peoniflorin and Pain

LPS has been widely used to induce inflammatory pain, attributing to production of inflammatory cytokines and sensitization of nociceptors. Paeoniflorin (PF) possesses anti-nociceptive property, but its effect on LPS-induced inflammatory pain has not been investigated. In this study, we aimed to investigate the analgesic effect of PF on an inflammatory pain mouse model and explore the underlying mechanisms. LPS-induced inflammatory pain model was established in C57BL/6J mice after PF treatment. Then, thermal hyperalgesia, neutrophil infiltration, inflammatory cytokine production, intracellular Ca

Topics: Animals; Calcium; Cytokines; Edema; Glucosides; Inflammasomes; Inflammation; Inflammation Mediators; Lipopolysaccharides; Macrophages; Male; Mice, Inbred C57BL; Models, Biological; Monoterpenes; Neutrophils; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Nociception; Pain; Protein Kinase C; Transcription, Genetic; TRPV Cation Channels

Paeoniflorin (PF) is known to have anti-inflammatory and paregoric effects, but the mechanism underlying its analgesic effect remains unclear. The aim of this study was to clarify the effect of PF on Freund's complete adjuvant (CFA)-induced inflammatory pain and explore the underlying molecular mechanism.. An inflammatory pain model was established by intraplantar injection of CFA in C57BL/6J mice. After intrathecal injection of PF daily for 8 consecutive days, thermal and mechanical withdrawal thresholds, the levels of inflammatory factors TNF-α, IL-1β and IL-6, microglial activity, and the expression of Akt-NF-κB signaling pathway in the spinal cord tissue were detected by animal ethological test, cell culture, enzyme-linked immunosorbent assay, immunofluorescence histochemistry, and western blot.. PF inhibited the spinal microglial activation in the CFA-induced pain model. The production of proinflammatory cytokines was decreased in the central nervous system after PF treatment both in vivo and in vitro. PF further displayed a remarkable effect on inhibiting the activation of Akt-NF-κB signaling pathway in vivo and in vitro.. These results suggest that PF is a potential therapeutic agent for inflammatory pain and merits further investigation.

Topics: Actin Cytoskeleton; Animals; Anti-Inflammatory Agents; Cell Line; Central Nervous System; Disease Models, Animal; Freund's Adjuvant; Glucosides; Inflammation; Interleukin-1beta; Interleukin-6; Male; Mice; Mice, Inbred C57BL; Microglia; Monoterpenes; NF-kappa B; Pain; Proto-Oncogene Proteins c-akt; Signal Transduction; Tumor Necrosis Factor-alpha

Recently, paeoniflorin (PF) administered systemically was found to have analgesic effects against inflammatory pain and hypersensitivity in a naloxone-reversible manner. In the present study, we adopted intrathecal administration to evaluate whether PF has direct antinociceptive actions at the spinal level. Pain-related behaviors and spinal c-Fos expression were induced by subcutaneous injection of bee venom (BV) into one hind paw of a rat. Intrathecal pretreatment of PF resulted in an inhibition of the BV-induced persistent spontaneous nociception and partially suppressed the occurrence of both thermal and mechanical hypersensitivity. Moreover, the PF-produced antinociception was completely reversed by naloxone. We further evaluated the intrathecal effects of the drug on the BV-induced c-Fos expression. The result showed that intrathecal PF preconditioning was effective to suppress spinal c-Fos expression in both superficial (lamina I-II) and deep (lamina IV-VI) layers of the L(4-5) dorsal spine. This result showed that PF has a direct pharmacological action in the spinal cord dorsal horn via activation of opioid receptors.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bee Venoms; Behavior, Animal; Benzoates; Bridged-Ring Compounds; Glucosides; Hot Temperature; Hyperalgesia; Injections, Spinal; Male; Monoterpenes; Naloxone; Narcotic Antagonists; Pain; Posterior Horn Cells; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Touch

The root of Paeonia lactiflora PALL (PL, Family Paeoniaceae) has been used frequently as an antipyretic and anti-inflammatory agent in traditional medicines of Korea, China and Japan. To evaluate antiallergic effect of PL, we isolated its main constituents, paeoniflorin and paeonol, and evaluated in vivo their inhibitory effects against passive cutaenous anaphylaxis (PCA) reaction induced by IgE-antigen complex and scratching behaviors induced by compound 48/80. PL, paeoniflorin and paeonol potently inhibited PCA reaction and scratching behaviors in mice. Paeoniflorin exhibited the most potent inhibition against scratching behaviors and the acetic acid-induced writhing syndrome in mice. Paeonol most potently inhibited PCA reaction and mast cells degranulation. These findings suggest that PL can improve IgE-induced anaphylaxis and scratching behaviors, and may be due to the effect of its constituents, paeoniflorin and paeonol.

Topics: Acetic Acid; Acetophenones; Analgesics; Animals; Anti-Allergic Agents; Antipruritics; Asthma; Behavior, Animal; Benzoates; Bridged-Ring Compounds; Cell Degranulation; Disease Models, Animal; Dose-Response Relationship, Drug; Glucosides; Male; Mast Cells; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Monoterpenes; Ovalbumin; p-Methoxy-N-methylphenethylamine; Paeonia; Pain; Pain Measurement; Passive Cutaneous Anaphylaxis; Plant Roots; Pruritus; Rats; Rats, Sprague-Dawley

In this study, we attempted to identify the mechanisms of paeoniflorin on antinociceptive effects in mice. Paeoniflorin (48, 96, 240, 480 microg, i.c.v.) showed dose-related antinociception both on the early and late phases of formalin test in mice. Moreover, paeoniflorin (48 microg, i.c.v.) could potentiate the antinociception of morphrine (0.5, 1.0 mg/kg, s.c.) in the formalin test. However, the antinociceptive effects of paeoniflorin were not potentiated by L-arginine (600 mg/kg, i.p.) or antagonized by beta-funaltrexamine (beta-FNA) (10 microg, i.c.v.), ICI-174,864 (1 microg, i.c.v.) and ryanodine (10 ng, i.c.v.) on both the early and late phases of formalin test. L-NAME (75 mg/kg, i.p.) could reverse the effect of paeoniflorin on the late phase of formalin test. Naloxone (1 mg/kg, i.p.) and nor-binaltorphimine (nor-BNI) (1 microg, i.c.v.) could block the paeoniflorin-induced antinociception on the early phase of formalin test. These results suggested that the central antinociceptive effects of paeoniflorin on formalin test in mice were mediated by the activation of kappa-opioid receptor and not related to the increase of intracellular calcium.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzoates; Bridged-Ring Compounds; Dose-Response Relationship, Drug; Formaldehyde; Glucosides; Injections, Intraventricular; Male; Mice; Mice, Inbred ICR; Monoterpenes; Pain

Thin layer chromatography was performed to identify the ingredients of Effervescent Granules for arresting cold pain (Hantongding Paoteng Chongji). The limited doses of aconitine, granularity, moisture, acidity, sugar content, etc. were detected, and the contents of paeoniflorin, glycyrrhetinic acid and total alkaloids were determined. Thus, the quality standards for pharmaceutical preparation were preliminarily worked out.

Topics: Aconitine; Alkaloids; Anti-Inflammatory Agents, Non-Steroidal; Benzoates; Bridged-Ring Compounds; Chromatography, Thin Layer; Drug Combinations; Drugs, Chinese Herbal; Glucosides; Glycyrrhetinic Acid; Humans; Monoterpenes; Pain; Particle Size; Quality Control

The pharmacological properties of the five samples of glycyrrhizic acid, paeoniflorin, the extracts of Glycyrrhizae Radix, the extracts of Paeoniae Radix and a preparation of Chinese drug Shakuyakukanzo-To were compared by investigating their actions in the carrageenan-induced paw edema, the cotton pellet granuloma formation and acetic acid-induced writhing syndrome tests, using ddY-strain mice. The concentrations of glycyrrhizic acid and paeniflorin, the main components of Glycyrrhizae Radix and Paeoniae Radix respectively, were determined in the preparations by high performance liquid chromatography. Anti-inflammatory activity was observed with the doses of glycyrrhizic acid, 3.0 and 30.0 mg/kg p.o., which are almost equivalent to the quantities contained in the extracts of Glycyrrhizae Radix, 18.0 (normal human dose per day) and 180.0 mg/kg, or in Shakuyakukanzo-To, 32.0 (normal human dose per day) and 320.0 mg/kg, respectively and with the doses of the extracts of Glycyrrhizae Radix, 18.0 and 180.0 mg/kg p.o., but not with the doses of Shakuyakukanzo-To, 32.0 and 320.0 mg/kg p.o., in carrageenan-induced edema and cotton pellet method. Doses of paeoniflorin (2.0, 20.0 and 200.0 mg/kg p.o.) and the extracts of Paeoniae Radix, 21.0 (normal human dose per day) and 210.0 mg/kg p.o., which contain almost equivalent quantities of paeoniflorin, 2.0 and 20.0 mg/kg, respectively, showed significant inhibitory effects in the writhing syndrome test. Furthermore, Shakuyakukanzo-To, 32.0 and 320.0 mg/kg p.o., which contain almost equivalent quantities of paeoniflorin, 2.0 and 20.0 mg/kg, showed strong effects in this test.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acetates; Acetic Acid; Animals; Anti-Inflammatory Agents; Benzoates; Bridged-Ring Compounds; Carrageenan; Chromatography, High Pressure Liquid; Drug Combinations; Drugs, Chinese Herbal; Edema; Glucosides; Glycyrrhetinic Acid; Glycyrrhiza; Glycyrrhizic Acid; Granuloma; Male; Mice; Monoterpenes; Paeonia; Pain; Plant Extracts; Plants, Medicinal