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1.
J Nat Med ; 78(2): 427-438, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38334900

RESUMEN

Angelica dahurica (A. dahurica) has a wide range of pharmacological effects, including analgesic, anti-inflammatory and hepatoprotective effects. In this study, we investigated the effect of A. dahurica extract (AD) and its effective component bergapten (BG) on hepatic fibrosis and potential mechanisms. Hepatic fibrosis was induced by intraperitoneal injection with carbon tetrachloride (CCl4) for 1 week, and mice were administrated with AD or BG by gavage for 1 week before CCl4 injection. Hepatic stellate cells (HSCs) were stimulated by transforming growth factor-ß (TGF-ß) and cultured with AD, BG, GW4064 (FXR agonist) or Guggulsterone (FXR inhibitor). In CCl4-induced mice, AD significantly decreased serum aminotransferase, reduced excess accumulation of extracellular matrix (ECM), inhibited caspase-1 and IL-1ß, and increased FXR expressions. In activated HSCs, AD suppressed the expressions of α-SMA, collagen I, and TIMP-1/MMP-13 ratio and inflammatory factors, functioning as FXR agonist. In CCl4-induced mice, BG significantly improved serum transaminase and histopathological changes, reduced ECM excessive deposition, inflammatory response, and activated FXR expression. BG increased FXR expression and inhibited α-SMA and IL-1ß expressions in activated HSCs, functioning as GW4064. FXR deficiency significantly attenuated the decreasing effect of BG on α-SMA and IL-1ß expressions in LX-2 cells. In conclusion, AD could regulate hepatic fibrosis by regulating ECM excessive deposition and inflammation. Activating FXR signaling by BG might be the potential mechanism of AD against hepatic fibrosis.


Asunto(s)
Cirrosis Hepática , Transducción de Señal , Ratones , Animales , 5-Metoxipsoraleno/efectos adversos , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Células Estrelladas Hepáticas , Factor de Crecimiento Transformador beta/farmacología , Hígado
2.
J Biochem Mol Toxicol ; 36(9): e23143, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35815753

RESUMEN

Bergapten (BeG) is explored for its anti-inflammatory and antioxidant properties. Myocardial infarction (MI) is reported to be one of the leading cardiovascular diseases characterized by mitochondrial dysfunction and apoptosis. The main purpose of this study is to assess the cardiopreventive effects of BeG (50 mg/kg) in isoproterenol (ISO)-induced MI in Wistar rats. The increased infarct size after ISO induction was reduced simultaneously on treatment with BeG. Similarly, augmented levels of cardiac biomarkers, namely cardiac troponin T, creatine kinase (CK), cardiac troponin I, and CK-MB were also suppressed by BeG. The increased rate of lipid hydroperoxides and thiobarbituric acid reactive substances owing to the oxidative stress caused by free radical generation in ISO-induced rats were also inhibited by BeG. Antioxidants reduce oxidative stress by scavenging free radicals. ISO induction reduces these antioxidant enzymes glutathione peroxidase, catalase, superoxide dismutase, and glutathione, and levels causing oxidative cardiac damage to the heart tissue. BeG supplementation improved these enzymes synthesis preventing potential damage to the myocardium. Inflammation caused by ISO pretreatment increased the secretion of proinflammatory cytokines in ISO-induced rats. Pretreatment with BeG suppressed these inflammatory cytokines to a normal level in ISO + BeG-treated rats. The histopathological examination of the morphological characteristics showed that the intensity of cardiac damage caused by ISO induction was less in BeG pretreated rats with less inflammatory cells and no necrosis. BeG also showed promising results in the molecular alteration of AMP-activated protein kinase/endothelial nitric oxide synthase/protein kinase B signaling molecules. These observations emphasize the cardioprotective effects of BeG and its potential use as a drug in the near future.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Infarto del Miocardio , 5-Metoxipsoraleno/efectos adversos , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Apoptosis , Biomarcadores/metabolismo , Catalasa/metabolismo , Forma MB de la Creatina-Quinasa , Citocinas/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Isoproterenol/toxicidad , Peróxidos Lipídicos/metabolismo , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/patología , Miocardio/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Wistar , Transducción de Señal , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Troponina I/efectos adversos , Troponina I/metabolismo , Troponina T/metabolismo , Troponina T/farmacología
3.
Int J Toxicol ; 40(3_suppl): 5S-38S, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34410830

RESUMEN

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 80 Citrus fruit-derived ingredients, which are most frequently reported to function in cosmetics as fragrances and/or skin-conditioning agents. The Panel reviewed the available data to determine the safety of these ingredients. Because final product formulations may contain multiple botanicals, each containing similar constituents of concern, formulators are advised to be aware of these constituents and to avoid reaching levels that may be hazardous to consumers. Industry should use good manufacturing practices to limit impurities that could be present in botanical ingredients. The Panel concluded that these ingredients are safe for use in both rinse-off and leave-on cosmetic products when formulated to be non-sensitizing and non-irritating, provided that leave-on products do not contain more than 0.0015% (15 ppm) 5-methoxypsoralen (5-MOP).


Asunto(s)
5-Metoxipsoraleno/efectos adversos , Citrus/efectos adversos , Seguridad de Productos para el Consumidor , Cosméticos/normas , Animales , Citrus/química , Cosméticos/efectos adversos , Humanos
4.
Int J Toxicol ; 40(3_suppl): 39S-52S, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34406100

RESUMEN

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 30 Citrus plant- and seed-derived ingredients, which are most frequently reported to function in cosmetics as fragrances and/or skin conditioning agents. Because final product formulations may contain multiple botanicals, each containing similar constituents of concern, formulators are advised to be aware of these constituents and to avoid reaching levels that may be hazardous to consumers. With Citrus plant- and seed-derived ingredients, the Panel was concerned about the presence of the hydroperoxides of limonene and linalool in cosmetics. Industry should use good manufacturing practices to limit impurities. The Panel reviewed the available data presented and concluded that 18 of these ingredients are safe in the present practices of use and concentration when formulated to be non-irritating and non-sensitizing. The data for the remaining 12 ingredients are insufficient to determine safety.


Asunto(s)
5-Metoxipsoraleno/efectos adversos , Citrus/efectos adversos , Seguridad de Productos para el Consumidor , Cosméticos/normas , Semillas/efectos adversos , Animales , Citrus/química , Cosméticos/efectos adversos , Humanos , Semillas/química
5.
Int J Toxicol ; 40(3_suppl): 77S-99S, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34304639

RESUMEN

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 47 Citrus peel-derived ingredients, which are most frequently reported to function in cosmetics as skin conditioning agents. The Panel reviewed the available data to determine the safety of these ingredients. Because final product formulations may contain multiple botanical ingredients, each containing similar constituents of concern, formulators are advised to be aware of these constituents and to avoid reaching levels that may be hazardous to consumers. Industry should use good manufacturing practices to limit impurities that could be present in botanical ingredients. The Panel concluded that Citrus peel-derived ingredients are safe in the present practices of use and concentration in both rinse-off and leave-on cosmetic products when formulated to be non-sensitizing and non-irritating, provided that leave-on products do not contain more than 0.0015% (15 ppm) 5-methoxypsoralen (5-MOP).


Asunto(s)
5-Metoxipsoraleno/efectos adversos , Citrus/efectos adversos , Seguridad de Productos para el Consumidor , Cosméticos/normas , Animales , Citrus/química , Cosméticos/efectos adversos , Humanos
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