The research team, led by Kenedy Kiyimba of the University of Nairobi and Busitema University, together with colleagues in Pakistan and Kenya, harvested stem bark from trees growing in Mabira Forest in central Uganda in June 2023. A taxonomist verified the species, and a voucher specimen was deposited at the Makerere University Herbarium. The bark was shade-dried for twenty-eight days, ground into powder, and soaked in seventy percent ethanol for seventy-two hours to produce a crude extract that mirrors the decoctions traditional practitioners prepare. That extract was then separated into fractions using solvents of increasing polarity, beginning with n-hexane, followed by ethyl acetate and methanol, so that each chemical family could be studied in isolation.

Gas chromatography-mass spectrometry, the workhorse technique for identifying volatile organic compounds, revealed a rich chemical inventory. The ethanolic extract alone produced twenty-two chromatographic peaks, while the hexane fraction yielded an astonishing 121 peaks. Across all fractions, the researchers identified nineteen major phytocompounds, each selected when its mass spectral match in the National Institute of Standards and Technology library exceeded a fifty percent probability threshold. Fourier transform infrared spectroscopy then confirmed the presence of characteristic functional groups, including alkenes, carboxylic acids, quinones, and polyglycines, which are the molecular machinery behind much of the plant’s biological activity. Qualitative screening added further depth, detecting flavonoids, tannins, steroids, glycosides, alkaloids, phenolics, and anthraquinones.

Many of these compounds carry impressive pharmacological credentials. One constituent from the ethanolic extract has documented anti-inflammatory, anti-apoptotic, and anti-infective properties. Another from the ethyl acetate fraction has shown antioxidant, antiviral, and antineoplastic activity, while a compound in the methanolic fraction is closely related to molecules with demonstrated antitumor effects. Alkene-containing compounds are known to exhibit antioxidant, antibacterial, and antiproliferative actions, and carboxylic acids have shown antimicrobial and anticancer potential. These findings lend chemical credibility to the plant’s traditional uses, which range from treating venereal infections in Cameroon to managing diabetes among the Nandi community in Kenya and addressing malaria, fever, mental illness, and epilepsy in the eastern Democratic Republic of Congo.

But chemistry alone cannot establish safety, so the team turned to computational toxicology. Using six online prediction platforms, including ADMET Lab 3.0, SWISS ADME, admetSAR, pkCSM, PreADMET, and ProTox 3.0, the researchers assessed the nineteen most abundant compounds for nine categories of toxic risk: cardiotoxicity, hepatotoxicity, mutagenicity, carcinogenicity, rat oral acute toxicity, skin sensitization, eye irritation, eye corrosion, and respiratory toxicity. The predictions flagged skin sensitization for most compounds and identified a significant respiratory toxicity risk for five of them. Encouragingly, no meaningful concerns emerged for cardiotoxicity, liver injury, mutagenicity, or carcinogenicity, and only a single compound was predicted to pose oral toxicity risks in rats.

The in vivo phase of the study followed internationally recognized protocols. For acute toxicity testing, female Wistar rats received a single oral dose of the ethanolic extract at either 2000 or 5000 milligrams per kilogram of body weight. Within thirty minutes, the animals showed decreased activity, lethargy, piloerection, and unusual vocalizations, effects that persisted for roughly twelve hours. More than half of the rats had recovered by twenty-four hours, and all animals returned to normal within forty-eight hours. Crucially, no deaths occurred during the fourteen-day observation period, meaning the lethal dose for fifty percent of the animals, the LD50, exceeds 5000 milligrams per kilogram, a threshold that classifies the extract as essentially non-toxic in acute terms.

The sub-acute study was more demanding. Forty young adult rats of both sexes received daily oral doses of 200, 400, or 800 milligrams per kilogram for twenty-eight days, corresponding to one-tenth, one-fifth, and two-fifths of the maximum tolerated acute dose, while a control group received distilled water. Blood samples collected on day twenty-nine underwent full hematological and biochemical analysis, covering red and white blood cell counts, hemoglobin, hematocrit, platelets, liver enzymes, kidney markers, lipids, and electrolytes. The results were largely reassuring: no significant toxic changes appeared in any biochemical or hematological parameter compared with controls, and the weights of the liver, kidneys, pancreas, lungs, heart, stomach, uterus, and testes remained unaltered.

Two subtle signals did emerge, however. Rats receiving the highest dose lost body weight in a dose-dependent pattern, and food consumption differed significantly between treated and control animals, hinting that the extract may influence appetite and metabolism, an observation that aligns with the plant’s traditional reputation for regulating appetite and supporting digestive health. Hemoglobin and hematocrit levels rose with dose, suggesting possible stimulation of blood cell production that could support the plant’s folk use as a blood tonic. The most consequential finding, though, came from the microscope. Histopathological examination of lung tissue revealed dose-dependent inflammation: the two lower doses produced mild bronchitis with mononuclear cell infiltration, while the highest dose caused marked accumulation of lymphoid cells around the bronchioles and blood vessels. No comparable lesions appeared in the liver, kidneys, or heart.

The lung findings dovetail strikingly with the computational predictions, which had flagged five compounds for potential respiratory toxicity. The authors suggest the damage may stem either from direct accumulation of phytocompounds in lung tissue or from immune-mediated reactions, though pinpointing the responsible chemicals will require further work. There is also an important caveat regarding the chemistry itself: gas chromatography primarily detects volatile and thermally stable compounds, so large non-volatile molecules such as polyphenols, alkaloids, and glycosides may have escaped detection. The researchers recommend follow-up analysis with liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy to build a more complete chemical picture, alongside mechanistic and clinical studies to bridge the gap between rats and humans.

For the millions of people across tropical Africa who brew Parasol Tree bark as medicine, the study delivers a nuanced verdict. The plant’s acute safety profile is genuinely strong, its effects on blood chemistry and organ function appear benign at traditional dose ranges, and its phytochemical arsenal plausibly underpins the anticancer, antibacterial, and hypoglycemic activities documented in earlier research. Yet the same analysis shows the plant is not entirely innocent: prolonged exposure may inflame the lungs, and several of its constituents are predicted to irritate skin and eyes. As modern science continues to validate traditional remedies, Polyscias fulva emerges as a valuable resource that merits both further investigation and careful conservation, used with respect for its power rather than blind faith in its safety.

Subject of Research: Phytochemical profiling and acute and sub-acute toxicity evaluation of Polyscias fulva stem bark extract

Article Title: Phytochemical analysis and toxicity evaluation of Polyscias fulva stem bark extract using gas chromatography-mass spectrometry, fourier transform infrared spectroscopy, in silico, and in vivo studies in wistar rats

Article References: Kiyimba, K., Ahmed, A., Choudhary, M. I., Obakiro, S. B., Gavamukulya, Y., Guantai, E. M., & Munyendo, W. L. (2025). Phytochemical analysis and toxicity evaluation of Polyscias fulva stem bark extract using gas chromatography-mass spectrometry, fourier transform infrared spectroscopy, in silico, and in vivo studies in wistar rats. Discover Toxicology, 2(1), Article 11. https://doi.org/10.1007/s44339-025-00031-z

Image Credits: AI Generated

DOI: 10.1007/s44339-025-00031-z

Keywords: Polyscias fulva, phytochemistry, GC-MS, FTIR, acute toxicity, sub-acute toxicity, Wistar rats, in silico toxicity prediction, traditional medicine, lung histopathology, medicinal plants, toxicology