Anti-inflammatory and antinociceptive action of the dimeric enkephalin peptide biphalin in the mouse model of colitis: New potential treatment of abdominal pain associated with inflammatory bowel diseases

Sobczak, Marcin; Pilarczyk, A.; Jonakowski, Mateusz; Jarmuż, Agata; Sałaga, Maciej; Lipkowski, Andrzej W.; Fichna, Jakub

doi:10.1016/j.peptides.2014.08.005

Cited by 33 publications

(31 citation statements)

References 26 publications

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“…Since only partial reversal of 240 anti-diarrheal activity was observed for each antagonist alone, a To summarize, here we demonstrated that biphalin produces a 246 significant inhibitory effect on the GI transit under physiological 247 conditions and in animal models mimicking IBS-D symptoms. In 248 our earlier study we showed that biphalin is a potent antinociceptive 249 agent in mouse models of visceral pain [19]. Taken together, we 250…”

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confidence: 69%

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Mixed MOP/DOP agonist biphalin elicits anti-transit effect in mouse models mimicking diarrhea-predominant irritable bowel syndrome symptoms

Zielińska

Jarmuż

Sałaga

et al. 2016

Pharmacological Reports

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confidence: 69%

“…antinociceptive effect of biphalin in the mouse models of 263 inflammatory bowel disease [19]. Others reported the anti-264 retroviral activity in vitro [28], anti-proliferative [29] and antioxi-265 dant [30] for Women in Science and Polpharma Foundation Scholarship.…”

mentioning

confidence: 99%

Mixed MOP/DOP agonist biphalin elicits anti-transit effect in mouse models mimicking diarrhea-predominant irritable bowel syndrome symptoms

Zielińska

Jarmuż

Sałaga

et al. 2016

Pharmacological Reports

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“…It was shown that biphalin has high affinity to mu opioid receptor (MOP) and delta opioid receptor (DOP) but lower affinity to kappa opioid receptor (KOP) [11, 12]. An antinociceptive character of biphalin was documented in an animal model of cancer pain [13], a semichronic colitis model [14], and in naïve animals [15, 16]. Biphalin exhibits 1000-fold greater analgesic potency than morphine [17, 18] and produces less side effects [17].…”

Section: Introductionmentioning

confidence: 99%

Biphalin, a Dimeric Enkephalin, Alleviates LPS-Induced Activation in Rat Primary Microglial Cultures in Opioid Receptor-Dependent and Receptor-Independent Manners

et al. 2017

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Neuropathic pain is relatively less responsive to opioids than other types of pain, which is possibly due to a disrupted opioid system partially caused by the profound microglial cell activation that underlines neuroinflammation. We demonstrated that intrathecally injected biphalin, a dimeric enkephalin analog, diminished symptoms of neuropathy in a preclinical model of neuropathic pain in rats (CCI, chronic constriction injury of the sciatic nerve) at day 12 postinjury. Using primary microglial cell cultures, we revealed that biphalin did not influence cell viability but diminished NO production and expression of Iba1 in LPS-stimulated cells. Biphalin also diminished MOP receptor level, as well as pronociceptive mediators (iNOS, IL-1β, and IL-18) in an opioid receptor-dependent manner, and it was correlated with diminished p-NF-κB, p-IκB, p-p38MAPK, and TRIF levels. Biphalin reduced IL-6, IL-10, TNFα, p-STAT3, and p-ERK1/2 and upregulated SOCS3, TLR4, and MyD88; however, this effect was not reversed by naloxone pretreatment. Our study provides evidence that biphalin diminishes neuropathy symptoms, which might be partially related to reduced pronociceptive mediators released by activated microglia. Biphalin may be a putative drug for future pain therapy, especially for the treatment of neuropathic pain, when the lower analgesic effects of morphine are correlated with profound microglial cell activation.

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“…It was observed that the pretreatment with naloxone completely prevented the antinociceptive effect of SLG (200 mg/Kg) during the first phase (neurogenic) of the formalin test, indicating the opioid system involvement. In order to confirm the opioid-like action, the effect of SLG over the gastrointestinal motility was also tested, since the opioids capacity of inhibiting the intestinal motility has been well established, mainly due to binding to μ opioid receptors [47]. Interestingly, the same doses of SLG that induced an evident increase of reaction time in the hot plate test (200 or 400 mg/Kg) induced a clear reduction of intestinal motility (Figure 6(b)), corroborating to the hypothesis that the antinociceptive effect of the extract may be related to the opioid system activation.…”

Section: Discussionmentioning

confidence: 99%

Phytochemical and Antinociceptive, Anti‐Inflammatory, and Antioxidant Studies of Smilax larvata (Smilacaceae)

Hirota

Paula

Oliveira

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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The tea of aerial parts of Smilax larvata Griseb. (Smilacaceae) has been ethnopharmacologically used in Southern Brazil due to its anti-inflammatory action. In this study, ethanolic and organic extracts from aerial parts of S. larvata were phytochemically and pharmacologically characterized. The phytochemical analysis of EtOAc extract of S. larvata revealed the presence of three flavonoids, drabanemoroside, kaempferol 3-O-α-L-rhamnopyranosyl(1→2)-α-L-rhamnopyranoside, and kaempferol, the first two being isolated for the first time in this genus, two phenolic compounds p-hydroxybenzoic acid and p-coumaric acid, and alkaloids. In vitro assays demonstrated a potential antioxidant property of SLG. The treatment with SLG induced a significant reduction of the formalin-evoked flinches in rats, an effect reversed by opioid antagonist naloxone. Treatment with SLG also induced a significant increase in the hot plate latency and a decrease of intestinal motility by 45%. No effect was observed over nociceptive responses induced by a TRPA1 agonist mustard oil or over acetic acid-induced writhing in mice. Together, our data suggested that SLG has an in vivo antinociceptive effect, which seems to be associated with the opioid system activation. These findings support previous claims of medical use of Smilax larvata in the treatment of pain conditions.

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Anti-inflammatory and antinociceptive action of the dimeric enkephalin peptide biphalin in the mouse model of colitis: New potential treatment of abdominal pain associated with inflammatory bowel diseases

Cited by 33 publications

References 26 publications

Mixed MOP/DOP agonist biphalin elicits anti-transit effect in mouse models mimicking diarrhea-predominant irritable bowel syndrome symptoms

Mixed MOP/DOP agonist biphalin elicits anti-transit effect in mouse models mimicking diarrhea-predominant irritable bowel syndrome symptoms

Biphalin, a Dimeric Enkephalin, Alleviates LPS-Induced Activation in Rat Primary Microglial Cultures in Opioid Receptor-Dependent and Receptor-Independent Manners

Phytochemical and Antinociceptive, Anti‐Inflammatory, and Antioxidant Studies of Smilax larvata (Smilacaceae)

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