Diosmetin as a novel transient receptor potential vanilloid 1 antagonist with antinociceptive activity in mice

Adamante, Gabriela de Oliveira; Almeida, Amanda Spring de; Rigo, Flávia Karine; Silveira, Edinara da Silva; Coelho, Yanka Oliveira; Prá, Samira Dal-Toé De; Milioli, Alessandra Marcone; Camponogara, Camila; Casoti, Rosana; Bellinaso, Fernando; Desideri, Alexandre Vinhal; Santos, Mário F. C.; Ferreira, Juliano; Oliveira, Sara Marchesan; Trevisan, Gabriela

doi:10.1016/j.lfs.2018.11.029

Cited by 25 publications

(16 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Diosmetin is a flavonoid isolated from the leaves of Olea europaea L 15 . Diosmetin has been studied to demonstrate anti‐proliferative and pro‐apoptotic activities in cancer, 16 antinociceptive properties in different pain models in mice 17 and suppressed inflammation under conditions of pneumococcal meningitis infection 18 . It has also been demonstrated that diosmetin could inhibit osteoclast formation and activation, and could serve as a potential therapeutic drug for osteolytic bone disease 19 .…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Diosmetin exerts cardioprotective effect on myocardial ischaemia injury in neonatal rats by decreasing oxidative stress and myocardial apoptosis

Zhang³

et al. 2020

Clin Exp Pharma Physio

View full text Add to dashboard Cite

Myocardial injury caused by the myocardial ischaemia (MI) is still a troublesome condition in the clinic, including apoptosis, oxidative stress and inflammation. Diosmetin inhibits the cellular apoptosis and inflammatory response and enhances antioxidant activity. So, this study was designed to investigate the cardioprotective effects of diosmetin on MI model neonatal rats. Forty Sprague Dawley (SD) rats 7 days old were randomly divided into five groups. Four groups of rats received diosmetin (50, 100, and 200 mg/kg) or vehicle (MI group) after ischaemia. Another group received vehicle without ischaemia to serve as a control group. Rats were pretreated with diosmetin intraperitoneally for 7 days and intoxicated with isoproterenol (ISO, 85 mg/kg, sc) on the last 2 days. The expression of apoptotic molecules, myocardial systolic function index, antioxidant enzymes and myocardial enzyme was analyzed. Compared with the control group, the proliferation marker proteins of Ki67 were increased significantly (P < .05), the MI group significantly increased the cardiac apoptosis, oxidative stress and myocardial enzymes, and weakened myocardial contractility. The levels of p‐P65/P65 were increased significantly (P < .05) with decreased p‐AKT/AKT and p‐Nrf2/Nrf2 (P < .05). Nevertheless, pretreatment with diosmetin reversed these changes, especially high‐dose group. In summary, diosmetin has significant potential as a therapeutic intervention to ameliorate myocardial injury after MI and provides the rationale for further clinical studies.

show abstract

Section: Introductionmentioning

confidence: 99%

RETRACTED: Diosmetin exerts cardioprotective effect on myocardial ischaemia injury in neonatal rats by decreasing oxidative stress and myocardial apoptosis

Zhang³

et al. 2020

Clin Exp Pharma Physio

View full text Add to dashboard Cite

show abstract

“…Pan et al (34) reported that TRPV1channel-related Ca 2+ plays an important role in osteoblasts in cytokinesis induced by singlenucleotide polymorphisms (SNPs). Adamante et al (35) identified DIO as a TRPV1 antagonist in different mice pain models.…”

Section: Discussionmentioning

confidence: 99%

Diosmetin reduces bone loss and osteoclastogenesis by regulating the expression of TRPV1 in osteoporosis rats

Huang

Chen

et al. 2020

Ann Transl Med

View full text Add to dashboard Cite

Background: Osteoporosis is a systemic skeletal disorder and occurs frequently in postmenopausal women and older men. This study aimed to examine whether diosmetin (DIO) can relieve estrogen deficiencyinduced osteoporosis and to explore the underlying mechanisms of this potential effect.Methods: Forty-nine Sprague-Dawley (SD) rats were divided into seven groups. Six groups underwent bilateral ovariectomy (OVX), while the sham group underwent ovarian exposure surgery. DIO and evodiamine were administered 3 days before surgery, and then subcutaneously every 3 days for 3 months in the following fashion: group I, DIO (100 mg/kg); group II, OVX; group III, OVX + DIO (50 mg/kg); group IV, OVX + DIO (100 mg/kg); group V, OVX + evodiamine (10 mg/kg) group; group VI, OVX + DIO (100 mg/kg) + evodiamine (10 mg/kg) group. Bone histopathological damage, bone loss, osteoclast production, and the expression level of transient receptor potential vanilloid 1 (TRPV1) were detected.Results: Compared with the sham group, the expression of bone resorption-related genes, osteoclastassociated receptor (OSCAR) (1.00%±0.16% versus 4.5%±0.28%, **, P<0.01) and tartrate-resistant acid phosphatase (TRAP) (2.0%±0.6% versus 18.00±1.2%, ***, P<0.001), was increased significantly. The protein level of osteogenic marker proteins, osterix (Osx) (1.0%±0.1% versus 0.03%±0.01%, **, P<0.01) and type 1 collagen (COL1A1) (1.0%±0.13% versus 0.13%±0.05%, **, P<0.01) was decreased significantly with the increase of TRPV1 (1.0%±0.15% versus 2.89%±0.28%, **, P<0.01) protein level. Notably, DIO can alleviate some abnormal symptoms related to osteoporosis.Conclusions: DIO can relieve typical osteoporosis symptoms in an OVX osteoporosis rat model. The underlying mechanism may be associated with the downregulation of TRPV1.

show abstract

“…Experiments on high-fat diet mouse indicate the impairment of TRPV1 response to mechanic stretch as the cause of overeating and obesity [110]. Thus, TRPV1 is in focus of new treatment approaches development [107] and recent data suggest both natural [111, 112] and synthetic [113] substances that affect TRPV1 as a potent treatment of various gastrointestinal disorders.…”

Section: Trpv1 In Vascular and Visceral Systemsmentioning

confidence: 99%

Multifunctional TRPV1 Ion Channels in Physiology and Pathology with Focus on the Brain, Vasculature, and Some Visceral Systems

Storozhuk

Moroz

Zholos

2019

BioMed Research International

View full text Add to dashboard Cite

TRPV1 has been originally cloned as the heat and capsaicin receptor implicated in acute pain signalling, while further research has shifted the focus to its importance in chronic pain caused by inflammation and associated with this TRPV1 sensitization. However, accumulating evidence suggests that, apart from pain signalling, TRPV1 subserves many other unrelated to nociception functions in the nervous system. In the brain, TRPV1 can modulate synaptic transmission via both pre- and postsynaptic mechanisms and there is a functional crosstalk between GABA receptors and TRPV1. Other fundamental processes include TRPV1 role in plasticity, microglia-to-neuron communication, and brain development. Moreover, TRPV1 is widely expressed in the peripheral tissues, including the vasculature, gastrointestinal tract, urinary bladder, epithelial cells, and the cells of the immune system. TRPV1 can be activated by a large array of physical (heat, mechanical stimuli) and chemical factors (e.g., protons, capsaicin, resiniferatoxin, and endogenous ligands, such as endovanilloids). This causes two general cell effects, membrane depolarization and calcium influx, thus triggering depending on the cell-type diverse functional responses ranging from neuronal excitation to secretion and smooth muscle contraction. Here, we review recent research on the diverse TRPV1 functions with focus on the brain, vasculature, and some visceral systems as the basis of our better understanding of TRPV1 role in different human disorders.

show abstract

Diosmetin as a novel transient receptor potential vanilloid 1 antagonist with antinociceptive activity in mice

Cited by 25 publications

References 57 publications

RETRACTED: Diosmetin exerts cardioprotective effect on myocardial ischaemia injury in neonatal rats by decreasing oxidative stress and myocardial apoptosis

RETRACTED: Diosmetin exerts cardioprotective effect on myocardial ischaemia injury in neonatal rats by decreasing oxidative stress and myocardial apoptosis

Diosmetin reduces bone loss and osteoclastogenesis by regulating the expression of TRPV1 in osteoporosis rats

Multifunctional TRPV1 Ion Channels in Physiology and Pathology with Focus on the Brain, Vasculature, and Some Visceral Systems

Contact Info

Product

Resources

About