RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Acute lung injury (ALI) can lead to respiratory failure and even death. KAT2A is a key target to suppress the development of inflammation. A herb, perilla frutescens, is an effective treatment for pulmonary inflammatory diseases with anti-inflammatory effects; however, its mechanism of action remains unclear. AIM OF THE STUDY: The purpose of this study was to investigate the therapeutic effect and underlying mechanism of perilla frutescens leaf extracts (PLE), in the treatment of ALI by focusing on its ability to treat inflammation. MATERIALS AND METHODS: In vivo and in vitro models of ALI induced by LPS. Respiratory function, histopathological changes of lung, and BEAS-2B cells damage were assessed upon PLE. This effect is also tested under conditions of KAT2A over expression and KAT2A silencing. RESULTS: PLE significantly attenuated LPS-induced histopathological changes in the lungs, improved respiratory function, and increased survival rate from LPS stimuation background in mice. PLE remarkably suppressed the phosphorylation of STAT3, AKT, ERK (1/2) and the release of cytokines (IL-6, TNF-α, and IL-1ß) induced by LPS via inhibiting the expression of KAT2A. CONCLUSIONS: PLE has a dose-dependent anti-inflammatory effect by inhibiting KAT2A expression to suppress LPS-induced ALI n mice. Our study expands the clinical indications of the traditional medicine PLE and provide a theoretical basis for clinical use of acute lung injury.

Asunto(s)

Lesión Pulmonar Aguda , Lipopolisacáridos , Perilla frutescens , Extractos Vegetales , Hojas de la Planta , Animales , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/patología , Lesión Pulmonar Aguda/inducido químicamente , Perilla frutescens/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Masculino , Ratones , Humanos , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/uso terapéutico , Citocinas/metabolismo , Línea Celular , Ratones Endogámicos C57BL , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Modelos Animales de Enfermedad

RESUMEN

The use of direct injection ion mobility mass spectrometry (DI-IM-MS) to detect and identify betacyanin pigments in A. hortensis 'rubra' extracts was explored for the first time, with results compared to conventional LC-MS/MS analysis. The anti-inflammatory activities of leaf and seed extracts, alongside purified amaranthin and celosianin pigments, were investigated using a model of lipopolysaccharide (LPS)-activated murine macrophages. Extracts and purified pigments significantly inhibited the production of prostaglandin E2 and NO by up to 90% and 70%, respectively, and reduced the expression of Il6, Il1b, Nos2, and Cox2. Leaf and seed extracts also decreased secretion of Il6 and Il1b cytokines and reduced protein levels of Nos2 and Cox2. Furthermore, extracts and purified pigments demonstrated potent dose-dependent radical scavenging activity in a cellular antioxidant activity assay (CAA) without any cytotoxic effects. Our research highlights the promising biological potential of edible, climate-resilient A. hortensis 'rubra' as a valuable source of bioactive compounds.

Asunto(s)

Lipopolisacáridos , Macrófagos , Estrés Oxidativo , Extractos Vegetales , Ratones , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Células RAW 264.7 , Estrés Oxidativo/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Lipopolisacáridos/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/inmunología , Ciclooxigenasa 2/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Espectrometría de Masas en Tándem

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Notopterygium incisum Ting ex H. T. Chang, also called 'Qianghuo', is a distinct umbelliferae plant in China. The rhizomes and roots of Notopterygium incisum have long been used to treat headaches, colds, analgesia and rheumatoid arthritis. It is a main traditional Chinese medicine in Qianghuo Yufeng Decoction, which was used to treat diseases such as liver and kidney insufficiency, mental paralysis and dementia. AIM OF THIS STUDY: As the most common dementia, Alzheimer's disease (AD) has a complicated pathogenesis. So far, there is no effective drug to prevent its pathological process. Previous research has shown that Notopterygium incisum root extract (NRE) may inhibit the release of Aß and the activation of tau in mice with AD. However, the effect of NRE on the pathological process of neuroinflammation is still unclear. MATERIALS AND METHODS: We determined the pro-inflammatory cytokines levels in BV2 cells exposed to LPS/Aß42 after treated with NRE. APP/PS1 and LPS-induced C57BL/6 neuroinflammatory mice were given NRE for 8 weeks and 5 days respectively to detect the pathological changes of neuroinflammation. RESULTS: The findings showed that NRE had a notable inhibitory effect on the levels of TNF-α and IL-1ß in BV2 cells induced by LPS/Aß42. The results of in vivo experiments show that following NRE treatment, there was a notable decrease in the number of activated microglia in the hippocampus of APP/PS1 mice as indicated by immunofluorescence results. Sholl analysis showed that microglia branches increased in NRE group, indicating that M1 microglia activation was inhibited. In the mice model injected with LPS in the tail vein, PCR and Western Blot results confirmed the anti-inflammatory effect of NRE, Nissl staining showed the protective effect of NRE on neurons, and immunofluorescence results also indicated that the activation of M1 microglia was inhibited. CONCLUSION: These results suggest that long term oral administration of NRE may inhibit neuroinflammation in the progression of AD.

Asunto(s)

Enfermedad de Alzheimer , Apiaceae , Ratones Endogámicos C57BL , FN-kappa B , Extractos Vegetales , Raíces de Plantas , Receptor Toll-Like 4 , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Receptor Toll-Like 4/metabolismo , Raíces de Plantas/química , Apiaceae/química , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Ratones , Transducción de Señal/efectos de los fármacos , Masculino , Lipopolisacáridos/toxicidad , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Microglía/efectos de los fármacos , Microglía/metabolismo , Línea Celular , Ratones Transgénicos , Péptidos beta-Amiloides/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Citocinas/metabolismo , Modelos Animales de Enfermedad , Hipocampo/efectos de los fármacos , Hipocampo/patología , Hipocampo/metabolismo

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a multifactorial, polygenic inflammatory disease. Mesua assamica (King & Prain) Kosterm. (MA) is an endangered medicinal plant indigenous to South Asia, primarily to Assam in India. The tree bark is claimed to possess anti-inflammatory, anti-diabetic, anti-cancer, and anti-malarial properties; nevertheless, its role in RA has not been elucidated. Hence, this study aims to investigate the in-vitro and in-vivo anti-arthritic effects of Mesua assamica bark ethanolic extract (MAE). AIM OF THE STUDY: This study aims to investigate the anti-rheumatic potential of MAE in-vitro on RAW 264.7 cells for its anti-oxidant and anti-inflammatory activities and in-vivo on the CFA-induced adjuvant arthritis in the rat model. MATERIALS AND METHODS: We investigated the possible therapeutic effects of MAE in-vitro using RAW 264.7 cells triggered by LPS. Meanwhile, adult Wistar rats were injected intradermally with 100 µl of CFA to induce arthritis, and they were given MAE orally at doses of 100 and 200 mg/kg for up to 28 days. Paw volume analysis, X-ray radiography, anti-oxidant levels analysis, gene and protein expression studies, and histological analysis were carried out to assess the effects of MAE in-vivo. RESULTS: MAE significantly mitigated the inflammation by reducing ROS levels and dropped the nitrite, PGE2, and COX-2 levels enhanced by LPS in-vitro. At the same time, MAE treatment reduced the paw and joint inflammation and increased the immune organ index in the CFA rats. Histopathology data revealed that MAE mitigated the CFA-induced lesions of the ankle joints and synovial tissues. Similarly, MAE significantly abated the secretion of pro-inflammatory cytokines, inhibited the protein expression of TLR4, NF-кB, COX-2, and iNOS, as well as improved the Nrf2 and HO-1 levels in-vitro and in-vivo. CONCLUSION: All the results highlighted the anti-rheumatic potential of MAE in RA in-vitro and in-vivo by inhibiting the TLR4/NF-кB/COX-2/iNOS and promoting the Nrf2/HO-1 signaling axis.

Asunto(s)

Artritis Experimental , Artritis Reumatoide , Ciclooxigenasa 2 , Etanol , Factor 2 Relacionado con NF-E2 , FN-kappa B , Corteza de la Planta , Extractos Vegetales , Receptor Toll-Like 4 , Animales , Extractos Vegetales/farmacología , Células RAW 264.7 , Ratones , Corteza de la Planta/química , Receptor Toll-Like 4/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Artritis Reumatoide/tratamiento farmacológico , FN-kappa B/metabolismo , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología , Etanol/química , Ciclooxigenasa 2/metabolismo , Masculino , Ratas , Ratas Wistar , Regulación hacia Abajo/efectos de los fármacos , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Antioxidantes/farmacología , Transducción de Señal/efectos de los fármacos , Hemo Oxigenasa (Desciclizante)/metabolismo , Antirreumáticos/farmacología , Antirreumáticos/aislamiento & purificación , Hemo-Oxigenasa 1/metabolismo , Proteínas de la Membrana

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia divinorum (Epling and Játiva) is a psychoactive plant traditionally used by the Latinos for various medicinal purposes. Salvinorin A (Sal A), the main bioactive constituent of S. divinorum, is a natural highly selective kappa opioid receptor (KOR) agonist. Considering the anti-inflammatory effect of S. divinorum and endogenous hippocampal dynorphin/kappa opioid receptor (KOR) system playing an anticonvulsant function, we hypothesis that Sal A can be a potential candidate to treat epilepsy. Here, we identified whether Sal A ameliorated epileptic seizures and neuronal damages in animal model and in vitro model and investigated its underlying mechanisms. MATERIALS AND METHODS: Mice epilepsy model was induced by pilocarpine following seizures assessed by Racine classification. Hippocampus tissues were obtained for genetic, protein, and histological investigation. Furthermore, lipopolysaccharide (LPS)-activated BV2 microglial cells were utilized to validate the anti-inflammatory and microglia polarization regulation effects of Sal A. RESULTS: Sal A treatment significantly prolonged the latency to status epileptics (SE) and shortened the duration of SE in the pilocarpine-induced model. It also alleviated neuronal damages via activation of the AMPK/JNK/p-38 MAPK pathway and inhibition of apoptosis-related protein in hippocampus tissues. Furthermore, Sal A dose-dependently reduced microglia-mediated expression of pro-inflammatory cytokines and increased anti-inflammatory factors levels in SE mice and LPS-activated BV2 microglial cells by regulating microglia polarization. In addition, the effect of Sal A in vitro was totally blocked by KOR antagonist nor-BNI. CONCLUSION: Sal A treatment protects against epileptic seizures and neuronal damages in pilocarpine-induced models by suppressing the inflammation response through regulating microglial M1/M2 polarization. This study might serve as a theoretical basis for clinical applications of Sal A and its analogs and provide a new insight into the development of anti-seizure drugs.

Asunto(s)

Diterpenos de Tipo Clerodano , Hipocampo , Microglía , Pilocarpina , Convulsiones , Animales , Microglía/efectos de los fármacos , Microglía/metabolismo , Pilocarpina/toxicidad , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Diterpenos de Tipo Clerodano/farmacología , Diterpenos de Tipo Clerodano/uso terapéutico , Masculino , Ratones , Convulsiones/tratamiento farmacológico , Convulsiones/inducido químicamente , Anticonvulsivantes/farmacología , Línea Celular , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antiinflamatorios/aislamiento & purificación

RESUMEN

This study was conducted to evaluate the potential anti-inflammatory and immune-enhancement properties of lipids derived from Aptocyclus ventricosus eggs on RAW264.7 cells. Firstly, we determined the fatty acid compositions of A. ventricosus lipids by performing gas chromatography analysis. The results showed that A. ventricosus lipids contained saturated fatty acids (24.37%), monounsaturated fatty acids (20.90%), and polyunsaturated fatty acids (54.73%). They also contained notably high levels of DHA (25.91%) and EPA (22.05%) among the total fatty acids. Our results for the immune-associated biomarkers showed that A. ventricosus lipids had immune-enhancing effects on RAW264.7 cells. At the maximum dose of 300 µg/mL, A. ventricosus lipids generated NO (119.53%) and showed greater phagocytosis (63.69%) ability as compared with untreated cells. A. ventricosus lipids also upregulated the expression of iNOS, IL-1ß, IL-6, and TNF-α genes and effectively upregulated the phosphorylation of MAPK (JNK, p38, and ERK) and NF-κB p65, indicating that these lipids could activate the MAPK and NF-κB pathways to stimulate macrophages in the immune system. Besides their immune-enhancing abilities, A. ventricosus lipids significantly inhibited LPS-induced RAW264.7 inflammatory responses via the NF-κB and MAPK pathways. The results indicated that these lipids significantly reduced LPS-induced NO production, showing a decrease from 86.95% to 38.89%. Additionally, these lipids downregulated the expression of genes associated with the immune response and strongly suppressed the CD86 molecule on the cell surface, which reduced from 39.25% to 33.80%. Collectively, these findings imply that lipids extracted from A. ventricosus eggs might have biological immunoregulatory effects. Thus, they might be considered promising immunomodulatory drugs and functional foods.

Asunto(s)

FN-kappa B , Transducción de Señal , Animales , Ratones , Células RAW 264.7 , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Lípidos , Macrófagos/efectos de los fármacos , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Huevos , Fagocitosis/efectos de los fármacos , Ácidos Grasos/farmacología , Óxido Nítrico/metabolismo , Citocinas/metabolismo

RESUMEN

Twenty-nine sesquiterpenoids, including pseudoguaiane-type (1-11), eudesmane-type (12-23), and carabrane-type (24-29), have been identified from the plant Carpesium abrotanoides. Of them, compounds 1-4, 12-15, and 24-27, namely carpabrotins A-L, are twelve previously undescribed ones. Compound 3 possessed a pseudoguaiane backbone with a rearrangement modification at C-11, C-12 and C-13, while compound 4 suffered a carbon bond break between the C-4 and C-5 to form a rare 4,5-seco-pseudoguaiane lactone. Compounds 1-3, 5, 13-16 and 25-27 exhibited anti-inflammatory activity by inhibiting NO production in LPS-induced RAW264.7 macrophages with IC50 values less than 40 µM, while compounds 1, 2, 5, 13, 14, 16, and 25-27 showed significant inhibitory activity comparable to that of dexamethasone. The anti-atopic dermatitis (AD) effects of compounds 5 and 16 were tested according to 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in KM mice, and the results revealed that the major products 5 and 16 improved the histological features of AD-like skin lesions and mast cell infiltration in mice. This study suggested that sesquiterpenoids in C. abrotanoides should play a key role in its anti-inflammatory use.

Asunto(s)

Asteraceae , Óxido Nítrico , Sesquiterpenos , Animales , Ratones , Sesquiterpenos/farmacología , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Asteraceae/química , Células RAW 264.7 , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Óxido Nítrico/metabolismo , Estructura Molecular , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Macrófagos/efectos de los fármacos , Masculino

RESUMEN

A bioassay-guided isolation from Atractylodes lancea (Thunb.) DC. obtained 22 compounds, including eight previously undescribed sesquiterpenoids and polyacetylenes (1, 3 and 12-17), as well as fourteen known analogues, and their structures were confirmed by extensive spectroscopic methods. This study evaluated their antibacterial activity against methicillin resistant Staphylococcus aureus (MRSA) for the first time, as well as anti-inflammatory activity. Most of them, including new compounds, showed varying degrees of antibacterial activity against S. aureus and MRSA. Notably, compound 21 exhibited significant antibacterial activity against four different bacteria (MIC 6.25-20.00 µg/mL). This suggested that 21 may have the potential to be developed into a broad-spectrum antibacterial agent. Moreover, except for 9 and 11, most compounds exhibited great anti-inflammatory activity (IC50 1.92-37.91 µM), and iNOS might be a potential target of these compounds according to the molecular docking analysis.

Asunto(s)

Antibacterianos , Antiinflamatorios , Atractylodes , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Atractylodes/química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Estructura Molecular , Simulación del Acoplamiento Molecular , Animales , Relación Estructura-Actividad , Ratones , Relación Dosis-Respuesta a Droga , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/metabolismo , Bioensayo , Células RAW 264.7 , Staphylococcus aureus/efectos de los fármacos

RESUMEN

As one of a traditional Chinese medicine with dual applications in both medicinal treatment and dietary consumption, the mature seeds of D. lablab were reported to be rich in saponins and have a good effect on inflammatory related diseases. However, the substance basis for its anti-inflammatory activity remains unclear. Thus, a comprehensive phytochemical investigation on triterpenoid saponins from D. lablab seeds was carried out, resulting in the isolation and identification of twenty-one new triterpenoid saponins including dolilabsaponins A1-A4, B, C, D1-D3, E-M, N1, N2 and O (1-21) along with thirteen known analogs (22-34). Notably, the known saponins, 31, 32, and 34 were obtained from Leguminosae family for the first time. The 1H and 13C NMR data of saponins 24 and 28 were firstly reported here. Additionally, lipopolysaccharide (LPS)-stimulated RAW264.7 cells model was utilized to assess inhibitory activities of compounds 1-34 on nitric oxide (NO) production. The results revealed that compounds 1-3, 9, 10, 13-15, 18, 22, 23 and 28-34 significantly suppressed the elevation of NO levels in LPS-induced RAW264.7 cells at the concentration of 30 µM, exhibiting a concentration-dependent manner at 3, 10, and 30 µM. The results suggested that compounds 1-3, 9, 10, 13-15, 18, 22, 23, and 28-34 possessed potential anti-inflammatory activity. Further western blot assay demonstrated that 1, 9, 10, 13, 14, and 18 suppressed inflammatory response via down-regulated the expression levels of inflammatory factors, tumor necrosis factor-alpha and interleukin-6.

Asunto(s)

Dolichos , Lipopolisacáridos , Óxido Nítrico , Saponinas , Semillas , Saponinas/farmacología , Saponinas/química , Saponinas/aislamiento & purificación , Ratones , Células RAW 264.7 , Animales , Semillas/química , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Estructura Molecular , Dolichos/química , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación

RESUMEN

Eighteen new oleanane-type triterpenoids were isolated from the stems of Sabia limoniacea, including sabialimon A (1), a triterpenoid with an unprecedented 6/6/6/7/7 pentacyclic skeleton and seventeen undescribed triterpenoids, sabialimons B-R (2 - 18), along with six previously described analogs (19 - 24). Their structures were fully elucidated via extensive spectroscopic analysis including 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), experimental electronic circular dichroism measurements and X-ray crystallographic studies. Compound 1 is the first triterpenoid that possesses a rare ring system (6/6/6/7/7) with an oxygen-bearing bridge between C-17 and C-18 and a hemiketal form at C-17, which is generated a larger ring by the degradation of C-28 and D/E-ring expansion. Biological evaluation revealed that sabialimon I (9), sabialimon K (11), sabialimon P (16) and 11,13(18)-oleanadien-28-hydroxymethyl 3-one (20) exhibited significantly inhibitory activities against nitric oxide (NO) release with IC50 values of 29.65, 23.41, 18.12 and 26.64 µM, respectively, as compared with the positive control (dexamethasone, IC50 value: 40.35 µM). Furthermore, sabialimon P markedly decreased the secretion of TNF-α, iNOS, IL-6 and NF-κB and inhibited the expression of COX-2 and NF-κB/p65 in LPS-induced RAW264.7 cells in a dose-dependent manner.

Asunto(s)

Ácido Oleanólico , Ratones , Animales , Células RAW 264.7 , Ácido Oleanólico/farmacología , Ácido Oleanólico/química , Ácido Oleanólico/aislamiento & purificación , Ácido Oleanólico/análogos & derivados , Estructura Molecular , Relación Estructura-Actividad , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Óxido Nítrico/metabolismo , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ciclooxigenasa 2/metabolismo

RESUMEN

Two novel sulfated polysaccharides (SPs), N10 and K5 were isolated from ammonium sulfate or potassium sulfate at concentrations of 10 mM and 5 mM in liquid cultures of Antrodia cinnamomea, respectively. N10 and K5 were galactoglucans with a galactose:glucose molar ratio of approximately 1:3. In lipopolysaccharide (LPS)-stimulated RAW264.7 cells, N10 and K5 exhibited strong anti-inflammatory potential, of 56 % and 23 % maximal inhibition of IL-6 and TNF-α production, respectively. Mechanical analysis revealed differences between N10 and K5, with N10 inhibiting the LPS-stimulated phosphorylation of ERK and p38 in RAW264.7 cells. K5 inhibited the LPS-stimulated phosphorylation of AKT and TGFßR-II. N10 and K5 were fragmented into F1, F2, and F3, the molecular weights of which were 455, 24, 0.9, and 327, 36, 1.9 kDa, respectively. K5 F2 and K5 F3 exhibited high degrees of sulfation of 1:3 and 1:8, resulting in strong anti-inflammation, of 83 % and 37 % highest inhibition of IL-6 and TNF-α production, respectively. Therefore, low-molecular-weight and high-sulfation-degree SPs exhibited strong anti-inflammatory activity. Specifically, K5 F2 inhibited the phosphorylation of p38, and K5 F3 suppressed the signaling pathway of p38/JNK. Overall, the sulfation degree of SPs is concluded to affect the anti-inflammatory responses.

Asunto(s)

Antiinflamatorios , Peso Molecular , Polisacáridos , Sulfatos , Ratones , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Células RAW 264.7 , Sulfatos/química , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Lipopolisacáridos/farmacología , Interleucina-6/metabolismo , Polyporales/química , Factor de Necrosis Tumoral alfa/metabolismo , Fosforilación/efectos de los fármacos , Antrodia/química

RESUMEN

Artemisia annua L., known for antimalarial activity, has demonstrated evidence of anti-inflammatory potential. Previously our research group reported the anti-inflammatory and antinociceptive effect of a sesquiterpene lactone-enriched fraction (Lac-FR) obtained from plant, containing artemisinin and deoxyartemisinin. Both the isolated compounds and Lac-FR evaluated on experimental animal models, in the formalin test showed that deoxyartemisinin reduced both neurogenic pain (56.55 %) and inflammatory pain (45.43 %). These findings were superior to the effect of artemisinin (reduction of 28.66 % and 33.35 %, respectively). In the tail flick test, the antinociceptive effect reported as a percentage of the maximum possible effect (%MPE), deoxyartemisinin showed a lower antinociceptive effect (41.57 %) compared to morphine (75.94 %) in 0.5 h. After 1.5 h, the MPE of deoxyartemisinin (87.99 %) exceeded the effect of morphine (47.55 %), without reversal with naloxone. The MPE of artemisinin (23.3 %) observed after 2 h was lower than deoxiartemisinin, without reversal with the opioid antagonist. Lac-FR and artemisinin demonstrated reductions in ear edema of 43.37 % and 48.19 %, respectively, higher than the effect of deoxyartemisinin (33.64 %). Artemisinin reduced tumor necrosis factor alpha (TNF-α) (76.96 %) more selectively when compared to interleukin-1beta (IL-1ß) (48.23 %) and interleukin-6 (IL-6) (44.49 %). Lac-FR showed greater selectivity in IL-6 reduction (56.49 %) in relationship to TNF-α (46.71 %) and IL-1ß (45.12 %), whereas deoxyartemisinin selectively reduced TNF-α (37.37 %). The results of our study indicate that the lactones isolated did not have relationship with the opioid system. Deoxyartemisinin showed a higher antinociceptive potential than artemisinin. Whereas, artemisinin showed a higher reduction of inflammation and mediators, with a better anti-inflammatory activity outcome.

Asunto(s)

Analgésicos , Antiinflamatorios , Artemisia annua , Artemisininas , Modelos Animales de Enfermedad , Artemisininas/farmacología , Artemisininas/aislamiento & purificación , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Artemisia annua/química , Masculino , Analgésicos/farmacología , Analgésicos/aislamiento & purificación , Ratones , Extractos Vegetales/farmacología , Extractos Vegetales/aislamiento & purificación , Inflamación/tratamiento farmacológico , Inflamación/patología , Dolor/tratamiento farmacológico

RESUMEN

Sixteen undescribed pyrrololactam alkaloids, including five 2-bromopyrrole-ε-lactam (1a, 1b, 4a, 4b and 5), two 3-bromopyrrole-ε-lactam (9 and 10), eight pyrrole-ε-lactam (2a-3 and 6a-8), and one pyrrole-δ-lactam alkaloids (11), along with three previously reported compounds (12-14) were isolated from the marine sponge Phakellia fusca collected in the South China Sea. The planar structures were determined by NMR and MS analyses, while the absolute configurations were clearly elucidated by comparing the experimental and calculated ECD spectra. Compounds 2a, 2b, 4a-7b, 10, 12 and 13 exhibited anti-inflammatory activity in inhibiting the production of inflammatory cytokines IL-6 in LPS-induced RAW264.7 macrophages.

Asunto(s)

Alcaloides , Interleucina-6 , Lactamas , Poríferos , Pirroles , Animales , Ratones , Alcaloides/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Poríferos/química , Interleucina-6/antagonistas & inhibidores , Interleucina-6/metabolismo , Células RAW 264.7 , Lactamas/química , Lactamas/farmacología , Lactamas/aislamiento & purificación , Pirroles/farmacología , Pirroles/química , Pirroles/aislamiento & purificación , China , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Estructura Molecular , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Relación Estructura-Actividad , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Relación Dosis-Respuesta a Droga

RESUMEN

Dictyophora species is an edible and medicinal fungus belonging to the Basidiomycotina, Gasteromycetes, Phallales, family Phallaceae, and genus Dictyophora, which is popular with consumers in China and across various Asian regions. Polysaccharides from Dictyophora species (DPs) are important bioactive macromolecules with multiple health benefits, according to published studies, including anti-tumor, antioxidative, anti-obesity, anti-hyperlipidemic, hepatoprotective, immunomodulatory, anti-inflammatory, regulation of gut microbiota, antibacterial, renoprotective, and other pharmacological effects. Based on their rich pharmacological activities, the preparation techniques, structural characteristics and pharmacological activities of DPs have been extensively studied. However, to the best of our knowledge, there is no dedicated review to shed light on recent advances in DPs. Therefore, in order to fill this gap, this review provides a comprehensive overview of the research on DPs, including the latest advances in extraction, isolation and purification, structural characteristics, pharmacological properties, safety assessment and potential utilizations, which will provide a theoretical basis for the research and development of subsequent DPs-related products.

Asunto(s)

Polisacáridos Fúngicos , Humanos , Polisacáridos Fúngicos/química , Polisacáridos Fúngicos/farmacología , Polisacáridos Fúngicos/aislamiento & purificación , Basidiomycota/química , Animales , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación

RESUMEN

Cistanche deserticola Y. C. Ma (CD), is mainly distributed in the regions of China (Xinjiang, Inner Mongolia, Gansu), Mongolia, Iran and India. Cistanche deserticola polysaccharide (CDPs), as one of the main components and a crucial bioactive substance of CD, has a variety of pharmacological activities, including immunomodulatory, anti-aging, anti-oxidant, hepatoprotective, anti-osteoporotic, anti-inflammatory, intestinal flora regulatory effects. Many polysaccharides have been successfully obtained in the last three decades from CD. However, there is currently no comprehensive review available concerning CDPs. Considering the importance of CDPs for biological study and drug discovery, the present review aims to systematically summarize the recent major studies on extraction and purification methods of polysaccharides from CD, as well as the characterization of their chemical structure, biological activity, structure-activity relationship, and the application of CDPs in pharmaceutical field. Meanwhile, the shortcomings of CDPs research are further discussed in detail, and new valuable insights for future CDPs research as therapeutic agents and functional foods are proposed.

Asunto(s)

Cistanche , Polisacáridos , Polisacáridos/química , Polisacáridos/farmacología , Polisacáridos/aislamiento & purificación , Cistanche/química , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/aislamiento & purificación , Humanos , Relación Estructura-Actividad , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación

RESUMEN

Phytochemical investigation of the 70% ethanol extract of Isodon henryi Kudô afforded fifteen ent-kaurane diterpenoids, including nine previously undescribed compounds, named isohenolides C-K (1-9). Compounds 1-6 featured an unusual 6,7;8,15-diseco-7,20-olide ent-kaurane diterpenoid scaffold, in which 1 also possessed an 11,15-lactone ring while 2-6 all contained a free α-methylene-γ-carboxylic acid. Compound 6 was also a rare 6,8-cyclo-7,20-olide ent-kauranoid. Their structures were elucidated primarily by HRESIMS, 1D and 2D NMR spectroscopy, electronic circular dichroism and X-ray diffraction (Cu Kα) methods. Additionally, most compounds were also screened for anti-inflammatory actions against lipopolysaccharide-induced RAW 264.7 cells, and compounds 9 and 13 exhibited stronger nitric oxide inhibition, with IC50 values of 15.99 ± 0.75 and 18.19 ± 0.42 µM, respectively.

Asunto(s)

Antiinflamatorios , Diterpenos de Tipo Kaurano , Isodon , Lipopolisacáridos , Óxido Nítrico , Diterpenos de Tipo Kaurano/farmacología , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/aislamiento & purificación , Ratones , Animales , Células RAW 264.7 , Isodon/química , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Estructura Molecular , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Conformación Molecular , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación

RESUMEN

Fig fruit is widely accepted in warm and tropical regions due to the sweet taste and health benefits. The polysaccharides in fig fruit are responsible for the health benefits. However, information regarding polysaccharide structure remains limited. In this study, the water-soluble polysaccharides (FFP) were extracted from fig fruit with a yield of 15.3 mg/g. Anion exchange chromatography and gel permeation chromatography were used for purification. A leading polysaccharide was purified and characterized as below. The monosaccharide composition of FFP included arabinose (Ara), galactose (Gal), galacturonic acid (GalA) and rhamnose (Rha). The glycosidic linkages were revealed to be L-Ara-(1→, →5)-L-Ara-(1→, →2,4)-L-Rha-(1→, →2)-L-Rha-(1→, →4)-D-Gal-(1→ and D-Gal-(1 â†’ . Nuclear magnetic resonnance (NMR) spectra revealed that FFP had →4)-α-D-GalpA-(1 â†’ 2)-α-L-Rhap-(1→ as backbone. The side chains included Galp-ß-D-(1 â†’ 4)-Galp-ß-D-(1 â†’ 4)-Galp-ß-D-(1 â†’ 4)-Galp-ß-D-(1→ and α-L-Araf-(1 â†’ 5)-α-L-Araf-(1 â†’ . They were linked to C-4 of Rhap. FFP inhibited the production of NO, IL-6 and IL-1ß levels induced by LPS. IL-6 and IL-1ß levels were returned to normal. These information are helpful to understand this functional fruit.

Asunto(s)

Antiinflamatorios , Ficus , Frutas , Pectinas , Pectinas/química , Pectinas/farmacología , Pectinas/aislamiento & purificación , Ficus/química , Frutas/química , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Ratones , Animales , Células RAW 264.7 , Conformación de Carbohidratos

RESUMEN

CONTEXT: Derris reticulata Craib. and Glycyrrhiza glabra L., of the Fabaceae, have been used as active components in Thai herbal formulas for the treatment of fever and skin diseases. OBJECTIVE: To evaluate the physicochemical and pharmacological properties of the developed herbal gel formulation containing the combined extract from D. reticulata stem wood and G. glabra root (RGF). MATERIALS AND METHODS: The potential of the herbal gel formulation containing RGF (8% w/w) as the active ingredient was studied by evaluating the anti-inflammatory, antioxidant, and anti-Staphylococcus aureus activities using quantitative reverse transcription-polymerase chain reaction assay, spectrophotometric method, and broth microdilution technique, respectively. The reference standards for the biological testing included Nω-nitro-L-arginine (L-NA), ascorbic acid, catechin, and penicillin G. The stability study of the RGF herbal gel was performed by a heating-cooling test (at 45 °C for 24 h and at 4 °C for 24 h/1 cycle; for 6 cycles), and the bioactive marker compounds in the herbal gel were investigated by the HPLC technique. RESULTS: RGF showed promising pharmacological effects, particularly on its anti-inflammatory property (IC50 73.86 µg/mL), compared to L-NA (IC50 47.10 µg/mL). The RGF-containing gel demonstrated anti-inflammatory (IC50 3.59 mg/mL) and free radical scavenging effects (IC50 0.05-4.39 mg/mL), whereas it had no anti-S. aureus activity (MIC > 10 mg/mL). The active ingredient in the developed herbal gel significantly inhibited lipopolysaccharide-induced nitric oxide production by downregulating iNOS mRNA levels. The contents of the bioactive markers in the RGF gel (lupinifolin and glabridin) did not change significantly after stability testing. DISCUSSION AND CONCLUSIONS: The RGF-containing gel has potential to be further developed as an herbal product for the treatment of skin inflammation.

Asunto(s)

Antiinflamatorios , Antioxidantes , Derris , Geles , Glycyrrhiza , Extractos Vegetales , Staphylococcus aureus , Glycyrrhiza/química , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/administración & dosificación , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Staphylococcus aureus/efectos de los fármacos , Animales , Derris/química , Antioxidantes/farmacología , Antioxidantes/administración & dosificación , Antioxidantes/aislamiento & purificación , Ratones , Raíces de Plantas/química , Antibacterianos/farmacología , Antibacterianos/aislamiento & purificación , Antibacterianos/administración & dosificación , Células RAW 264.7 , Estabilidad de Medicamentos

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Peucedanum praeruptorum Dunn (PPD) was used to treat gastrointestinal disease in China before the Tang Dynasty, and it was considered a "Top-grade" herb in Shennong Bencaojing, known for its ability to relieve the stomach Qi and indigestion. AIM OF THE STUDY: Alcohol consumption can induce severe gastric mucosal injury that lacks effective and safe interventions. We aimed to investigate the gastroprotective effects of Peucedanum praeruptorum Dunn leaf (PPL) after bolting in alcohol-induced gastric damage in mice. MATERIALS AND METHODS: Mice were orally administered PPL aqueous extract at doses of 2.5, 5, and 10 g/kg for 5 consecutive days prior to the induction of gastric damage model with ethanol. Gastric tissue was stained by hematoxylin and eosin (H&E), and the levels of pro-inflammatory cytokines and oxidative stress indicators were determined using ELISA and RT-qPCR. RNA-seq was used to detect differentially expressed genes (DEGs) in the gastric tissue, while Western blotting was employed to measure the expressions of IL-17, TNF-a, and AKT pathways. RESULTS: Treatment with PPL alleviated alcohol-induced gastric damage in mice, whereas dried root (PPD) and stem (PPS) of Peucedanum praeruptorum Dunn had no gastroprotective function. The content of peucedanocoumarin I was higher in the dried PPL compared to PPD and PPS, with an increase in peucedanocoumarin I content in PPL after boiling. Additionally, PPL administration (5, 10 g/kg) decreased pro-inflammatory factors, such as interleukin-6 (IL-6), IL-8, IL-4, IL-1ß, IL-18, and tumor necrosis factor (TNF-a) in alcohol-induced gastric injury mice (p < 0.05), and improved oxidative stress markers, including superoxide dismutase enzymes (SOD), catalase (CAT), and malondialdehyde (MDA) (p < 0.05). RNA-seq data revealed that PPL treatment inhibited alcohol-induced inflammation-related signals, including IL-17 and TNF pathways, and restored alcohol-inhibited gastric digestive and metabolic functions, such as xenobiotics metabolism of cytochrome P450, and protein digestion and absorption pathways. Notably, treatment with PPL downregulated the expressions of IL-17 A, TNF-a, monocyte chemoattractant protein-1 (MCP-1), and AKT-phosphorylation induced by ethanol exposure (p < 0.05). Thus, the aqueous extract of PPL provided protection against alcohol-induced gastric injury by mitigating inflammation and oxidative stress in mice, suggesting a potential novel therapeutic approach for alcohol-induced gastric damage.

Asunto(s)

Apiaceae , Etanol , Estrés Oxidativo , Extractos Vegetales , Hojas de la Planta , Animales , Estrés Oxidativo/efectos de los fármacos , Hojas de la Planta/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Ratones , Etanol/química , Masculino , Apiaceae/química , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Mucosa Gástrica/metabolismo , Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/prevención & control

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Hymenaea eriogyne Benth (Fabaceae) is popularly known as "Jatobá". Despite its use in folk medicine to treat inflammatory disorders, there are no descriptions that show its anti-inflammatory potential. AIM OF THE STUDY: In this sense, this study aimed to evaluate the anti-inflammatory and antivenom action of bark and leaves extract of H. eriogyne. MATERIALS AND METHODS: The in vivo anti-inflammatory activity was conducted by carrageenan-induced paw edema and zymosan-induced air pouch models, evaluating the edematogenic effect, leukocyte migration, protein concentration, levels of pro-inflammatory cytokines, malondialdehyde (MDA) and myeloperoxidase (MPO) activity. The antivenom potential was investigated in vitro on the enzymatic action (proteolytic, phospholipase and hyaluronidase) of Bothrops brazili and B. leucurus venom, as well as in vivo on the paw edema model induced by B. leucurus. Furthermore, the influence of its markers (astilbin and rutin) on MPO activity was investigated in silico. For molecular docking, AutodockVina, Biovia Discovery Studio, and Chimera 1.16 software were used. RESULTS: The extracts and bark and leaves of H. eriogyne revealed a high anti-inflammatory effect, with a reduction in all inflammatory parameters evaluated. The bark extract showed superior results when compared to the leaf extract, suggesting the influence of the astilbin concentration, higher in the bark, on the anti-inflammatory action. In addition, only the H. eriogyne bark extract was able to reduce MDA, indicating an associated antioxidant effect. Regarding the in vitro antivenom action, the extracts (bark and leaves) revealed the ability to inhibit the proteolytic, phospholipase and hyaluronidase action of both bothropic venom, with a greater effect against B. leucurus venom. In vivo, extracts from the bark and leaves of H. eriogyne (50-200 mg/kg) showed antiedematogenic activity, reducing the release of MPO and pro-inflammatory cytokines, indicating the presence of bioactive components useful in controlling the inflammatory process induced by the venom. In the in silico assays, astilbin and rutin showed reversible interactions of 9 possible positions and orientations towards MPO, with affinities of -9.5 and -10.4 kcal/mol and interactions with Phe407, Gln91, His95 and Arg239, important active pockets of MPO. Rutin demonstrated more effective types of interactions with MPO. CONCLUSION: This approach reveals for the first time the anti-inflammatory action of H. eriogyne bark and leaf extracts in vivo, as well as its antiophidic potential. Moreover, the distinct effect of pharmacogens as antioxidant agents and distinct effect of astilbin and rutin under MPO sheds light on the different anti-inflammatory mechanisms of bioactive compounds present in H. eriogyne extracts, with high potential for the prospection of new pharmacological agents.

Asunto(s)

Antiinflamatorios , Carragenina , Edema , Simulación del Acoplamiento Molecular , Corteza de la Planta , Extractos Vegetales , Hojas de la Planta , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/química , Edema/tratamiento farmacológico , Edema/inducido químicamente , Hojas de la Planta/química , Corteza de la Planta/química , Masculino , Relación Estructura-Actividad , Peroxidasa/metabolismo , Fabaceae/química , Antivenenos/farmacología , Antivenenos/química , Ratas Wistar , Venenos de Crotálidos/toxicidad , Ratones , Bothrops , Citocinas/metabolismo , Zimosan , Biomarcadores/metabolismo , Rutina/farmacología