Oral treatment with Berberine reduces peripheral nociception: Possible interaction with different nociceptive pathways activated by different allogeneic substances.

ETHNOPHARMACOLOGICAL RELEVANCE: Berberine was identified in extracts of Berberis ruscifolia Lam., a plant used in traditional medicine as an analgesic. Its presence may be involved in the reported pharmacological activity of this species. However, there is still a lack of scientific research concerning its analgesic activity in the peripheral nervous system. AIM OF THE STUDY: To investigate Berb-induced antinociception in the formalin test and to evaluate several pathways related to its pharmacological antinociceptive effects in chemical models of nociception in mice. MATERIALS AND METHODS: The antinociceptive activity of Berb was assessed by inducing the paw licking in mice with different allodynic agents. In the formalin test, the antiedematous and antithermal effect of Berb was evaluated simultaneously in the same experiment. Other nociceptive behavior produced by endogenous [prostaglandin E2 (PGE2), histamine (His), glutamate (Glu) or bradykinin (BK)] or exogenous [capsaicin (Caps) and cinnamaldehyde (Cin)] chemical stimuli, and activators as protein kinase A (PKA) and C (PKC), were also evaluated.The in vivo doses for p.o. were 3 and 30 mg/kg. RESULTS: Berb, at 30 mg/kg p.o., showed a significant inhibition of the nociceptive action in formalin in both phases being stronger at the inflammatory phase (59 ± 9%) and more active than Asp (positive control) considering the doses evaluated. Moreover, Berb inhibited the edema (34 ± 10%), but not the temperature in the formalin test. Regarding the different nociceptive signaling pathways evaluated, the most relevant data were that the administration of p.o. of Berb, at 30 mg/kg, caused significant inhibition of nociception induced by endogenous [His (72 ± 11%), PGE2 (78 ± 4%), and BK (51 ± 7%)], exogenous [Cap (68 ± 4%) and Cinn (57 ± 5%)] compounds, and activators of the PKA [(FSK (86 ± 3%)] and PKC [(PMA(86 ± 6%)] signaling pathway. Berb did not inhibit the nociceptive effect produced by Glu. CONCLUSION: The present study demonstrated, for the first time, the potential of Berb in several nociceptive tests, with the compound present in B. ruscifolia contributing to the analgesic effect reported for this species.

Antinociceptive effect and identification of berberine alkaloid in Berberis ruscifolia extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: Aerial parts (leaves and stems) of Berberis ruscifolia Lam. are a usual preparation as an analgesic, anti-inflammatory, antimalarial, antibacterial, and digestive in folk medicine. However, there were no previous studies of its chemical composition and biological activity related to analgesic effects. THE OBJECTIVE OF THE STUDY: The evaluation of the anti-nociception of the infusion (I), the decoction (D), and the ethanolic extract (EE) obtained from aerial parts of B. ruscifolia and its main chemical constituent in them, in mouse models. MATERIAL AND METHODS: The chemical constituent of B. ruscifolia extracts was evaluated and quantified by LC-MS and HPLC methodology. The inhibition of nociception in mice was analyzed by formalin and acetic acid-induced contortions tests. Also, when the formalin test was performed to evaluate the antinociceptive activity, the inhibition of edema formation and the antipyretic effect of each extract were simultaneously evaluated in the same experiment. For the oral administration in the in vivo assays, doses ranging from 10 to 1000 mg/kg and 10-30 mg/kg were used for extract and the chemical compound, respectively. RESULTS: The presence of berberine (Berb) was identified in the three evaluated extracts where the EE showed the highest content of this compound getting a yield of 2%, while in the I and D, Berb is present at 0.2%. The three extracts promoted a reduction of the contortions induced by acetic acid, being observed in EE the highest activity with 63 ± 6% of significant inhibition of the nociceptive behavior at a dose of 300 mg/kg, while D significantly inhibited 32 ± 12% at the same dose and for I at a dose of 1000 mg/kg an inhibition of 44 ± 8% was observed. Likewise, in the formalin trial, I and EE reduced nociception at a dose of 1000 (31 ± 5%) and 300 (35 ± 3%) mg/kg, respectively in the neurogenic phase, while in the second phase of the experiment, all the extracts evaluated showed an antinociceptive effect, with significant inhibition of I of 54 ± 6% and D of 44 ± 5% at a dose of 1000 mg/kg and for EE showed a 63 ± 2% inhibition at a dose of 300 mg/kg being the one with the highest antinociceptive activity. These extracts showed no inhibition in temperature and formalin-injected paw edema formation when compared to the control. As for Berb, at a 30 mg/kg dose, it showed significant inhibition of 70 ± 5% in the acetic acid-induced contortion test. CONCLUSION: Altogether, the present results evidenced the analgesic properties of B. ruscifolia, scientific information presented for the first time, and also provided important knowledge not reported so far about the chemical composition of its extracts, by identifying the presence of Berb in them. Finally, we were able to conclude that the analgesic effect demonstrated by this medicinal plant is partly due to the presence of Berb.

Molecular Characterization of Carbapenem-Resistant Acinetobacter baumannii in the Intensive Care Unit of Uruguay's University Hospital Identifies the First rmtC Gene in the Species.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections are an increasing concern in intensive care units (ICUs) worldwide. The combination of carbapenemases and 16S rRNA-methyltransferases (16S-RMTases) further reduces the therapeutic options. OXA-carbapenemase/A. baumannii clone tandems in Latin America have already been described; however, no information exists in this region regarding the occurrence of 16S-RMTases in this microorganism. In addition, the epidemiology of A. baumannii in ICUs and its associated resistance profiles are poorly understood. Our objectives were as follows: to study the clonal relationship and antibiotic resistance profiles of clinical and digestive colonizing A. baumannii isolates in an ICU, to characterize the circulating carbapenemases, and to detect 16S-RMTases. Patients admitted between August 2010 and July 2011 with a clinically predicted hospital stay > 48 hr were included. Pharyngeal and rectal swabs were obtained during the first fortnight after hospitalization. Resistance profiles were determined with MicroScan® and VITEK2 system. Carbapenemases and 16S-RMTases were identified by PCR and sequencing, and clonality was assessed by pulsed-field gel electrophoresis and multilocus sequence typing. Sixty-nine patients were studied and 63 were diagnosed with bacterial infections. Among these, 29 were CRAB isolates; 49 A. baumannii were isolated as digestive colonizers. These 78 isolates were clustered in 7 pulsetypes, mostly belonging to ST79. The only carbapenemase genes detected were blaOXA-51 (n = 78), blaOXA-23 (n = 62), and blaOXA-58 (n = 3). Interestingly, two clinical isolates harbored the rmtC 16S-RMTase gene. To the best of our knowledge, this is the first description of the presence of rmtC in A. baumannii.