Center for Innovative Biomedicine and Biotechnology

Funder

Organizational Unit

Publications

Comparative studies on the photoreactivity, efficacy, and safety of depigmenting agents

Publication . Mota, Sandra; Rosa, Gonçalo P.; Barreto, Maria Carmo; Garrido, Jorge; Sousa, Emília; Cruz, Maria T.; Almeida, Isabel F.; Quintas, Clara

Depigmenting products are increasingly used to counteract skin hyperpigmentation and related psychosocial issues. This study aimed to compare different depigmenting agents—4-butylresorcinol; bakuchiol; tranexamic acid; ascorbyl glucoside; α-arbutin; and ascorbic acid—for photoreactivity; tyrosinase inhibition; and safety. Photoreactivity was assessed using the Reactive Oxygen Species assay. In vitro tyrosinase inhibition was compared, and cell viability was assessed in B-16V melanocytes to evaluate safety. Results showed 4-butylresorcinol, ascorbyl glucoside, and α-arbutin are non-photoreactive, while for ascorbic acid and bakuchiol it was not possible to reach conclusive results due to the lack of specificity of the ROS assay. 4-Butylresorcinol, acting as a competitive inhibitor, displayed potent tyrosinase inhibition, followed by ascorbic acid and bakuchiol. Both 4-butylresorcinol and bakuchiol reduced cell viability in a concentration-dependent manner. The insights obtained in this work support the development of depigmenting products by providing useful scientific guidance on the photostability, tyrosinase inhibitory efficacy, and skin safety of depigmenting agents.

2023Journal article

Open access

Boosting caffeic acid performance as antioxidant and monoamine oxidase B/catechol-O-methyltransferase inhibitor

Publication . Chavarria, Daniel; Benfeito, Sofia; Soares, Pedro; Lima, Carla; Garrido, Jorge; Serrão, Paula; Soares-da-Silva, Patrício; Remião, Fernando; Oliveira, Paulo J.; Borges, Fernanda

Increased oxidative stress (OS) and depletion of nigrostriatal dopamine (DA) are closely linked to the neurodegeneration observed in Parkinson’s Disease (PD). Caffeic acid (CA)-based antioxidants were developed, and their inhibitory activities towards monoamine oxidases (MAOs) and catechol O-methyltransferases (COMT) were screened. The results showed that the incorporation of an extra double bond maintained or even boosted the antioxidant properties of CA. α-CN derivatives displayed redox potentials (Ep) similar to CA (1) and inhibited hMAO-B with low μM IC50 values. Moreover, catechol amides acted as MB-COMT inhibitors, showing IC50 values within the low μM range. In general, CA derivatives presented safe cytotoxicity profiles at concentrations up to 10 μM. The formation of reactive oxygen species (ROS) induced by CA derivatives may be underlying the cytotoxic effects observed at higher concentrations. Catechol amides 3–6, 8–11 at 10 μM protected cells against oxidative damage. Compounds 3 and 8 were predicted to cross the blood-brain barrier (BBB) by passive diffusion. In summary, we report for the first time BBB-permeant CA-based multitarget lead compounds that may restore DAergic neurotransmission (dual hMAO-B/MB-COMT inhibition) and prevent oxidative damage. The data represents a groundbreaking advancement towards the discovery of the next generation of new drugs for PD.

2022Journal article

Restricted access

Microglia dysfunction caused by the loss of rhoa disrupts neuronal physiology and leads to neurodegeneration

Publication . Socodato, Renato; Portugal, Camila C.; Canedo, Teresa; Rodrigues, Artur; Almeida, Tiago O.; Henriques, Joana F.; Vaz, Sandra H.; Magalhães, João; Silva, Cátia M.; Baptista, Filipa I.; Alves, Renata L.; Coelho-Santos, Vanessa; Silva, Ana Paula; Paes-de-Carvalho, Roberto; Magalhães, Ana; Brakebusch, Cord; Sebastião, Ana M.; Summavielle, Teresa; Ambrósio, António F.; Relvas, João B.

Nervous tissue homeostasis requires the regulation of microglia activity. Using conditional gene targeting in mice, we demonstrate that genetic ablation of the small GTPase Rhoa in adult microglia is sufficient to trigger spontaneous microglia activation, producing a neurological phenotype (including synapse and neuron loss, impairment of long-term potentiation [LTP], formation of β-amyloid plaques, and memory deficits). Mechanistically, loss of Rhoa in microglia triggers Src activation and Src-mediated tumor necrosis factor (TNF) production, leading to excitotoxic glutamate secretion. Inhibiting Src in microglia Rhoa-deficient mice attenuates microglia dysregulation and the ensuing neurological phenotype. We also find that the Rhoa/Src signaling pathway is disrupted in microglia of the APP/PS1 mouse model of Alzheimer disease and that low doses of Aβ oligomers trigger microglia neurotoxic polarization through the disruption of Rhoa-to-Src signaling. Overall, our results indicate that disturbing Rho GTPase signaling in microglia can directly cause neurodegeneration.

2020Journal article

Open access