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1.
J Ethnopharmacol ; 318(Pt B): 117048, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37586441

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis bungeana Turcz. (KDD) is a Chinese herbal medicine with anti-inflammatory, lung cleansing, detoxification and other functions. Clinically, it is commonly used to treat respiratory infections. This study uses ALI as the research model, which is consistent with the clinical use of KDD. Acetylcorynoline (AC) is the main alkaloid component of the KDD extracts, and network pharmacology studies suggest that it may be the main active ingredient in the prevention of ALI. AIM OF THE STUDY: The aim of this study is to explore the underlying mechanisms and to study the efficacy material basis of KDD in anti-ALI effect by LPS-induced mice and using a combination of RNA sequencing (RNA-Seq) technology and network pharmacology. MATERIALS AND METHODS: Establish a mouse model of ALI by intraperitoneal injection of LPS (5 mg/kg). The main active ingredients of KDD were identified and analyzed by high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS) and network pharmacology. IL-18, IL-1ß, and IL-6 levels in serum and bronchoalveolar lavage fluid (BALF), lung histopathological changes, and lung myeloperoxidase (MPO) activity were assessed. We investigated the possible molecular mechanisms of KDD and AC in an LPS-induced mouse ALI models with RNA-Seq technology. In addition, the anti-inflammatory effect of AC was verified in vitro by establishing an LPS-stimulated RAW264.7 inflammation model. Molecular docking further validated AC as the efficacy material basis of KDD in anti-ALI. RESULTS: Based on HPLC-QTOF-MS technology and network pharmacology, KDD is more strongly associated with lung tissue, and that AC may be the main active ingredient of KDD. Subsequently, in vivo experiments results showed that KDD and AC reduced the levels of pro-inflammatory cytokines in serum and BALF, reduced MPO levels and reduced inflammatory damage in the lungs. To elucidate its underlying mechanism, based on RNA-Seq analysis techniques performed in lung tissue, enrichment analysis showed that KDD and AC intervened through the NLR signaling pathway, thereby mitigating LPS-induced ALI. Then, RT-qPCR, IF, WB and other technologies were used to verify the anti-ALI core difference genes of KDD and AC from the gene transcription and protein expression levels of the NLR signaling pathway, and confirmed the anti-ALI. In vitro experimental results also showed that AC has anti-inflammatory effects in RAW264.7. Finally, the biotransformation and molecular docking results also further indicated that AC is the active ingredient of KDD in anti-ALI. CONCLUSIONS: Studies have shown that KDD has a good therapeutic effect on ALI, and AC is the main pharmacodynamic material basis for its therapeutic effect in ALI.


Assuntos
Lesão Pulmonar Aguda , Corydalis , Camundongos , Animais , Corydalis/química , Lipopolissacarídeos/farmacologia , Simulação de Acoplamento Molecular , Farmacologia em Rede , RNA-Seq , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/prevenção & controle , Pulmão , Extratos Vegetais/efeitos adversos , Anti-Inflamatórios/efeitos adversos , NF-kappa B/metabolismo
2.
J Ethnopharmacol ; 318(Pt A): 116948, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37482260

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Si Jun Zi decoction (SJZT) is a traditional Chinese medicine (TCM) formula with the effect of invigorating the spleen qi and replenishing qi. TCM believes that a strong spleen qi helps to strengthen lung qi. Lung cancer is often caused by a deficiency of lung qi. Based on this theory, TCM often applies SJZT to the treatment of lung cancer and has achieved remarkable results. However, the mechanism of SJZT in the treatment of lung cancer remains unclear and requires further study. AIM OF THE STUDY: The main purpose of this study is to explore the mechanism of SJZT against lung cancer. MATERIALS AND METHODS: In this study, the chemical constituents in SJZT were analyzed by UPLC-Q-Exactive-MS/MS. MTT and cell scratch test were used to determine the cell viability and inhibition of migration in vitro. The effect of SJZT on the expression of PD-L1 protein in A549 cells was detected by Western Blotting (WB). Apoptosis was detected by crystal violet staining. The mouse model of Lewis lung cancer was established in vivo, and the levels of serum TNF-α and IL-2 were detected by enzyme linked immunosorbent assay (ELISA). The protein levels of TLR4, MyD88, NF-κB and PD-L1 in tumor tissues of mice were detected by WB. Quantitative real-time PCR (qRT-PCR) was used to detect the levels of TLR4, MyD88, NF-κB and PD-L1 mRNA. Finally, hematoxylin and eosin (H&E) staining were used to detect the pathological status of tumor tissues in mice. RESULTS: A total of 16 active chemical constituents were identified in SJZT. In vitro experiments showed that SJZT could inhibit the growth of A549, induce apoptosis and reduce the expression of PD-L1. In vivo experiments showed that SJZT regulated TLR4/MyD88/NF-κB signaling pathway, decreased the expression of PD-L1, and inhibited tumor growth. CONCLUSIONS: SJZT inhibits the growth of lung cancer by regulating TLR4/MyD88/NF-κB signal pathway and reducing the expression of PD-L1.


Assuntos
Neoplasias Pulmonares , NF-kappa B , Camundongos , Animais , NF-kappa B/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Espectrometria de Massas em Tandem , Neoplasias Pulmonares/tratamento farmacológico
3.
J Ethnopharmacol ; 318(Pt B): 116930, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37487966

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Eclipta prostrata (L.) L. is a medicinal plant used by many ethnic groups in Brazil to treat respiratory diseases, hepatitis and the bites of venomous animals. A methanolic extract of E. prostrata (MEEP), the major components of which are wedelolactone (WED) and demethylwedelolactone (DMW), exhibited anti-inflammatory activity in acute asthma models but the effects on lung inflammation and the mechanisms of action of MEEP in a chronic asthma model are not known. AIM OF THE STUDY: To study the effects of MEEP in vivo using a chronic ovalbumin (OVA)-induced allergic asthma model in mice. MATERIALS AND METHODS: The identities of WED and DMW in MEEP were confirmed and the concentrations determined by liquid chromatography and tandem mass spectrometry. Male Balb/c mice were sensitized and challenged with OVA and experimental animals were treated with MEEP (100, 250 or 500 mg/kg) while control animals were treated with dexamethasone (2 mg/kg) or normal saline. Bronchial hyperresponsiveness, total and differential cell counts in bronchoalveolar lavage (BAL), and the production of Th2 cytokines in lung homogenates were assessed. Lung inflammation and mucus production were evaluated by histological analysis while nuclear factor kappa-B (NF-κB) activation was assessed immunohistochemically. RESULTS: Concentrations of WED and DMW in MEEP were 5.12% and 1.04%, respectively. Treatments with MEEP (250 or 500 mg/kg) significantly decreased bronchial hyperresponsiveness, reduced total cell and eosinophil counts in BAL and IL-4 concentrations in lung homogenate, and inhibited NF-κB activation. Treatment with MEEP at 500 mg/kg reduced the level of IL-5 in lung homogenates but did not decrease IL-13 concentration or mucus production. CONCLUSIONS: MEEP attenuated bronchial hyperresponsiveness and decreased lung and airway inflammation in a chronic asthma model in mice. The mechanism of action involves inhibition of NF-κB activation, most likely associated with the presence of the coumestans WED and DMW. These results support the ethnopharmacological evidence for the use of E. prostrata against asthma and other respiratory inflammatory diseases.


Assuntos
Asma , Hiper-Reatividade Brônquica , Eclipta , Hipersensibilidade , Animais , Camundongos , NF-kappa B/metabolismo , Metanol/uso terapêutico , Modelos Animais de Doenças , Líquido da Lavagem Broncoalveolar , Asma/patologia , Pulmão , Hipersensibilidade/patologia , Inflamação/tratamento farmacológico , Hiper-Reatividade Brônquica/tratamento farmacológico , Ovalbumina/farmacologia , Camundongos Endogâmicos BALB C
4.
J Ethnopharmacol ; 318(Pt A): 116921, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37490990

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: An essential factor related to the acute alcoholic liver injury is damage to the intestinal mucosal barrier. Yajieshaba (YJSB) is a commonly used formulation of Dai people in China and protects the liver. AIM OF THE STUDY: This study investigated whether YJSB can prevent acute alcoholic liver injury by regulating the intestinal mucosal barrier. MATERIALS AND METHODS: The mice received 0.39 g/kg, 1.17 g/kg, and 3.51 g/kg dose YJSB for 7 days, a mouse model of acute alcoholic liver injury was established by a single instillation of 56% alcohol. Plasma biochemical markers were analyzed, liver injury was identified by histopathology, lipopolysaccharide (LPS), nuclear factor-k-gene binding (NF-κB), hepatic inflammatory factors, oxidative stress factors and reactive oxygen species (ROS) content was analyzed. The morphological changes of intestinal histology were observed by H&E staining, and the ultrastructure of ileal cells was observed by transmission electron microscopy. Immunofluorescence and Western blot was used to determine the expression levels of transporters and enzymes involved in Claudin 1, Occludin and zona occludens 1 (ZO-1) homeostasis in the liver and intestine. RESULTS: The findings showed that YJSB reduced the levels of aspartate aminotr ansferase (AST), alanine aminotransferase (ALT) and total bile acid (TBA), both of which are indicators of liver function and had a protective effect against liver injury. In the liver homogenate, YJSB reduced the level of LPS, NF-κB, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), decreased the level of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-PX) and catalase (CAT) and ROS. The results of hematoxylin and eosin (H&E) staining and transmission electron microscopy analysis revealed that YJSB reduced the degree of damage to intestinal tissue and intracellular organelles, implying that YJSB can reduce the "attack factor" that causes intestinal barrier damage, increase the "defense factor" that protects the intestinal barrier. The results of immunohistochemistry and Western blotting analysis showed that YJSB could increase the expression of claudin 1, occludin, and ZO-1 proteins, suggesting that the mechanism of action of YJSB against acute alcohol liver injury involves the upregulation of the expression of the intestinal barrier-related proteins and the repair of the damaged intestinal barrier. CONCLUSIONS: YJSB can block LPS, oxidative stress factors, and other harmful substances in the blood and protect the liver resisting acute alcoholic liver injury.


Assuntos
Lipopolissacarídeos , NF-kappa B , Camundongos , Animais , Espécies Reativas de Oxigênio/metabolismo , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Ocludina/metabolismo , Claudina-1/metabolismo , Fígado , Estresse Oxidativo , Etanol/farmacologia , Interleucina-6/metabolismo
5.
J Ethnopharmacol ; 318(Pt A): 116966, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37499845

RESUMO

BACKGROUND: Hosta plantaginea (Lam.) Aschers flower is a famous Mongolian folk medicine in China and has a therapeutic effect on acute pharyngitis (AP). However, the effect and potential mechanism of H. plantaginea flower on AP have not been fully elucidated. AIM OF THE STUDY: The present work aimed to evaluate the effects and mechanisms of the crude extract of H. plantaginea flowers (HP) and its four fractions of petroleum ether fraction (HPA), ethyl acetate fraction (HPB), n-butanol fraction (HPC), and water residue (HPD) against AP in rats. MATERIALS AND METHODS: A 15% ammonia-induced AP rat model in rats was established. Therapeutic effects of HP and HPA∼D in model rats were evaluated based on body weight, histopathological analysis, and inflammatory parameters, including tumor necrosis factor α (TNF-α), prostaglandin E2 (PGE2), interleukin 1ß (IL-1ß), and IL-6. The protein expression of nuclear factor kappa-B p65 (NF-κB p65), inhibitor of NF-κB alpha (IκBα), c-Jun N-terminal kinases (JNK), mitogen-activated protein kinase (MAPK) p38, extracellular signal-regulated kinase (Erk), just another kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) were detected by a Western blotting assay. RESULTS: HP, HPB, and HPC treatments markedly alleviated AP in rats by increasing body weight and improving pathological damages in pharyngeal tissues. In addition, HP, HPB, and HPC treatments significantly inhibited inflammation, including decreasing the levels of TNF-α, PGE2, IL-1ß, and IL-6, and suppressing phosphorylated protein expression of p65, IκBα, JNK, p38, Erk, JAK1, STAT3, PI3K, and Akt in pharyngeal tissues of rats. CONCLUSION: Collectively, HP, HPB, and HPC can attenuate pharynx injury in rats by suppressing inflammation via inhibition of NF-κB, MAPKs, JAK-STAT, and PI3K-Akt pathways, which supports the traditional use of H. plantaginea flowers.


Assuntos
Hosta , Faringite , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Inibidor de NF-kappaB alfa/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Hosta/metabolismo , Interleucina-6 , Inflamação/tratamento farmacológico , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Flores/metabolismo
6.
J Ethnopharmacol ; 318(Pt B): 116953, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37506780

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Phyllostachys nigra (PN) is an herbal medicine that originates from the inner bark of Phyllostachys nigra Munro var. henosis Stapf or Phyllostachys bambusoides Siebold et Zuccarini. It has long been used to relieve fever and to treat diarrhea and inflammation. PN has been shown to possess inhibitory effects on pneumonia, intestinal inflammation, tumors, and fatigue. However, its potential efficacy in the treatment of atopic dermatitis (AD) has not been extensively studied or reported. AIM OF THE STUDY: The objective of this research was to investigate the impact of PN on HaCaT and HMC-1 cells, as well as its potential in an experimental model of AD induced by 1-chloro-2,4-dinitrobenzene (DNCB). METHODS: We analyzed the anti-inflammatory efficacy of PN in HaCaT cells and HMC-1 cells using ELISA and PCR, and investigated invasion of inflammatory cell, change of dermis and epidermis, and the SCORAD index in AD-like mice model. We also measured the MAPK signaling pathway using the dorsal tissue of mice. RESULTS: Our results show that PN reduced the expressions of TARC, GM-CSF, TNF-α, MCP-1, and IL-6 in vitro. PN also decreased the SCORAD index, thickening of epidermis and dermis, and inhibited the invasions of mast cells and eosinophils as well as CD4+ T and CD8+ T cells. Furthermore, PN suppressed the level of IgE and IL-6, and also inhibited the MAPK phosphorylation in the dorsal skin. CONCLUSION: These results demonstrate that PN could be an effective alternative medicine for allergic inflammatory disease.


Assuntos
Dermatite Atópica , Dinitroclorobenzeno , Animais , Camundongos , Dinitroclorobenzeno/toxicidade , Interleucina-6/metabolismo , Dinitrobenzenos/farmacologia , Camundongos Endogâmicos BALB C , Linfócitos T CD8-Positivos/metabolismo , NF-kappa B/metabolismo , Pele , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/metabolismo , Quimiocinas/metabolismo , Inflamação/patologia , Citocinas/metabolismo
7.
J Ethnopharmacol ; 318(Pt A): 116922, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37516390

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hosta plantaginea (Lam.) Aschers flowers (HPF) are well-known for their high flavonoid content, which contribute to their widely as traditional Chinese medicine for alleviating inflammation. Despite their recognized potential, information regarding the total flavonoid (TF) of HPF and its therapeutic application in treating chronic prostatitis (CP) remains unknown. AIM OF THE STUDY: We aimed to investigate the extraction optimization, constituent analysis, and alleviating effect of TF on CP as well as its potential mechanism. MATERIALS AND METHODS: The optimized extraction of TF from HPF was explored using response surface methodology with a Box-Behnken design model. The major flavonoids in TF were identified based on UHPLC-MS approach. Efficacy of TF (25 and 100 mg/kg, p.o.) on CP was evaluated in prostate antigen emulsion-induced autoimmune CP rat model by measuring prostatic index, the levels of leukocytes and lecithin bodies, as well as histopathological examination. The protein expression contents were detected by western blotting. Additionally, the antioxidant (DPPH and ABTS) and anti-inflammatory (cyclooxygenase 2, COX-2 inhibitory) effects of TF were also evaluated in vitro. RESULTS: The optimized conditions for TF extraction were determined as 60% ethanol concentration, 30 mL/g liquid-to-solid ratio, 30 min extraction time, and 90 °C extraction temperature, and the extraction ratio is 65.98 ± 2.14%. A total of 15 major flavonoids in TF were characterized by comparison with reference standards. TF ameliorated the efficacy of CP in rats in a dose-independent manner, including reduced prostatic index and leukocytes levels, elevated lecithin body levels, ameliorated histopathological damage to prostate, and suppressed phosphorylated protein expressions of nuclear factor kappa-B (NF-κB) p65, inhibitor of NF-κB alpha (IκBα), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (Erk), just another kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt). Simultaneously, the IC50 of TF to DPPH, ABTS radicals, and COX-2 were 2.02, 1.79, and 0.0838 mg/mL, respectively. CONCLUSIONS: We first demonstrated that TF from HPF represents a promising candidate to alleviate CP through suppression of NF-κB, MAPKs, JAK-STAT, and PI3K-Akt signaling pathways.


Assuntos
Hosta , Prostatite , Humanos , Masculino , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Hosta/metabolismo , Prostatite/tratamento farmacológico , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Lecitinas , Flores/metabolismo , Lipopolissacarídeos/farmacologia
8.
J Ethnopharmacol ; 318(Pt B): 116980, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37536644

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Particulate matter 2.5 (PM2.5) is a dangerous airborne pollutant that has become a global issue due to its detrimental effect on macrophages. Chenopodium formosanum Koidz (Djulis), a native plant from Taiwan well known for its high antioxidant content and is frequently used in ethnomedicine, shows promise as a novel phytomedicine to combat against oxidative stress caused by PM2.5. However, the protective mechanism of Djulis against PM2.5 still remains unclear. AIM OF THE STUDY: This study aimed to characterize the deleterious effect of emerging PM2.5 contaminants on the alveolar macrophage cell of the respiratory system and explore the underlying mechanisms in the suppression of PM2.5-induced inflammation using the extract of fermented Djulis. METHODS AND MATERIALS: RNA sequencing, immunoblot, and ChIP assay approaches were used to gain insight into the deleterious effect of PM2.5 on the macrophage cell at the transcriptional and translational level; and to elucidate the contribution of fermented Djulis extract (FCS) as the remedy of PM-induced MH-S cell inflammation. UHPLC-ESI-MS/MS and LC-QQQ/MS were used to identify the bioactive compounds potentially contributing to phytomedicinal properties in the water fraction of FCS. Multiple ligands docking analysis was conducted to predict the in-silico interaction of Djulis metabolites and NF-κB. RESULTS: Here, we showed that PM2.5 exposure at 200 ppm accelerated the production of intracellular ROS and phosphorylated NF-κB (p-NFκB), and negatively affecting the alveolar macrophage cell viability. Treating the cells with water-extracted FCS can restore their viability to 76% while simultaneously suppressing the generation of ROS and p-NFκB up to 38%. These ameliorative effects can be attributed to the occurrence of bioactive compounds such as gluconic acid, uridine, pantothenic acid, L-pyroglutamic acid, L-(-)-malic acid, and acetyl-L-carnitine in the water-extracted FCS which potentially dock to the RELA subunit site and consequently inhibit NF-κB activity along with its downstream inflammation signaling cascade. CONCLUSION: This work demonstrated the hazardous effect of PM2.5 on alveolar macrophage and unveiled the potential of FCS as a therapeutic phytomedicine to alleviate PM-induced inflammation.


Assuntos
Chenopodium , NF-kappa B , NF-kappa B/metabolismo , Material Particulado/toxicidade , Macrófagos Alveolares/metabolismo , Espectrometria de Massas em Tandem , Espécies Reativas de Oxigênio , Chenopodium/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Água
9.
J Ethnopharmacol ; 318(Pt B): 116986, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37536645

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia argyi H.Lév. & Vaniot (AA) has been extensively utilized as an important medicine and food homology in China, Japan, Korea, and eastern parts of Russia, owing to its pharmacological effects, which include anti-inflammatory, antibacterial, antitussive, and antiallergic properties. Despite the extract of AA can significantly alleviate gastric mucosal injury, its precise material basis for effectiveness is not yet clear. As one of the polymethoxy flavonoids with high content in AA, the gastroprotective activity and molecular mechanism of eupatilin (EUP) require further investigation. AIM OF THE STUDY: This study aims to investigate the gastroprotective effects and possible mechanisms of EUP by using an ethanol-induced gastric mucosal injury model in rats. MATERIALS AND METHODS: EUP was isolated from 95% ethanol extract of AA using a systematic phytochemical method. The gastroprotective activity of EUP was evaluated using a male SD rat model with ethanol-induced gastric mucosa injury. Histopathology evaluation of gastric tissues was performed using hematoxylin and eosin (H&E) staining. The levels of cytokines in the plasma and tissues were tested using the ELISA kits, while western blot analysis was employed to assess the expressions of COX-2, iNOS, and NF-κB pathway proteins. RESULTS: A sufficient amount of EUP was obtained from AA through chromatographic methods and identified by NMR experiment. In vivo, experimental results proved that EUP could significantly alleviate pathological features, increased SOD, GSH, and IL-10 levels, and decreased the contents of MDA, TNF-α, IL-1ß, and IL-6. Further in vitro and in vivo Western blot experimental results showed that EUP significantly down-regulates the expressions of the NF-κB signal pathway to relieve inflammatory responses. CONCLUSION: This study demonstrated that EUP could exert gastroprotective effects by inhibiting inflammation, enhancing gastric mucosal defense, and ameliorating oxidative stress, which is beneficial for providing scientific data for the development of gastric protection.


Assuntos
Artemisia , Gastropatias , Úlcera Gástrica , Ratos , Masculino , Animais , NF-kappa B/metabolismo , Etanol/farmacologia , Artemisia/química , Ratos Sprague-Dawley , Mucosa Gástrica , Gastropatias/metabolismo , Transdução de Sinais , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Extratos Vegetais/efeitos adversos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle
10.
J Ethnopharmacol ; 318(Pt B): 117000, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37544345

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Eriocephalus africanus infusion is used as a diuretic and a diaphoretic and is also used in the treatment of gastrointestinal disorders and gynaecological conditions, inflammation and dermal disorders, asthma, coughs, fevers, and painful ailments. The plant has been used traditionally as a medication to cure inflammation and skin problems. AIM OF THE STUDY: Studying E. africanus essential oil (EAEO) as a potential hepatoprotective measure against concanavalin (Con) A-induced hepatitis in mice and investigating its underlying mechanism. MATERIALS AND METHODS: Hydro-distilled oil of the fresh plant aerial shoots is subjected to GC/MS analysis. Autoimmune hepatitis (AIH) was induced in mice by intravenous injection of Con A (15 mg/kg). EAEO was administered orally before Con A injection to test its hepatoprotective activity. RESULTS: GC/MS analysis revealed the presence of 22 compounds representing 99.43% of the oil components. The monoterpene artemisia ketone (41.02%) and the sesquiterpene juniper camphor (14.17%) are the major components. The in vivo study showed that the oil suppressed Con A-induced neutrophil and CD4+T cell infiltration into the liver, restored hepatic redox balance, inhibited Con A-induced elevation of tumor necrosis factor-alpha (TNF-α), interleukin (IL-6), and interferon-gamma (IFN-γ) hepatic levels which were correlated with its ability to suppress nuclear factor kappa B (NF-κB) and Signal Transducer and Activator of Transcription (STAT1) activation in the liver. CONCLUSION: EAEO showed hepatoprotective potential against Con A-induced hepatitis in mice collectively through selective anti-oxidant, anti-inflammatory, and anti-necrotic effects.


Assuntos
Hepatite , Óleos Voláteis , Animais , Camundongos , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Concanavalina A/metabolismo , Concanavalina A/farmacologia , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Óleos Voláteis/metabolismo , Transdução de Sinais , Hepatite/metabolismo , Fígado , Inflamação/patologia , Citocinas/metabolismo
11.
J Ethnopharmacol ; 318(Pt B): 117009, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37557936

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis hendersonii Hemsl. (CH), is a traditional Tibetan medicine used in highland areas for the treatment of alpine polycythemia, ulcers and various inflammatory diseases. Its antioxidant and anti-inflammatory effects have been demonstrated in experimental mice. Loss of dopaminergic neurons due to oxidative damage is thought to be an important factor in the development of PD, the potential antioxidant, anti-inflammatory effects of CH could potentially be used for PD treatment. AIM OF THE STUDY: To identify potential targets of CH using network pharmacology and to investigate the neuroprotective effects in cultured cell models and in MPTP-intoxicated mice. MATERIALS AND METHODS: The main chemical components of CH were analyzed by UPLC-MS/MS and their potential targets of action or signaling pathways were analyzed using network pharmacology. MPP + or LPS was added to SH-SY5Y or BV2 cells, respectively, to establish cellular models. MPTP was administered to C57BL/6J mice to induce inflammation and dopaminergic neuron loss as well as dyskinesia, followed by behavioral analysis to determine the role of CH in eliminating inflammation, avoiding neuron loss, and improving dyskinesia. RESULTS: CH contains 241 alkaloids, 213 flavonoids, 177 terpenoids and 114 phenolic compounds. The targets crossover between CH and PD yielded 210 potential therapeutic targets, especially growth factors and inflammatory pathway-related genes, such as BDNF, NF-κB, as potential key targets. In cultured cells, CHE eliminated MPP + -induced impairment of cell viability as well as LPS-induced inflammation, respectively. In mice, CHE ameliorated MPTP-induced dyskinesia and rescued the loss of dopaminergic neurons in the substantia nigra and striatum. Mechanistically, CHE effectively maintained the activity of the BDNF-TrkB/Akt signaling pathway, accordingly, inhibited inflammatory signaling pathways such as HIF-1α/PKM2 and Notch/NF-kB. CONCLUSIONS: CH performed well in eliminating inflammation and improving locomotor deficits in mice, and its potent active ingredients are worthy of subsequent research and development.


Assuntos
Corydalis , Neuroblastoma , Fármacos Neuroprotetores , Humanos , Animais , Camundongos , Doenças Neuroinflamatórias , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Antioxidantes/farmacologia , Cromatografia Líquida , Lipopolissacarídeos/farmacologia , Farmacologia em Rede , Camundongos Endogâmicos C57BL , Neuroblastoma/tratamento farmacológico , Espectrometria de Massas em Tandem , Inflamação/tratamento farmacológico , Inflamação/metabolismo , NF-kappa B/metabolismo , Neurônios Dopaminérgicos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/metabolismo , Modelos Animais de Doenças
12.
J Ethnopharmacol ; 318(Pt A): 116792, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37356745

RESUMO

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.


Assuntos
Alcaloides , Disfunção Cognitiva , Saponinas , Camundongos , Animais , Escopolamina/farmacologia , Acetilcolinesterase/metabolismo , Saponinas/farmacologia , Saponinas/uso terapêutico , Flavonoides/farmacologia , Flavonoides/uso terapêutico , NF-kappa B/metabolismo , Doenças Neuroinflamatórias , Alcaloides/efeitos adversos , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Antioxidantes/farmacologia , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Estresse Oxidativo , Colinérgicos/farmacologia , Receptores Proteína Tirosina Quinases/efeitos adversos , Receptores Proteína Tirosina Quinases/metabolismo , Aprendizagem em Labirinto
13.
J Ethnopharmacol ; 318(Pt A): 116869, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37390876

RESUMO

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.


Assuntos
Candidíase Vulvovaginal , Camundongos , Humanos , Feminino , Animais , Candidíase Vulvovaginal/microbiologia , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Interleucina-18/metabolismo , Interleucina-18/farmacologia , Interleucina-18/uso terapêutico , NF-kappa B/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Amarelo de Eosina-(YS)/farmacologia , Hematoxilina/farmacologia , Candida albicans , Citocinas/metabolismo , Caspases/metabolismo
14.
J Ethnopharmacol ; 318(Pt A): 116769, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37400007

RESUMO

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.


Assuntos
Demência Vascular , NF-kappa B , Ratos , Animais , NF-kappa B/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Microglia , Demência Vascular/tratamento farmacológico , Demência Vascular/metabolismo , Farmacologia em Rede , Transdução de Sinais , Inflamação/metabolismo , Receptores Toll-Like/metabolismo
15.
J Ethnopharmacol ; 318(Pt A): 116843, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37414197

RESUMO

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.


Assuntos
Diabetes Mellitus Experimental , Retinopatia Diabética , Leucostasia , Ratos , Camundongos , Animais , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/metabolismo , NF-kappa B/metabolismo , Curcuma , Molécula 1 de Adesão Intercelular/genética , Diabetes Mellitus Experimental/tratamento farmacológico , Leucostasia/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator de Necrose Tumoral alfa , Oxigênio , Anti-Inflamatórios/efeitos adversos , RNA Mensageiro
16.
J Ethnopharmacol ; 318(Pt A): 116863, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37423516

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Angelica decursiva Franchet & Savatier is a traditional medicinal plant used to treat asthma, cough, headache, pyrexia and thick phlegm in China, Japan and Korea. A. decursiva contains many types of coumarins, which can exert several pharmacological activities including anti-inflammatory and antioxidant properties for treating various diseases such as pneumonitis, atopic dermatitis, diabetes, and Alzheimer's disease. AIM OF THE STUDY: In this study, we analyzed the components of A. decursiva ethanol extract (ADE) by high performance liquid chromatography (HPLC) and investigated the therapeutic effects of ADE against allergic asthma using lipopolysaccharide (LPS) stimulated RAW264.7 cells and an ovalbumin (OVA)-exposed allergic asthma model. To elucidate the mechanism of action of ADE, we examined the protein expression through network pharmacological analysis. MATERIALS AND METHODS: To establish asthma model, the mice were sensitized on day 0 and 14 via intraperitoneal injection of OVA with aluminum hydroxide. The mice were inhaled with OVA using an ultrasonic nebulizer on day 21, 22 and 23. ADE (50 and 100 mg/kg) was administered to mice by oral gave form day 18-23. On day 24, airway hyperresponsiveness (AHR) was measured using flexivent. On day 25, the mice were sacrificed and collected bronchoalveolar lavage fluids (BALF), serum and lung tissue. In LPS-stimulated RAW264.7 cell, nitric oxide and cytokines were measured. Additionally, expression of nuclear factor erythroid-2-related factor (Nrf2) and suppression of nuclear factor (NF)-κB were detected using double-immunofluorescence. RESULTS: We detected the five coumarin components which included nodakenin, umbelliferon, (-)-marmesin (=nodakenetin), bergapten, and decursin, in ADE by high performance liquid chromatography. Treatment with ADE decreased the production of nitric oxide, interleukin (IL)-6 and tumor necrosis factor (TNF)-α in LPS-stimulated RAW264.7 cells accompanied by the enhanced expression of nuclear factor erythroid-2-related factor (Nrf2) and suppression of nuclear factor (NF)-κB. In the asthma model, the administration of ADE reduced inflammatory cell count and airway hyperresponsiveness in OVA-exposed animals with decreased levels of IL-4, IL-13, and OVA-specific immunoglobulin E. These results were accompanied by the reduction of pulmonary inflammation and mucus secretion. Furthermore, ADE administration inhibited the expression of NF-κB and matrix metalloproteinase (MMP)-9 in OVA-exposed animals, which was consistent with the results of network pharmacological analysis. CONCLUSION: This study demonstrated that ADE effectively attenuated allergic inflammation induced by OVA inhalation through the enhancement of Nrf2 expression and suppression of NF-κB expression. Therefore, ADE may be a potential therapeutic agent for controlling asthma.


Assuntos
Angelica , Asma , Hipersensibilidade , Pneumonia , Animais , Camundongos , Ovalbumina/toxicidade , NF-kappa B/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Óxido Nítrico/metabolismo , Asma/induzido quimicamente , Asma/tratamento farmacológico , Asma/metabolismo , Hipersensibilidade/tratamento farmacológico , Pulmão , Pneumonia/metabolismo , Líquido da Lavagem Broncoalveolar , Interleucina-6/metabolismo , Camundongos Endogâmicos BALB C , Modelos Animais de Doenças
17.
J Ethnopharmacol ; 318(Pt A): 116896, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37437790

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shrub kava has long been grown and utilized, primarily in the South Pacific region, for ceremonial, religious, and social occasions. It has been used as a pain reliever and muscle relaxant in medicinal practices from the eighteenth century. Interestingly, relatively low incidence of lung cancer may attribute to the high consumption of kava products in this region. AIM OF THE STUDY: Kava extracts were used to produce the kava chalcones Flavokawain A, B and C, which have a variety of bioactivities. In the present study, we show that Flavokawain A has positive effects on endometriosis. MATERIALS AND METHODS: The endometriosis rat model was surgically induced by the autologous transplantation of endometrial tissue. Rats were evaluated for clinical ratings and lesion volume following a 6-week Flavokawain A therapy. Peritoneal fluid and blood samples were taken and ELISA assay was used to measure the cytokines and chemokines levels. Transcriptional and expression levels of Akt, PI3K, NF-kB, iNOS, Bcl-2, Bax and caspase-3 were evaluated by Western blotting and RT-qPCR. Implanted tissue sections of the rats were also analyzed by immunofluorescent and histopathological staining. RESULTS: Lesion volumes and adhesion scores were successfully decreased. Blood and peritoneal fluid levels of associated cytokines and chemokines were markedly down-regulated. Besides, Flavokawain A also mediated cell apoptosis of endometrial implants. Additionally, VEGF expression was reduced, which inhibited the angiogenesis process. As for the expression of Akt, p-Akt, PI3K, p-PI3K, and NF-kB in endometriosis lesions, Flavokawain A significantly reduced them. CONCLUSION: Flavokawain A has beneficial effects on the surgically induced endometriosis rat model, by reducing inflammation, promoting apoptosis, and decreasing angiogenesis. Our findings suggest that these effects may be mediated through the regulation of PI3K/Akt and NF-κB signaling pathways.


Assuntos
Chalcona , Chalconas , Endometriose , Kava , Humanos , Feminino , Ratos , Animais , Chalconas/farmacologia , Chalconas/uso terapêutico , NF-kappa B/metabolismo , Endometriose/tratamento farmacológico , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Chalcona/farmacologia , Citocinas , Apoptose
18.
J Ethnopharmacol ; 318(Pt A): 116903, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37442494

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The prescription of Yiqi Jiedu decoction (YQJD) originated from the classic Chinese herbal prescriptions of Danggui Buxue Decoction and Wuzi Yanzong Pill. A previous study has shown that 4 Gy irradiation induced the apoptosis of spermatocytes and revealed autophagosomes in cells exposed to radiation. YQJD decoction has the effect of preventing radiation injury. AIM OF THE STUDY: We used spermatocytes (GC-2spd cell line) to investigate the relationship between autophagy and apoptosis of spermatogenic cells after radiation, and the mechanisms of YQJD decoction. MATERIALS AND METHODS: Establish an in vitro radiation injury model by irradiating GC-2spd cells with 60Co γ-rays (4 Gy or 8 Gy). Autophagy agonists, autophagy inhibitors and YQJD were used to intervene cells. Cell apoptosis and inflammatory factors were measured. NF-κB localization was observed by immunofluorescence. Autophagy and apoptosis-related proteins and IκBα/NF-κB pathway factors were detected. RESULTS: Ionizing radiation promoted the growth of spermatogenic autophagosomes. After radiation, NF-κB was translocated to the nucleus, inflammatory factors were secreted, and IκBα/NF-κB pathway was activated, which promoted autophagy and apoptosis. YQJD decoction can inhibit the phosphorylation of IκBα/NF-κB pathway related factors, regulate the expression of Beclin-1 and Bcl-2 proteins, and inhibit the occurrence of autophagy and apoptosis of irradiated spermatocyte. CONCLUSIONS: The research results indicate that ionizing radiation can activate the IκBα/NF-κB signaling pathway in spermatocytes, promote cell autophagy and apoptosis by regulating the expression of Beclin-1 and Bcl-2 factors. The YQJD decoction inhibits the IκBα/NF-κB signaling pathway so as to regulate Beclin-1 and Bcl-2.


Assuntos
NF-kappa B , Lesões por Radiação , Masculino , Humanos , NF-kappa B/metabolismo , Inibidor de NF-kappaB alfa , Proteína Beclina-1 , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Reguladoras de Apoptose , Autofagia
19.
J Ethnopharmacol ; 318(Pt A): 116918, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37453619

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: As the second-largest traditional medical system in China, Tibetan medicine has a long history and abundant resources. To promote the development of the Tibetan medicine industry, it is essential to study the pharmacological activities of Tibetan medicine based on its traditional usage methods. AIM OF THE STUDY: Pneumonia has been a worldwide health problem with high morbidity and mortality rates, especially in the context of the COVID-19 epidemic. Given the unique advantages of traditional Tibetan medicine in treating pulmonary diseases, further research is warranted to develop potential anti-pneumonia drugs. MATERIALS AND METHODS: In our study, the potential combined decoction from traditional Tibetan medicine was determined by the data mining method. The antioxidant activity in vitro, anti-inflammatory effects on the macrophage cell model, as well as the anti-pulmonary inflammation effects on the LPS-induced mice model, have been explored to investigate the potential anti-pneumonia role of the decoction. Additionally, we conducted network pharmacology analysis to identify the potential targets against pneumonia, which were further confirmed by western blot assays. RESULTS: Following the combination therapy of Pterocephalodes hookeri (C.B.Clarke) V.Mayer & Ehrend. and Onosma hookeri var. longiflora (Duthie) A.V.Duthie ex Stapf ('P-O'), the clearance of DPPH radical and the total reducing power were all improved, as well as alleviated the toxicity. On the in vitro level, 'P-O' pre-treatment reduced the secretion of NO, TNF-α, IL-6, and IL-1ß in LPS-stimulated RAW264.7 cells, while promoting the concentration of IL-10. Meanwhile, on the in vivo level, the 'P-O' pre-treating also could alleviate LPS-induced pulmonary inflammation by reducing the pulmonary edema and leakage of the lung microvascular, improving the pathological change of lung tissue and regulating the cytokines content in bronchoalveolar lavage fluid (BALF). Furthermore, network pharmacology analysis revealed that the mechanism of 'P-O' in treating pneumonia in a multi-component, multi-target, and multi-pathway network, with the TLR4/NF-κB signaling pathway playing a crucial role, as demonstrated by the western blot assay results. CONCLUSION: In summary, the combination therapy of 'P-O' exhibited good antioxidant activity and anti-inflammatory activity in vitro, as well as a therapeutic effect against pulmonary inflammation in vivo. These findings provide evidence for the clinical application of 'P-O' and offer new approaches for treating pneumonia.


Assuntos
COVID-19 , Pneumonia , Camundongos , Animais , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Lipopolissacarídeos/toxicidade , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Transdução de Sinais , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico , Pneumonia/prevenção & controle , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico
20.
J Ethnopharmacol ; 318(Pt A): 116868, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37454749

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Previous studies have found that Yang-Xin-Shu-Mai granule (YXSMG) has certain advantages in the treatment of stable coronary heart disease. However, YXSMG can inhibit the progression of atherosclerotic plaque and stabilize vulnerable plaque needs to be further explored and studied. This research, mass spectrometry analysis, network pharmacology, in vivo and in vitro experimental studies were conducted to explore the mechanism of YXSMG on atherosclerosis. AIM OF THE STUDY: To decipher the mechanism of atherosclerotic plaque, stabilization for YXSMG by analysis of its active ingredients and biological network and activity in whole animal and at cellular and molecular levels. METHODS: The active components of YXSMG were determined using high performance liquid chromatography-mass spectrometry/mass spectrometry (HPLC-MS/MS) analysis. The 'Disease-Compound-Target-Pathway' network diagram was constructed using network pharmacology, and the stability of binding between core targets and core compounds was analyzed with molecular docking. After intervention with YXSMG, the pathology of aortic plaque, inflammation in the surrounding tissue, expression of TLR9/MyD88/NF-κB pathway protein in plaque and M1/M2 polarization of plaque macrophages were evaluated in vivo in apolipoprotein E-deficient (ApoE-/-) mice fed with high-fat diet. To verify whether it suppressed inflammation by inhibiting Toll-like receptor 9 (TLR9) reprogramming of macrophage polarization, we used RAW264.7 macrophages treated with specific TLR9 agonist (ODN1826) and inhibitor (ODN2088). RESULTS: Five active compounds were identified in YXSMG: catechin, formononetin, tanshinone IIA, cryptotanshinone and glycitein. Network pharmacology studies revealed TLR9 as one of the core targets of YXSMG intervention in atherosclerosis. Computer simulation of molecular docking showed that TLR9 could interact with the core compound to form a stable complex. In vivo experiments confirmed that YXSMG could significantly inhibit atherosclerotic plaque, reduce levels of blood lipids and inflammatory factors, downregulate TLR9/MyD88/NF-κB pathway protein and inhibit aortic sinus macrophages polarization to M1, but promote their polarization to M2 to inhibit inflammation. In vitro experiments revealed that YXSMG could downregulate expression of TLR9 gene and protein in ODN1826-activated RAW264.7 macrophages. ODN2088 had a synergistic effect with YXSMG on the TLR9/MyD88/NF-κB signaling pathway, and reprogrammed macrophages polarization from M1 to M2 by inhibiting TLR9, thus reducing immuno-inflammatory response. CONCLUSION: YXSMG can reduce the level of blood lipid and improve the size of atherosclerotic plaque and inflammatory infiltration in ApoE-/- mice fed with high fat. It is concluded that YXSMG can improve the mechanism of atherosclerotic plaque by inhibiting TLR9/MyD88/NF-κB pathway reprogramming macrophage M1/M2 polarization and reducing arterial inflammation.


Assuntos
Aterosclerose , Placa Aterosclerótica , Camundongos , Animais , Placa Aterosclerótica/patologia , NF-kappa B/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor Toll-Like 9/metabolismo , Simulação por Computador , Simulação de Acoplamento Molecular , Espectrometria de Massas em Tandem , Aterosclerose/genética , Transdução de Sinais , Macrófagos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Inflamação/patologia , Lipídeos/farmacologia , Apolipoproteínas E/genética , Camundongos Endogâmicos C57BL
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