Antihyperalgesic Properties of Honokiol in Inflammatory Pain Models by Targeting of NF-κB and Nrf2 Signaling

Abstract

The present study investigates the possible anti-nociceptive effect of intraperitoneal (i.p.) honokiol: a phenolic compound originally isolated from Magnolia officinalis, in acute and chronic inflammatory pain models. Doses of 0.1, 5, and 10 mg/kg honokiol were administered in carrageenan induced pain and the dose (honokiol 10 mg/kg i.p.) with most significant response among behavioral tests was selected for further experiments. The i.p. administration of honokiol inhibits mechanical hyperalgesia, mechanical allodynia, and thermal hyperalgesia, without causing any apparent toxicity. To elucidate the effect of honokiol on various cytokines and antioxidant enzymes, quantitative real-time-PCR was performed to determine the expression levels of pro-inflammatory cytokines and antioxidant enzymes. It is demonstrated that honokiol significantly reduced the expression levels of tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF). Similarly, honokiol was also found to potentiate the expression of nuclear factor erythroid 2–related factor 2 (Nrf2), superoxide dismutase 2 (SOD2), and heme oxygenase-1 (HO-1) levels. Additionally, honokiol significantly reduced plasma nitrite levels as compared to complete Freund’s adjuvant (CFA) induced group. X-ray analysis and hematoxylin and eosin (H&E) staining of inflamed and treated paws showed that honokiol reduced the inflammation with significantly less leukocyte infiltration and soft tissue inflammation. In order to explore the possible mechanism of action of honokiol, agonists [piroxicam (5 mg/kg), tramadol (50 mg/kg), and gabapentin (5 mg/kg) i.p.] as well as antagonists [naloxone (4 mg/kg), olanzapine (10 mg/kg), and flumazenil (0.2 mg/kg) i.p.] were used to study involvement of various receptors on the anti-nociceptive effect of honokiol. The potential side effects of honokiol on muscle activity were assessed. An adverse effect testing of honokiol by liver and renal functions were also carried out. The effect of oral honokiol was also assessed on gastrointestinal (GIT) mucosa. Our results demonstrate that honokiol has a significant anti-nociceptive activity through inhibition of anti-inflammatory mediators.

Role of High-affinity Choline Transporter 1 in Colonic Hypermotility in a Rat Model of Irritable Bowel Syndrome

“…Firstly, Wang and Liu 37 reported that activation of NF-κB signaling contributed to the occurrence of inflammation-related IBS-diarrhea. In addition, recently, we detected that NF-κB signaling was also implicated in IBS-related hyperalgesia in an unpublished research, consistent with previous studies reporting that NF-κB signaling participated in the pain modulation in inflammatory diseases, 38 cancer, 39 and autoimmune diseases, 40 via the release of inflammatory cytokines such as IL-1β, IL-6, and TNF-α. Moreover, our findings indicate that the excitatory effect of CHT1 in GI motility is closely associated with increased ACh release.…”

Honokiol induces apoptosis of lung squamous cell carcinoma by targeting FGF2‐FGFR1 autocrine loop

“…These results suggested that honokiol might suppress the FGF2‐FGFR1 autocrine loop signaling pathway by inhibiting the expression of FGF2.It has been reported that NF‐κB may serve as a transcription factor for the FGF2 gene, regulating the expression and release of FGF2 . In our investigation, we found considerable evidence that honokiol could inhibit the activation of the NF‐κB pathway . Hence, we infer that honokiol reduces the expression of FGF2 via the NF‐κB signaling pathway.…”

Antinociceptive properties of 25‐methoxy hispidol A, a triterpinoid isolated from Poncirus trifoliata (Rutaceae) through inhibition of NF‐κB signalling in mice

“…The mice were administered 25‐MHA (10 mg/kg, i.p) 40 min prior to the administration of CFA (20 μl/paw) and 1 h before the injection of carrageenan (100 μg/paw). Mechanical hyperalgesia in mice was determined using the Randall Selitto test according to the previously described methods (Khalid et al, ; Khan et al, ). Before the start of the test, the mice were placed in a quiet room for 15–30 min to acclimatise to the environment.…”