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Shikonin possess a diverse spectrum of pharmacological properties in multiple therapeutic areas. However, the nociceptive effect of shikonin is not largely known. To investigate the antinociceptive potential of shikonin, panel of GPCRs, ion channels, and enzymes involved in pain pathogenesis were studied. To evaluate the translation of shikonin efficacy in vivo, it was tested in 3 established rat pain models. Our study reveals that shikonin has significant inhibitory effect on pan sodium channel/N1E115 and NaV1.7 channel with half maximal inhibitory concentration (IC50) value of 7.6 µmol/L and 6.4 µmol/L, respectively, in a cell-based assay. Shikonin exerted significant dose dependent antinociceptive activity at doses of 0.08%, 0.05%, and 0.02% w/v in pinch pain model. In mechanical hyperalgesia model, dose of 10 and 3 mg/kg (intraperitoneal) produced dose-dependent analgesia and showed 67% and 35% reversal of hyperalgesia respectively at 0.5 h. Following oral administration, it showed 39% reversal at 30 mg/kg dose. When tested in first phase of formalin induced pain, shikonin at 10 mg/kg dose inhibited paw flinching by ~71%. In all studied preclinical models, analgesic effect was similar or better than standard analgesic drugs. The present study unveils the mechanistic role of shikonin on pain modulation, predominantly via sodium channel modulation, suggesting that shikonin could be developed as a potential pain blocker. Key words: shikonin, pain, ion channel, sodium channel, NaV1.7, pinch pain, hyperalgesia, formalin induced pain. La shikonine est dotee d'une vaste gamme de proprietes pharmacologiques applicables dans de nombreux domaines therapeutiques. Cependant, on ne connait pas tres bien les effets de la shikonine sur la nociception. Nous avons donc etudie les effets antinociceptifs eventuels de la shikonine ainsi qu'un ensemble de recepteurs couples aux proteines G et des canaux ioniques et enzymes intervenant dans la pathogenese de la douleur. Pour ce faire, nous avons utilise 3 modeles de douleur bien etablis chez le rat pour evaluer la transposition de l'efficacite de la shikonine in vivo. A l'aide d'un test cellulaire, nos travaux ont revele que la shikonine avait un effet inhibiteur notable sur les canaux sodiques non specifiques exprimes par la lignee N1E115 et les canaux NaV1.7, avec une CI50 de 7,6 et de 6,4 µmol/L, respectivement. Par ailleurs, la shikonine avait un important effet antinociceptif dependant de la dose a 0,08 %, 0,05 % et 0,02 % p/v dans un modele de pincement douloureux. De plus, l'administration par voie intraperitoneale de 10 et de 3 mg/kg du produit a permis d'obtenir, dans un modele d'hyperalgie mecanique, une analgesie dependante de la dose avec retrocession de l'hyperalgesie de 67 % et de 35 %, respectivement, apres 0,5 h. En revanche, la retrocession de l'hyperalgesie etait de 39 % a la dose de 30 mg/kg. Nous avons aussi observe que l'administration de shikonine a raison de 10 mg/kg permettait d'inhiber le tressaillement de la patte d'environ 71 %. Dans tous les modeles precliniques etudies, l'effet analgesique de la shikonine etait similaire ou superieur a celui des analgesiques standard. En somme, la presente etude revele l'importance mecanistique de la shikonine dans la modulation de la douleur, principalement par la modulation du canal sodique, ce qui laisse presumer que l'on pourrait developper la shikonine en tant qu'inhibiteur de la douleur. [Traduit par la Redaction] Mots-cles: shikonine, douleur, canal ionique, canal sodique, NaV1.7, douleur au pincement, hyperalgesie, douleur causee par la formaline., Introduction Shikonin is a natural medicinal substance, found in the roots of Lithospermum erythrorhizon. Arnebia hispidissima is another plant, mostly confined to Asia, that also contains shikonin pigment in its [...]

Salvia is the largest genus of plants in the mint family and is one of the important medicinal plants. Salvia spp. are valued for essential oil, flavor compounds and their possible uses have been registered as an antisweating agent, antibiotic, antifungal, astringent, antispasmodic, estrogenic, hypoglycemic and tonic agents. In the present investigation the specie, Salvia moorcroftiana was for the first time found infected with Sclerotium rolfsii Sacc. in Himachal Pradesh (India) causing typical crown rot symptoms, the losses of which amounted upto 25% in plantation areas surveyed during June-September 2011-12. Initially the symptoms appeared as yellowing and drooping of leaves proceeded by browning and later the leaves get distorted with wilting of plants and white cottony mycelial growth at the collar region. The mycelial growth spread to the stem and roots, with associated tissue rotting. The morphological characters of the crown rot causing fungus resembles to Sclerotium rolfsii. The botanicals and fungicides were considered for possible management of the disease. Out of eight plant leaf extracts, only three Melia azedarach, Bougainvellia and Aloe barbidensis showed high efficacy and recorded maximum inhibition of mycelial growth of the test pathogen (S. rolfsii) by 62.80, 58.61 and 55.34% over control under in vitro. Similarly fungicides, chlorothalonil, propineb, carbendazim and benlate not only reduced the disease incidence but improved the seed germination of the infected seeds and final plant stand with minimum pre- and post-emergence mortality rate hence can be recommended in managing the crown rot disease in Salvia moorcroftiana. [ABSTRACT FROM AUTHOR]