**Background**
Breast cancer remains a significant global health challenge, characterized by high recurrence rates and the potential for metastasis. The aldehyde dehydrogenase (ALDH) family of enzymes, particularly ALDH1A, plays a critical role in cellular detoxification and the maintenance of cancer stem cells, making them attractive targets for therapeutic intervention. Beyond oncology, chronic inflammation and associated pain, such as that seen in pleurisy or endometritis, require effective agents that can modulate immune responses and prevent tissue damage. Finding natural compounds that exhibit both antitumor and anti-inflammatory properties is a key focus of biomedical research. In this context, we will introduce a natural monoterpene compound – Citral.
**Definition**
Citral is an orally active monoterpene found in lemon grass essential oil that serves as a natural ALDH1A inhibitor.
**In Vitro and In Vivo Studies**
According to the Citral description, this compound is classified as a ketone/aldehyde with the Citral Formula $\text{C}_{10}\text{H}_{16}\text{O}$. Citral biological activity has been extensively studied across various models. Citral in vitro studies demonstrate that the compound (10, 50, 100 $\mu\text{g/mL}$; 72 h) exhibits no cytotoxicity toward J774 macrophages. However, it shows significant potency against breast cancer cells; specifically, Citral (0-0.5 $\mu\text{M}$; 72 h) inhibits cell proliferation and induces apoptosis and cell cycle arrest in the MCF-7 breast cancer cell line. Similarly, Citral (0-100 $\mu\text{g/mL}$; 72 h) exhibits anti-proliferative and pro-apoptotic activities in the MDA-MB-231 breast cancer cell line, highlighting its potential in Citral Cancer research.
Citral In Vivo evaluations have further revealed its therapeutic versatility. In adult male Swiss mice with pleurisy, Citral (100 mg/kg; p.o.) improved anti-hyperalgesic and anti-inflammatory activities, resulting in reduced white blood cell counts and decreased TNF-$\alpha$ expression levels. Furthermore, in female BALB/c mice, Citral (10, 20, 40 mg/kg; i.p.) was found to prevent LPS-induced endometritis by activating the Nrf2 signaling pathway and inhibiting ferroptosis, thereby attenuating uterine pathological damage and inflammation. In conclusion, Citral is a natural ALDH1A inhibitor with potent anti-cancer, anti-inflammatory, and analgesic properties.
Keywords
Citral, 5392-40-5, Parasite, analgesic, anti-inflammatory, MCF-7 cell, MDA-MB-231 cell, Inhibitor, inhibitor, inhibit
References
[1] Campos CA, et al. Anti-hyperalgesic and anti-inflammatory effects of citral with β-cyclodextrin and hydroxypropyl-β-cyclodextrin inclusion complexes in animal models. Life Sci. 2019 Jul 15;229:139-148.
[2] Chaouki W, et al. Citral inhibits cell proliferation and induces apoptosis and cell cycle arrest in MCF-7 cells. Fundam Clin Pharmacol. 2009 Oct;23(5):549-56.
[3] Souza ACS, et al. Citral presents cytotoxic and genotoxic effects in human cultured cells. Drug Chem Toxicol. 2020 Jul;43(4):435-440.
[4] Zhao W, et al. Citral protects against LPS-induced endometritis by inhibiting ferroptosis through activating Nrf2 signaling pathway. Inflammopharmacology. 2023 Jun;31(3):1551-1558.