betadex and bisabolol

Inflammatory arthritis is the most prevalent chronic inflammatory disease worldwide. The pathology of the disease is characterized by increased inflammation and oxidative stress, which leads to chronic pain and functional loss in the joints. Conventional anti-arthritic drugs used to relieve pain and other arthritic symptoms often cause severe side effects. α-bisabolol (BIS) is a sesquiterpene that exhibits high anti-inflammatory potential and a significant antinociceptive effect. This study evaluates the anti-arthritic, anti-inflammatory and antihyperalgesic effects of BIS alone and in a β-cyclodextrin (βCD/BIS) inclusion complex in a CFA-induced arthritis model. Following the intra-articular administration of CFA, male mice were treated with vehicle, BIS and βCD/BIS (50 mg/kg, p.o.) or a positive control and pain-related behaviors, knee edema and inflammatory and oxidative parameters were evaluated on days 4, 11, 18 and/or 25. Ours findings shows that the oral administration of BIS and βCD/BIS significantly attenuated spontaneous pain-like behaviors, mechanical hyperalgesia, grip strength deficit and knee edema induced by repeated injections of CFA, reducing the joint pain and functional disability associated with arthritis. BIS and βCD/BIS also inhibited the generation of inflammatory and oxidative markers in the knee and blocked MAPK in the spinal cord. In addition, ours results also showed that the incorporation of BIS in cyclodextrin as a drug delivery system improved the pharmacological profile of this substance. Therefore, these results contribute to the pharmacological knowledge of BIS and demonstrated that this terpene appears to be able to mitigate deleterious symptoms of arthritis.

Topics: Animals; Anti-Inflammatory Agents; Arthritis; Arthritis, Experimental; beta-Cyclodextrins; Chronic Pain; Disease Models, Animal; Edema; Hyperalgesia; Interleukin-1beta; Interleukin-6; Male; Mice; Monocyclic Sesquiterpenes

Chronic pain is a continuous or recurring pain which exceeds the normal course of recovery to an injury or disease. According to the origin of the chronic pain, it can be classified as inflammatory or neuropathic. This study aimed to evaluate the antinociceptive and anti-inflammatory effect of (-)-α-bisabolol (BIS) alone and complexed with β-cyclodextrin (βCD) in preclinical models of chronic pain. Chronic pain was induced by Freund's Complete Adjuvant (FCA) or partial lesion of the sciatic nerve (PLSN). Swiss mice were treated with BIS, BIS-βCD (50 mg/kg, p.o) or vehicle (control) and mechanical hyperalgesia, thermal hyperalgesia, muscle strength and motor coordination were evaluated. In addition, levels of TNF-α and IL-10 and expression of the ionized calcium-binding adapter protein (IBA-1) were assessed in the spinal cord of the mice. The complexation efficiency of BIS in βCD was evaluated by High-Performance Liquid Chromatography. BIS and BIS-βCD reduced (p < 0.001) mechanical and thermal hyperalgesia. No alterations were found in force and motor coordination. In addition, BIS and BIS-βCD inhibited (p < 0.05) TNF-α production in the spinal cord and stimulated (p < 0.05) the release of IL-10 in the spinal cord in PLSN-mice. Further, BIS and BIS-βCD reduced IBA-1 immunostaining. Therefore, BIS and BIS-βCD attenuated hyperalgesia, deregulated cytokine release and inhibited IBA-1 expression in the spinal cord in the PLSN model. Moreover, our results show that the complexation of BIS in βCD reduced the therapeutic dose of BIS. We conclude that BIS is a promising molecule for the treatment of chronic pain.

Topics: Animals; beta-Cyclodextrins; Calcium-Binding Proteins; Cytokines; Freund's Adjuvant; Gliosis; Hot Temperature; Hyperalgesia; Inflammation; Male; Mice; Microfilament Proteins; Monocyclic Sesquiterpenes; Muscle Strength; Neuralgia; Psychomotor Performance; Sciatic Neuropathy; Spinal Cord; Stereoisomerism

Vanillosmopsis arborea Baker has recognized economic value owing to the high content of (-)-α-bisabolol (BISA) in the essential oil of its stem (EOVA). The antinociceptive effect of EVOA has already been demonstrated, and β-cyclodextrin (βCD) is known to improve the analgesic effect of various substances.. Thus, we aimed to evaluate the orofacial antinociceptive effect of a complex containing EOVA-βCD in rodents.. EOVA was obtained by simple hydrodistillation, and the essential oil was complexed with βCD. The animals (n = 6/group) were treated orally with EOVA-βCD (10 or 50 mg/kg), or vehicle (control), and subjected to cutaneous orofacial nociception (formalin, capsaicin, acidic saline or glutamate), corneal (hypertonic saline) or temporomandibular (formalin) tests. The expression of FOS protein was analyzed in the spinal cord. Molecular docking was performed using the 5-HT. The oral administration of EOVA-βCD reduced nociceptive behaviour. Moreover, EOVA-βCD decreased FOS expression. The molecular docking study indicates that BISA interacts with 5-HT3 and M2 receptors, indicating the potential mechanism of action of the tested compound.. Our results indicate that EOVA-βCD possesses orofacial antinociceptive effect, indicating that this complex can be used in analgesic drug development.

Topics: Analgesics; Animals; Asteraceae; beta-Cyclodextrins; Facial Pain; Male; Monocyclic Sesquiterpenes; Nociception; Oils, Volatile; Plant Extracts; Plant Stems; Rodentia; Sesquiterpenes

The present study aimed to evaluate the antibacterial and modulatory potential of α-bisabolol, β-cyclodextrin and α-bisabolol/β-cyclodextrin complex. The minimum inhibitory concentration was determined through the broth microdilution technique using the bacterial strains: Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. The drugs norfloxacin, imipenem and gentamicin were used in the tests, and the compounds α-bisabolol and β-cyclodextrin; all the compounds were diluted in DMSO. To obtain the minimum inhibitory concentration (MIC) a serial microdilution of the substances in volumes corresponding to the sub-inhibitory concentration (MIC/8), and microdilution with the antibiotic until the penultimate well were performed. The results showed that β-cyclodextrin did not present synergistic effects when combined with the antibiotics. It was found that α-bisabolol presented a synergistic effect against S. aureus, when combined with the antibiotic norfloxacin. Moreover, α-bisabolol presented synergism against E. coli when combined with gentamicin. The results of this study show that α-bisabolol presents a modulatory synergistic effect for some antibiotics, as gentamicin, and this is an interesting result against multidrug resistant bacteria (MDR). By other side, the complexation of α-bisabolol with β-cyclodextrin apparently reduces the modulatory effect, maybe due the polarity enhancement of the polarity of α-bisabolol, affecting the interaction of this compound with the cell membrane bilayer. However, more studies are necessary to demonstrate or not these interactions.

Topics: alpha-Cyclodextrins; Anti-Bacterial Agents; beta-Cyclodextrins; Drug Compounding; Drug Resistance, Multiple, Bacterial; Drug Synergism; Escherichia coli; Gentamicins; Microbial Sensitivity Tests; Monocyclic Sesquiterpenes; Norfloxacin; Pseudomonas aeruginosa; Sesquiterpenes; Staphylococcus aureus

The present research deals with the multi-collection of the most important sesquiterpene alcohols belonging to sandalwood essential oil, as reported by the international regulations: (Z)-α-santalol, (Z)-α-trans bergamotol, (Z)-β-santalol, epi-(Z)-β-santalol, α-bisabolol, (Z)-lanceol, and (Z)-nuciferol. A versatile multidimensional preparative system, based on the hyphenation of liquid and gas chromatography techniques, was operated in the LC-GC-GC-prep or GC-GC-GC-prep configuration, depending on the concentration to be collected from the sample, without any hardware or software modification. The system was equipped with a silica LC column in combination with polyethylene glycol-poly(5% diphenyl/95% dimethylsiloxane)-medium polarity ionic liquid or β-cyclodextrin based GC stationary phases. The GC-GC-GC-prep configuration was exploited for the collection of four components, by using a conventional split/splitless injector, while the LC-GC-GC-prep approach was applied for three low abundant components (<5%), in order to increase the quantity collected within a single run, by the LC injection of a high sample amount. All target compounds, whose determination is hampered by the unavailability of commercial standards, were collected at milligram levels and with a high degree of purity (>87%).

Topics: beta-Cyclodextrins; Chromatography, Gas; Chromatography, Liquid; Dimethylpolysiloxanes; Monocyclic Sesquiterpenes; Oils, Volatile; Plant Oils; Polycyclic Sesquiterpenes; Polyethylene Glycols; Santalum; Sesquiterpenes; Silicon Dioxide

(-)-Alpha-bisabolol was found to form an inclusion complex with beta-cyclodextrin (beta-CD) in solution as well as in the solid state. To investigate molecular associations of beta-CD with pure (-)-alpha-bisabolol or (-)-alpha-bisabolol as a component of camomile essential oil, phase solubility studies were undertaken. A B(s) type solubility with an apparent complex constant of 273 M(-1) for the pure (-)-alpha-bisabolol and 304 M(-1) for (-)-alpha-bisabolol as a constituent of the essential oil were obtained. The two curves in the phase solubility diagram reach their plateau at different concentrations of (-)-alpha-bisabolol, 7.04 x 10(-4) M for the pure substance and 2.88 x 10(-4) M for the substance as a component of the essential oil. Although the shapes of the curves are almost similar, the intrinsic solubility's of pure (-)-alpha-bisabolol (4.85 x 10(-4) M) and (-)-alpha-bisabolol as a component of the essential oil (1.82 x 10(-4) M) differ significantly. An inclusion complex having a stoichiometric composition of 2:1 (beta-CD: drug) was obtained. A mechanism of complexation has been proposed on the basis of the stability constant calculated from phase solubility data and the stoichiometric ratio of the solid state complexation.

Topics: beta-Cyclodextrins; Chamomile; Chemistry, Pharmaceutical; Chromatography, Gas; Cyclodextrins; Drug Stability; Ethanol; Models, Molecular; Monocyclic Sesquiterpenes; Oils, Volatile; Sesquiterpenes; Solubility; Surface Tension; Time Factors; Water