Inhibiting IL-6 in medicine: a new twist to sustain inhibition of his cytokine tin the therapy of Pulmonary Arterial Hypertension

Gugliandolo, Enrico; Macrı̀, Francesco; Fusco, Roberta; Siracusa, Rosalba; Cordaro, Massimiliano; D’Amico, Ramona; Peritore, Alessio Filippo; Impellizzeri, Daniela; Genovese, Tiziana; Cuzzocrea, Salvatore; Paola, Rosanna Di; Crupi, Rosalia

doi:10.1016/j.phrs.2023.106750

Cited by 3 publications

(1 citation statement)

References 60 publications

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“…In addition to targeting NF-κB, recent reports have shown that a promising therapeutic strategy for PH and its complications may be to inhibit IL-6. The use of a monoclonal antibody (IL-6R Ab) against the interleukin-6 receptor (IL-6R) was effective in reducing elevated pulmonary artery pressure and RVSP, and reduced RV remodeling and inflammation [ 18 ]. It is known that one of the anti-inflammatory properties of CBD is the inhibition of IL-6 expression [ 19 ], which can directly improve the clinical condition of patients with PH, as well as prevent the development of RV failure and associated CH.…”

Section: Introductionmentioning

confidence: 99%

Cannabidiol may prevent the development of congestive hepatopathy secondary to right ventricular hypertrophy associated with pulmonary hypertension in rats

Krzyżewska,

Baranowska-Kuczko,

Galicka

et al. 2024

Pharmacol. Rep

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Background Pulmonary hypertension (PH) can cause right ventricular (RV) failure and subsequent cardiohepatic syndrome referred to as congestive hepatopathy (CH). Passive blood stasis in the liver can affect inflammation, fibrosis, and ultimately cirrhosis. Cannabidiol (CBD) has many beneficial properties including anti-inflammatory and reduces RV systolic pressure and RV hypertrophy in monocrotaline (MCT)-induced PH in rats. Thus, it suggests that CBD may have the potential to limit CH development secondary to RV failure. The present study aimed to determine whether chronic administration of CBD can inhibit the CH secondary to RV hypertrophy associated with MCT-induced PH. Methods The experiments involved rats with and without MCT-induced PH. CBD (10 mg/kg) or its vehicle was administered once daily for 3 weeks after MCT injection (60 mg/kg). Results Monocrotaline administration increased the liver/body weight ratio. In histology examinations, we observed necrosis and vacuolar degeneration of hepatocytes as well as sinusoidal congestion. In biochemical studies, we observed increased levels of nuclear factor-κappa B (NF-κB), tumour necrosis factor-alpha (TNA-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). CBD administration to PH rats reduced the liver/body weight ratio, improved the architecture of the liver, and inhibited the formation of necrosis. Cannabidiol also decreased the level of NF-κB, TNF-α, IL-1β and IL-6. Conclusions The studies show that CBD can protect the liver from CH probably through attenuating PH, protective effects on the RV, and possibly direct anti-inflammatory effects on liver tissue through regulation of the NF-κB pathway. Graphical abstract

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Section: Introductionmentioning

confidence: 99%

Cannabidiol may prevent the development of congestive hepatopathy secondary to right ventricular hypertrophy associated with pulmonary hypertension in rats

Krzyżewska,

Baranowska-Kuczko,

Galicka

et al. 2024

Pharmacol. Rep

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Targeting IL-11 system as a treatment of pulmonary arterial hypertension

Milara,

Roger,

Montero

et al. 2023

Pharmacological Research

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Identification of the Role of Mume fructus in Treating Nocturnal Asthma Based on Network Pharmacology and In vitro Investigation

Tang,

Xu,

Yang

et al. 2024

World Journal of Traditional Chinese Medicine

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Objective: Mume fructus is commonly used in traditional Chinese medicine to treat nocturnal asthma symptoms. However, the molecular mechanisms underlying its effects on nocturnal asthma have not yet been established. This study evaluated the therapeutic mechanisms of Mume fructus in treating nocturnal asthma. Materials and Methods: Network pharmacology was used to investigate the chemical composition, critical targets, and potential mechanisms of action of Mume fructus in treating nocturnal asthma. “Mume fructus” and “nocturnal asthma” were used as keywords to search the relevant databases. The 16HBE and RAW264.7 cells were treated with various concentrations of Mume fructus and lipopolysaccharides (LPSs). Data provided included analyses of cell viability detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, cell proliferation and apoptosis detected by 5-ethynyl-2’-deoxyuridine and Hoechst 33342, messenger ribonucleic acid (mRNA) levels obtained by real-time polymerase chain reaction, and protein expression detected by Western blotting. Additionally, immunofluorescence was used to detect nuclear translocation. Results: Network pharmacology analyses were mainly enriched in nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK) pathway, and interleukin (IL)-6. Mume fructus and LPS had no effect on viability, proliferation, and apoptosis in 16HBE and RAW264.7 cells under certain concentration conditions. Mume fructus counteracted LPS-stimulated mRNA and protein expression of IL-6. In addition, Mume fructus treatment prevented the LPS-induced phosphorylation of NF-κB and MAPK pathways, as well as the nuclear translocation of NF-κB p-p65 in the 16HBE and RAW264.7 cells. Conclusions: Mume fructus can treat nocturnal asthma by regulating the NF-κB and MAPK pathways and counteracting IL-6 expression. These findings provide a scientific basis for the use of Mume fructus in the treatment of nocturnal asthma.

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Inhibiting IL-6 in medicine: a new twist to sustain inhibition of his cytokine tin the therapy of Pulmonary Arterial Hypertension

Cited by 3 publications

References 60 publications

Cannabidiol may prevent the development of congestive hepatopathy secondary to right ventricular hypertrophy associated with pulmonary hypertension in rats

Cannabidiol may prevent the development of congestive hepatopathy secondary to right ventricular hypertrophy associated with pulmonary hypertension in rats

Targeting IL-11 system as a treatment of pulmonary arterial hypertension

Identification of the Role of Mume fructus in Treating Nocturnal Asthma Based on Network Pharmacology and In vitro Investigation

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