Substances extracted from the Annona squamosa leaf have analgesic and anti-arthritic potential, study reveals

In Brazil, researchers have identified substances with analgesic, anti-inflammatory, anti-hyperalgesic (against persistent pain) and anti-arthritic activity in the leaves of Annona squamosa, a tree popularly known in the country as fruta-do-conde or pinha. The results of the research, supported by FAPESP through five projects (09/05992-6, 14/17436-9, 15/03726-8, 16/06407-3 and 21/09693-5), were published in the journal Pharmaceuticals.

The work involved scientists from the Federal University of Grande Dourados (UFGD), the Federal University of Mato Grosso do Sul (UFMS), the State University of Campinas (UNICAMP) and São Paulo State University (UNESP). The group evaluated the plant’s methanolic extract (methanol is used as a solvent and then removed by evaporation to obtain a dry extract) and an isolated substance called palmatine.

As the authors explain, Annona squamosa is already used medicinally in several countries and is used in folk medicine to treat pain and arthritis. Several pharmacological properties have been observed, such as gastroprotective, antibacterial, antiviral and anti-inflammatory properties. It represents a possible alternative to the main pharmacological treatments for pain, opioid analgesics and non-steroidal anti-inflammatory drugs, whose prolonged use can cause various side effects such as addiction, ulcers and cardiovascular thrombotic events. It can also be an alternative to the main anti-inflammatory drugs, such as glucocorticoid analogs and non-steroidal anti-inflammatory drugs, which in chronic treatment can lead to adrenal insufficiency and insulin resistance, among other problems.

“In view of this, the aim of the study was to investigate the analgesic, anti-arthritic and anti-inflammatory potential of the methanolic extract and palmatine obtained from Annona squamosa,” says Marcos José Salvador, full professor at the Department of Plant Biology at UNICAMP and co-author of the research.

To do this, the leaves of the plant were dried and turned into powder. The substances to be analyzed were then extracted. The methanolic extract and the alkaloid palmatine were administered orally to mice and studied in several experimental models, including pleurisy (inflammation of the pleura, the membranes that line the lungs and chest wall) induced by a substance called carrageenan; joint inflammation induced by zymosan; and mechanical hyperalgesia (increased sensitivity to painful stimuli) induced by TNF (tumor necrosis factor, a signaling protein produced by defense cells that plays a crucial role in regulating the immune response).

“The results showed that the methanolic extract and palmatine extracted from A. squamosa have analgesic and anti-inflammatory potential. Palmatine also has anti-hyperalgesic properties, which may involve inhibition of the tumor necrosis factor-mediated pathway,” explains Salvador. “We also concluded that palmatine may be one of the components responsible for the anti-arthritic properties of the plant.”

The conclusions of the analysis are very relevant and help to prove the therapeutic effects of the samples analyzed and to elucidate their mechanisms of action, which are not yet fully understood. However, further studies are needed before they can be used in practice to treat diseases.

“Further studies are needed to assess whether, in other formulations, the effects and pharmacokinetic properties of palmatine would be altered,” says the researcher, noting that more research is also needed to assess the toxicity of the compounds and the doses needed to achieve the therapeutic effect for clinical use.

About FAPESP

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the state of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration.