Milonine, a Morphinandienone Alkaloid, Has Anti-Inflammatory and Analgesic Effects by Inhibiting TNF-α and IL-1β Production

Silva, Larissa Rodrigues; Alves, Adriano Francisco; Cavalcante‐Silva, Luiz Henrique Agra; Braga, Renan Marinho; Almeida, Reinaldo Nóbrega de; Barbosa-Filho, José Maria; Piuvezam, Márcia Regina

doi:10.1007/s10753-017-0647-9

Cited by 17 publications

(21 citation statements)

References 53 publications

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“…Previous researches suggest that the pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β are considered as the central mediators for ruling the inflammatory biomarkers and overproduction of these cytokines support the expansion of diabetes linked inflammation (Oliveira et al., 2008), coagulation (Silva et al., 2017) and endothelial dysfunction (López-Bojórquez et al., 2004). During DM, the overproduction of TNF-α decreased the insulin sensitivity by affecting the insulin receptor (Wachlin et al., 2003).…”

Section: Discussionmentioning

confidence: 99%

Design and optimization of crocetin loaded PLGA nanoparticles against diabetic nephropathy via suppression of inflammatory biomarkers: a formulation approach to preclinical study

Yang

2019

Drug Delivery

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Diabetic nephropathy (DN) is a serious complication of diabetes mellitus whose expand process is linked with the fibrosis, renal hypertrophy and inflammation. The current study was to formulate and optimize the nano-formulation of crocetin (CT-PLGA-NPs) against Streptozotocin-induced renal nephropathy in rats. Double emulsion evaporation technique was used for the preparation of CT-PLGA-NPs. CT-PLGA-NPs were scrutinized for polydispersity index, size, gastric stability, entrapment, drug-loading capacity and in-vitro drug release and in vivo preclinical study. Single intraperitoneal injection of streptozotocin (STZ) (55 mg/kg) and rats were divided into different group. Renal function and metabolic parameters of urine and serum were estimated. Fibrotic protein, renal pro-inflammatory cytokines and degree of renal damage expression were also determined. We also estimated the fibronectin, type IV collagen and transforming growth factor-β1 for a possible mechanism of action. Crocetin supplement (10 mg/kg) and CT-PLGA-NPs exhibited the accumulation of the drug in kidney and liver of diabetic rats. Crocetin reduced the BGL and enhanced plasma insulin and body weight. Dose dependent treatment of crocetin significantly (p < .001) down-regulated the expression of renal tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin (IL)-1β (IL-1β) and Monocyte Chemoattractant Protein-1 (MCP-1). Crocetin significantly (p < .001) altered the expression of fibronectin, type IV collagen, and transforming growth factor-β1 (TGF-1β). Crocetin significantly (p < .001) down-regulated the protein kinase C activity and the expression of nuclear factor κB (NF-κB) p65 activity and protein production in renal tissue. On the basis of the available result, we can conclude that nano-formulation of crocetin could attenuate the diabetic nephropathy via antifibrotic and anti-inflammatory effect.

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Section: Discussionmentioning

confidence: 99%

Design and optimization of crocetin loaded PLGA nanoparticles against diabetic nephropathy via suppression of inflammatory biomarkers: a formulation approach to preclinical study

Yang

2019

Drug Delivery

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“…In a paw edema model, milonine ( 60 ) extracted from C. sympodialis inhibited histamine release of activated mast cells [71] . In Silva et al .’s study, the anti‐inflammatory activity of milonine extracted from C. sympodialis was evaluated [72] . Warifteine from the C. sympodialis in BALB/c mice (2.0 or 10 mg/kg) also significantly reduced paw edema formation after 30 min of OVA administration [73] …”

Section: Pharmacological Activitiesmentioning

confidence: 99%

Phytochemical Constituents and Biological Activities of Plants from the GenusCissampelos

Yan

et al. 2021

Chemistry & Biodiversity

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Cissampelos is a significant genus comprising of approximately 21 species of the medicinal plants (Menispermaceae). The plants of this genus are used in traditional medicine for the treatment of various ailments such as asthma, arthritis, dysentery, hyperglycemia, cardiopathy, hypertension and other related problems. These plants are rich in bioactive dibenzylisoquinoline and aborphine as well as small amounts of other ingredients. In recent years, the chemical constituents and pharmacological activities of Cissampelos genus have been paid more and more attention due to their diversity. Herein, we compile the chemical constituents and biological activities on this genus, and summarize the 13C‐NMR data of the main bioactive ingredients. All information comes from scientific databases such as Google Scholar, PubMed, Sci‐Finder, ScienceDirect, Web of Science and CNKI. It provides valuable data for the future research and development of Cissampelos genus.

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“…The animals of the saline group (healthy animals) were treated and challenged with saline and the animals of the lipopolysaccharide (LPS) group (sick animals) were LPSchallenged and treated with saline. The chosen dose of milonine was de ned previously [16,17].…”

Section: Animal Groupsmentioning

confidence: 99%

Milonine Protects Against Acute Lung Injury By Modulating The Akt And NF-κB Signaling Pathway

Bernardo

Ferreira

et al. 2021

Preprint

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Acute lung injury (ALI) is an inflammation that triggers acute respiratory distress syndrome (ARDS) with perialveolar neutrophil infiltration, alveolar-capillary barrier damage, and lung edema. Activation of the toll-like receptor 4 complex and its downstream signaling pathways are responsible for the cytokine storm and cause alveolar damage on ARDS. Due to the complexity of inflammatory events on ALI, a defined pharmacotherapy has not been established. Thus, this study aimed to evaluate the anti-inflammatory potential of milonine, an alkaloid of Cissampelos sympodialis Eichl, in an ALI experimental model. BALB/c mice were lipopolysaccharide (LPS)-challenged and treated with milonine at 2.0 mg/kg. Twenty-four hours later, the bronchoalveolar lavage fluid (BALF), peripheral blood, and lungs were collected for cellular and molecular analysis. The milonine treatment decreased the inflammatory cell migration (principally neutrophils) to the alveolar cavity, the protein exudate, the pulmonary edema, and the level of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) into the BALF. The systemic level of IL-6 level was also reduced. In the lung tissue, milonine reduced the bronchoalveolar damage. The milonine docking analyzes demonstrated that the molecule formed hydrophobic interactions with the amino-acids Ile124 and Phe126 of the TLR4/MD2 groove. Indeed, the anti-inflammatory effect of milonine was due to the negative regulation of cytoplasmic kinase-Akt and NF-κB by interacting with the TLR4/MD2 complex. Therefore, milonine is an effective inflammatory modulator by blocking the interaction of the LPS-TLR4/MD2 complex and downregulating the intracellular inflammatory pathway axis being a potential molecule for the treatment of ALI.

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Milonine, a Morphinandienone Alkaloid, Has Anti-Inflammatory and Analgesic Effects by Inhibiting TNF-α and IL-1β Production

Cited by 17 publications

References 53 publications

Design and optimization of crocetin loaded PLGA nanoparticles against diabetic nephropathy via suppression of inflammatory biomarkers: a formulation approach to preclinical study

Design and optimization of crocetin loaded PLGA nanoparticles against diabetic nephropathy via suppression of inflammatory biomarkers: a formulation approach to preclinical study

Phytochemical Constituents and Biological Activities of Plants from the GenusCissampelos

Milonine Protects Against Acute Lung Injury By Modulating The Akt And NF-κB Signaling Pathway

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