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Bioprocess."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) is a global health challenge with limited therapeutic options. The effectiveness of conventional medication like cisplatin is often compromised by their severe toxicity. This study investigated carob pod aqueous extract (CPAE), a polyphenol-rich natural product, as a potential adjunct therapy to enhance efficacy and mitigate cisplatin toxicity in a preclinical HCC animal model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A rat model of HCC was established using diethylnitrosamine (DEN) and carbon tetrachloride (CCl\u2084). Forty-two Wistar rats were divided into seven groups, receiving various treatments: control, CPAE, vehicle, HCC only, HCC+CPAE, HCC+cisplatin, and HCC+CPAE+cisplatin. Liver and kidney function, metabolic profiles, oxidative stress\/antioxidant parameters, gene and protein expression (AMPK, PGC-1\u03b1, TFAM, SIRT1, iNOS, NF-\u03baB, I\u03baK, p53, SREBP-2), histopathology, and statistical analyses were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HCC induction caused significant liver dysfunction, metabolic disturbances, oxidative stress, alongside dysregulation of AMPK\/PGC-1\u03b1\/TFAM and NF-\u03baB\/iNOS pathways. CPAE, alone or with cisplatin, markedly ameliorated these changes, improving liver and kidney function, restoring antioxidant status, reducing the tumor marker AFP, suppressing pro-inflammatory and oncogenic signaling, and enhancing histological architecture. Furthermore, Combination therapy demonstrated synergistic benefits, with CPAE reducing cisplatin-induced nephrotoxicity and enhancing its antitumor efficacy, primarily via modulation of mitochondrial biogenesis, redox balance, and inflammatory signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CPAE exhibits potent hepatoprotective and anti-HCC activity, especially when combined with cisplatin. This combination modulates mitochondrial and inflammatory pathways while mitigating cisplatin-induced toxicity. These finding position CPAE as a promising natural adjuvant for integrative HCC management. Further translational studies are warranted to validate these findings and explore clinical applicability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40643-026-01029-0","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:09:12Z","timestamp":1782101352000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Carob pod aqueous extract potentiates cisplatin efficacy and reduces toxicity in experimental hepatocellular carcinoma via mitochondrial and inflammatory pathway modulation"],"prefix":"10.1186","volume":"13","author":[{"given":"Wael Sobhy","family":"Darwish","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abada","family":"El Sayed Khadr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maher","family":"Abd El Naby Kamel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3797-9155","authenticated-orcid":false,"given":"Tamer A.","family":"Addissouky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Zaki","family":"Ghareeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mabrouk A. 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