ORCID Profile
0000-0003-2884-5227
Current Organisations
Victoria University of Wellington
,
University of Oxford
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Publisher: Wiley
Date: 04-2020
Publisher: Frontiers Media SA
Date: 13-04-2021
DOI: 10.3389/FENDO.2021.615446
Abstract: Asperuloside is an iridoid glycoside found in many medicinal plants that has produced promising anti-obesity results in animal models. In previous studies, three months of asperuloside administration reduced food intake, body weight, and adipose masses in rats consuming a high fat diet (HFD). However, the mechanisms by which asperuloside exerts its anti-obesity properties were not clarified. Here, we investigated homeostatic and nutrient-sensing mechanisms regulating food intake in mice consuming HFD. We confirmed the anti-obesity properties of asperuloside and, importantly, we identified some mechanisms that could be responsible for its therapeutic effect. Asperuloside reduced body weight and food intake in mice consuming HFD by 10.5 and 12.8% respectively, with no effect on mice eating a standard chow diet. Fasting glucose and plasma insulin were also significantly reduced. Mechanistically, asperuloside significantly reduced hypothalamic mRNA ghrelin, leptin, and pro-opiomelanocortin in mice consuming HFD. The expression of fat lingual receptors (CD36, FFAR1-4), CB1R and sweet lingual receptors (TAS1R2-3) was increased almost 2-fold by the administration of asperuloside. Our findings suggest that asperuloside might exert its therapeutic effects by altering nutrient-sensing receptors in the oral cavity as well as hypothalamic receptors involved in food intake when mice are exposed to obesogenic diets. This signaling pathway is known to influence the subtle hypothalamic equilibrium between energy homeostasis and reward-induced overeating responses. The present pre-clinical study demonstrated that targeting the gustatory system through asperuloside administration could represent a promising and effective new anti-obesity strategy.
Publisher: MDPI AG
Date: 18-10-2022
DOI: 10.3390/ENDOCRINES3040055
Abstract: Obesity produces a systemic low-grade inflammation associated with many adverse health conditions and, as we recently learned, with complications of COVID-19. Functional studies in animal models have demonstrated that asperuloside, an iridoid glycoside found in many medicinal plants, has produced promising anti-obesity results. However, the safety profile and the anti-inflammatory properties of asperuloside remain unknown. Here, we confirmed the previously reported anti-obesity properties of asperuloside, and, importantly, we performed toxicity studies assessing cell viability providing a dose reference for future animal experiments. Asperuloside significantly reduced blood levels of leptin and the mRNA levels of orexigenic peptides, such as NPY and AgRP in mice consuming HFD, with no effect on mice eating a standard chow diet. In addition, our results indicate that ASP reduced both hypothalamic and hepatic mRNA levels of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-α as well as the blood levels of plasminogen activator inhibitor-1 (PAI-1), which are known to play a major role in the development of insulin resistance and cardiovascular complications. Collectively, our findings suggest that asperuloside is a safe compound for long-term use in animal models and that it reduces the elevated levels of pro-inflammatory cytokines occurring in obesity.
Publisher: Elsevier BV
Date: 11-2022
DOI: 10.1016/J.PHARMTHERA.2022.108195
Abstract: Post-traumatic stress disorder (PTSD), characterized by abnormally persistent and distressing memories, is a chronic debilitating condition in need of new treatment options. Current treatment guidelines recommend psychotherapy as first line management with only two drugs, sertraline and paroxetine, approved by U.S. Food and Drug Administration (FDA) for treatment of PTSD. These drugs have limited efficacy as they only reduce symptoms related to depression and anxiety without producing permanent remission. PTSD remains a significant public health problem with high morbidity and mortality requiring major advances in therapeutics. Early evidence has emerged for the beneficial effects of psychedelics particularly in combination with psychotherapy for management of PTSD, including psilocybin, MDMA, LSD, cannabinoids, ayahuasca and ketamine. MDMA and psilocybin reduce barrier to therapy by increasing trust between therapist and patient, thus allowing for modification of trauma related memories. Furthermore, research into the memory reconsolidation mechanisms has allowed for identification of various pharmacological targets to disrupt abnormally persistent memories. A number of pre-clinical and clinical studies have investigated novel and re-purposed pharmacological agents to disrupt fear memory in PTSD. Novel therapeutic approaches like neuropeptide Y, oxytocin, cannabinoids and neuroactive steroids have also shown potential for PTSD treatment. Here, we focus on the role of fear memory in the pathophysiology of PTSD and propose that many of these new therapeutic strategies produce benefits through the effect on fear memory. Evaluation of recent research findings suggests that while a number of drugs have shown promising results in preclinical studies and pilot clinical trials, the evidence from large scale clinical trials would be needed for these drugs to be incorporated in clinical practice.
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.JPSYCHIRES.2022.03.045
Abstract: Post-traumatic stress disorder (PTSD) develops after an exposure to a life-threatening event and is characterized by intrusive memories. According to memory reconsolidation theory retrieval of memory under certain conditions leads to its labilization and subsequent re-storage which could be disrupted by drugs. Propranolol has been the most commonly investigated drug for memory reconsolidation therapy in clinical trials. Intervention with propranolol have shown mixed results in PTSD patients with some studies showing improvement in symptoms while other failing to replicate these findings. We conducted a systematic review and meta-analysis to determine the efficacy of trauma memory disruption by propranolol on PTSD symptoms and physiological responses in PTSD patients. 3224 publications were assessed for eligibility. Seven studies on effects of propranolol on PTSD symptoms and 3 studies on effects of propranolol on physiological responses were incorporated in the meta-analyses. Overall, results indicate that propranolol did not show a beneficial effect on PTSD symptoms (standardized mean difference: 1.29 95% CI = -2.16 - 0.17). Similarly, propranolol did not influence skin conductance (standardized mean difference: 0.77 95% CI = -1.85 - 0.31) or EMG response (standardized mean difference: 0.16 95% CI = -0.65 - 0.33). However, propranolol significantly reduced heart rate after trauma memory recall compared to placebo (standardized mean difference: 0.67 95% CI = -1.27 to -0.07). This study finds a lack of evidence for the efficacy of propranolol on traumatic memory disruption, in PTSD patients, to recommend its routine clinical use. However, a high level of heterogeneity, variation in propranolol dosage and inadequate s le sizes mean that these findings require cautious interpretation.
Publisher: Informa UK Limited
Date: 23-08-2022
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Juan J. Canales.