Contribution of spathulenol to the anti-nociceptive effects of Psidium guineense

ABSTRACT

Objectives: Araçá-verdadeiro is the popular name of Psidium guineense (Myrtaceae), whose fruits and leaves are used in Brazilian folk medicine for treatment of inflammation and pain. The focus of the present research was an investigation of the anti-nociceptive, and anti-inflammatory effects of the essential oil from P. guineense (EOPG) leaves, and of spathulenol. The anxiolytic and antidepressive effects associated with chronic pain were also investigated in models of acute or persistent nociception or/and inflammatory pain.

Methods and Results: Oral treatment with EOPG (10–100 mg/kg) or spathulenol (10 mg/kg) significantly inhibited formalin-induced nociceptive responses, both sensitivity to cold and edema. Oral treatment with EOPG (10 mg/kg) and spathulenol (10 mg/kg) did not reduce locomotor activity (open field test). Local administration of spathulenol (1000 µg/paw) significantly prevented formalin-induced nociceptive sensitivity to cold and paw edema, and carrageenan-induced mechanical hyperalgesia, paw edema and sensitivity to cold. In the Freund's complete adjuvant (CFA) model, oral treatment with EOPG (10 mg/kg) or spathulenol (10 mg/kg) for 21 days significantly inhibited all analyzed parameters. The percentage maximal inhibition by spathulenol was 76.00% (mechanical hyperalgesia), 71.90% (cold response), 85.00% (edema), 77.16% (myeloperoxidase activity), 97.72% (time in the closed arms in the elevated plus maze), and 49.00% (immobility time in the tail suspension test), in the CFA model. Models employed male Swiss mice, except for the CFA test, which employed C57bL6 male mice (n=6 /group).

Conclusion: This study demonstrates that EOPG is an anti-nociceptive and anti-hyperalgesic agent, in acute and continuous treatment, and an anxiolytic and antidepressive agent when tested with the chronic pain experimental state.

KEYWORDS:

• Spathulenol
• Psidium guineense
• Myrtaceae
• mice
• pain
• anxiety

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics approval

Approval from the ethics committee was obtained.

Additional information

Funding

This research did not receive specific funding. The general funding was supported by the National Council for Scientific and Technological Development (CNPq), Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Mato Grosso do Sul (FUNDECT), and Coordination for the Improvement of Higher Education Personnel (CAPES).

Notes on contributors

Elisangela Dos Santos

Elisangela Dos Santos Graduated in Physical Education at the University Center of Grande Dourados UNIGRAN (2009). Specialization in School Physical Education from the Federal University of Grande Dourados - UFGD (2012). Graduated in nutrition from the Federal University of Grande Dourados-UFGD 2017. Master's degree in Health Sciences from the Federal University of Grande Dourados-UFGD 2020. Studying Doctorate in Health Sciences pale Federal University of Grande Dourados- UFGD.

Joyce Alencar Santos Radai

Joyce Alencar Santos Radai received a bachelor's degree in Pharmacy from Centro Universitário da Grande Dourados in 2009 and a PhD from Universidade Federal da Grande Dourados in Biotechnology and Biodiversity in 2017. In the postdoctoral period Joyce researched inflammation, pain and animal models of infections.

Kamilla Felipe do Nascimento

Kamilla Felipe do Nascimento PhD student at the Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, Brazil.

Anelise Samara Nazari Formagio

Anelise Samara Nazari Formagio is a research at the Faculty of Health Sciences and Faculty of Biological and Environmental Sciences, Federal University of Grande Dourados, Dourados, Brazil. Her research interest line is to isolation and identification of secondary metabolites monitored by biological assays.

Natália de Matos Balsalobre

Natália de Matos Balsalobre graduated in Nutrition in 2018 from the Federal University of Grande Dourados and will complete a master's degree in Food, Nutrition and Health from the Federal University of Grande Dourados in 2021. Conducts studies on pain, inflammatory processes and natural products at the Faculty of Sciences of the Health at the Federal University of Grande Dourados.

Edward Benjamin Ziff

Edward Benjamin Ziff received a bachelor's degree in Chemistry from Columbia University in 1963 and a PhD from Princeton University in Biochemistry in 1969. As a postdoctoral student with Nobel Prize winner, Fred Sanger, in Cambridge he conducted early genome sequencing studies. Ed served on the faculties of the Imperial Cancer Research Fund in London and Rockefeller University in New York. In 1982, he joined New York University School of Medicine, where he is Professor of Biochemistry and Molecular Pharmacology and Neural Science and was an Investigator of the Howard Hughes Medical Institute. Ed researches brain function and neurological disease and was a Visiting Researcher at UFGD in Dourados.

Elisabete Castelon Konkiewitz

Elisabete Castelon Konkiewitz received a medical degree from UNIFESP (São Paulo Federal University) in 1993 and a doctorate in Neurology from the German university Technische Universität München, in 2002. She received the title of specialist in Neurology from the Brazilian Academy of Neurology and the title of specialist in Psychiatry from the Brazilian Association of Psychiatry. She has been an associate professor at the Federal University of Grande Dourados (UFGD) since 2008. She is also part of the post graduation program. Her research focuses on the effects of HIV virus on the central nervous system and the relationship between childhood trauma, traumatic memory, depression, neuroinflammation and HIV infection. She published some books in the area of neurodevelopment and learning, among them High Skills / Giftedness, Intelligence and Creativity - A Multidisciplinary Vision, awarded with the Jabuti award in 2015; Autism Spectrum, Creativity and Emotions: A New Point of View Through Camila Falchi's Work and Neuro adventure: Autism, Art and the Brain.

Candida Aparecida Leite Kassuya

Candida Aparecida Leite Kassuya received a bachelor's degree in Pharmacy in 1996 from the State University of Maringá and a PhD from Federal University of Santa Catarina in Pharmacology in 1996. As a postdoctoral student at Federal University of Paraná. She carried out several studies on pain, infection and inflammatory investigations. In May, 2009, she joined Federal University of Grande Dourados, where she is a Professor of Clinical Pharmacology and Toxicology. Candida researched about pain, natural products, inflammation topics when she was a Visitor Researcher at UFPR in Curitiba.