle actin,CD86 and CD206 expression.Results Curcumin had no significant effect on fibroblast activity at concentrations less than 20 mol·L-1;curcumin scavenged hydrogen peroxide-induced intracellular ROS in fibroblasts;curcumin decreased the mRNA expression of CD86 and IL-6 while increasing CD206 and ARG1 in lipopolysaccharide-induced RAW 264.7 macrophages.After in vivo administration,compared with the control group,wound healing was significantly faster in the curcumin(15,30 mg·mL-1)group after 7 d and 14 d of wound perforation(P＜0.01).Hematoxylin-eosin(HE)and Masson staining results confirmed a significant increase in granulation tissue and a significant increase in collagen deposition in the curcumin(15,30 mg·mL-1)group.Immunofluorescence assay showed significantly higher expression of CD206(P＜0.01)and significantly reduced expression of CD86(P＜0.01)in the skin wounds of curcumin(15,30 mg·mL-1)for 14 d.In addition,the expression of α-SMA in the wound of the high-dose curcumin(30 mg·mL-1)group was significantly higher than that of the low-dose curcumin group(P＜0.01).Conclusion Curcumin accelerates diabetic wound healing by promoting granulation tissue proliferation and collagen deposition in refractory diabetic wounds in mice through its anti-inflammatory and antioxidant effects.

Effects of polysaccharide content and anti-inflammatory,hemostatic,and antioxidant activities before and after preparation of Mosla chinensis-Jiangxiangru / 中国比较医学杂志

Objective Explore changes in polysaccharides in Jiangxiangru before and after ginger juice preparation,and evaluate polysaccharide anti-inflammatory and antioxidant activities before and after processing.Methods The contents of Jiangxiangru polysaccharide(JXRPs)and Ginger juice processed of Jiangxiangru polysaccharide(JZJXRPs)before and after processing were determined by phenol-sulfuric acid method.We used the swelling model in rats and endotoxin(LPS)to establish the RAW264.7 mouse macrophage inflammation model.The optimal administration concentration was determined using a cell proliferation(MTT)assay.Enzyme-linked immunosorbent assay(ELISA)were used to measure Interleukin-6(IL-6),Interleukin-12(IL-12),Nitric oxide(NO),Interleukin-4(IL-4),and Interleukin-10(IL-10).Bleeding time of mice by tail cutting was observed to evaluate the hemostatic effect.The ability to remove 1,1-diphenyl-2-picryl-hydrazyl radical(DPPH)and 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate)(ABTS)was used to evaluate in vitro antioxidant activity.Results The contents of JXRPs and JZJXRPs were 13％and 22％,respectively.In swollen rats at 4 h after injection,compared with the model group,200 mg/kg JXRPs and 100 mg/kg JZJXRPs significantly reduced rat swelling(P＜0.05).In vitro anti-inflammation assessment showed that the polysaccharides before and after processing significantly inhibited secretion of IL-6,IL-12,and NO(P＜0.01)and promoted secretion of IL-4 and IL-10(P＜0.01),and also that processing post-effects were stronger.The hemostatic experiment show that,compared with the control group,JXRPs increased hemostasis,but without a significant difference,and no significant difference was found using JZJXRPs,although high doses showed a trend to increase hemostasis.In vitro antioxidant activity showed that JXRPs and JZJXRPs had different scavenging abilities for DPPH and ABTS with IC50 values of JXRPs of 0.2215 and 0.2110 mg/ml,respectively,and IC50 values of JZJXRPs of 0.1651 and 0.1884 mg/mL,respectively.Conclusions After Jiangxiangru is produced in ginger juice,it promotes dissolution of polysaccharides and increases polysaccharide content.Anti-inflammatory,hemostasis,and antioxidant capacities are stronger in JZJXRPS than JXRPS,which lays the foundation for follow-up research and clinical applications of JXRPS.

Research progress of vagus nerve in regulation of inflammatory response in sepsis / 中华危重病急救医学

The vagus nerve, as an important "guardian" of the body, is involved in the steady-state regulation of cardiovascular, respiratory, gastrointestinal digestion and endocrine systems. Recent studies have shown that the vagus nerve plays an important regulatory role in inflammatory response via the inflammatory reflex, which is closely related to the fact that the afferent and efferent fibers of the vagus nerve can sense and regulate inflammation, respectively. The pathophysiological mechanism of sepsis is based on the dysregulation of immune response, and it is often initiated by the excessive inflammatory response of the innate immune system. In recent years, in order to expand intervention strategies for the immune dysregulation of sepsis, researchers have made many efforts on regulating the inflammatory response of the vagus nerve in sepsis. This article focuses on the mechanism of vagus nerve-mediated inflammatory reflex and the regulatory role of vagus nerve in inflammatory response of sepsis, in order to reveal new therapeutic strategies for the treatment of sepsis.

Differential expression of inflammatory proteins in diabetic skin ulcers and ordinary skin ulcers / 中国医师杂志

Objective:To study and screen the differential expression of inflammatory proteins in diabetes skin ulcers and common skin ulcers, so as to provide experimental basis for further research on anti-inflammatory and healing drug targets of diabetes skin ulcers.Methods:The tissues of 11 patients with diabetes skin ulcer, 12 patients with common skin ulcer and 11 patients with normal skin were collected from the First Hospital of Hunan University of Chinese Medicine. The levels of inflammatory protein Toll like receptor 4 (TLR4), nuclear factor κB (NF-κB), pro-inflammatory factor interferon -γ (IFN -γ), tumor necrosis factor - α (TNF -α), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1β (IL-1β), macrophage chemotactic protein-1 (MCP-1), anti-inflammatory factors epidermal growth factor (EGF), interleukin-4 (IL-4), and interleukin-10 (IL-10) were detected in three groups of tissues using enzyme-linked immunosorbent assay (ELISA).Results:Compared with normal tissues, the concentrations of TLR4, NF-κB, IFN -γ, TNF -α, IL-1β, IL-6, IL-8, MCP-1 and EGF in common ulcer skin tissues and diabetes ulcer tissues were higher, and the concentrations of IL-10 were lower, with statistically significant differences (all P<0.05); Compared with the normal tissue, the concentration of IL-4 in diabetes ulcer tissue was lower, the difference was statistically significant ( P<0.05); Compared with ordinary ulcer skin tissue, the concentrations of TLR4, NF-κB and MCP-1 in diabetes ulcer tissue were higher, and the concentrations of IL-4 were lower, with statistically significant differences (all P<0.05). Conclusions:The skin ulcer in diabetes patients will have inflammatory reaction, and high glucose promotes the inflammatory reaction of skin ulcer, which may be related to the abnormal expression of TLR4, NF-κB, MCP-1 and IL-4. TLR4/NF-κB signal pathway and inflammatory factors MCP-1 and IL-4 may be the target of the inflammation regulation of diabetes skin ulcer.

Correlation between long-term use of aspirin and Helicobacter pylori infection in elderly people and its effectiveness on Helicobacter pylori eradication / 中华老年医学杂志

Objective:To investigate the correlation between long-term use of low-dose aspirin and Helicobacter pylori(HP)infection in elderly people and its effectiveness on HP eradication and recurrence.Methods:A retrospective analysis was conducted on 2 834 elderly people aged 60 and above who underwent the C 13-or C 14-urea breath test(UBT)for the first time in the Physical Examination Center of the First Hospital of Lanzhou University between March 2010 and December 2019.According to the results of UBT, people were divided into an HP infection group with 1 510 patients and a non-HP infection group with 1 324 patients.Univariate and multivariate Logistic regression analysis were used to investigate the relationship between aspirin use and HP infection.Additionally, in a prospective case-control analysis, 544 elderly hypertensive patients diagnosed with HP infection between March 2015 and December 2020 were selected and divided into an aspirin group(402 cases)and an observation group(142 cases), based on whether aspirin was used.The aspirin group was further divided into a 1 to <2 years group(134 cases), a ≥2 to <5 years group(142 cases)and a ≥5 years group(126 cases)based on the duration of aspirin treatment.The rates of HP eradication, safety and one-year post-treatment HP recurrence with bismuth-containing quadruple therapy were compared. Results:The overall HP infection rate was 53.28%(1 510/2 834).Univariate analysis showed that the infection rate in women was higher than in men[56.86%(584/1 027) vs.51.25%(926/1 807), χ2=8.307, P=0.004].The infection rate in aspirin users was higher than in non-aspirin users[57.29%(920/1 606) vs.48.05%(590/1 228), χ2=23.866, P<0.001], with no significant difference between aspirin use for 1-<2 years, ≥2-<5 years and ≥5 years[60.22%(162/269) vs.56.4%(273/484) vs.56.86%(485/853), χ2=1.166, P=0.558].Fasting blood glucose levels in the HP infection group were higher than in the non-HP infection group[(5.92±1.78)mmol/L vs.(5.77±1.40)mmol/L, t=2.317, P=0.021].Multivariate Logistic regression analysis showed the risk of HP infection in women was higher than in men( OR=1.254, 95% CI: 1.075-1.464, P=0.004).Long-term aspirin use increased the risk of HP infection( OR=1.450, 95% CI: 1.249-1.684, P<0.001).Among the 544 cases selected for eradication therapy, 522 completed the treatment protocol, with 479 achieving successful eradication.The overall eradication rate was 91.76%(479/522)according to per-protocol(PP)analysis and 88.05%(479/544)according to intention-to-treat(ITT).After 1 year, 472 cases underwent reexamination, with an overall recurrence rate of 3.6%(17/472).There was no statistical significance in the eradication rate and recurrence rate among the groups with different durations of aspirin treatment and the observation group. Conclusions:Long-term use of low-dose aspirin increases the risk of HP infection in the elderly, but does not affect the eradication rate and one-year recurrence rate of bismuth-containing quadruple therapy.Therefore, periodic screening and eradication of HP should be performed.

Chemical constituents from stems and leaves of Lonicera confusa and their anti-inflammatory activities / 中成药

AIM To study the chemical constituents and their anti-inflammatory activities of stems and leaves of Lonicera confusa DC.METHODS The 80%methanol extract from stems and leaves of L.confusa DC was isolated and purified by Diaion HP20SS,Sephadex LH-20,HSCCC and preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities were evaluated by measuring NO production of LPS-stimulated RAW264.7 cells in vitro.RESULTS Thirteen compounds were isolated and identified as benzyl alcohol-O-β-D-glucopyranosyl-(1 →6)-β-D-glucopyranoside(1),sweroside(2),epi-vogeloside(3),vogeloside(4),secologanoside(5),secoxyloganin(6),secologanin dimethyl acetal(7),methyl chlorogenate(8),apigenin-7-O-β-D-glucopyranoside(9),luteolin-7-O-β-D-glucopyranoside(10),rhoifolin(11),luteolin-7-O-α-L-arabinopyranosyl(1→6)-β-D-glucopyranoside(12),and lonicerin(13).Compounds 2-8,11-13 inhibited the NO production of LPS-induced cells.CONCLUSION Compound 1 is first isolated from family Lonicera,compounds 3,5,7,9,11,and 12 are obtained from the stems and leaves of this plant for the first time.Compounds 2-8,11-13 exhibited anti-inflammatory activities.

The Anti-inflammatory Effects of Qinggan Tongyin Based on the Network Pharmacology and UHPLC-MS/MS / 中药新药与临床药理

Objective To preliminary explore the in vitro anti-inflammatory effects of Qinggan Tongyin based on serum pharmacology and network pharmacology.Methods The effects of the serum containing Qinggan Tongyin on the release of NO,cell necrosis factor-α(TNF-α),and interleukin-6(IL-6)in LPS-induced RAW264.7 cells were confirmed using serum pharmacology.UHPLC-MS/MS was used to determine the index components of Qinggan Tongyin.The possible targets and pathways of active components in Qinggan Tongyin for anti-inflammatory properties were predicted by using network pharmacology.Results The results of cellular assay showed that Qinggan Tongyin could dramatically lessen the levels of NO,TNF-α,and IL-6(P＜0.05,P＜0.01,P＜0.001).The higher contents of Qinggan Tongyin were phillyrin A,arctiin,chlorogenic acid,scutellarin,gallic acid,rosmarinic acid,paeoniflorin and phillyrin.A totsl of 215 intersection targets between 17 active components in Qinggan Tongyin and inflammation were obtained,and the 31 core targets were ALB,VEGFA,IL-6,TNF-α,etc..The primary targets can exhibit anti-inflammatory actions by regulating several signaling pathways,such as AGE-RAGE,PI3K-Akt,and MAPK signaling pathway.Conclusion Qinggan Tongyin exerts its anti-inflammatory effects with the characteristic of multiple components and multiple targets.

Research progress on oral lichenoid drug reactions / 口腔疾病防治

@#Oral lichenoid drug reactions (OLDRs) are inflammatory reactions of the oral mucosa caused by the use of specific drugs in sensitive individuals and are classified as oral lichenoid lesions (OLLs). Its clinical and pathological manifestations do not have significant specificity compared to other types of OLL. Various types of drugs have been reported to induce OLDR, including antihypertensive drugs, nonsteroidal anti-inflammatory drugs, hypoglycemic drugs, antipsychotics, and immunosuppressants, among other drugs. Apart from local or systemic administrate glucocorticoids, the most effective treatment measure is to stop using suspicious drugs. Most patients can achieve significant relief from mucosal ulcers and erosion, but white lines may still remain. OLDR has been widely reported in the literature. However, due to a lack of systematic understanding, we do not have a recognized standard for the diagnosis and treatment of this disease. There are still doubts about the causal relationship between related drugs and oral lichen-like lesions. In response to the abovementioned problems, we searched the literature on drug-related oral lichen planus and lichen-like lesions at home and abroad over the past 20 years, most of which were case reports and only a few of which were case-control studies. This article describes the current research status of lichenoid lesions from four perspectives: concepts, suspicious drugs, clinical and pathological manifestations, and treatment prognosis. We hope to provide a theoretical reference for the prevention, diagnosis, and clinical treatment of related lichenoid lesions. A literature review demonstrated that there are still many unclear issues related to the etiology, pathogenesis, clinical diagnosis and treatment, treatment prognosis, and other aspects of this disease, and further clinical and basic research is needed for in-depth exploration.

Modified Weijingtang Regulates Pyroptosis of Macrophages via Caspase-1/GSDMD Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of modified Weijingtang on the pyroptosis of RAW264.7 macrophages via the cysteinyl aspartate-specific protease-1 （Caspase-1）/gasdermin D （GSDMD） pathway. MethodLipopolysaccharide （LPS） was used to induce pyroptosis of RAW264.7 cells. The blank group was treated with the blank serum， and the intervention groups were treated with the sera containing different doses of modified Weijingtang. After 24 h， the viability of cells in different groups was examined by the cell counting kit-8 （CCK-8）. The pyroptosis and morphology of cells in each group were observed by a scanning electron microscope and a phase-contrast microscope， respectively. The mRNA and protein levels of nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3）， Caspase-1， and GSDMD in each group were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The levels of interleukin （IL）-18 and IL-1β in each group were measured by enzyme-linked immunosorbent assay. ResultUnder the electron microscope， RAW264.7 cells presented the best morphology and structure in the blank group and obvious pyroptosis and leakage of cell contents in the model （LPS） group. Compared with the model group， the intervention groups showed reduced pyroptosis to varying degrees， and the high-dose group had the closest cell morphology and structure to the blank group. Under the optical microscope， RAW264.7 cells were spherical in the blank group and irregular with protrusions in the model group. Compared with the model group， the intervention groups showed improved cell morphology， and the cell morphology in the group with the dose of 20% was the closest to that in the blank group. The mRNA and protein levels of NLRP3， Caspase-1， and GSDMD in the model group were higher than those in the blank group （P<0.05）. Compared with the model group， each intervention group showed down-regulated expression of the above indicators （P<0.05）. Compared with the blank group， the model group presented elevated levels of IL-18 and IL-1β （P<0.05）， which were lowered in the intervention （10%， 20%） groups （P<0.01）. ConclusionModified Weijingtang inhibits the pyroptosis of macrophages by down-regulating the Caspase-1/GSDMD pathway and reducing the release of proinflammatory cytokines.

Anti-inflammatory Effect and Mechanism of Active Constituents from Lonicerae Japonicae Flos and Lonicerae Flos： A Review / 中国实验方剂学杂志

Inflammation is involved in the development of various acute and chronic diseases in the body. Sustained inflammatory responses are key driving factors for diseases such as cancer， neurodegenerative diseases， cardiovascular diseases， metabolic syndrome， inflammatory bowel disease， and arthritis. Therefore， finding anti-inflammatory drugs is crucial for the prevention and treatment of various diseases. In recent years， there has been increasing attention to finding natural drugs with minimal toxic side effects. Lonicerae Japonicae Flos and Lonicerae Flos， as traditional Chinese medicines potent in clearing heat and removing toxins， have strong biological activity and multiple pharmacological effects. They are widely distributed in the plant world and have significant medicinal value. With the continuous advancement of the research on Lonicerae Japonicae Flos and Lonicerae Flos， they have been widely used in the medical field and possess great development potential. Currently， research mainly focuses on the anti-inflammatory mechanisms of Lonicerae Japonicae Flos and Lonicerae Flos， while systematic summaries of their anti-inflammatory active ingredients are rare. Therefore， this paper focuses on the differential analysis of the anti-inflammatory active components of Lonicerae Japonicae Flos and Lonicerae Flos. In addition， it reviewed the possible mechanisms by which extracts and active ingredients of Lonicerae Japonicae Flos and Lonicerae Flos may exert anti-inflammatory effects through various pathways， such as influencing the release of cellular inflammatory factors， regulating inflammatory signaling pathways such as nuclear factor-κB （NF-κB）， mitogen-activated protein kinase （MAPK）， signal transducer and activator of transcription 3 （STAT3）， MAPK/extracellular signal-regulated kinase （ERK）/c-Jun N-terminal kinase （JNK）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/NF-κB， and Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathways， increasing antioxidant stress capacity， enhancing immune defense capabilities， and improving intestinal microbiota， aiming to provide a theoretical basis for the rational clinical application of Lonicerae Japonicae Flos and Lonicerae Flos.

Research Progress in Extraction Technology， Structural Characteristics and Pharmacological Activities of Hippophae rhamnoides Polysaccharides / 中国实验方剂学杂志

Hippophae rhamnoides is a traditional Chinese medicine with homology of medicine and food， which has the effects of relieving cough and resolving phlegm， strengthening the stomach and digestion， and promoting blood circulation and resolving blood stasis. H. rhamnoides contains not only flavonoids， phenols， proteins， vitamins， and amino acids but also abundant polysaccharides. In order to explore the functional value and current research status of H. rhamnoides polysaccharides， this study systematically summarized the extraction process， structural characteristics， pharmacological effects， and mechanism of action of H. rhamnoides polysaccharides by reviewing Chinese and foreign literature. The results showed that H. rhamnoides polysaccharides have anti-tumor， hypoglycemic， antioxidant， immune regulation， anti-inflammatory， and anti-hyperlipidemia functions and could improve intestinal microbiota. There were various extraction processes for polysaccharides， including hot water extraction， microwave extraction， ultrasonic extraction， enzymatic extraction， flash extraction， ultrasonic-microwave synergistic extraction， emerald hot water extraction， enzymatic-ultrasonic synergistic extraction， etc. Based on comprehensive analysis， hot water extraction is suitable for industrial development and application. However， multiple homogeneous polysaccharides have been isolated and purified from H. rhamnoides polysaccharides， but their efficacy， structure， and structure-activity relationship still need to be further explored and studied. This study can provide a reference for the research and development of H. rhamnoides polysaccharides.

Design, synthesis and biological study of BTK/JAK3 dual-target inhibitors / 中国药科大学学报

@#Abstract: In the present study, the compound XL-12 from our previous work was utilized as a lead compound. Through the optimization of the terminal phenyl ring, 12 target compounds were designed and synthesized. The structures of all target compounds were confirmed by 1H NMR, 13C NMR, and H RMS. In vitro enzyme activity assay showed that most compounds demonstrated significant inhibitory activity toward Bruton’s tyrosine kinase (BTK) and Janus kinase 3 (JAK3). Among them, compound I-3 exhibited moderate cell proliferation inhibitory activity toward Daudi cells and BaF3-JAK3 cells. In the evaluation of anti-inflammatory activity in vitro, compound I-3 could effectively inhibit the production of inflammatory factors IL-6; besides, it exhibited superior anti-inflammatory activity compared to ibrutinib in xylene-induced ear swelling model in mice.

Progress in application of engineered microorganisms in different diseases / 国际生物医学工程杂志

The human body contains a large microbial community composed of eukaryotes, archaea, bacteria, and phages. Bacteria are the most prominent members of this community, numbering in the same order of magnitude as human cells. Many commensal or pathogenic bacteria interact with their hosts through biochemical signals. Based on these bacterial properties, commensal and attenuated pathogens have been designed to deliver therapeutic molecules to target specific diseases. The engineered bacteria or bacteria-derived particles and their encapsulation, secretion, and expression of surface therapeutic molecules developed in the past five years were introduced. Their applications in anti-inflammatory, anti-tumor, thrombosis treatment, and imaging were reviewed, and the clinical translational potential of microbial drug delivery systems was discussed.

Research progress on the effect of α7 nicotinic acetylcholine receptor on perioperative neurocognitive function / 解放军医学杂志

α7 nicotinic acetylcholine receptor(α7nAChR)is widely expressed in the central nervous system and immune system,and plays a neuro-immunoregulatory role.On the one hand,α7nAChR is involved in the transmission of neurotransmitters,the conduction of excitatory signals and the maintenance of synaptic plasticity,which is of great significance for maintaining the normal and stable neurocognitive function.On the other hand,as an important part of the cholinergic anti-inflammatory pathway,α7nAChR is involved in the regulation of physiological and pathological processes such as inflammatory response,oxidative stress,apoptosis and autophagy in the central system,and plays an immunomodulatory and neuroprotective role,thus being potential target for improving perioperative neurocognitive function.This article reviews the biological characteristics of α7nAChR and its effect on perioperative neurocognitive function,in order to provide ideas and methods for clinical improvement of perioperative neurocognitive function in surgical patients.

Research progress on association between macrophages and ischemia-reperfusion injury / 器官移植

Ischemia-reperfusion injury (IRI) is an extremely complicated pathophysiological process, which may occur during the process of myocardial infarction, stroke, organ transplantation and temporary interruption of blood flow during surgery, etc. As key molecules of immune system, macrophages play a vital role in the pathogenesis of IRI. M1 macrophages are pro-inflammatory cells and participate in the elimination of pathogens. M2 macrophages exert anti-inflammatory effect and participate in tissue repair and remodeling and extracellular matrix remodeling. The balance between macrophage phenotypes is of significance for the outcome and treatment of IRI. This article reviewed the role of macrophages in IRI, including the balance between M1/M2 macrophage phenotype, the mechanism of infiltration and recruitment into different ischemic tissues. In addition, the potential therapeutic strategies of targeting macrophages during IRI were also discussed, aiming to provide reference for alleviating IRI and promoting tissue repair.

Anti-inflammatory activity and mechanism of Clematis ranunculoides extract / 中国药房

OBJECTIVE To investigate the anti-inflammatory activity and potential mechanism of Clematis ranunculoides extract. METHODS The ear swelling was induced by xylene to establish an acute inflammation model of mice； using aspirin （0.25 g/kg） as a positive control， the effects of 1.25， 2.5， 5 g/kg C. ranunculoides extract on the degree of ear swelling were investigated. The chronic inflammation model of rats was also established by implanting cotton balls； using aspirin （0.17 g/kg） as a positive control， the effects of 0.88， 1.75， 3.5 g/kg C. ranunculoides extract on the net weight of granulomas were investigated. Furthermore， RAW264.7 cells were induced by lipopolysaccharide to establish an inflammatory injury model； the effects of 12.5， 25， 50 μg/mL C. ranunculoides extract on the contents of nitric oxide（NO）， prostaglandin E2（PGE2）， tumor necrosis factor-α （TNF-α）， interleukin-6（IL-6） and monocyte chemotactic protein-1（MCP-1） in the cell supernatant， the protein expressions of inducible nitric oxide synthase（iNOS）， cyclooxygenase-2（COX-2）， p65 and phosphorylated p65（p-p65） in cells as well as nuclear translocation of p65 protein were assessed. RESULTS C. ranunculoides extract with 5 g/kg significantly relieved ear swelling in mice， and C. ranunculoides extract with 1.75， 3.5 g/kg significantly decreased the net weight of granulomas in rats （P＜0.05）. C. ranunculoides extract with 12.5， 25， 50 μg/mL significantly reduced the contents of NO （except for 12.5 μg/mL C. ranunculoides extract）， PGE2， TNF-α， IL-6 and MCP-1 in the cell supernatant， as well as the relative expressions of iNOS and COX-2 protein， and relative expression ratio of p-p65 and p65 protein （P＜0.05 or P＜0.01）； C. ranunculoides extract with 25， 50 μg/mL inhibited the translocation of p65 protein to the cell nucleus. CONCLUSIONS C. ranunculoides extract exhibits significant anti- inflammatory activity， the mechanism of which may be attributed to the inhibition of the activation of nuclear factor-κB signaling pathway， down-regulation of COX-2 and iNOS protein expression， and the reduction of inflammatory cytokines release.