Korean J Physiol Pharmacol.  2012 Jun;16(3):187-192. 10.4196/kjpp.2012.16.3.187.

Hop Extract Produces Antinociception by Acting on Opioid System in Mice

• Park SH
• Sim YB
• Kang YJ
• Kim SS
• Kim CH
• Kim SJ
• Seo JY
• Lim SM
• Suh HW

• KMID: 1768012
• DOI: http://doi.org/10.4196/kjpp.2012.16.3.187

Abstract

In the present study, the antinociceptive profiles of hop extract were characterized in ICR mice. Hop extract administered orally (from 25 to 100 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Antinociceptive action of hop extract was maintained at least for 60 min. Moreover, cumulative response time of nociceptive behaviors induced with intraplantar formalin injection was reduced by hop extract treatment during the 2nd phases. Furthermore, the cumulative nociceptive response time for intrathecal injection of substance P (0.7 microg) or glutamate (20 microg) was diminished by hop extract. Intraperitoneal pretreatment with naloxone (an opioid receptor antagonist) attenuated antinociceptive effect induced by hop extract in the writhing test. However, methysergide (a 5-HT serotonergic receptor antagonist) or yohimbine (an alpha2-adrenergic receptor antagonist) did not affect antinociception induced by hop extract in the writhing test. Our results suggest that hop extract shows an antinociceptive property in various pain models. Furthermore, the antinociceptive effect of hop extract may be mediated by opioidergic receptors, but not serotonergic and alpha2-adrenergic receptors.

Keyword

Hop; Antinociception; Inflammatory pain; Opioid receptor

MeSH Terms

Animals
Formaldehyde
Glutamic Acid
Humulus
Injections, Spinal
Methysergide
Mice
Mice, Inbred ICR
Naloxone
Reaction Time
Receptors, Opioid
Serotonin
Substance P
Yohimbine
Formaldehyde
Glutamic Acid
Methysergide
Naloxone
Receptors, Opioid
Serotonin
Substance P
Yohimbine

Figure

• 

  Fig. 1 Effect of hop extract on the nociceptive response induced by acetic acid. Various does (from 25 to 100 mg/kg) of hop extract were administered orally and then, 0.25 ml of 1% acetic acid solution was injected intraperitoneally 30 min after treatment. The number of writhing was counted for 30 min following acetic acid injection (A). Hop extract (100 mg/kg) was administered orally and then, 0.25 ml of 1% acetic acid solution was injected intraperitoneally 30, 60 and 120 min after treatment (B). The number of writhing was counted for 30 min following acetic acid injection. The vertical bars indicate the standard error of the mean. The number of animal used for each group was 8~10 (**p<0.01, ***p<0.001, compared with control group).

• 

  Fig. 2 Effect of hop extract on the nociceptive response induced by formalin. Animal were pretreated orally with hop extract (100 mg/kg) for 30 min prior to the formalin (5%, 10 µl) injection subcutaneously into the plantar aspect of the left side hindpaw. The cumulative response time of licking, biting and shaking the injected paw was measured during the period of 0~5 min (1st phase) and 20~40 min (2nd phase). The vertical bars indicate the standard error of the mean. The number of animal used for each group was 8~10 (***p<0.001, compared with control group).

• 

  Fig. 3 Effect of hop extract on the nociceptive response induced by substance P or glutamate. Hop extract (100 mg/kg) was administered orally for 30 min prior to the substance P (A: 0.7 µg per 5 µl) or glutamate (B: 20 µg per 5 µl) injection intrathecally. The cumulative response time of licking, scratching and biting episodes was measured for 30 min. The vertical bars indicate the standard error of the mean. The number of animal used for each group was 8~10 (***p<0.001, compared with control group).

• 

  Fig. 4 Effect of naloxone (A), methysergide (B) and yohimbine (C) injected intraperitoneally (i.p.) on inhibition of the writhing response induced by hop extract administered orally. Naloxone (5 mg/kg), Methysergide (5 mg/kg) or yohimbine (5 mg/kg) was pretreated intraperitoneally for 10 min, before oral administration of vehicle or hop extract (100 mg/kg). Hop extract or vehicle was administered orally and then, 0.25 ml of 1% acetic acid solution was injected i.p. 30 min after treatment. The number of writhing was counted for 30 min following acetic acid injection. The vertical bars denote the standard error of the mean. The number of animal used for each group was 8~10 (***p<0.001, compared with control group).

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