A. N. Mendes

Integrative Network Pharmacology and ADMET Modeling Reveal the Multitarget Therapeutic Potential of Geraniol

Background: Geraniol is an acyclic monoterpene widely distributed in the essential oils of aromatic species such as Cymbopogon citratus, Pelargonium graveolens, and Rosa damascena, It is known for its antioxidant, anti-inflammatory, neuroprotective, and antitumor activities. Methods: This study aimed to investigate, through network pharmacology and computational ADMET modeling, the molecular mechanisms and pharmacological potential of geraniol, integrating drug-likeness parameters, toxicity prediction, and multitarget interactions. Results: A total of 25 core targets were identified, mainly involved in inflammation, oxidative stress, apoptosis, and transcriptional regulation. Geraniol exhibited a favorable drug-likeness profile, high predicted intestinal absorption, and low systemic toxicity, supporting its pharmaceutical applicability. Mechanistically, it modulates the Nrf2/HO-1 ↔ NF-κB axis, reducing reactive oxygen species, pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and apoptotic markers (caspases, Bax), while enhancing antioxidant enzymes (SOD, CAT, GPx) and antiapoptotic proteins (Bcl-2). Conclusions: These findings confirm its multitarget and pleiotropic nature, highlighting its potential as a therapeutic candidate for inflammatory, metabolic, and neurodegenerative disorders. Furthermore, this study provides a robust mechanistic rationale for future in vitro and in vivo validation, as well as for the design of nanostructured formulations to improve geraniol’s bioavailability and therapeutic safety.

A mechanistic approach about oxidative, mutagenic, and cytotoxic effects of an organotellurane.

Organotellurium (OTe) compounds have pharmacological properties, including leishmanicidal, antimalarial, and antifungal activities. Herein, we assessed cytotoxicity effects of OTe RF07 in a panel of tumor cell lines, as well as its oxidative, toxicity, and hemolytic actions. The toxicity was evaluated on Allium cepa and Artemia salina larvae. Cell viability was also assessed by resazurin in murine cells (Sarcoma 180), human cells (HL-60, leukemia; AGP01, gastric adenocarcinoma; SKMEL-28, human melanoma; MRC-5, normal fibroblasts), and dog erythrocytes. The oxidative capacity of RF07 was evaluated by wild-type and antioxidant-mutated enzyme strains of Saccharomyces cerevisiae. RF07 presented cytotoxic action on all normal and tumor cells, whose IC50 ranged from 0.07 μg/mL (HL-60) to 73.45 μg/mL (Sarcoma 180) and toxicological activity on A. salina nauplii in a concentration-dependent manner after exposure for 24 h and 48 h (LC50 values of 15.02 and 5.43 μg/mL for 24 h and 48 h, respectively). Moreover, RF07 reduced mitotic index of meristematic A. cepa cells at 5, 10 and 20 μg/mL, caused arrest in interphase, and increased chromosomal changes, including micronucleus, c-metaphases, and chromosomal bridges, loss, and delays. In summary, RF07 exhibits antiproliferative action on animal cells, high toxicity on Artemia salina nauplii, as well as clastogenic effects on growing roots. This antimitotic action is not related to direct membrane damage, although it relies on chromosomal injuries and may be related to the induction of oxidative stress as observed in yeast cells.

Computational Study of Enzyme Inhibition.