Том 24, № 19 (2024)

Background:Germacrone, a naturally occurring active compound found in essential oils extracted from medicinal plants within the Zingiberaceae family, has garnered attention for its potential therapeutic applications. Extensive research has highlighted its multi-targeting capabilities, positioning it as a promising treatment for various chronic diseases, including cancer, cardiovascular conditions, and neurodegenerative disorders like Alzheimer's disease.

Objective:This review aims to provide a comprehensive overview of germacrone as a scaffold for developing multi-targeting drugs with therapeutic potential against a range of chronic disorders. The study delves into the molecular mechanisms that underlie the therapeutic effects of germacrone and explores its potential targets, including NF-κB, PI3K/AKT/mTOR, p53, JAK/STAT, caspase, apoptosis, and autophagy induction.

Methods:A systematic review of literature databases was conducted to gather relevant studies on germacrone and its therapeutic applications. The molecular mechanisms and potential targets of germacrone were examined to elucidate its multi-targeting capabilities.

Results:Germacrone exhibits significant potential in the management of chronic diseases, with demonstrated effects on various cellular pathways. The review highlights its impact on NF-κB, PI3K/AKT/mTOR, p53, JAK/STAT, caspase, apoptosis, and autophagy induction, showcasing its versatility in targeting multiple pathways associated with chronic conditions. Germacrone has emerged as a promising candidate for the treatment of diverse chronic diseases. The understanding of its multi-targeting capabilities, coupled with its natural origin, positions it as a valuable scaffold for developing therapeutics.

Conclusion::The exploration of germacrone as a structural framework for multi-targeting drugs offers a potential avenue to enhance efficacy while minimizing potential side effects. Further research and clinical trials are warranted to validate the therapeutic potential of germacrone in diverse medical contexts.

Objectives:Non-Small Cell Lung Cancer (NSCLC) has attracted much attention on account of the high incidence and mortality of cancers. Vascular Endothelial Growth Factor Receptor 3 (VEGFR3/FLT4), which is a highly expressed receptor in NSCLC, greatly regulates cancer proliferation and migration. Pseudolaric Acid B (PAB) is a diterpenoid acid with antitumor activity isolated from Pseudolarix kaempferi. This study aimed to explore the inhibitory effect of PAB targeting FLT4 in NSCLC.

Methods:Cell membrane chromatography was used to evaluate the affinity of PAB binding on FLT4. NCIH1299 cells were used in this study, and an MTT assay was performed to determine the anti-proliferation effect of PAB. Cell cycle analysis was conducted to study the cycle arrest of PAB. Wound healing and Transwell assays assessed the rate of cell migration. Western blot analysis evaluated the expression of related proteins.

Results:PAB showed strong affinity to FLT4 with a KD value of 3.01 × 10- 6 M. Targeting FLT4 by PAB inactivated downstream P38MAPK and PI3K/AKT pathways, which inhibited the proliferation of NCI-H1299 cells. Meanwhile, PAB promoted G2/M phase arrest by influencing CyclinB1 and CDK1 complex formation to inhibit NCI-H1299 cell growth, but the effect was attenuated by knocking down the FLT4. Besides, PAB regulated MMP9 secretion through the Wnt/β-catenin signaling pathway to inhibit NCI-H1299 cell migration. However, the ability of PAB to inhibit migration was significantly weakened by FLT4 knockdown in NCI-H1299 cells.

Conclusion:PAB can inhibit the proliferation and migration of NSCLC cells through targeting FLT4 and is expected to be a promising FLT4 inhibitor for NSCLC treatment.

Introduction:The side effects of anti-cancer chemotherapy remain a concern for patients. So, designing alternative medications seems inevitable. In this research, the immunological mechanisms of BCc1 nanomedicine on tumor-bearing mice were investigated.

Methods:BALB/c mice underwent tumor transplantation and were assigned into four groups. Group 1 was orally administered with PBS buffer, Group 2 was orally administered BCc1 10 mg/kg, and Group 3 was orally administered BCc1 40 mg/kg daily, respectively. In addition, a group of mice was administered Cyclophosphamide, 20 mg/kg daily. The weight and tumor volume of mice were evaluated bi-weekly. After 24 days of treatment, cytokines and CTL assay in the spleen cell and the tumor were assessed. Furthermore, the spleen, liver, kidney, lung, gut, and uterine tissue were stained with hematoxylin and eosin. Finally, the tumor samples were stained and analyzed for FOXP3. The survival rate of mice was recorded.

Results:The results confirmed the histological safety of BCc1. This nanomedicine, especially BCc1 10 mg/kg, led to a strong IFN-γ response and suppressed TGF-β cytokine. The frequency of Treg in the tumor tissue of BCc1 nanomedicine groups was decreased. In addition, nanomedicine repressed tumor volume and tumor weight significantly, which was comparable to Cyclophosphamide. These immunologic events increased the survival rate of BCc1-treated groups. The results indicate that BCc1 nanomedicine can suppress tumor growth and thereby increase the survival rate of experimental mice.

Conclusion:It seems a modulation in the tumor microenvironment and polarization toward a Th1 response may be involved. So, BCc1 nanomedicine is efficient for human cancer therapy.