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1.
Sci Rep ; 14(1): 7766, 2024 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-38565927

RESUMEN

The occurrence of major depressive disorder is widespread and can be observed in individuals belonging to all societies. It has been suggested that changes in the NO pathway and heightened oxidative stress may play a role in developing this condition. Anethole is a diterpene aromatic compound found in the Umbelliferae, Apiaceae, and Schisandraceae families. It has potential pharmacological effects like antioxidant, anxiolytic, analgesic, anti-inflammatory, antidiabetic, gastroprotective, anticancer, estrogenic, and antimicrobial activities. This study aimed to investigate the potential antidepressant properties of Anethole in a mouse model experiencing maternal separation stress while also examining its impact on oxidative stress and nitrite levels. The research involved the participation of 40 male NMRI mice, separated into five distinct groups to conduct the study. The control group was administered 1 ml/kg of normal saline, while the MS groups were given normal saline and Anethole at 10, 50, and 100 mg/kg doses. The study comprised various behavioural tests, including the open field test (OFT), forced swimming test (FST), and splash test, to assess the effects of Anethole on the mice. In addition to the behavioural tests, measurements were taken to evaluate the total antioxidant capacity (TAC), malondialdehyde (MDA), and nitrite levels in the hippocampus of the mice. According to the findings, maternal separation stress (MS) led to depressive-like conduct in mice, including a rise in immobility duration during the FST and a reduction in the duration of grooming behaviour in the splash test. Additionally, the results indicated that MS correlated with an increase in the levels of MDA and nitrite and a reduction in the TAC in the hippocampus. However, the administration of Anethole resulted in an increase in grooming activity time during the splash test and a decrease in immobility time during the FST. Anethole also exhibited antioxidant characteristics, as demonstrated by its ability to lower MDA and nitrite levels while increasing the TAC in the hippocampus. The results suggest that Anethole may have an antidepressant-like impact on mice separated from their mothers, likely partly due to its antioxidant properties in the hippocampus.


Asunto(s)
Derivados de Alilbenceno , Anisoles , Antioxidantes , Trastorno Depresivo Mayor , Humanos , Ratones , Masculino , Animales , Antioxidantes/farmacología , Antioxidantes/metabolismo , Depresión/tratamiento farmacológico , Depresión/metabolismo , Nitritos/metabolismo , Trastorno Depresivo Mayor/tratamiento farmacológico , Privación Materna , Solución Salina/farmacología , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Antidepresivos/metabolismo , Estrés Oxidativo , Hipocampo/metabolismo , Modelos Animales de Enfermedad , Conducta Animal
2.
Eur Rev Med Pharmacol Sci ; 28(6): 2297-2304, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38567592

RESUMEN

OBJECTIVE: This study aimed to analyze the effect of hyperbaric oxygen treatment (HBOT) in hepatopulmonary syndrome (HPS). MATERIALS AND METHODS: Five-month-old female Wistar-Albino rats were randomly divided into three groups: Group I, the control group; Group II, the cirrhosis group; and Group III, the cirrhosis group + HBOT group. Rats were exposed to HBO sessions (2.4 atm./60 min) for 20 days. Animals were sacrificed 24 hours after the last HBO session. Biochemical analysis, oxygenation parameters, NO and NO synthase (NOS) levels, histopathological changes in the liver and lungs, and pulmonary artery diameter were measured. RESULTS: A total of 24 rats (10 rats were included in Group I, six rats in Group II, and eight rats in Group III) weighing 220-250 g were included in the study. Significant differences were observed for NO and NOS (9.10±1.05 to 12.17±1.85 µmol/L, p<0.05 and 0.46±0.31 to 1.17±0.39 U/ml, p<0.05, respectively) at baseline and day 36 only in group II. Inflammatory cell infiltration and bronchial injury were significantly increased in group II compared to group I (p=0.007 and p=0.008, respectively) but not in group III (p=0.266 and p=0.275, respectively). Pulmonary artery diameter was significantly lower in group III compared with group II at all sites in both lungs (p<0.05). CONCLUSIONS: HBOT may be a promising treatment for HPS by reducing NO and NOS activity, perialveolar arteriolar dilation, lung inflammation, and injury and guiding future clinical trials.


Asunto(s)
Síndrome Hepatopulmonar , Oxigenoterapia Hiperbárica , Ratas , Femenino , Animales , Ratas Wistar , Síndrome Hepatopulmonar/terapia , Modelos Animales de Enfermedad , Oxígeno , Cirrosis Hepática
3.
Med Oncol ; 41(5): 111, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38592504

RESUMEN

The use of doxorubicin (Dox) in the treatment of breast cancer negatively affects the intestines and other tissues. Many studies have proven that probiotics and vitamin D3 have antitumor and intestinal tissue-protecting properties. To achieve effectiveness and minimize side effects, the current study aims to administer Dox together with probiotics (Lactobacillus acidophilus and Lactobacillus casei) and vitamin D3. Forty-two female BALB/c inbred mice were divided into six groups: Group 1 (Control), Group 2 (Dox), Group 3 (Dox and probiotics), Group 4 (Dox and vitamin D3), Group 5 (Dox, probiotics, and vitamin D3), and Group 6 (probiotics and vitamin D3). The 4T1 mouse carcinoma cell line was injected into the mammary fat pad of each mouse. Gene expression was examined using quantitative real-time PCR. The treated groups (except group 6) showed significantly reduced tumor volume and weight compared to the control group (P < 0.05, P < 0.01). Probiotics/vitamin D3 with Dox reduced chemotherapy toxicity and a combination of supplements had a significant protective effect against Dox (P < 0.05, 0.01, 0.001). The treated groups (except 6) had significantly higher expression of Bax/Caspase 3 genes and lower expression of Bcl-2 genes than the control group (P < 0.05, 0.01). Coadministration of Dox with probiotics and vitamin D3 showed promising results in reducing tumor size, protecting intestinal tissue and influencing gene expression, suggesting a strategy to enhance the effectiveness of breast cancer treatment while reducing side effects.


Asunto(s)
Lacticaseibacillus casei , Neoplasias , Probióticos , Femenino , Animales , Ratones , Lactobacillus acidophilus , Doxorrubicina/farmacología , Probióticos/farmacología , Modelos Animales de Enfermedad , Colecalciferol/farmacología , Ratones Endogámicos BALB C
4.
J Ethnopharmacol ; 328: 118131, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38565408

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Sarcandra glabra is officially named Zhong Jie Feng as a traditional medicine. In the nationality of Yao and Zhuang, it has been used to treat digestive diseases like stomachache and dysentery. Similarly, in Dai nationality, it has been used to treat intestinal diseases like gastric ulcers. However, the effect and mechanism of S. glabra on experimental ulcerative colitis (UC) are known. AIM OF STUDY: The main objective of this study was to investigate the effect and mechanism of S. glabra on experimental UC. MATERIALS AND METHODS: The chemical components in the water extract of S. glabra (ZJF) were analyzed by UPLC-MS/MS method. The HCoEpiC cell line was used to assess the promotive effect on intestinal proliferation and restitution. RAW264.7 cells were used to assess the in vitro anti-inflammatory effect of ZJF. The 3% DSS-induced colitis model was used to evaluate the in vivo effect of ZJF (4.5 g/kg and 9.0 g/kg). Mesalazine (0.5 g/kg) was used as the positive drug. ELISA, RT-qPCR, Western blot, and multiplex immunohistochemical experiments were used to test gene levels in the colon tissue. The H&E staining method was used to monitor the pathological changes of colon tissue. TUNEL assay kit was used to detect apoptosis of epithelial colonic cells. RESULTS: ZJF could alleviate the DSS-caused colitis in colon tissues, showing a comparative effect to that of the positive drug mesalazine. Mechanism study indicated that ZJF could promote normal colonic HCoEpiC cell proliferation and restitution, inhibit overexpression of pro-inflammatory cytokines, restore the M1/M2 ratio, decrease epithelial colonic cell apoptosis, rescue tight junction protein levels, and modulate IL-17/Notch1/FoxP3 pathway to treat experimental UC. CONCLUSION: Our results indicated that S. glabra can promote intestinal cell restitution, balance immune response, and modulate IL-17/Notch1/FoxP3 pathway to treat experimental UC.


Asunto(s)
Colitis Ulcerosa , Colitis , Animales , Ratones , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Mesalamina/efectos adversos , Cromatografía Liquida , Interleucina-17/metabolismo , Espectrometría de Masas en Tándem , Colon , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Factores de Transcripción/metabolismo , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL
5.
Molecules ; 29(7)2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38611770

RESUMEN

Irritable bowel syndrome (IBS), a common gastrointestinal disorder worldwide, is characterized by chronic abdominal pain, bloating, and disordered defecation. IBS is associated with several factors, including visceral hypersensitivity, gut motility, and gut-brain interaction disorders. Because currently available pharmacological treatments cannot adequately improve symptoms and may cause adverse effects, the use of herbal therapies for managing IBS is increasing. Lysimachia vulgaris var. davurica (LV) is a medicinal plant used in traditional medicine to treat diarrhea. However, information on whether LV can effectively improve diarrhea-predominant IBS (IBS-D) remains limited. In this study, using an experimental mouse model of IBS-D, we elucidated the effects of the LV extract. The methanol extract of LV decreased fecal pellet output in the restraint stress- or 5-hydroxytryptamine (5-HT)-induced IBS mouse model and inhibited 5-HT-mediated [Ca2+]i increase in a dose-dependent manner. Furthermore, we developed and validated a high-performance liquid chromatography method using two marker compounds, namely, chlorogenic acid and rutin, for quality control analysis. Our study results suggest the feasibility of the methanol extract of LV for developing therapeutic agents to treat IBS-D by acting as a 5-HT3 receptor antagonist.


Asunto(s)
Encefalopatías , Síndrome del Colon Irritable , Animales , Ratones , Síndrome del Colon Irritable/tratamiento farmacológico , Cromatografía Líquida de Alta Presión , Lysimachia , Metanol , Serotonina , Diarrea/tratamiento farmacológico , Modelos Animales de Enfermedad , Extractos Vegetales/farmacología
6.
Molecules ; 29(7)2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38611918

RESUMEN

Fever is a serious condition that can lead to various consequences ranging from prolonged illness to death. Tetrastigma hemsleyanum Diels et Gilg (T. hemsleyanum) has been used for centuries to treat fever, but the specific chemicals responsible for its antipyretic effects are not well understood. This study aimed to isolate and identify the chemicals with antipyretic bioactivity in T. hemsleyanum extracts and to provide an explanation for the use of T. hemsleyanum as a Chinese herbal medicine for fever treatment. Our results demonstrate that kaempferol 3-rutinoside (K3OR) could be successfully isolated and purified from the roots of T. hemsleyanum. Furthermore, K3OR exhibited a significant reduction in rectal temperature in a mouse model of fever. Notably, a 4 µM concentration of K3OR showed more effective antipyretic effects than ibuprofen and acetaminophen. To explore the underlying mechanism, we conducted an RNA sequencing analysis, which revealed that PXN may act as a key regulator in the fever process induced by lipopolysaccharide (LPS). In the mouse model of fever, K3OR significantly promoted the secretion of IL-6 and TNF-α during the early stage in the LPS-treated group. However, during the middle to late stages, K3OR facilitated the elimination of IL-6 and TNF-α in the LPS-treated group. Overall, our study successfully identified the chemicals responsible for the antipyretic bioactivity in T. hemsleyanum extracts, and it answered the question as to why T. hemsleyanum is used as a traditional Chinese herbal medicine for treating fever. These findings contribute to a better understanding of the therapeutic potential of T. hemsleyanum in managing fever, and they provide a basis for further research and development in this field.


Asunto(s)
Antocianinas , Antipiréticos , Medicamentos Herbarios Chinos , Flavonas , Animales , Ratones , Temperatura Corporal , Factor de Necrosis Tumoral alfa/genética , Antipiréticos/farmacología , Antipiréticos/uso terapéutico , Interleucina-6 , Quempferoles/farmacología , Medicamentos Herbarios Chinos/farmacología , Lipopolisacáridos , Fiebre/tratamiento farmacológico , Flavonas/farmacología , Flavonas/uso terapéutico , Modelos Animales de Enfermedad
7.
J Nutr Biochem ; 129: 109638, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38583499

RESUMEN

Maternal infection during pregnancy is an important cause of autism spectrum disorder (ASD) in offspring, and inflammatory infiltration caused by maternal immune activation (MIA) can cause neurodevelopmental disorders in the fetus. Medicine food homologous (MFH) refers to a traditional Chinese medicine (TCM) concept, which effectively combines food functions and medicinal effects. However, no previous study has screened, predicted, and validated the potential targets of MFH herbs for treating ASD. Therefore, in this study, we used comprehensive bioinformatics methods to screen and analyze MFH herbs and drug targets on a large scale, and identified resveratrol and Thoc5 as the best small molecular ingredient and drug target, respectively, for the treatment of MIA-induced ASD. Additionally, the results of in vitro experiments revealed that resveratrol increased the expression of Thoc5 and effectively inhibited lipopolysaccharide-induced inflammatory factor production by BV2 cells. Moreover, in vivo, resveratrol increased the expression of Thoc5 and effectively inhibited placental and fetal brain inflammation in MIA pregnancy mice, and improved ASD-like behaviors in offspring.


Asunto(s)
Trastorno del Espectro Autista , Efectos Tardíos de la Exposición Prenatal , Resveratrol , Resveratrol/farmacología , Animales , Femenino , Embarazo , Ratones , Masculino , Lipopolisacáridos/toxicidad , Conducta Animal/efectos de los fármacos , Ratones Endogámicos C57BL , Trastorno Autístico/inducido químicamente , Modelos Animales de Enfermedad
8.
J Ethnopharmacol ; 330: 118152, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38614260

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Xinyang tablet (XYT) has been used for heart failure (HF) for over twenty years in clinical practice, but the underlying molecular mechanism remains poorly understood. AIMS OF THE STUDY: In the present study, we aimed to explore the protective effects of XYT in HF in vivo and in vitro. MATERIALS AND METHODS: Transverse aortic constriction was performed in vivo to establish a mouse model of cardiac pressure overload. Echocardiography, tissue staining, and real-time quantitative PCR (qPCR) were examined to evaluate the protective effects of XYT on cardiac function and structure. Adenosine 5'-triphosphate production, reactive oxygen species staining, and measurement of malondialdehyde and superoxide dismutase was used to detect mitochondrial damage. Mitochondrial ultrastructure was observed by transmission electron microscope. Immunofluorescence staining, qPCR, and Western blotting were performed to evaluate the effect of XYT on the mitochondrial unfolded protein response and mitophagy, and to identify its potential pharmacological mechanism. In vitro, HL-1 cells and neonatal mouse cardiomyocytes were stimulated with Angiotensin II to establish the cell model. Western blotting, qPCR, immunofluorescence staining, and flow cytometry were utilized to determine the effects of XYT on cardiomyocytes. HL-1 cells overexpressing receptor-interacting serum/three-protein kinase 3 (RIPK3) were generated by transfection of RIPK3-overexpressing lentiviral vectors. Cells were then co-treated with XYT to determine the molecular mechanisms. RESULTS: In the present study, XYT was found to exerta protective effect on cardiac function and structure in the pressure overload mice. And it was also found XYT reduced mitochondrial damage by enhancing mitochondrial unfolded protein response and restoring mitophagy. Further studies showed that XYT achieved its cardioprotective role through regulating the RIPK3/FUN14 domain containing 1 (FUNDC1) signaling. Moreover, the overexpression of RIPK3 successfully reversed the XYT-induced protective effects and significantly attenuated the positive effects on the mitochondrial unfolded protein response and mitophagy. CONCLUSIONS: Our findings indicated that XYT prevented pressure overload-induced HF through regulating the RIPK3/FUNDC1-mediated mitochondrial unfolded protein response and mitophagy. The information gained from this study provides a potential strategy for attenuating mitochondrial damage in the context of pressure overload-induced heart failure using XYT.


Asunto(s)
Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Ratones Endogámicos C57BL , Mitofagia , Miocitos Cardíacos , Respuesta de Proteína Desplegada , Animales , Mitofagia/efectos de los fármacos , Respuesta de Proteína Desplegada/efectos de los fármacos , Ratones , Masculino , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/fisiopatología , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/ultraestructura , Comprimidos , Línea Celular , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo
9.
J Ethnopharmacol ; 330: 118189, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38615700

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Shentong Zhuyu Decoction (STZYD) is a traditional prescription for promoting the flow of Qi and Blood which is often used in the treatment of low back and leg pain clinicall with unclear mechanism. Neuropathic pain (NP) is caused by disease or injury affecting the somatosensory system. LncRNAs may play a key role in NP by regulating the expression of pain-related genes through binding mRNAs or miRNAs sponge mechanisms. AIM OF THE STUDY: To investigate the effect and potential mechanism of STZYD on neuropathic pain. METHODS: Chronic constriction injury (CCI) rats, a commonly used animal model, were used in this study. The target of STZYD in NP was analyzed by network pharmacology, and the analgesic effect of STZYD in different doses (H-STZYD, M-STZYD, L-STZYD) on CCI rats was evaluated by Mechanical withdrawal thresholds (MWT) and thermal withdrawal latency (TWL). Meanwhile, RNA-seq assay was used to detect the changed mRNAs and lncRNAs in CCI rats after STZYD intervention. GO analysis, KEGG pathway analysis, and IPA analysis were used to find key target genes and pathways, verified by qPCR and Western Blot. The regulatory effect of lncRNAs on target genes was predicted by co-expression analysis and ceRNA network construction. RESULTS: We found that STZYD can improve hyperalgesia in CCI rats, and H-STZYD has the best analgesic effect. The results of network pharmacological analysis showed that STZYD could play an analgesic role in CCI rats through the MAPK/ERK/c-FOS pathway. By mRNA-seq and lncRNA-seq, we found that STZYD could regulate the expression of Cnr1, Cacng5, Gucy1a3, Kitlg, Npy2r, and Grm8, and inhibited the phosphorylation level of ERK in the spinal cord of CCI rats. A total of 27 lncRNAs were associated with the target genes and 30 lncRNAs, 83 miRNAs and 5 mRNAs participated in the ceRNA network. CONCLUSION: STZYD has the effect of improving hyperalgesia in CCI rats through the MAPK/ERK/c-FOS pathway, which is related to the regulation of lncRNAs to Cnr1 and other key targets.


Asunto(s)
Analgésicos , Medicamentos Herbarios Chinos , Farmacología en Red , Neuralgia , ARN Largo no Codificante , Ratas Sprague-Dawley , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Neuralgia/tratamiento farmacológico , Neuralgia/genética , Masculino , Analgésicos/farmacología , Analgésicos/uso terapéutico , Ratas , ARN Largo no Codificante/genética , RNA-Seq , Modelos Animales de Enfermedad , ARN Mensajero/metabolismo , ARN Mensajero/genética , Redes Reguladoras de Genes/efectos de los fármacos
10.
J Ethnopharmacol ; 330: 118191, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38621468

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: The Mijiao (MJ) formula, a traditional herbal remedy, incorporates antlers as its primary constituent. It can effectively treat osteoporosis (OP), anti-aging, enhance immune activity, and change depression-like behavior. In this study, we investigated that MJ formula is a comprehensive treatment strategy, and may provide a potential approach for the clinical treatment of postmenopausal osteoporosis. AIM OF THE STUDY: The purpose of this study was to determine whether MJ formula promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and improved osteoporosis in ovariectomized rats by regulating the NAT10-mediated Runx2 mRNA ac4C modification. MATERIALS AND METHODS: Female Sprague-Dawley (SD) rats were used to investigate the potential therapeutic effect of MJ formula on OP by creating an ovariectomized (OVX) rat model. The expression of osteogenic differentiation related proteins in BMSCs was detected in vivo, indicating their role in promoting bone formation. In addition, the potential mechanism of its bone protective effect was explored via in vitro experiments. RESULTS: Our study showed that MJ formula significantly mitigated bone mass loss in the OVX rat model, highlighting its potential as an OP therapeutic agent. We found that the possible mechanism of action was the ability of this formulation to stabilize Runx2 mRNA through NAT10-mediated ac4C acetylation, which promoted osteogenic differentiation of BMSCs and contributed to the enhancement of bone formation. CONCLUSIONS: MJ formula can treat estrogen deficiency OP by stabilizing Runx2 mRNA, promoting osteogenic differentiation and protecting bone mass. Conceivably, MJ formulation could be a safe and promising strategy for the treatment of osteoporosis.


Asunto(s)
Diferenciación Celular , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Medicamentos Herbarios Chinos , Células Madre Mesenquimatosas , Osteogénesis , Osteoporosis , Ovariectomía , ARN Mensajero , Ratas Sprague-Dawley , Animales , Femenino , Osteogénesis/efectos de los fármacos , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Células Madre Mesenquimatosas/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , ARN Mensajero/metabolismo , Osteoporosis/tratamiento farmacológico , Ratas , Modelos Animales de Enfermedad , Células Cultivadas
11.
J Ethnopharmacol ; 330: 118150, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38631487

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: JiaWei DaChaiHu is composed of Bupleurum chinense, Scutellaria baicalensis, Pinellia ternata, Paeonia lactiflora, Zingiber officinaleRoscoe, Poncirus tuifoliata, Rheum palmatum L., Curcumae Radix, Herba Lysimachiae, Ziziphus. JiaWei DaChaiHu is one of the most common traditional Chinese medicines for the treatment of depression. AIM OF THE STUDY: The chronic unpredictable mild stress (CUMS) has been shown to promote atherosclerosis (AS). Dachaihu has been widely used in traditional Chinese medicine and has been known to exert distinct pharmacological effects. This investigation aims to examine the therapeutic effect of Jiawei Dachaihu extract on AS animal models with CUMS. METHODS: AS-CUMS mice model was established by Apoe-/- mice. Mice were treated with Jiawei Dachaihu. Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C) levels were measured using ELISA kits. Aortic tissue pathologic changes detected by oil red O staining. Mice behavioral changes detected by sucrose preference test and sucrose preference test. The relative mRNA expression levels of CRH, ND1, and TFAM were determined by qRT-PCR. 5-HT1A, BDNF, LON, TFAM, PGC-1α, and SIRT1 protein expression determined by western blotting. ATP content detected by ATP kits. RESULTS: The treatment with Jiawei Dachaihu extract alleviated the veins plaque and reduced stress signs in vitro and in vivo. It increased the ATP and HDL-C levels while decreased the TC, TG, LDL-C levels. Jiawei Dachaihu extract treatment upregulated Lon, SIRT1, TFAM, PGC-1α, BDNF, and 5-HT1A protein expression and regained mitochondrial function. CONCLUSION: Jiawei Dachaihu extract could alleviate AS and reduce CUMS by upregulating the SIRT1/PGC-1α signaling and promoted its crosstalk with Lon protein to maintain mitochondrial stability.


Asunto(s)
Aterosclerosis , Medicamentos Herbarios Chinos , Mitocondrias , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Transducción de Señal , Sirtuina 1 , Estrés Psicológico , Animales , Aterosclerosis/tratamiento farmacológico , Sirtuina 1/metabolismo , Sirtuina 1/genética , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Masculino , Transducción de Señal/efectos de los fármacos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Ratones , Estrés Psicológico/tratamiento farmacológico , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Ratones Noqueados para ApoE
12.
J Ethnopharmacol ; 330: 118105, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38631485

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) XYQFT is composed of 10 herbs. According to the NHIRD, XYQFT is one of the top ten most commonly used TCM prescriptions for asthma treatment. AIM OF THE STUDY: The aim of this study was to explore whether XYQFT reduces asthma symptoms in a mouse model of chronic asthma and determine the immunomodulatory mechanism of mast cells. MATERIALS AND METHODS: BALB/c mice were intratracheally (it) stimulated with 40 µL (2.5 µg/µL) of Dermatophagoides pteronyssinus (Der p) once a week for 6 consecutive weeks and orally administered XYQFT at 1 g/kg 30 min before Der p stimulation. Airway hypersensitivity, inflammatory cells in the BALF and total IgE in the blood were assessed in mice. In addition, RBL-2H3 cells (mast cells) were stimulated with DNP-IgE, after which different concentrations of XYQFT were added for 30 min to evaluate the effect of XYQFT on the gene expression and degranulation of DNP-stimulated RBL-2H3 cells. After the compounds in XYQFT were identified using LC‒MS/MS, the PBD method was used to identify the chemical components that inhibited the expression of the GM-CSF and COX-2 genes in mast cells. RESULTS: The airway hypersensitivity assay demonstrated that XYQFT significantly alleviated Der p-induced airway hypersensitivity. Moreover, cell counting and typing of bronchoalveolar lavage fluid revealed a significant reduction in Der p-induced inflammatory cell infiltration with XYQFT treatment. ELISA examination further indicated a significant decrease in Der p-induced total IgE levels in serum following XYQFT administration. In addition, XYQFT inhibited the degranulation and expression of genes (IL-3, IL-4, ALOX-5, IL-13, GM-CSF, COX-2, TNF-α, and MCP-1) in RBL-2H3 cells after DNP stimulation. The compounds timosaponin AIII and genkwanin in XYQFT were found to be key factors in the inhibition of COX-2 and GM-CSF gene expression in mast cells. CONCLUSION: By regulating mast cells, XYQFT inhibited inflammatory cell infiltration, airway hypersensitivity and specific immunity in a mouse model of asthma. In addition, XYQFT synergistically inhibited the expression of the GM-CSF and COX-2 genes in mast cells through timosaponin AIII and genkwanin.


Asunto(s)
Asma , Ciclooxigenasa 2 , Medicamentos Herbarios Chinos , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Mastocitos , Ratones Endogámicos BALB C , Animales , Medicamentos Herbarios Chinos/farmacología , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 2/genética , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Asma/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Ratones , Ratas , Inmunoglobulina E/sangre , Masculino , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Línea Celular , Antiasmáticos/farmacología , Modelos Animales de Enfermedad
13.
J Ethnopharmacol ; 330: 118193, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38636578

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Saiga antelope horn (SAH) is a traditional Chinese medicine for treating hypertension with liver-yang hyperactivity syndrome (Gan-Yang-Shang-Kang, GYSK), that has a long history of clinical application and precise efficacy, but its mechanism and functional substances are still unknown. Based on the demand for alternative research on the rare and endangered SAH, the group designed and carried out the following studies. AIM OF THE STUDY: The purpose of this research was to demonstrate the functional substances and mechanisms of SAH in the treatment of GYSK hypertension. MATERIALS AND METHODS: The GYSK-SHR model was constructed by administering a decoction of aconite to spontaneously hypertensive rats (SHRs). Blood pressure (BP), behavioural tests related to GYSK, and pathological changes in the kidneys, heart and aorta were measured to investigate the effects of SAH on GYSK-SHRs. Proteomic analysis was used to identify the keratins and peptides of SAH. Moreover, network pharmacology and plasma metabolomics studies were carried out to reveal the mechanisms by which functional peptides in SAH regulate GYSK-hypertension. RESULTS: SAH has a significant antihypertensive effect on GYSK hypertensive animals. It has also been proven to be effective in protecting the function and structural integrity of the kidneys, heart and aorta. Moreover, SAH improved the abnormalities of 31 plasma biomarkers in rats. By constructing a "biomarker-target-peptide" network, 10 functional peptides and two key targets were screened for antihypertensive effects of SAH. The results indicated that SAH may exert a therapeutic effect by re-establishing the imbalance of renin-angiotensin (RAS) system. CONCLUSIONS: Functional peptides from keratin contained in SAH are the main material basis for the treatment of GYSK-hypertension and exhibited the protective effect on the GYSK-SHR model through the RAS system.


Asunto(s)
Antihipertensivos , Hipertensión , Medicina Tradicional China , Metabolómica , Farmacología en Red , Ratas Endogámicas SHR , Animales , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Masculino , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Ratas , Medicina Tradicional China/métodos , Presión Sanguínea/efectos de los fármacos , Antílopes , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Cuernos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Modelos Animales de Enfermedad
14.
J Ethnopharmacol ; 330: 118215, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38641073

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys malacophylla (Pall.) Fisch (O. malacophylla) is a succulent herbaceous plant that is the Orostachys genus of Crassulaceae family. O. malacophylla has been widely used as a traditional Chinese medicine with antioxidant, anti-inflammatory, anti-febrile, antidote, anti-Toxoplasma gondii properties. However, the biological function of alleviating intestinal inflammation and key bioactive compounds were still unknown. AIM OF THE STUDY: We used a Drosophila model to study the protective effects and bioactive compounds of O. malacophylla water extract (OMWE) and butanol extract (OMBE) on intestinal inflammation. MATERIALS AND METHODS: Drosophila intestinal inflammation was induced by oral invasion of dextran sodium sulfate (DSS) or Erwinia carotovora carotovora 15 (Ecc15). We revealed the protective effects of two extracts by determining intestinal reactive oxygen species (ROS) and antimicrobial peptide (AMP) levels and intestinal integrity, and using network pharmacology analysis to identify bioactive compounds. RESULTS: We demonstrated that both OMWE and OMBE could ameliorate the detrimental effects of DSS, including a decreased survival rate, elevated ROS levels, increased cell death, excessive proliferation of ISCs, acid-base imbalance, and disruption of intestinal integrity. Moreover, the overabundance of lipid droplets (LDs) and AMPs by Ecc15 infection is mitigated by these extracts, thereby enhancing the flies' resistance to adverse stimuli. In addition, we used widely targeted metabolomics and network pharmacology analysis to identify bioactive compounds associated with IBD healing that are present in OMWE and OMBE. CONCLUSIONS: In summary, our research indicates that OMWE and OMBE significantly mitigate intestinal inflammation and have the potential to be effective therapeutic agents for IBD in humans.


Asunto(s)
Sulfato de Dextran , Pectobacterium carotovorum , Extractos Vegetales , Especies Reactivas de Oxígeno , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/química , Especies Reactivas de Oxígeno/metabolismo , Pectobacterium carotovorum/efectos de los fármacos , Crassulaceae/química , Intestinos/efectos de los fármacos , Intestinos/patología , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Drosophila melanogaster/efectos de los fármacos , Modelos Animales de Enfermedad , Drosophila , Farmacología en Red , Inflamación/tratamiento farmacológico , Péptidos Catiónicos Antimicrobianos/farmacología
15.
J Ethnopharmacol ; 330: 118214, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38641076

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Ferroptosis, a recently identified non-apoptotic form of cell death reliant on iron, is distinguished by an escalation in lipid reactive oxygen species (ROS) that are iron-dependent. This phenomenon has a strong correlation with irregularities in iron metabolism and lipid peroxidation. Salvia miltiorrhiza Bunge (DS), a medicinal herb frequently utilized in China, is highly esteemed for its therapeutic effectiveness in enhancing blood circulation and ameliorating blood stasis, particularly during the treatment of cardiovascular diseases (CVDs). Numerous pharmacological studies have identified that DS manifests antioxidative stress effects as well as inhibits lipid peroxidation. However, ambiguity persists regarding the potential of DS to impede ferroptosis in cardiomyocytes and subsequently improve myocardial damage post-myocardial infarction (MI). AIM OF THE STUDY: The present work focused on investigating whether DS could be used to prevent the ferroptosis of cardiomyocytes and improve post-MI myocardial damage. MATERIALS AND METHODS: In vivo experiments: Through ligation of the left anterior descending coronary artery, we constructed both a wild-type (WT) and NF-E2 p45-related factor 2 knockout (Nrf2-/-) mouse model of MI. Effects of DS and ferrostatin-1 (Fer-1) on post-MI cardiomyocyte ferroptosis were examined through detecting ferroptosis and myocardial damage-related indicators as well as Nrf2 signaling-associated protein levels. In vitro experiments: Erastin was used for stimulating H9C2 cardiomyocytes to construct an in vitro ferroptosis cardiomyocyte model. Effects of DS and Fer-1 on cardiomyocyte ferroptosis were determined based on ferroptosis-related indicators and Nrf2 signaling-associated protein levels. Additionally, inhibitor and activator of Nrf2 were used for confirming the impact of Nrf2 signaling on DS's effect on cardiomyocyte ferroptosis. RESULTS: In vivo: In comparison to the model group, DS suppressed ferroptosis in cardiomyocytes post-MI and ameliorated myocardial damage by inducing Nrf2 signaling-related proteins (Nrf2, xCT, GPX4), diminishing tissue ferrous iron and malondialdehyde (MDA) content. Additionally, it enhanced glutathione (GSH) levels and total superoxide dismutase (SOD) activity, effects that are aligned with those of Fer-1. Moreover, the effect of DS on alleviating cardiomyocyte ferroptosis after MI could be partly inhibited through Nrf2 knockdown. In vitro: Compared with the erastin group, DS inhibited cardiomyocyte ferroptosis by promoting the expression of Nrf2 signaling-related proteins, reducing ferrous iron, ROS, and MDA levels, but increasing GSH content and SOD activity, consistent with the effect of Fer-1. Additionally, Nrf2 inhibition increased erastin-mediated ferroptosis of cardiomyocytes through decreasing Nrf2 signaling-related protein expressions. Co-treatment with DS and Nrf2 activator failed to further enhance the anti-ferroptosis effect of DS. CONCLUSION: MI is accompanied by cardiomyocyte ferroptosis, whose underlying mechanism is probably associated with Nrf2 signaling inhibition. DS possibly suppresses ferroptosis of cardiomyocytes and improves myocardial damage after MI through activating Nrf2 signaling.


Asunto(s)
Ferroptosis , Ratones Endogámicos C57BL , Ratones Noqueados , Infarto del Miocardio , Miocitos Cardíacos , Factor 2 Relacionado con NF-E2 , Salvia miltiorrhiza , Transducción de Señal , Factor 2 Relacionado con NF-E2/metabolismo , Ferroptosis/efectos de los fármacos , Animales , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Salvia miltiorrhiza/química , Transducción de Señal/efectos de los fármacos , Masculino , Ratones , Ratas , Modelos Animales de Enfermedad , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Línea Celular
16.
J Ethnopharmacol ; 330: 118223, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38642624

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear. AIMS OF THE STUDY: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH. MATERIALS AND METHODS: The study employed network pharmacology, UPLC-Q-TOF-MS technique, molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms. RESULTS: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression. CONCLUSION: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.


Asunto(s)
Apoptosis , Hemorragia Cerebral , Leonurus , Simulación del Acoplamiento Molecular , Farmacología en Red , Neuronas , Animales , Apoptosis/efectos de los fármacos , Leonurus/química , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ratones , Masculino , Hemorragia Cerebral/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Extractos Vegetales/farmacología , Extractos Vegetales/química , Janus Quinasa 1/metabolismo , Factor de Transcripción STAT1/metabolismo , Modelos Animales de Enfermedad
17.
J Ethnopharmacol ; 330: 118230, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38643862

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Ferulic acid (FA) has shown potential therapeutic applications in treating lung diseases. However, the underlying mechanisms by which FA ameliorates acute lung injury (ALI) have not been distinctly elucidated. AIM OF THE STUDY: The project aims to observe the therapeutic effects of FA on lipopolysaccharide-induced ALI and to elucidate its specific mechanisms in regulating epithelial sodium channel (ENaC), which majors in alveolar fluid clearance during ALI. MATERIALS AND METHODS: In this study, the possible pathways of FA were determined through network pharmacology analyses. The mechanisms of FA in ALI were verified by in vivo mouse model and in vitro studies, including primary alveolar epithelial type 2 cells and three-dimensional alveolar organoid models. RESULTS: FA ameliorated ALI by improving lung pathological changes, reducing pulmonary edema, and upregulating the α/γ-ENaC expression in C57BL/J male mice. Simultaneously, FA was observed to augment ENaC levels in both three-dimensional alveolar organoid and alveolar epithelial type 2 cells models. Network pharmacology techniques and experimental data from inhibition or knockdown of IkappaB kinase ß (IKKß) proved that FA reduced the phosphorylation of IKKß/nuclear factor-kappaB (NF-κB) and eliminated the lipopolysaccharide-inhibited expression of ENaC, which could be regulated by nuclear protein NF-κB p65 directly. CONCLUSIONS: FA could enhance the expression of ENaC at least in part by inhibiting the IKKß/NF-κB signaling pathway, which may potentially pave the way for promising treatment of ALI.


Asunto(s)
Lesión Pulmonar Aguda , Ácidos Cumáricos , Canales Epiteliales de Sodio , Lipopolisacáridos , Ratones Endogámicos C57BL , Farmacología en Red , Animales , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Ácidos Cumáricos/farmacología , Masculino , Canales Epiteliales de Sodio/metabolismo , Lipopolisacáridos/toxicidad , Ratones , Sodio/metabolismo , Modelos Animales de Enfermedad , Transducción de Señal/efectos de los fármacos , Quinasa I-kappa B/metabolismo , FN-kappa B/metabolismo , Células Epiteliales Alveolares/efectos de los fármacos , Células Epiteliales Alveolares/metabolismo
18.
Discov Med ; 36(183): 753-764, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38665024

RESUMEN

BACKGROUND: Dental fluorosis is a discoloration of the teeth caused by the excessive consumption of fluoride. It represents a distinct manifestation of chronic fluorosis in dental tissues, exerting adverse effects on the human body, particularly on teeth. The transmembrane protein 16a (TMEM16A) is expressed at the junction of the endoplasmic reticulum and the plasma membrane. Alterations in its channel activity can disrupt endoplasmic reticulum calcium homeostasis and intracellular calcium ion concentration, thereby inducing endoplasmic reticulum stress (ERS). This study aims to investigate the influence of calcium supplements and TMEM16A on ERS in dental fluorosis. METHODS: C57BL/6 mice exhibiting dental fluorosis were subjected to an eight-week treatment with varying calcium concentrations: low (0.071%), medium (0.79%), and high (6.61%). Various assays, including Hematoxylin and Eosin (HE) staining, immunohistochemistry, real-time fluorescence quantitative polymerase chain reaction (qPCR), and Western blot, were employed to assess the impact of calcium supplements on fluoride content, ameloblast morphology, TMEM16A expression, and endoplasmic reticulum stress-related proteins (calreticulin (CRT), glucose-regulated protein 78 (GRP78), inositol requiring kinase 1α (IRE1α), PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6)) in the incisors of mice affected by dental fluorosis. Furthermore, mice with dental fluorosis were treated with the TMEM16A inhibitor T16Ainh-A01 along with a medium-dose calcium to investigate the influence of TMEM16A on fluoride content, ameloblast morphology, and endoplasmic reticulum stress-related proteins in the context of mouse incisor fluorosis. RESULTS: In comparison to the model mice, the fluoride content in incisors significantly decreased following calcium supplements (p < 0.01). Moreover, the expression of TMEM16A, CRT, GRP78, IRE1α, PERK, and ATF6 were also exhibited a substantial reduction (p < 0.01), with the most pronounced effect observed in the medium-dose calcium group. Additionally, the fluoride content (p < 0.05) and the expression of CRT, GRP78, IRE1α, PERK, and ATF6 (p < 0.01) were further diminished following concurrent treatment with the TMEM16A inhibitor T16Ainh-A01 and a medium dose of calcium. CONCLUSIONS: The supplementation of calcium or the inhibition of TMEM16A expression appears to mitigate the detrimental effects of fluorosis by suppressing endoplasmic reticulum stress. These findings hold implications for identifying potential therapeutic targets in addressing dental fluorosis.


Asunto(s)
Calcio , Suplementos Dietéticos , Fluorosis Dental , Animales , Masculino , Ratones , Factor de Transcripción Activador 6/metabolismo , Adenina/análogos & derivados , Ameloblastos/metabolismo , Ameloblastos/patología , Ameloblastos/efectos de los fármacos , Anoctamina-1/metabolismo , Anoctamina-1/antagonistas & inhibidores , Anoctamina-1/genética , Calcio/metabolismo , Modelos Animales de Enfermedad , eIF-2 Quinasa/metabolismo , eIF-2 Quinasa/genética , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Endorribonucleasas/metabolismo , Fluoruros/toxicidad , Fluoruros/efectos adversos , Fluorosis Dental/patología , Fluorosis Dental/metabolismo , Fluorosis Dental/etiología , Indoles , Ratones Endogámicos C57BL , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores
19.
Int J Biol Macromol ; 266(Pt 2): 131254, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38565362

RESUMEN

Acorus tatarinowii, a famous traditional Chinese medicine, is used for the clinical treatment of memory impairment and dementia. In this research, AT50, the crude polysaccharide extracted from A. tatarinowii rhizome, significantly improved the memory and learning ability of mice with Alzheimer's disease (AD) and exerted excellent anti-neuroinflammatory effects. More importantly, AT50 returned the levels of NO, TNF-α, IL-1ß, PGE-2, and IL-6 in AD mouse brains to normal levels. To identify the active ingredients in AT50, a heteropolysaccharide ATP50-3 was obtained from AT50. Structural analysis indicated ATP50-3 consisted of α-L-Araf-(1→, →2)-α-L-Araf-(1→, →3)-α-L-Araf-(1→, →5)-α-L-Araf-(1→, α-D-Xylp-(1→, →3,4)-ß-D-Xylp-(1→, →3)-α-D-Galp-(1→, →3,6)-α-D-Galp-(1→, →6)-4-OAc-α-D-Galp-(1→, →3,4,6)-α-D-Galp-(1→, →4)-α-D-Glcp-(1→, →2,3,6)-ß-D-Glcp-(1→, →4,6)-α-D-Manp-(1→, →3,4)-α-L-Rhap-(1→, →4)-α-D-GalpA-(1→, and →4)-α-D-GlcpA-(1 â†’ residues and terminated with Xyl and Ara. Additionally, ATP50-3 significantly inhibited the release of proinflammatory factors in lipopolysaccharide-stimulated BV2 cells. ATP50-3 may be an active constituent of AT50, responsible for its anti-neuroinflammatory effects, with great potential to treat AD.


Asunto(s)
Acorus , Antiinflamatorios , Polisacáridos , Rizoma , Acorus/química , Animales , Rizoma/química , Ratones , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Antiinflamatorios/farmacología , Antiinflamatorios/química , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Masculino , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Modelos Animales de Enfermedad
20.
World J Gastroenterol ; 30(13): 1911-1925, 2024 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-38659485

RESUMEN

BACKGROUND: Liuweiwuling Tablet (LWWL) is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus (HBV) infection. Previous studies have indicated an anti-HBV effect of LWWL, specifically in terms of antigen inhibition, but the underlying mechanism remains unclear. AIM: To investigate the potential mechanism of action of LWWL against HBV. METHODS: In vitro experiments utilized three HBV-replicating and three non-HBV-replicating cell lines. The in vivo experiment involved a hydrodynamic injection-mediated mouse model with HBV replication. Transcriptomics and metabolomics were used to investigate the underlying mechanisms of action of LWWL. RESULTS: In HepG2.1403F cells, LWWL (0.8 mg/mL) exhibited inhibitory effects on HBV DNA, hepatitis B surface antigen and pregenomic RNA (pgRNA) at rates of 51.36%, 24.74% and 50.74%, respectively. The inhibition rates of LWWL (0.8 mg/mL) on pgRNA/covalently closed circular DNA in HepG2.1403F, HepG2.2.15 and HepG2.A64 cells were 47.78%, 39.51% and 46.74%, respectively. Integration of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis (PI3K-AKT, CASP8-CASP3 and P53 pathways). Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group (CG) among HBV-replicating cell lines, including HepG2.2.15 (2.92% ± 1.01% vs 6.68% ± 2.04%, P < 0.05), HepG2.A64 (4.89% ± 1.28% vs 8.52% ± 0.50%, P < 0.05) and HepG2.1403F (3.76% ± 1.40% vs 7.57% ± 1.35%, P < 0.05) (CG vs LWWL-treated group). However, there were no significant differences in apoptosis rates between the non-HBV-replicating HepG2 cells (5.04% ± 0.74% vs 5.51% ± 1.57%, P > 0.05), L02 cells (5.49% ± 0.80% vs 5.48% ± 1.01%, P > 0.05) and LX2 cells (6.29% ± 1.54% vs 6.29% ± 0.88%, P > 0.05). TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBV-replicating mouse model, while no noticeable difference in apoptosis rates between the two groups was observed in the non-HBV-replicating mouse model. CONCLUSION: Preliminary results suggest that LWWL exerts a potent inhibitory effect on wild-type and drug-resistant HBV, potentially involving selective regulation of apoptosis. These findings offer novel insights into the anti-HBV activities of LWWL and present a novel mechanism for the development of anti-HBV medications.


Asunto(s)
Antivirales , Apoptosis , ADN Viral , Medicamentos Herbarios Chinos , Virus de la Hepatitis B , Comprimidos , Replicación Viral , Apoptosis/efectos de los fármacos , Animales , Humanos , Virus de la Hepatitis B/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Ratones , Células Hep G2 , Antivirales/farmacología , Replicación Viral/efectos de los fármacos , Modelos Animales de Enfermedad , Antígenos de Superficie de la Hepatitis B/metabolismo , Masculino , Hepatitis B/tratamiento farmacológico , Hepatitis B/virología , ARN Viral/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Hígado/virología
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