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SÃO PAULO, Brazil — Pain relief might grow on trees after all. In a collaborative effort spanning multiple Brazilian universities, researchers have found compelling evidence that leaves from the sugar apple tree — traditionally used in folk medicine — contain anti-arthritic powerful compounds that fight both pain and inflammation.
Sugar apple, known in Brazil as “fruta-do-conde” or “pinha,” has long been valued for its sweet fruit. However, its leaves (Annona squamosa) have drawn scientific interest for their potential therapeutic properties, particularly in treating pain and inflammation.
Published in the journal Pharmaceuticals, the study was conducted by teams from the Federal University of Grande Dourados, Federal University of Mato Grosso do Sul, State University of Campinas (UNICAMP), and São Paulo State University.
Modern pain management often relies heavily on two classes of drugs: opioids and nonsteroidal anti-inflammatory drugs (NSAIDs). While effective, both come with significant drawbacks. Opioids carry risks of dependence and addiction, while long-term NSAID use can lead to ulcers and cardiovascular problems. These limitations drive the ongoing search for safer alternatives.
The research team’s approach was methodical. They created a methanolic extract (EMAS) from dried sugar apple leaves using methanol as a solvent, and also isolated a specific compound called palmatine, which would prove crucial to their findings.
In several experiments, both EMAS and palmatine demonstrated significant ability to reduce inflammation and pain. When tested against pleurisy (inflammation of the lung lining), the higher doses proved particularly effective, with EMAS reducing inflammatory cell migration by up to 81% and palmatine by up to 75%.
The compounds showed particular promise in addressing joint inflammation. When researchers induced joint inflammation in mice using zymosan, both substances reduced pain sensitivity, swelling, and inflammatory cell accumulation. Notably, palmatine’s effectiveness matched that of prednisolone, a conventional anti-inflammatory medication used as a reference drug.
Using the formalin test, a standard method for evaluating pain responses, researchers found that palmatine specifically reduced inflammatory pain rather than acute pain, suggesting potential applications for chronic pain conditions such as arthritis.
“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 study co-author Marcos José Salvador, full professor at the Department of Plant Biology at UNICAMP, in a statement. “We also concluded that palmatine may be one of the components responsible for the anti-arthritic properties of the plant.”
These findings are particularly intriguing because current long-term treatments with glucocorticoid analogs can lead to serious complications like adrenal insufficiency and insulin resistance. While it would be premature to position these compounds as direct alternatives to existing medications, their promising performance warrants further investigation.
Neither EMAS nor palmatine showed toxic effects on white blood cells in laboratory tests, indicating a promising initial safety profile. “Further studies are needed to assess whether, in other formulations, the effects and pharmacokinetic properties of palmatine would be altered,” says Salvador.
As modern medicine grapples with an opioid crisis and the long-term risks of conventional pain relievers, nature continues to offer intriguing alternatives. The sugar apple tree, quietly growing in tropical gardens, reminds us that sometimes the most powerful medicines aren’t created in laboratories — they’re simply waiting to be discovered
Paper Summary
Methodology
The researchers conducted multiple experiments using mice models to test both EMAS and palmatine. They first created inflammation in different ways – including injecting irritants into the chest cavity or joints – then measured how EMAS and palmatine affected various markers of inflammation and pain. They used sophisticated techniques to measure pain sensitivity, swelling, and inflammatory cell counts, while also conducting chemical analyses to identify the active compounds in the leaf extract.
Results
Both substances showed significant anti-inflammatory and pain-reducing properties across multiple tests. EMAS proved effective at doses of 100-300 mg/kg, while palmatine showed effects at 1-3 mg/kg. The results were comparable to conventional anti-inflammatory drugs in many cases, particularly in reducing joint inflammation and inflammatory pain.
Limitations
The study was conducted solely in mice, so human trials would be needed to confirm these effects in people. The researchers also didn’t evaluate long-term toxicity or investigate all possible mechanisms of action. Additionally, only a few doses were tested, leaving questions about optimal dosing unanswered.
Discussion and Takeaways
This research provides scientific support for traditional medicinal uses of sugar apple leaves. The identification of palmatine as a key active compound could lead to new drug development opportunities. The study suggests these natural compounds might offer alternatives to current pain medications, potentially with fewer side effects.
Funding and Disclosures
The study received support from FAPESP through five distinct projects, alongside funding from several Brazilian research organizations including CAPES, CNPq, and various university grants. The research represents a significant collaborative effort among multiple Brazilian universities and research institutions, demonstrating the robust nature of the investigation. The authors declared no conflicts of interest.
