Journal of ethnopharmacology最新文献

Ethnopharmacological relevance: Huachansu (HCS), a traditional Chinese medicine (TCM), has been used as an adjuvant therapy for colorectal cancer (CRC). However, its underlying mechanisms for combating CRC require further investigation.

Aim of this study: To comprehensively evaluate the anti-CRC effects of HCS and elucidate its underlying mechanisms, with a focus on elucidating the key pathways and targets involved.

Materials and methods: A series of cell experiments and xenograft tumor models were used to evaluate the inhibitory effects of HCS. The key components and potential targets of HCS against CRC were identified through network pharmacology and molecular docking. To further investigate the mechanisms, transcriptomics and proteomics were integrated, and the findings were supported by systematic pharmacological validation. Finally, the efficacy of HCS was further confirmed in CRC Patients-derived organoid and orthotopic models.

Results: HCS could inhibit proliferation, disrupt the cell cycle, induce apoptosis of CRC cells, and suppress the growth of CRC xenograft tumors. Then eight components and six proteins (PIK3CA, CTNNB1, TP53, AKT1, CCND1, and CDH1) were identified as critical for HCS's anti-CRC activity. Notably, HCS inhibited the PI3K/AKT signaling pathway and glycolysis in CRC cells, with these findings validated in both in vitro and in vivo models. Additionally, HCS reduced growth in CRC patient-derived organoids and orthotopic models.

Conclusion: This study elucidates the mechanisms of HCS to combat CRC, offering a valuable reference for future clinical applications. It also presents a distinctive strategy for exploring TCM formulations' active components and effective mechanisms.

Ethnopharmacological relevance: Marsdenia tenacissima dried stems have been used to treat asthma, trachitis, rheumatism, and carbuncles. M. Tenacissima extract is now available in China under the brand name "Xiao Ai Ping" and is commonly used in conjunction with chemotherapy to treat a number of diseases, including liver cancer, gastric cancer, colon cancer, and non-small cell lung cancer.

Purpose of the study: The research focused on the potential mechanisms contributing to the in vivo therapeutic effects on breast cancer using the ethyl acetate portion of M. tenacissima extract (EMTE), demonstrating significant promise in treating lung cancer in our initial experiments.

Materials and methods: We examined the impact of EMTE on the growth of breast cancer through experiments on homoplastic breast cancer mice. Moreover, we utilised UPLC-Q-TOF/MS analysis to identify the components of EMTE and anticipate its potential therapeutic targets. Through network pharmacology, we predicted the potential targets and pathways affected by EMTE in relation to breast cancer. Additionally, we analysed the metabolic changes induced by EMTE during its anti-breast cancer effects.

Results: The MAPK pathway was identified as the most likely route by which EMTE could influence breast cancer through network pharmacological enrichment of pathways. Research on animals showed that EMTE could successfully inhibit the development of breast tumours in the homoplastic breast cancer mouse model. We observed that EMTE treatment affected the metabolism of breast cancer mice, particularly in the biosynthesis of phenylalanine, tyrosine, tryptophan, linoleic acid metabolism, and pyrimidine metabolism. These metabolic alterations may have contributed to the effects of glycolysis, tumour immune evasion, and pyrimidine de novo synthesis.

Conclusion: Based on the results of network pharmacological and metabolomic analysis, we postulate that the inhibition of the MAPK/ERK pathway may have played a role in promoting apoptosis in breast cancer cells and confirmed relevant protein expression of the MAPK/ERK signaling pathway with Western blotting in tumour tissue of homoplastic breast cancer mice.

Ethnopharmacological relevance: Pulmonary fibrosis is an irreversible lung disease with a high mortality rate. Zhebeimu (ZBM, Fritillaria thunbergii Miq.) is a Chinese medicine commonly used for the treatment of pulmonary fibrosis in China.

Aim of the study: In this study, the protective effect and mechanism of ZBM extract in the treatment of pulmonary fibrosis were investigated in vivo and in vitro.

Materials and methods: The protective effect of ZBM extract was assessed using an in vivo model of bleomycin (BLM) tracheal drip and transforming growth factor-β(TGF-β1)-induced fibroblasts to simulate pulmonary fibrosis, and lung function, lung histopathological status and hydroxyproline were tested. Relevant pathways were detected using protein blotting, immunofluorescence and immunohistochemistry.

Results: ZBM extract effectively improved lung function, inflammatory changes and fibrotic deposition in the lungs, and reduced the expression of fibroblast markers in mice. In addition, ZBM extract significantly inhibited TGF-β1-induced hyperphosphorylation of FOXO3, and simultaneously improved the low expression level of FOXO3 prototype protein and significantly reduced the phosphorylation level of PI3K-p85 and AKT1, suggesting that ZBM extract improves lung fibrosis by inhibiting the over-activation of PI3K/AKT/FOXO signalling pathway.

Conclusion: The PI3K/AKT/FOXO signalling pathway is critical for ZBM extract to improve pulmonary fibrosis.

Ethnopharmacological relevance: Li-Chong-Xiao-Zhen granules (LCXZG) has the effect of " activate blood and resolve stasis," " soften hardness and dissipate binds " properties, and was widely used in the clinic for decades to treat uterine fibroids and ovarian cancer (OC), which is called "zheng jia" in traditional Chinese medicine.

Aim of the study: The aim of this study is to identify the active components of LCXZG and elucidate the mechanism of LCXZG in ovarian cancer by combining network pharmacology, metabolomics and proteomics.

Material and methods: The absorbed compounds in serum of LCXZG was identified by liquid chromatography-mass spectrometry. Network pharmacology was used to predict the active components and target genes of LCXZG. The therapy mechanism of LCXZG on OC were determined by establishing a nude mouse xenograft tumor model and using combined metabolomics and proteomics analysis.

Results: A total of 218 absorbed compounds in serum of LCXZG were identified by UPLC-MS. Network pharmacology results showed that lipid and atherosclerosis, chemical carcinoma-receptor activation and PI3K-AKT signaling were potential target pathways of LCXZG in the treatment of OC. Further metabolomics and proteomics studies demonstrated that LCXZG altered glycerophospholipid metabolism in ovarian cancer.

Conclusions: This study demonstrated that most of the active Compound of LCXZG are Paeoniflorin, Sucrose, Amygdalin and Benzoylpaeoniflorin, which may exert their anti-tumor effects by regulating glycerophospholipid metabolism in ovarian cancer.

Ethnopharmacological relevance: As a traditional Chinese medicine, Morus alba L. root bark (MAR) has diuretic and detumescent effects, which is used in prescriptions like Niaoduqing granules for hyperuricemia treatment. However, the anti-hyperuricemic and nephroprotective activities, underlying mechanism and material basis of MAR have not been reported.

Aim of the study: This research aimed to explore the anti-hyperuricemic and nephroprotective activity and mechanism of MAR, along with the pursuit of potential xanthine oxidase (XOD) inhibitors within MAR.

Materials and methods: XOD inhibitory assay and hyperuricemic mice model were employed to screen and estimate the active fraction of MAR. Then, active compositions were isolated and elucidated by diverse separation and spectroscopic techniques. The enzyme inhibition mechanism of the active compositions was investigated by enzyme kinetic and molecular docking.

Results: The ethyl acetate fraction (MAR-EA) showed the strongest inhibitory activity against XOD. In hyperuricemic mice, MAR-EA decreased serum uric acid levels by suppressing XOD activity and modulating renal uric acid transporters (URAT1, GLUT9, ABCG2). Moreover, it alleviated hyperuricemia-induced kidney damage, which may be related to inhibiting the production of inflammatory factors. Noticeably, the combination of MAR-EA with allopurinol showed a synergistic effect. Meanwhile, a Diels-Alder adduct, albanol A (1) was isolated from MAR-EA with excellent XOD inhibition activity (IC₅₀ = 0.116 mg/mL), which was categorized as a mixed-type XOD inhibitor. The molecular docking outcomes demonstrated that albanol A (1) exhibited a desirable interaction with XOD.

Conclusion: This research supports MAR and albanol A as anti-hyperuricemic drug candidates, laying a foundation for further exploration.

Ethnopharmacological relevance: Danggui Buxue Decoction (DBD), a traditional Chinese medicinal formula, has historically been used for cardiovascular health, including managing atherosclerotic plaques (ASP). However, its precise mechanisms remain elusive.

Aim of the study: The purpose of this study was to use a novel integrative bioinformatics analysis and experimental validation approach to provide a molecular basis for ASP's stabilization by DBD.

Materials and methods: A mice model of ApoE-deficient atherosclerosis fed with a high-fat diet was employed to evaluate the efficacy of DBD in stabilizing ASP. The potential mechanism underlying the stabilization effect of DBD on ASP was systematically investigated using an integrated approach combining network pharmacology, molecular docking, and molecular dynamics simulation. Additionally, an ox-LDL-induced macrophage foam cell model and multivariate statistical analysis were utilized to validate the pharmacodynamic material basis and target of DBD in stabilizing ASP.

Results: Firstly, it was found that DBD can significantly alleviate ASP, which is manifested as a significant reduction in the atherosclerosis index, ratio of area for plaque to lumen, and vulnerability index. Afterwards, network pharmacology investigation identified quercetin and kaempferol as the primary active compounds in DBD anti-ASP. Key core targets mainly involved TP53, AKT1, IL-6 and TNF. The main action pathways included lipid and atherosclerosis, PI3K-Akt signaling, and other pathways. Subsequently, molecular docking and molecular dynamics simulation results confirmed the strong stability of the main active compounds with the key target. Finally, the cell validation experiment in vitro revealed that both quercetin and kaempferol could significantly inhibit RAW264.7 macrophage foaming formation induced by ox-LDL and improve its lipid metabolism disorder. Meanwhile, they could also significantly reverse ox-LDL induced abnormal expression of core protein predicted by network pharmacology in RAW264.7 foam cells. Further correlation analysis revealed that the improvement effect of quercetin and kaempferol on macrophage foaming had a close correlation with the inhibition of core protein expression.

Conclusion: DBD mainly utilized active ingredients such as quercetin and kaempferol, through regulating multiple targets like TP53, AKT1, IL-6 and TNF, to stabilize ASP.

Ethnopharmacological relevance: Garcinia cowa Roxb. commonly known as asam kandis in Indonesia and Cha muang in Thailand, has been extensively utilized as traditional medicine. This plant contains compounds such as xanthones, phloroglucinol, depsidones, terpenoids, steroids, and flavonoids. These compounds have been extensively studied for various bioactivities. However, the utilization of this plant as an anti-inflammatory agent is still limited.

Aim of the study: This study aims to evaluate newly derived compounds from Garcinia cowa Roxb., focusing on their ADMET profiles (Absorption, Distribution, Metabolism, Excretion, and Toxicity) and anti-inflammatory bioactivity. The assessment will be carried out using a combination of in silico and in vitro experiments to determine their pharmacological potential as anti-inflammatory agents.

Materials and methods: Isolation of compounds from Garcinia cowa Roxb. was carried out using column chromatography, purified with radial chromatography, and recycling HPLC. The compounds' structures were evaluated for their ADMET profiles and anti-inflammatory bioactivity using the NF-ĸB protein (PDB Code: 2RAM) as the target. The in vitro experiment was conducted using Raw 264.7 macrophages cell to assess cytotoxicity, phagocytic activity, IL-6, and TNF-α secretion. The determination of the anti-inflammatory mechanism is carried out by testing the activity of NF-ĸB and IKB-α using the western blot method.

Results: We successfully analyzed the structure of a new compound from the bark of Garcinia cowa Roxb., named Garciacowanin (NC). In silico analysis suggests that the drug shows promising absorption potential, there are concerns related to its metabolism and toxicity that warrant further investigation during the development process and does not show mutagenic properties based on the negative AMES test results. There is a risk of hepatotoxicity (liver damage) and the drug can also interfere with the hERG II ion channel, which can cause side effects on the heart. The compound can affect the NF-ĸB protein, while in vitro studies have demonstrated its ability to suppress phagocytic activity, as well as the production of IL-6 and TNF-α. Western blot analysis suggests that NC's anti-inflammatory mechanism functions via the NF-ĸB signaling pathway.

Conclusion: NC has the potential to be developed as an anti-inflammatory agent with a mechanism of inhibiting the inflammatory response through the NF-ĸB signaling pathway.