Curcumin for Treating Breast Cancer: A Review of Molecular Mechanisms, Combinations with Anticancer Drugs, and Nanosystems.

Breast cancer (BC) has become the fifth most prevalent cause of cancer-related morbidity, attracting significant attention from researchers due to its heightened malignancy and drug resistance. Conventional chemotherapy approaches have proven inadequate in addressing all BC subtypes, highlighting the urgent need for novel therapeutic approaches or drugs. Curcumin (CUR), a phytochemical derived from Curcuma longa (turmeric), has shown substantial potential in inhibiting BC cell migration, metastasis, and proliferation. However, the use of CUR in this context comes with challenges due to its dynamic and easily degradable nature, poor aqueous solubility, low bioavailability, rapid metabolism, and swift systemic elimination, collectively limiting its clinical applications. As such, we provide an overview of the properties, synthesis, and characterization of the hybridization of CUR and its analogue with chemo-drug building blocks. We reviewed research from the last five years on CUR's biogenesis with respect to the regulation of BC, revealing that CUR participates in arresting BC cells in the cell cycle and significantly induces apoptosis in BC cells. Information on the chemotherapeutic and antitumor mechanisms of CUR in BC, including regulation of the cell cycle, increased cell apoptosis, and inhibition of multidrug resistance (MDR), was compiled. Additionally, we provide an overview of CUR loaded into nanomaterials that are cotreated with other chemotherapeutic drugs, such as paclitaxel, thymoquinone, and tamoxifen. In this review, we discuss different types of nanoparticles that can be used for CUR delivery, such as polymeric nanoparticles, carbon nanotubes, and liposomes. By comparing the size, entrapment efficiency, drug-loading capacity, release time, biocompatibility, pharmaceutical scale, and reproducibility of various nanomaterials, we aimed to determine which formulations are better suited for loading CUR or its analogue. Ultimately, this review is expected to offer inspiring ideas, promising strategies, and potential pathways for developing advanced anti-BC strategy nanosystems in clinical practice.

Evodiamine via targeting nNOS and AMPA receptor GluA1 inhibits nitroglycerin-induced migraine-like response.

ETHNOPHARMACOLOGICAL RELEVANCE: Evodiamine (EVO) is a natural compound derived from Tetradium ruticarpum (A.Juss.) T.G.Hartley used to treat pain and migraine in traditional Chinese medicine. EVO is the primary active ingredient of Tetradium ruticarpum. However, the preventive effect of EVO against migraine remains unexplored. AIM OF THE STUDY: To investigate the preventive effect of EVO against nitroglycerin (NTG)-induced acute migraine in rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were intragastrically administered EVO (45 or 90 mg/kg) for nine days. To establish an acute migraine model, we subcutaneously injected rats with a 10 mg/kg NTG solution. The migraine-like behavior of the rats was evaluated via the formalin test and the warm water tail-withdrawal assay. The periaqueductal gray (PAG) and serum samples were collected from the rats and used to determine the effect of EVO on the levels of serum nitric oxide (NO), CGRP, c-Fos, neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS) and the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor GluA1. RESULTS: The formalin test and the warm water tail-withdrawal assay showed that EVO inhibited the licking foot/shaking response and reversed the shortened tail-withdrawal latency in NTG-treated rats. Additionally, EVO suppressed serum NO levels and reduced the mRNA/protein expression of c-Fos and nNOS, but not iNOS, in the PAG. Furthermore, EVO suppressed total protein expression of the AMPA receptor GluA1 and its phosphorylation at Ser831 and Ser845. CONCLUSIONS: This study showed that EVO inhibits the migraine-like pain response and that this beneficial effect might be attributed to the regulation of nNOS and suppression of the AMPA receptor GluA1. We suggest that EVO has the potential to treat migraine as a lead compound of natural origin.

trans-Cinnamaldehyde Inhibits Microglial Activation and Improves Neuronal Survival against Neuroinflammation in BV2 Microglial Cells with Lipopolysaccharide Stimulation.

BACKGROUND: Microglial activation contributes to neuroinflammation and neuronal damage in neurodegenerative disorders including Alzheimer's and Parkinson's diseases. It has been suggested that neurodegenerative disorders may be improved if neuroinflammation can be controlled. trans-cinnamaldehyde (TCA) isolated from the stem bark of Cinnamomum cassia possesses potent anti-inflammatory capability; we thus tested whether TCA presents neuroprotective effects on improving neuronal survival by inhibiting neuroinflammatory responses in BV2 microglial cells. RESULTS: To determine the molecular mechanism behind TCA-mediated neuroprotective effects, we assessed the effects of TCA on lipopolysaccharide- (LPS-) induced proinflammatory responses in BV2 microglial cells. While LPS potently induced the production and expression upregulation of proinflammatory mediators, including NO, iNOS, COX-2, IL-1ß, and TNF-α, TCA pretreatment significantly inhibited LPS-induced production of NO and expression of iNOS, COX-2, and IL-1ß and recovered the morphological changes in BV2 cells. TCA markedly attenuated microglial activation and neuroinflammation by blocking nuclear factor kappa B (NF-κB) signaling pathway. With the aid of microglia and neuron coculture system, we showed that TCA greatly reduced LPS-elicited neuronal death and exerted neuroprotective effects. CONCLUSIONS: Our results suggest that TCA, a natural product, has the potential of being used as a therapeutic agent against neuroinflammation for ameliorating neurodegenerative disorders.

Phytochemical screening and chemical variability in volatile oils of aerial parts of Morinda morindoides.

Morinda morindoides is an important Liberian traditional medicine for the treatment of malaria, fever, worms etc. The plant was subjected to integrated approaches including phytochemical screening and gas chromatography mass spectrometry (GC-MS) analyses. Phytochemical investigation of the powdered plant revealed the presence of phenolics, tannins, flavonoids, saponins, terpenes, steroidal compounds and volatile oil. Steam distillation followed by GC-MS resulted in the identification of 47 volatiles in its aerial parts: 28 were in common including various bioactive volatiles. Major constituents of leaves were phytol (43.63%), palmitic acid (8.55%) and geranyl linalool (6.95%) and stem were palmitic acid (14.95%), eicosane (9.67%) and phytol (9.31%), and hence, a significant difference in the percentage composition of aerial parts was observed. To study seasonal changes, similarity analysis was carried out by calculating correlation coefficient (r) and vector angle cosine (z) that were more than 0.91 for stem-to-stem and leaf-to-leaf batches indicating considerable consistency.