Zainul Amiruddin Zakaria, Mohammad Amil Zulhilmi Benjamin, Nur Liana Md Nasir, Hussin Muhammad, Lilis Sulistyorini, Roro Azizah, Gurmeet Kaur, Gurmeet Kaur Surindar Singh, Meor Mohd Redzuan, Meor Mohd Redzuan Meor Mohd Affandi, Nornazirah Azizan, Azmahani Abdullah, Muhammad Nazrul, Muhammad Nazrul Hakim Abdullah
Growing demand for Schizophyllum commune Fr. reflects its pharmaceutical and nutraceutical potential, although its safety profile remains underexplored despite long-standing traditional use. This study aimed to evaluate the in vitro cytotoxicity, in vivo acute and subacute oral toxicity, and mycochemical composition of the aqueous extract of S. commune (AESC). Cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on human gastric adenocarcinoma (AGS) and human hepatocellular carcinoma (HepG2) cell lines. Acute toxicity was evaluated in Sprague-Dawley rats given a single oral dose of 5000 mg/kg bw, while subacute toxicity involved daily oral doses of 250, 500, and 1000 mg/kg bw for 28 days. Parameters including clinical signs, body weight, relative organ weight, food and water intake, and haematological, biochemical, and histopathological changes were monitored throughout the study. Mycochemical characterisation was performed using qualitative screening tests and liquid chromatography–quadrupole time-of-flight mass spectrometry (LC–QTOF–MS). The MTT assay indicated minimal cytotoxicity, with half-maximal inhibitory concentration (IC50) values exceeding 1000 µg/mL for both AGS and HepG2 cells. No mortality or adverse signs occurred in the acute toxicity study, indicating a median lethal dose (LD50) greater than 5000 mg/kg bw. Similarly, the subacute study showed no adverse effects at any tested dose in either sex, with a no-observed-adverse-effect level (NOAEL) greater than 1000 mg/kg bw. Qualitative screening revealed no detectable levels of major secondary metabolite classes, while LC–QTOF–MS profiling identified amino acids, fatty acids, and low-abundance phenolic compounds as the predominant constituents of AESC. These findings confirm a favourable safety profile of AESC, supporting further evaluation for gastro- and hepato-protective applications. © The Author(s) 2026.
Borneo Research on Algesia, Inflammation and Neurodegeneration (BRAIN) Group, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Jalan UMS, Sabah, Kota Kinabalu, 88400, Malaysia; Department of Environmental Health, Faculty of Public Health, Universitas Airlangga, Kampus C, Jl. Dr. Ir. H. Soekarno, East Java, Surabaya, 60115, Indonesia; Department of Nutrition, Faculty of Health Sciences, Universitas Brawijaya, East Java, Malang, 65151, Indonesia; Institute for Tropical Biology and Conservation, Universiti Malaysia Sabah, Jalan UMS, Sabah, Kota Kinabalu, 88400, Malaysia; Herbal Medicine Research Centre, Institute for Medical Research, National Institutes of Health, Jalan Setia Murni U13/52, Setia Alam, Selangor, Shah Alam, 40170, Malaysia; Department of Pharmacology and Life Sciences, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Selangor Branch, Puncak Alam Campus, Selangor, Bandar Puncak Alam, 42300, Malaysia; Department of Pharmaceutics, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Selangor Branch, Puncak Alam Campus, Selangor, Bandar Puncak Alam, 42300, Malaysia; Department of Pathology and Microbiology, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Jalan UMS, Sabah, Kota Kinabalu, 88400, Malaysia; School of Biomedicine, Faculty of Health Sciences, Universiti Sultan Zainal Abidin, Gong Badak Campus, Terengganu, Kuala Nerus, 21300, Malaysia; Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Serdang, 43400, Malaysia
