**Background**
Colorectal cancer remains a significant global health challenge characterized by high morbidity and the need for effective therapeutic interventions. Research into antineoplastic agents often focuses on compounds that can induce apoptosis, inhibit cell proliferation, and disrupt the cell cycle of malignant cells. Beyond oncology, there is a growing interest in compounds that can modulate metabolic disorders and provide neuroprotection by regulating oxidative stress and inflammatory pathways. Natural alkaloids have emerged as promising candidates due to their diverse biological activities and potential to target multiple signaling pathways. In this context, we will introduce a versatile alkaloid with potent antineoplastic and metabolic properties – Berberine.
**Definition**
Berberine is an isoquinoline alkaloid isolated from plants such as Coptis chinensis Franch. It acts as an antibiotic and antineoplastic agent that induces reactive oxygen species (ROS) generation and inhibits DNA topoisomerase.
**In Vitro and In Vivo Studies**
The Berberine description highlights that the sulfate form of this compound is utilized to improve its bioavailability. Regarding Berberine biological activity, in vitro studies demonstrate that Berberine sulfate (1.25-160 μM; 72 hours) inhibits the proliferation of four colorectal carcinoma cell lines: LoVo, HCT116, SW480, and HT-29, with IC50 values ranging from 40.8±4.1 μM (LoVo) to 98.6±2.9 μM (HCT116). Specifically, in LoVo cells, treatment with 1.25-160 μM for 24-72 hours induces time- and dose-dependent growth inhibition, with 160.0 μM resulting in 71.1±1.9% inhibition by 72 hours. Furthermore, exposure to 40 μM for 24 hours induces G2/M-phase cell cycle arrest and suppresses the expression of cyclin B1, cdc2, and cdc25c proteins.
Beyond Berberine Cancer research, the compound exhibits broad pharmacological effects. It demonstrates antimicrobial activity by inhibiting the cell division protein FtsZ, anti-inflammatory activity via inhibition of TNF-α and the NF-κB/AP-1 pathways, and neuroprotective efficacy through the activation of the PI3K/Akt pathway and HO-1 expression. Additionally, it attenuates metabolic diseases by regulating lipid composition and inhibiting insulin resistance.
In terms of Berberine in vivo efficacy, administration of Berberine sulfate (10, 30, or 50 mg/kg/day via gastrointestinal gavage for 10 consecutive days) inhibits the growth of human colorectal adenocarcinoma xenografts in nude mice. Doses of 30 and 50 mg/kg/day showed inhibitory rates of 33.1% and 45.3%, respectively. In conclusion, Berberine is a multi-functional alkaloid with significant potential in treating colorectal cancer, metabolic disorders, and inflammatory diseases.
Keywords
Berberine, 633-66-9, Natural Yellow 18, Natural Yellow18, Natural Yellow-18, Antibiotic, Topoisomerase, Autophagy, Bacterial, Reactive Oxygen Species (ROS), Parasite, Apoptosis, PI3K, Akt, Caspase
References
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