No abstract

Coffee is one of the most widely consumed beverages worldwide. It is usually identified as a stimulant because of a high content of caffeine. However, caffeine is not the only coffee bioactive component. The coffee beverage is in fact a mixture of a number of bioactive compounds such as polyphenols, especially chlorogenic acids (in green beans) and caffeic acid (in roasted coffee beans), alkaloids (caffeine and trigonelline), and the diterpenes (cafestol and kahweol). Extensive research shows that coffee consumption appears to have beneficial effects on human health. Regular coffee intake may protect from many chronic disorders, including cardiovascular disease, type 2 diabetes, obesity, and some types of cancer. Importantly, coffee consumption seems to be also correlated with a decreased risk of developing some neurodegenerative conditions such as Alzheimer’s disease, Parkinson’s disease, and dementia. Regular coffee intake may also reduce the risk of stroke. The mechanism underlying these effects is, however, still poorly understood. This review summarizes the current knowledge on the neuroprotective potential of the main bioactive coffee components, i.e., caffeine, chlorogenic acid, caffeic acid, trigonelline, kahweol, and cafestol. Data from both in vitro and in vivo preclinical experiments, including their potential therapeutic applications, are reviewed and discussed. Epidemiological studies and clinical reports on this matter are also described. Moreover, potential molecular mechanism(s) by which coffee bioactive components may provide neuroprotection are reviewed.

The purpose of the study was to investigate whether the co-administration of Mg2+ and Zn2+ with selective A1 and A2A receptor antagonists might be an interesting antidepressant strategy. Forced swim, tail suspension, and spontaneous locomotor motility tests in mice were performed. Further, biochemical and molecular studies were conducted. The obtained results indicate the interaction of DPCPX and istradefylline with Mg2+ and Zn2+ manifested in an antidepressant-like effect. The reduction of the BDNF serum level after co-administration of DPCPX and istradefylline with Mg2+ and Zn2+ was noted. Additionally, Mg2+ or Zn2+, both alone and in combination with DPCPX or istradefylline, causes changes in Adora1 expression, DPCPX or istradefylline co-administered with Zn2+ increases Slc6a15 expression as compared to a single-drug treatment, co-administration of tested agents does not have a more favourable effect on Comt expression. Moreover, the changes obtained in Ogg1, MsrA, Nrf2 expression show that DPCPX-Mg2+, DPCPX-Zn2+, istradefylline-Mg2+ and istradefylline-Zn2+ co-treatment may have greater antioxidant capacity benefits than administration of DPCPX and istradefylline alone. It seems plausible that a combination of selective A1 as well as an A2A receptor antagonist and magnesium or zinc may be a new antidepressant therapeutic strategy.

The purpose of this study was to determine if asiatic acid may act efficiently in the model of cyclophosphamide (CYP)-induced cystitis in rats. We performed experiments after administration of CYP (single dose 200 mg/kg, intraperitoneally), asiatic acid (30 mg/kg/day for 14 consecutive days, by oral gavage), or CYP plus asiatic acid, during which conscious cystometry, measurements of urothelium thickness and bladder edema, as well as selected biomarkers analyses were conducted. In rats that received asiatic acid together with CYP, a drop in bladder basal pressure, detrusor overactivity index, non-voiding contraction amplitude, non-voiding contraction frequency, and the area under the pressure curve were observed, when compared to the CYP group. Furthermore, a significant increase in threshold pressure, voided volume, intercontraction interval, bladder compliance, and volume threshold to elicit NVC were found in that group accordingly. Administration of the asiatic acid successfully restored concentrations of biomarkers both in bladder urothelium (BDNF, CGRP, OCT-3, IL-1β, IL-6, NGF, nitrotyrosine, malondialdehyde, TNF-α, SV2A, SNAP23, SNAP25, PAC-1, ORM1, occludin, IGFBP-3, HB-EGF, T–H protein, Z01, and HPX) and detrusor muscle (Rho kinase and VAChT) in CYP-treated rats. Finally, asiatic acid significantly decreased urothelium thickness and bladder oedema. Asiatic acid proved to be a potent and effective drug in the rat model of CYP-induced cystitis.

Scientists have been constantly looking for new synthetic and natural compounds that could have beneficial effects in bladder overactivity. Our attention was drawn by asiatic acid that influences a number of molecules and signaling pathways relevant for the proper functioning of the urinary tracts in humans. In the present project we wanted to check whether asiatic acid would have positive effects in the confirmed animal model of detrusor overactivity (DO) and whether it would affect the bladder blood flow, urothelium thickness, inflammatory and oxidative stress markers, neurotrophic and growth factors, and other parameters important for the activity of the urinary bladder. The outcomes of our study showed that a 14-day administration of asiatic acid (30 mg/kg/day) by oral gavage normalizes the cystometric parameters corresponding to DO and reduces the accompanying oxidative stress (measured by the levels of malondialdehyde–61,344 ± 24,908 pg/ml vs. 33,668 ± 5,071 pg/ml, 3-nitrotyrosine–64,615 ± 25,433 pg/ml vs. 6,563 ± 1,736 pg/ml, and NOS2–2,506 ± 411.7 vs. 3,824 ± 470.1 pg/ml). Moreover, it decreases the urinary secretion of neurotrophins (BDNF–304.4 ± 33.21 pg/ml vs. 119.3 ± 11.49 pg/ml and NGF–205.5 ± 18.50 vs. 109.7 ± 15.94 pg/ml) and prevents the changes in a range of biomarkers indicating the dysfunction of the urinary bladder, CGRP (421.1 ± 56.64 vs. 108.1 ± 11.73 pg/ml), E-Cadherin (773.5 ± 177.5 pg/ml vs. 1,560 ± 154.5 pg/ml), OCT3 (3,943 ± 814.6 vs. 1,018 ± 97.07 pg/ml), SNAP-23 (6,763 ± 808.9 pg/ml vs. 3,455 ± 554.5 pg/ml), SNAP-25 (2,038 ± 162.7 pg/ml vs. 833.3 ± 65.48), substance P (171.7 ± 16.86 pg/ml vs. 65.07 ± 8.250 pg/ml), SV2A (1,927 ± 175.3 pg/ml vs. 1,154 ± 254.9 pg/ml), tight junction protein 1 (360.1 ± 95.05 pg/ml vs. 563.4 ± 65.43 pg/ml), VAChT (16,470 ± 2,419 pg/ml vs. 7,072 ± 1,339 pg/ml), VEGFA (318.3 ± 37.89 pg/ml vs. 201.5 ± 22.91 pg/ml). The mentioned parameters are associated with smooth muscle contractions, urothelial barrier, transportation and release of transmitters, or bladder compensation. Thus, the presented findings allow to suggest a possible future role of asiatic acid in the prevention of conditions accompanied by DO, such as overactive bladder.