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Métodos Terapéuticos y Terapias MTCI
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1.
J Ethnopharmacol ; 319(Pt 3): 117285, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-37839769

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Ulmus macrocarpa Hance (UmH) bark has been traditionally utilized for medicinal purposes. The bark extract of this plant has diverse health benefits, and its potential role in enhancing bone health is of distinct interest, particularly when considering the substantial health and economic implications of bone-related pathologies, such as osteoporosis. Despite the compelling theoretical implications of UmH bark in fortifying bone health, no definitive evidence at the in vivo level is currently available, thus highlighting the innovative and as-yet-unexplored potential of this field of study. AIM OF THE STUDY: Primarily, our study aims to conduct a meticulous analysis of the disparity in the concentration of active compounds in the UmH root bark (Umrb) and trunk bark (Umtb) extracts and confirm UmH bark's efficacy in enhancing bone health in vivo, illuminating the cellular mechanisms involved. MATERIALS AND METHODS: The Umrb and Umtb extracts were subjected to component analysis using high-performance liquid chromatography and then assessed for their inhibitory effects on osteoclast differentiation through the TRAP assay. An ovariectomized (OVX) mouse model replicates postmenopausal conditions commonly associated with osteoporosis. Micro-CT was used to analyze bone structure parameters, and enzyme-linked immunosorbent assay and staining were used to assess bone formation markers and osteoclast activity. Furthermore, this study investigated the impact of the extract on the expression of pivotal proteins and genes involved in bone formation and resorption using mouse bone marrow-derived macrophages (BMMs). RESULTS: The findings of our study reveal a significant discrepancy in the concentration of active constituents between Umrb and Umtb, establishing Umtb as a superior source for promoting bone health. I addition, a standardized pilot-scale procedure was conducted for credibility. The bone health benefits of Umtb were verified using an OVX model. This validation involved the assessment of various parameters, including BMD, BV/TV, and BS/TV, using micro-CT imaging. Additionally, the activation of osteoblasts was evaluated by Umtb by measuring specific factors such as ALP, OCN, OPG in blood samples and through IHC staining. In the same investigations, diminished levels of osteoclast differentiation factors, such as TRAP, NFATc1, were also observed. The observed patterns exhibited consistency in vitro BMM investigations. CONCLUSIONS: Through verification at both in vitro levels using BMMs and in vivo levels using the OVX-induced mouse model, our research demonstrates that Umtb is a more effective means of improving bone health in comparison to Umrb. These findings pave the way for developing health-functional foods or botanical drugs targeting osteoporosis and other bone-related disorders and enhance the prospects for future research extensions, including clinical studies, in extract applications.


Asunto(s)
Osteoporosis , Ulmus , Femenino , Humanos , Animales , Ratones , Osteoclastos , Corteza de la Planta , Osteoporosis/prevención & control , Modelos Animales de Enfermedad , Ovariectomía
2.
J Nat Prod ; 86(4): 751-758, 2023 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-36812487

RESUMEN

A chemical investigation of the endophytic Streptomyces sp. HBQ95, associated with the medicinal plant Cinnamomum cassia Presl, enabled the discovery of four new piperazic acid-bearing cyclodepsipeptides, lydiamycins E-H (1-4), and one known compound (lydiamycin A). Their chemical structures, including absolute configurations, were defined by a combination of spectroscopic analyses and multiple chemical manipulations. Lydiamycins F-H (2-4) and A (5) exhibited antimetastatic activity against PANC-1 human pancreatic cancer cells without significant cytotoxicity.


Asunto(s)
Cinnamomum aromaticum , Plantas Medicinales , Piridazinas , Streptomyces , Humanos , Cinnamomum aromaticum/química , Streptomyces/química , Piridazinas/química
3.
Int J Mol Sci ; 22(11)2021 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-34071042

RESUMEN

Osteoporosis is a chronic disease that has become a serious public health problem due to the associated reduction in quality of life and its increasing financial burden. It is known that inhibiting osteoclast differentiation and promoting osteoblast formation prevents osteoporosis. As there is no drug with this dual activity without clinical side effects, new alternatives are needed. Here, we demonstrate that austalide K, isolated from the marine fungus Penicillium rudallenes, has dual activities in bone remodeling. Austalide K inhibits the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and improves bone morphogenetic protein (BMP)-2-mediated osteoblast differentiation in vitro without cytotoxicity. The nuclear factor of activated T cells c1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), dendritic cell-specific transmembrane protein (DC-STAMP), and cathepsin K (CTSK) osteoclast-formation-related genes were reduced and alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and osteopontin (OPN) (osteoblast activation-related genes) were simultaneously upregulated by treatment with austalide K. Furthermore, austalide K showed good efficacy in an LPS-induced bone loss in vivo model. Bone volume, trabecular separation, trabecular thickness, and bone mineral density were recovered by austalide K. On the basis of these results, austalide K may lead to new drug treatments for bone diseases such as osteoporosis.


Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Resorción Ósea/prevención & control , Osteoblastos/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Penicillium/química , Xantenos/uso terapéutico , Animales , Conservadores de la Densidad Ósea/aislamiento & purificación , Conservadores de la Densidad Ósea/farmacología , Resorción Ósea/inducido químicamente , Diferenciación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Regulación de la Expresión Génica/efectos de los fármacos , Sedimentos Geológicos/microbiología , Lipopolisacáridos/toxicidad , Masculino , Ratones , Ratones Endogámicos ICR , Estructura Molecular , Factores de Transcripción NFATC/biosíntesis , Factores de Transcripción NFATC/genética , Osteoporosis , Penicillium/aislamiento & purificación , Ligando RANK/farmacología , Fosfatasa Ácida Tartratorresistente/antagonistas & inhibidores , Xantenos/aislamiento & purificación , Xantenos/farmacología
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