Crataegus almaatensis, an endemic ornamental plant in Kazakhstan is used in popular medicine due to its cardiotonic properties. The most studied species of the same genus are commonly found in Europe, which shows the importance of having the Kazakh species validated via its chemical and pharmacological studies. High-speed countercurrent chromatography (HSCCC) operated under optimized conditions enabled an isolation of the three main compounds from the aqueous phase of the leaves ethanol extract, further identified by nuclear magnetic resonance (NMR), as quercetin 3-O-rhamnoside (quercitrin) (4.02% of the crude extract-CECa); quercetin 3-O-β-galactoside (hyperoside) (1.82% of CECa); kaempferol 3-O-α-L-rhamnoside (afzelin) (0.94% of CECa). The CECa, the aqueous phase of the crude extract (APCa) together with the isolates were evaluated for their vascular (vascular reactivity in human internal mammary artery-HIMA), anti-nociceptive (formalin-induced liking response and hot plate) and anti-inflammatory (subcutaneous air-pouch model-SAP) activities. CECa at the concentrations of 0.014 and 0.14 mg/mL significantly increased the maximum contractility response of HIMA to noradrenaline. The APCa CR curve (0.007–0.7 mg/mL) showed an intrinsic relaxation effect of the HIMA. APCa at the dose of 100 mg/kg i.p. significantly decreased the total leukocyte count and the IL-1β release in the SAP wash.
Background Sinusoidal current stimuli preferentially activate C‐nociceptors. Sodium channel isoforms NaV1.7 and NaV1.8 have been implicated in this. Sympathetic efferent neurons lack NaV1.8 and were explored upon sinusoidal activation. Methods Quantitative Sudomotor Axon Reflex Test (QSART) was performed in hairy (n = 16) and glabrous (n = 12) skin. Responses of sympathetic efferents (n = 10) and nociceptive afferents (n = 21) to sinusoidal current stimulation (4 Hz, 0.05–0.15 mA) were recorded in humans by microneurography (n = 11). Activation of sympathetic units upon supra‐threshold sinusoidal currents (>0.8 mA) was recorded in pigs (n = 8). Results Sinusoidal stimuli (4 Hz, 0.4 mA) evoked weak sweat output (30 ml/h/m2) in hairy skin compared to rectangular pulses (4 Hz, 5 mA, 53 ml/h/m2, p < .00001, ANOVA). No change in sweat output was recorded from glabrous skin to sine wave stimuli. Sinusoidal current at intensities ranging from 0.05 to 0.15 mA activated almost all (85%) nociceptors but only 40% of sympathetic units in human. Stimuli lead to a significantly lower activation in sympathetic versus nociceptive fibres as measured by activity‐dependent slowing (ADS) of conduction (sympathetic efferents average ADS 100 ± 0.2% vs. C‐nociceptors average ADS 113 ± 4%, p < .003, ANOVA). Conclusions Sympathetic efferent neurons are less apt to convert slow depolarizations into action potentials as compared to nociceptors. Distinctive sodium channel expression patterns between nociceptors and sympathetic efferent neurons may account for this difference. Sinusoidal stimulation therefore provokes weak sweat responses and provides no alternative for clinical assessment of autonomic function. Significance C‐nociceptors in hairy skin are activated by 4 Hz sinusoidal current stimulation at lower intensities than myelinated fibres. Sympathetic efferent neurons—albeit also unmyelinated—are less responsive to sinusoidal activation than nociceptors within the same skin area. Cutaneous sympathetic efferent neurons apparently are less apt than nociceptors to convert slow depolarization into action potentials.
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