PMID- 36362104
OWN - NLM
STAT- MEDLINE
DCOM- 20221212
LR  - 20221212
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 21
DP  - 2022 Nov 1
TI  - Natural and Synthetic Xanthone Derivatives Counteract Oxidative Stress via Nrf2 
      Modulation in Inflamed Human Macrophages.
LID - 10.3390/ijms232113319 [doi]
LID - 13319
AB  - Natural products have attracted attention due to their safety and potential 
      effectiveness as anti-inflammatory drugs. Particularly, xanthones owning a unique 
      9H-xanthen-9-one scaffold, are endowed with a large diversity of medical 
      applications, including antioxidant and anti-inflammatory activities, because 
      their core accommodates a vast variety of substituents at different positions. 
      Among others, alpha- and gamma-mangostin are the major known xanthones purified from 
      Garcinia mangostana with demonstrated anti-inflammatory and antioxidant effects 
      by in vitro and in vivo modulation of the Nrf2 (nuclear factor erythroid-derived 
      2-like 2) pathway. However, the main mechanism of action of xanthones and their 
      derivatives is still only partially disclosed, and further investigations are 
      needed to improve their potential clinical outcomes. In this light, a library of 
      xanthone derivatives was synthesized and biologically evaluated in vitro on human 
      macrophages under pro-inflammatory conditions. Furthermore, structure-activity 
      relationship (SAR) studies were performed by means of matched molecular pairs 
      (MMPs). The data obtained revealed that the most promising compounds in terms of 
      biocompatibility and counteraction of cytotoxicity are the ones that enhance the 
      Nrf2 translocation, confirming a tight relationship between the xanthone scaffold 
      and the Nrf2 activation as a sign of intracellular cell response towards 
      oxidative stress and inflammation.
FAU - Gallorini, Marialucia
AU  - Gallorini M
AUID- ORCID: 0000-0002-2283-4159
AD  - Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, Via dei 
      Vestini 31, 66100 Chieti, Italy.
FAU - Carradori, Simone
AU  - Carradori S
AUID- ORCID: 0000-0002-8698-9440
AD  - Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, Via dei 
      Vestini 31, 66100 Chieti, Italy.
FAU - Resende, Diana I S P
AU  - Resende DISP
AUID- ORCID: 0000-0002-4077-6060
AD  - Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical 
      Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
AD  - CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, Avenida 
      General Norton de Matos, S/N, 4450-208 Matosinhos, Portugal.
FAU - Saso, Luciano
AU  - Saso L
AUID- ORCID: 0000-0003-4530-8706
AD  - Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza 
      University of Rome, P. le Aldo Moro 5, 00185 Rome, Italy.
FAU - Ricci, Alessia
AU  - Ricci A
AUID- ORCID: 0000-0002-9033-0104
AD  - Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, Via dei 
      Vestini 31, 66100 Chieti, Italy.
FAU - Palmeira, Andreia
AU  - Palmeira A
AUID- ORCID: 0000-0002-1391-2143
AD  - Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical 
      Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
AD  - CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, Avenida 
      General Norton de Matos, S/N, 4450-208 Matosinhos, Portugal.
FAU - Cataldi, Amelia
AU  - Cataldi A
AD  - Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, Via dei 
      Vestini 31, 66100 Chieti, Italy.
FAU - Pinto, Madalena
AU  - Pinto M
AUID- ORCID: 0000-0002-4676-1409
AD  - Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical 
      Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
AD  - CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, Avenida 
      General Norton de Matos, S/N, 4450-208 Matosinhos, Portugal.
FAU - Sousa, Emilia
AU  - Sousa E
AUID- ORCID: 0000-0002-5397-4672
AD  - Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical 
      Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
AD  - CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, Avenida 
      General Norton de Matos, S/N, 4450-208 Matosinhos, Portugal.
LA  - eng
PT  - Journal Article
DEP - 20221101
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antioxidants)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Xanthones)
SB  - IM
MH  - Humans
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Antioxidants/pharmacology
MH  - Macrophages
MH  - *NF-E2-Related Factor 2
MH  - Oxidative Stress
MH  - *Xanthones/pharmacology
PMC - PMC9659273
OTO - NOTNLM
OT  - Nrf2
OT  - inflammation
OT  - macrophages
OT  - mangostins
OT  - oxidative stress
OT  - xanthones
COIS- The authors declare no conflict of interest.
EDAT- 2022/11/12 06:00
MHDA- 2022/11/15 06:00
PMCR- 2022/11/01
CRDT- 2022/11/11 01:27
PHST- 2022/09/21 00:00 [received]
PHST- 2022/10/25 00:00 [revised]
PHST- 2022/10/26 00:00 [accepted]
PHST- 2022/11/11 01:27 [entrez]
PHST- 2022/11/12 06:00 [pubmed]
PHST- 2022/11/15 06:00 [medline]
PHST- 2022/11/01 00:00 [pmc-release]
AID - ijms232113319 [pii]
AID - ijms-23-13319 [pii]
AID - 10.3390/ijms232113319 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Nov 1;23(21):13319. doi: 10.3390/ijms232113319.