Clelia Akiko Hiruma-Lima is a full professor at the Department of Structural and Functional Biology (Physiology) at the Bioscience Institute of the São Paulo State University - UNESP (Botucatu, São Paulo, Brazil). Her work has been mainly focused on understanding the action of natural products (flavonoids and essential oil) in the treatment of gastrointestinal diseases (gastroesophageal reflux, peptic ulcers, intestinal inflammation and obesity). The morphofunctional, biochemical, and molecular aspects of gastrointestinal disorders are analyzed in rodents (mice and rats). The focus of the studies also involves the ethnopharmacological evaluation of Brazilian medicinal plants and all their therapeutic potential.
EDUCATION
Clelia Akiko Hiruma-Lima is a biologist from the State University of São Paulo (UNESP), holds a Master's degree in Pharmacology and Chemistry of Natural Products from UFPB, and a PhD in Physiology from Unicamp.
RESEARCH, TEACHING, or OTHER INTERESTS
Drug Discovery, Physiology, Structural Biology, Pharmacology (medical)
The Anthocyanidins Malvidin and Cyanidin Alleviate Irinotecan-Triggered Intestinal Mucositis by Modulating Oxidative Stress and Cytokine Release Giovana Filócomo Machado, Quélita Cristina Pereira, Felipe Leonardo Fagundes, Maycon Tavares Emílio-Silva, Vinícius Peixoto Rodrigues, et al. International Journal of Molecular Sciences, 2025 Chemotherapy with irinotecan (CPT-11) induces intestinal mucositis via oxidative stress and NF-κB-driven cytokine amplification. We investigated the protective effects of the anthocyanidins cyanidin and malvidin (5 mg/kg) in a murine CPT-11 mucositis model. Both compounds increased duodenal glutathione level (GSH) and reduced lipid peroxidation (MDA), with distinct antioxidant profiles: malvidin enhanced catalase (CAT) activity, while cyanidin elevated superoxide dismutase (SOD). In the colon, cyanidin lowered MDA, whereas other oxidative and inflammatory markers remained largely unchanged. Malvidin significantly reduced IL-1β and IL-17 in both intestinal segments; cyanidin selectively decreased IL-6 in the colon, and this reduction was also observed for malvidin treatment. Gene expression analysis revealed broad transcriptional suppression in the duodenum for both compounds (Nrf2, NF-κB, TNF-α, IL-1β, IL-6, IL-17, IL-10), while colonic effects were more limited (suppression in IL-6 for both compounds). Despite these biochemical and transcriptional improvements—which were more pronounced with malvidin—neither compound prevented CPT-11-induced weight loss or colonic histopathology, indicating that redox and cytokine modulation alone are insufficient to restore mucosal integrity. Overall, malvidin demonstrated a more significant modulation in the antioxidant response in the duodenum, with anti-inflammatory activity in both segments, while cyanidin showed targeted modulation of oxidative stress. These findings position both anthocyanidins as complementary agents with distinct mechanistic profiles, warranting further investigation into dose–response, pharmacokinetics, NRF2 protein dynamics, and barrier-repair strategies. Early-phase clinical evaluation is recommended to assess their potential as adjunctive therapies for chemotherapy-induced intestinal mucositis.
Flavonoids with gastroprotective activity Kelly Samara De Lira Mota, Guilherme Eduardo Nunes Dias, Meri Emili Ferreira Pinto, Ânderson Luiz-Ferreira, Alba Regina Monteiro Souza-Brito, et al. Molecules, 2009
Analgesic effect of rotundifolone in rodents Fitoterapia, 1996
Medicinal plants popularly used in Brazilian Amazon Fitoterapia, 1994
RECENT SCHOLAR PUBLICATIONS
Citral exerts a more pronounced antinociceptive effect in obese adult male C57BL/6J mice mediated through the CB2 receptor FL Dario, MLA Aquino, MT Emílio-Silva, FL Fagundes, LVF de Oliveira, ... European Journal of Pharmacology, 178894 , 2026 2026
Citral impairs intestinal changes caused by ulcerative colitis through modulation of antioxidant, anti-inflammatory and healing activities MT Emílio-Silva, VP Rodrigues, AJ Ruiz-Malagon, IG Guidolin, FL Dario, ... Inflammopharmacology 34 (1), 655-669 , 2026 2026
Myrcene suppressed fever by downregulating systemic TNF-α levels in acute LPS-induced systemic inflammation in rats MT Emilio-Silva, VP Rodrigues, MM Fioravanti, LGS Branco, ... Advances in Traditional Medicine, 1-10 , 2025 2025
The Anthocyanidins Malvidin and Cyanidin Alleviate Irinotecan-Triggered Intestinal Mucositis by Modulating Oxidative Stress and Cytokine Release GF Machado, QC Pereira, FL Fagundes, MT Emílio-Silva, VP Rodrigues, ... International Journal of Molecular Sciences 26 (21), 10747 , 2025 2025 Citations: 1
Citral protects against metabolic endotoxemia, and systemic disorders caused by high-fat diet-induced obesity via intestinal modulation MT Emílio-Silva, VP Rodrigues, MM Fioravanti, AJ Ruiz-Malagon, ... Frontiers in Pharmacology 16, 1567217 , 2025 2025 Citations: 7
A high-fat diet changes the interaction of the extracellular matrix, cytokines, and growth factors in gastric ulcer repair R Ohara, FL Dario, MT Emílio-Silva, R Assunção, VP Rodrigues, G Bueno, ... Biochemical and Biophysical Research Communications 755, 151565 , 2025 2025 Citations: 1
Melatonin enhances cell death and suppresses the metastatic capacity of ovarian cancer cells by attenuating the signaling of multiple kinases MS Cucielo, PP Freire, MT Emílio-Silva, GG Romagnoli, RF Carvalho, ... Pathology-Research and Practice 248, 154637 , 2023 2023 Citations: 24
Orofacial anti-hypernociceptive effect of citral in acute and persistent inflammatory models in rats BM Santos, WS Santos, IG Solon, FS Garcia, MT Emilio-Silva, AA Jesus, ... Archives of Oral Biology 152, 105734 , 2023 2023 Citations: 9
Citral modulates MMP-2 and MMP-9 activities on healing of gastric ulcers associated with high-fat diet-induced obesity R Ohara, FL Dario, MT Emílio-Silva, R Assunção, VP Rodrigues, G Bueno, ... International Journal of Molecular Sciences 24 (5), 4888 , 2023 2023 Citations: 21
Role of the antioxidant pathway in the healing of peptic ulcers induced by ischemia–reperfusion in male and female rats treated with Eugenia punicifolia L Lucena Périco, R de Cássia dos Santos, V Peixoto Rodrigues, ... Inflammopharmacology 30 (4), 1383-1394 , 2022 2022 Citations: 8
Effect of Baccharis trimera Less (DC) essential oil in obese mice on a high-fat diet, part 1. adipose tissues evaluation. G Bueno, VP Rodrigues, R Ohara, MTE Silva, R Assunção, V Gomes, ... MDPI , 2021 2021
Antipyretic effect of myrcene (MCN) as a potential therapeutic alternative for the treatment of systemic inflammation response (SI) in euthermic rats model MT Emílio-Silva, ML Zarricueta, VP Rodrigues, PR Raimundo, ... MDPI , 2021 2021
Citral, a valuable aid against metabolic inflammation? VP Rodrigues, MT Emílio-Silvaa, R Oharaa, G Buenoa, PR Raimundoa, ... MDPI , 2021 2021
Is citrals anti-inflammatory action capable of changing the hypothalamic inflammation in obese mice? PR Raimundoa, VP Rodrigues, MT Emílio-Silvaa, G Buenoa, VG Gomesa, ... MDPI , 2021 2021 Citations: 1
Modulation of matrix metalloproteinases exerted by Citral in the healing of gastric ulcers in eutrophic and obese mice R Ohara, F Dario, G Bueno, V Rodrigues, M Silva, R Assunção, ... MDPI , 2021 2021
Evaluation of protective effect of citral on gastroesophageal reflux disease in eutrophic and obese mice A Fioretto, R Ohara, MTE Silva, VP Rodrigues, G Bueno, R Assunçao, ... MDPI , 2021 2021
Phytomedicinal study on Brazilian medicinal plants for their potential in chronic diseases treatment MJD Silva, LL Périco, MA da Silva, D Rinaldo, A Gambero, LC dos Santos, ... Phytochemicals in Food and Health, 151-196 , 2021 2021 Citations: 7
Genotoxicity induced by nerol, an essential oil present in citric plants using human peripheral blood mononuclear cells (PBMC) and HepG2/C3A cells as a model BO Silva, JB Orlando, CL Pires, CA Hiruma-Lima, ... Journal of Toxicology and Environmental Health, Part A 84 (12), 518-528 , 2021 2021 Citations: 17
The essential oil from Baccharis trimera (Less.) DC improves gastric ulcer healing in rats through modulation of VEGF and MMP-2 activity G Bueno, SLC Rico, LL Perico, R Ohara, VP Rodrigues, MT Emilio-Silva, ... Journal of ethnopharmacology 271, 113832 , 2021 2021 Citations: 29
Increased oxidative stress and cancer biomarkers in the ventral prostate of older rats submitted to maternal malnutrition LMF Portela, SAA Santos, FB Constantino, ACL Camargo, KT Colombelli, ... Molecular and cellular endocrinology 523, 111148 , 2021 2021 Citations: 28
MOST CITED SCHOLAR PUBLICATIONS
Flavonoids with gastroprotective activity KS de Lira Mota, GEN Dias, MEF Pinto, Â Luiz-Ferreira, ... Molecules 14 (3), 979-1012 , 2009 2009 Citations: 593
Plantas medicinais na Amazônia e na Mata Atlântica LC Di Stasi, CA Hiruma-Lima Editora Unesp , 2002 2002 Citations: 574
Effects of limonene and essential oil from Citrus aurantium on gastric mucosa: role of prostaglandins and gastric mucus secretion TM Moraes, H Kushima, FC Moleiro, RC Santos, LRM Rocha, ... Chemico-Biological Interactions 180 (3), 499-505 , 2009 2009 Citations: 276
Flavonoids and antiulcerogenic activity from Byrsonima crassa leaves extracts M Sannomiya, VB Fonseca, MA Da Silva, LRM Rocha, LC Dos Santos, ... Journal of Ethnopharmacology 97 (1), 1-6 , 2005 2005 Citations: 233
Gastroprotective mechanisms of Citrus lemon (Rutaceae) essential oil and its majority compounds limonene and β-pinene: Involvement of heat-shock protein-70, vasoactive … AL Rozza, T de Mello Moraes, H Kushima, A Tanimoto, MOM Marques, ... Chemico-biological interactions 189 (1-2), 82-89 , 2011 2011 Citations: 210
Evaluation of the analgesic and antiedematogenic activities of Quassia amara bark extract W Toma, JS Gracioso, CA Hiruma-Lima, FDP Andrade, W Vilegas, ... Journal of Ethnopharmacology 85 (1), 19-23 , 2003 2003 Citations: 207
The juice of fresh leaves of Boerhaavia diffusa L.(Nyctaginaceae) markedly reduces pain in mice CA Hiruma-Lima, JS Gracioso, EJB Bighetti, LG Robineou, ARMS Brito Journal of ethnopharmacology 71 (1-2), 267-274 , 2000 2000 Citations: 194
A review of the role of flavonoids in peptic ulcer (2010–2020) C Serafim, ME Araruna, EA Júnior, M Diniz, C Hiruma-Lima, L Batista Molecules 25 (22), 5431 , 2020 2020 Citations: 190
Plantas medicinais na Amazônia D Stasi Plantas medicinais na Amazônia, 194-194 , 1989 1989 Citations: 176
Antiulcerogenic activity of Alchornea castaneaefolia: effects on somatostatin, gastrin and prostaglandin CA Hiruma-Lima, TR Calvo, CM Rodrigues, FDP Andrade, W Vilegas, ... Journal of Ethnopharmacology 104 (1-2), 215-224 , 2006 2006 Citations: 173
The effect of a minor constituent of essential oil from Citrus aurantium: The role of β-myrcene in preventing peptic ulcer disease F Bonamin, TM Moraes, RC Dos Santos, H Kushima, FM Faria, MA Silva, ... Chemico-biological interactions 212, 11-19 , 2014 2014 Citations: 163
Medicinal plants popularly used in Brazilian Amazon. LC Stasi, CA Hiruma, EM Guimarães, CM Santos 1994 Citations: 140
Polyphenols with Antiulcerogenic Action from Aqueous Decoction of Mango Leaves ( Mangifera indica L.) JA Severi, ZP Lima, H Kushima, AR Monteiro Souza Brito, ... Molecules 14 (3), 1098-1110 , 2009 2009 Citations: 137
Preliminary studies of Mammea americana L.(Guttiferae) bark/latex extract point to an effective antiulcer effect on gastric ulcer models in mice W Toma, CA Hiruma-Lima, RO Guerrero, ARMS Brito Phytomedicine 12 (5), 345-350 , 2005 2005 Citations: 130
Hancornia speciosa: Indications of gastroprotective, healing and anti-Helicobacter pylori actions T de Mello Moraes, CM Rodrigues, H Kushima, TM Bauab, W Villegas, ... Journal of Ethnopharmacology 120 (2), 161-168 , 2008 2008 Citations: 127
Can the aqueous decoction of mango flowers be used as an antiulcer agent? ZP Lima, JA Severi, CH Pellizzon, A Brito, PN Solis, A Cáceres, LM Girón, ... Journal of Ethnopharmacology 106 (1), 29-37 , 2006 2006 Citations: 127
Antiulcerogenic activity of trans-dehydrocrotonin from Croton cajucara ARMS Brito, JA Rodriguez, CA Hiruma-Lima, M Haun, DS Nunes Planta Medica 64 (02), 126-129 , 1998 1998 Citations: 118
Antimicrobial activity of some medicinal plants of the Cerrado, Brazil ES Costa, CA Hiruma‐Lima, EO Lima, GC Sucupira, AO Bertolin, SF Lolis, ... Phytotherapy Research: An International Journal Devoted to Pharmacological … , 2008 2008 Citations: 115
Effect of Mouriri pusa extracts on experimentally induced gastric lesions in rodents: role of endogenous sulfhydryls compounds and nitric oxide in gastroprotection MA Andreo, KVR Ballesteros, CA Hiruma-Lima, LRM da Rocha, ... Journal of Ethnopharmacology 107 (3), 431-441 , 2006 2006 Citations: 115
Anti-inflammatory and Antinociceptive Effects in Rodents of the Essential Oil of Croton cajucara Benth EJB Bighetti, CA Hiruma-Lima, JS Gracioso, ARMS Brito Journal of Pharmacy and Pharmacology 51 (12), 1447-1453 , 1999 1999 Citations: 109