Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. Recently, polyphenols derived from the husk of T. acornis (HTA) have shown promise as potential cancer treatment agents. This study aimed to explore the anti-TNBC effects and mechanisms of HTA polyphenols in vitro using MDA-MB-231 TNBC cells, a representative cell line of this type. Initially, we assessed the impact of HTA polyphenols on cell proliferation, invasion, migration, cell cycle, and apoptosis. Key active compounds, 1,2,3,6-tetra-O-galloyl-beta-d-glucose (TGG) and gallic acid (GA), were identified for their anti-TNBC properties. Transcriptome data analysis, GO annotation, KEGG enrichment, and protein-protein interaction (PPI) analysis revealed significant pathways in HTA polyphenol-treated MDA-MB-231 cells. A total of 3312 differentially expressed genes (DEGs) were identified, including 19 related to the Fanconi anemia (FA) pathway. Many of these DEGs are primarily involved in processes such as DNA replication, cell cycle regulation, and extracellular matrix (ECM)-receptor interactions. Consistent with these changes, FANCD2 and FANCG, among the 19 DEGs, were found to be downregulated in cells treated with HTA polyphenols, TGG, and GA. This was confirmed by western blotting and immunofluorescence assays. In conclusion, HTA has a significant anti-TNBC effect by inhibiting cancer occurrence and development. The underlying molecular mechanism may be associated with its modulation of the FA pathway. Overall, these findings underscore the potential of HTA polyphenols as a therapeutic agent or functional food for TNBC patients.

01 Sep 2024·Fitoterapia

Effects of Camellia oleifera seed shell polyphenols and 1,3,6-tri-O-galloylglucose on androgenic alopecia via inhibiting 5a-reductase and regulating Wnt/β-catenin pathway

Article

Author: Wu, Xiaoqin ; Ru, Qi ; Yu, Ruining ; Huang, Kun ; Shen, Jianfu

Androgenetic alopecia (AGA) is the leading cause of hair loss in adults. Its pathogenesis remains unclear, but studies have shown that the androgen-mediated 5α-reductase-AR receptor pathway and the Wnt/β-catenin signaling pathway play significant roles. Camellia oleifera is an oil plant, and its fruits have been documented in folklore as having a hair cleansing effect and preventing hair loss. In this study, we used UPLC-Q-TOF-MS/MS to identify the structure of the substances contained in the polyphenols of Camellia oleifera seed shell. These polyphenols are mainly used for shampooing and anti-hair loss purposes. Next, we used molecular docking technology to dock 41 polyphenols and steroidal 5 alpha reductase 2 (SRD5A2). We found that the docking scores and docking sites of 1,3,6-tri-O-galloylglucose (TGG) and finasteride were similar. We constructed a mouse model of DHT-induced AGA to evaluate the effects of Camellia oleifera seed shell polyphenols (CSSP) and TGG in vivo. Treatment with CSSP and TGG alleviated alopecia symptoms and reduced DHT levels. Additionally, CSSP and TGG were able to reduce androgen levels by inhibiting the SRD5A2-AR receptor signaling pathway. Furthermore, by regulating the secretion of growth factors and activating the Wnt/β-catenin signaling pathway, CSSP and TGG were able to extend the duration of hair growth. In conclusion, our study showed that CSSP and TGG can improve AGA in C57BL/6 J mice and reduce the effect of androgen on hair follicle through the two signaling pathways mentioned above. This provides new insights into the material basis and mechanism of the treatment of AGA by CSSP.

01 Jun 2024·Journal of Ethnopharmacology

Mechanism of Tianma-Gouteng granules lowering blood pressure based on the bile acid-regulated Farnesoid X Receptor-Fibroblast Growth Factor 15- Cholesterol 7α-hydroxylase pathway

Article

Author: Ouyang, Hui ; Zhu, Qing ; Zhou, Maofu ; Yu, Jianjun ; Huang, Xiaofang ; Le, Yimin ; Cheng, Shaomin

ETHNOPHARMACOLOGICAL RELEVANCETianma-Gouteng granules (TGG) is a traditional Chinese medicine (TCM) compound that was first recorded by modern medical practitioner Hu Guangci in "New Meaning of the Treatment of Miscellaneous Diseases in Traditional Chinese Medicine". It is widely used to treat hypertensive vertigo, headache and insomnia.AIM OF STUDYTo investigate the antihypertensive effect of TGG and explore its mechanism.MATERIALS AND METHODSSpontaneously hypertensive rats (SHR) were prepared a model of the ascendant hyperactivity of liver yang syndrome (AHLYS), blood pressure and general state of rats were recorded. A series of experiments were performed by enzyme-linked immunosorbent assay (ELISA), ultra high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS), 16S rRNA sequencing, real-time fluorescence quantitative PCR (RT-qPCR), and enzymatic colorimetry.RESULTSTGG can effectively lower blood pressure and improve related symptoms. TGG significantly reduced the levels of IL-1β, IL-6, TNF-α, Renin and AngII. A total of 17 differential metabolites were found in plasma, with the two most potent metabolic pathways being glycerophospholipid metabolism and primary bile acid biosynthesis. After TGG intervention, 7 metabolite levels decreased and 10 metabolite levels increased. TGG significantly increased the relative abundance of Desulfovibio, Lachnoclostridium, Turicibacter, and decreased the relative abundance of Alluobaculum and Monoglobu. TGG also downregulated Farnesoid X Receptor (FXR) and Fibroblast Growth Factor 15 (FGF15) levels in the liver and ileum, upregulated Cholesterol 7α-hydroxylase (CYP7A1) levels, and regulated total bile acid (TBA) levels.CONCLUSIONTGG can regulate bile acid metabolism through liver-gut axis, interfere with related intestinal flora and plasma metabolites, decrease blood pressure, and positively influence the pathologic process of SHR with AHLYS. When translating animal microbiota findings to humans, validation studies are essential to confirm reliability and applicability, particularly through empirical human research.

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Indication	Highest Phase	Country/Location	Organization	Date
Bacterial Infections	Preclinical	China	Nanjing University of Science & Technology	10 Jan 2024

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