Antinociceptive Effects of St. John's Wort, Harpagophytum Procumbens Extract and Grape Seed Proanthocyanidins Extract in Mice

Uchida, Shinya; Hirai, Keita; Hatanaka, Junya; Hanato, Junko; Umegaki, Keizo; Yamada, Shizuo

doi:10.1248/bpb.31.240

Cited by 62 publications

(42 citation statements)

References 36 publications

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“…These reports confirm and support the hypothesis for the role that SJW has in the modulation of pain perception. This hypothesis has been suggested in a recent paper that indicates the antinociceptive properties of SJW in the mouse formalin test [29].…”

Section: Discussionmentioning

confidence: 74%

St. John's Wort reduces neuropathic pain through a hypericin-mediated inhibition of the protein kinase C γ and ɛ activity

Galeotti

Vivoli

Bilia

et al. 2010

Biochemical Pharmacology

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Section: Discussionmentioning

confidence: 74%

St. John's Wort reduces neuropathic pain through a hypericin-mediated inhibition of the protein kinase C γ and ɛ activity

Galeotti

Vivoli

Bilia

et al. 2010

Biochemical Pharmacology

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“…Uchida et al reported that GSPE had a significant antinociceptive effect in mice during the formalin test (Uchida et al, 2008), and Cui et al showed that GSPE plays a protective role against diabetic peripheral neuropathy by ameliorating nerve damage associated with oxidation (Cui et al, 2008). These results suggest that GSPE has an antinociceptive effect.…”

Section: Discussionmentioning

confidence: 97%

Grape seed proanthocyanidin extract ameliorates monosodium iodoacetate-induced osteoarthritis

et al. 2011

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Abbreviations: GSPE, grape seed proanthocyanidin extract; MIA, monosodium iodoacetate; MMP, matrix metalloproteinase; O2 -, superoxide anion; OA, osteoarthritis; OH, hydroxyl radicals; ONOO -, peroxynitrite; PWL, paw withdrawal latency; PWT, paw withdrawal threshold; ROS, reactive oxygen species; TRP, transient receptor potential; VIP, vasoactive intestinal peptide Abstract Osteoarthritis (OA) is an age-related joint disease that is characterized by degeneration of articular cartilage and chronic pain. Oxidative stress is considered one of the pathophysiological factors in the progression of OA. We investigated the effects of grape seed proanthocyanidin extract (GSPE), which is an antioxidant, on monosodium iodoacetate (MIA)-induced arthritis of the knee joint of rat, which is an animal model of human OA. GSPE (100 mg/kg or 300 mg/kg) or saline was given orally three times per week for 4 weeks after the MIA injection. Pain was measured using the paw withdrawal latency (PWL), the paw withdrawal threshold (PWT) and the hind limb weight bearing ability. Joint damage was assessed using histological and microscopic analysis and microcomputerized tomography. Matrix metalloproteinase-13 (MMP13) and nitrotyrosine were detected using immunohistochemistry. Administration of GSPE to the MIA-treated rats significantly increased the PWL and PWT and this resulted in recovery of hind paw weight distribution (P ＜ 0.05). GSPE reduced the loss of chondrocytes and proteoglycan, the production of MMP13, nitrotyrosine and IL-1β and the formation of osteophytes, and it reduced the number of subchondral bone fractures in the MIA-treated rats. These results indicate that GSPE is antinociceptive and it is protective against joint damage in the MIA-treated rat model of OA. GSPE could open up novel avenues for the treatment of OA.

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“…A recent study reported that an SJW extract was devoid of any antinociceptive effect in the mouse tail-flick test. 35 This discrepancy might be explained by considering that the SJW-induced antinociception is endowed with a bell-shaped trend. The authors looked for an increase in the pain threshold at a concentration about 15 times higher than the effective ones.…”

Section: Discussionmentioning

confidence: 99%

“…In agreement with our findings, recent experiments performed in the mouse formalin test observed that the SJW antinociception was unaffected by naloxone. 35 It should also be noted that different mechanisms have been proposed for hyperforin, 23 including mechanisms that might be involved in the modulation of the pain threshold. For these reasons, mechanisms other than the opioid cannot be excluded.…”

Section: Binding Of [mentioning

confidence: 99%

“…35 Thus, the aim of this study was to characterize the antinociceptive profile of SJW with the mechanism that might underlie this effect in a condition of acute thermal (hot-plate test) and chemical (abdominal-constriction test) pain. The role of the SJW main components-hypericin, hyperforin, and flavonoids-in the modulation of the pain threshold was also investigated since, at present, very little is known on this aspect.…”

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confidence: 99%

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A prolonged protein kinase C-mediated, opioid-related antinociceptive effect of St. John's Wort in mice

Galeotti¹,

Vivoli²,

Bilia³

et al. 2010

Planta Med

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The antinociceptive profile of St. John's Wort (SJW) was investigated in mice in a condition of acute thermal and chemical pain, together with the mechanism that might underlie this effect. A dried extract of SJW induced a prolonged antinociception that persisted for 120 minutes after administration. The thermal antinociception was prevented by naloxone and by the protein kinase C (PKC) activator PMA, whereas the chemical antinociception was prevented by PMA, remaining naloxone insensitive. A chloroform (CHL) and a methanol (MET) fraction, obtained to investigate the involvement of the SJW main components, hyperforin and hypericin/flavonoid, respectively, increased pain threshold with a time course comparable to the dried extract. The CHL antinociception was prevented by naloxone, whereas the MET antinociception was antagonized by PMA. Purified hyperforin and hypericin showed an antinociceptive efficacy comparable to CHL and MET, respectively. Conversely, flavonoids were devoid of any effect. The administration of yohimbine and atropine did not modify SJW, CHL and MET antinociception. These results indicate that both CHL and MET fractions mediate the SJW-induced antinociception. In particular, the presence of hypericin was fundamental to induce both thermal and chemical antinociception through the inhibition of the PKC activity, whereas hyperforin selectively produced a thermal opioid antinociception.Perspective: This article presents evidence of a persistent thermal and chemical antinociception of SJW that is mainly mediated by PKC-inhibiting mechanisms. These findings identify important targets for a longer-acting activation of endogenous pain systems and should potentially help clinicians who seek safe, tolerable, and prolonged treatments for pain relief. H ypericum perforatum L., popularly called St. John's Wort (SJW), is a herbaceous perennial plant long known for its putative medicinal properties. It has been used, topically, in popular medicine since ancient times for the treatment of skin wounds, eczema, burns and inflammation. 2,6 In 1525, the Swiss physician Paracelsus established its use for the treatment of psychiatric disorders; since then, it has been used in traditional European medicine to treat neuralgia, anxiety, neurosis, and depression.5 Although clinical trials have given contradictory results, alcoholic extracts of SJW are presently used mainly for the treatment of mild-to-moderate forms of depression as an alternative to classic antidepressants, with a favorable side-effect profile. 21The most common SJW preparations used are hydroalcoholic extracts of the aerial portion of the plant. These contain at least 10 different kinds of biochemical compounds: flavonoids (including rutin, hyperoside, quercetin, and quercitrin), naphtodianthrones (including hypericin and pseudohypericin), acylphloroglucinols (including hyperforin and adhyperforin), proanthocyanidins, procyanidines, tannins, essential oils, amino acids, phenylpropanes, xantones, and other hydrosoluble compounds (organic aci...

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Antinociceptive Effects of St. John's Wort, Harpagophytum Procumbens Extract and Grape Seed Proanthocyanidins Extract in Mice

Cited by 62 publications

References 36 publications

St. John's Wort reduces neuropathic pain through a hypericin-mediated inhibition of the protein kinase C γ and ɛ activity

St. John's Wort reduces neuropathic pain through a hypericin-mediated inhibition of the protein kinase C γ and ɛ activity

Grape seed proanthocyanidin extract ameliorates monosodium iodoacetate-induced osteoarthritis

A prolonged protein kinase C-mediated, opioid-related antinociceptive effect of St. John's Wort in mice

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