Ethnopharmacological relevance: Coptidis Rhizoma (CR), a typical bitter-cold herbal medicine in traditional Chinese medicine (TCM), is commonly employed in treating metabolic diseases like diabetes.
Aim of the study: This study investigated the effects of CR on whole-body metabolic status and elucidate the scientific basis of its "cold" property.
Materials and methods: A CR water decoction was prepared and its major constituents were identified and quantified. C57BL/6J mice were orally administered the CR decoction, and changes in core body temperature (CBT) were monitored using thermocouples. The thermal preference was assessed using dual-temperature choice tests and thermal gradient experiment. Serum metabolomic profiling and transcriptomic analysis of brown adipose tissue (BAT) was conducted. Key targets were validated using RT-qPCR and immunoblotting. Integrated multi-omics analysis was carried out via MetaboAnalyst online database.
Results: The prepared CR decoction identified 11 components. CR administration significantly reduced CBT and altered behavioral thermal preference. Metabolomics identified 45 differential metabolites, enriched in 9 metabolic pathways like the TCA cycle. Transcriptomics revealed 711 significantly differentially expressed genes, prominently associated with thermogenesis and the TCA cycle. Key genes (Acsl1, Elovl3, Hadh, Dio2, Scd1, and Lep) were verified. Integrated metabolomic and transcriptomic analysis underscored CR's impact on the TCA cycle and fatty acid degradation.
Conclusion: CR enhances adaptive thermogenesis in BAT, accelerates the TCA cycle and lipid metabolism, and promotes energy substrate consumption, thereby modulating systemic energy homeostasis. These effects are similar to physiological responses to cold stimulation, providing a mechanistic rationale for the "cold" property of CR in TCM.
Introduction: Ferroptosis contributes to Parkinson's disease progression given dysregulation of iron homeostasis and redox status. Polygala virgata is used ethnomedicinally for memory enhancement. This study assessed the cytoprotective and antioxidant properties of crude extracts and fractions of P. virgata using a 6-hydroxydopamine-induced (6-OHDA) SH-SY5Y neuroblastoma cytotoxicity model.
Method: Dried roots of P. virgata (14% w/v) were sequentially extracted using dichloromethane/methanol (1:1) and methanol, which was combined to give a crude extract. The crude extract was separated into seven fractions using different ratios of water, acetonitrile and methanol on solid phase extraction (SPE). Inherent cytotoxicity of the samples (10 μg/mL), as well as their ability to reduce 6-OHDA-induced cytotoxicity (35 μM), was determined using the sulforhodamine B (SRB) assay after 48-hour (h) exposure. The active fractions' cytoprotective effect in relation to reactive oxygen species (ROS), glutathione levels (GSH), lipid peroxidation, and mitochondrial integrity was determined fluorometrically. Cytoprotective fractions' phytochemical constituency was elucidated using liquid chromatography high resolution mass-spectrometry (UPLC-HRMS).
Results: Fractions 3 to 7 increased cell density after exposure to 6-OHDA by 31.14%, 28.08%, 30.72%, 40.58% (p < 0.01) and 28.86%, respectively, with no inherent cytotoxicity observed. Fraction 4 reduced 6-OHDA-induced ROS generation (2.09-fold) and lipid peroxidation (0.28-fold). Non-significant increases in GSH were noted (1.34 to 19.25%), while all fractions hyperpolarised the mitochondrial membrane. Multi-hydroxylated xanthones, flavones and flavans were tentatively identified using UPLC-HRMS.
Conclusion: P. virgata fractions reduced 6-OHDA-induced cytotoxicity via decreased oxidative stress and hyperpolarisation of the mitochondrial membrane, most likely ascribed to the identified xanthones, flavones and flavans. Isolation and purification of these compounds are warranted as potential antioxidant scaffolds.
Ethnopharmacological relevance: The modified Zuojin formula (SQQT) has been clinically prescribed for gastric metaplasia (GM) for several decades in China. The therapeutic efficacy of SQQT and potential mechanisms have been demonstrated in our previous studies. This research will further investigate its mechanism in the immune microenvironment.
Aim of the study: We aimed to determine the influence of SQQT on the ILC2-mediated JAK-2/STAT5/c-Myc pathway during GM.
Methods: The mechanism of GM in patients was measured through single-cell RNA sequencing. The constituents of SQQT have been examined before. The role of SQQT targets JAK-2/STAT5/c-Myc pathway was verified by network pharmacology and molecular docking. The model of GM was induced by tamoxifen (5 mg/20 g), CD90.2 protein (200 μg) or SQQT (1.69, 3.38, 6.76 g/kg) was given to treat GM mice. The SQQT mechanism was confirmed by both in vitro and in vivo studies. Histological analysis, serum cytokines, and protein levels were assessed.
Results: Single-cell RNA sequencing analysis indicated that ILC2 increased in the GM patients, the goblet cells in GM were probably transferred from endocrine cells. Compounds in SQQT are related to cell proliferation and can bind to the JAK-2/STAT5/c-Myc pathway proteins. The main components of SQQT, can spontaneously bind to the JAK-2 protein in 9 sites. Tamoxifen caused body weight decrease, spleen weight increase, stomach injury, ILC2 increase, and cytokines increase in the GM group. After examining the cytokines, IL-5 was the only one significantly increased in the GM group. CD90.2 and SQQT can alleviate histological changes of the stomach corpus, inflammation cytokines, and other GM-related indicators. Moreover, cell proliferation and JAK-2 pathway markers were depressed in GM mice. Besides, SQQT protects GES-1 cells from IL-5 injury related to upregulating JAK-2/STAT5/c-Myc proteins in 24h, 48h and 72h.
Conclusion: The mechanism of SQQT protected the stomach from metaplasia associated to ILC2 activation and the subsequent cell proliferation through IL-5/JAK-2/STAT5/c-Myc pathway.
Ethnopharmacological relevance: The Chinese herbal medicine Banxia Xiexin Decoction (BXD) and its modified version (mBXD) are traditional polyherbal formulations used to treat gastrointestinal diseases. Increasing evidence indicates that mBXD exhibits distinct anti-cancer properties; however, the mechanisms through which it modulates mitochondrial dynamics to inhibit colon cancer remain unclear.
Aims of the study: To investigate the mechanisms by which mBXD suppresses colon cancer by regulating mitochondrial fusion-fission dynamics.
Materials and methods: The chemical composition of mBXD was analyzed using UPLC-MS/MS. A subcutaneous CT26 colon cancer model was established and treated with mBXD. mBXD drug-containing serum was prepared and applied to HCT116 and CT26 cells. Tumor volume, small-animal live imaging, and histopathological features were evaluated. The effects of mBXD on mitochondria were examined through mitochondrial ultrastructure analysis, JC-1 detection, and assessment of ATP concentration and ROS levels. WB and qPCR were performed to determine the expression of molecules associated with the CHD6-TMEM65 axis and mitochondrial dynamics.
Results: The main components of mBXD were identified as flavonoids and alkaloids. These compounds significantly inhibited tumor growth, with higher concentrations of mBXD drug-containing serum reducing the survival, invasion, and migration of HCT116 and CT26 cells. Moreover, mBXD markedly promoted mitochondrial fission in cancer cells, reduced ATP levels, and induced ROS accumulation. It significantly upregulated DRP1 expression while inhibiting CHD6 and TMEM65, with no notable effect on OPA1.
Conclusions: The chemical constituents of mBXD mainly comprise flavonoids and alkaloids. These components markedly inhibit the growth of subcutaneous tumors in CT26 colon cancer-bearing mice and suppress the viability, invasiveness, and migratory capacity of HCT116 and CT26 cells. The underlying mechanism may involve the promotion of mitochondrial fission in cancer cells through inhibition of the CHD6-TMEM65 axis, ultimately leading to apoptosis. Nonetheless, the present study has certain limitations. The precise mechanisms by which mBXD induces mitochondrial fission and inhibits the CHD6-TMEM65 axis warrant further investigation in future research.
Ethnopharmacological relevance: Cyclocarya paliurus (Batal.) Iljinsk, a millennia-old traditional Chinese herb, is prized for its ability to clear the lungs and nourish the liver. Additionally, it is employed in traditional Chinese medicine practice for heat clearance and detoxification, addressing conditions such as lung diseases.
Aim of the study: This study aimed to evaluate beneficial effects of polysaccharides (CPP) from C. paliurus on chronic obstructive pulmonary disease (COPD) and its potential mechanisms.
Materials and methods: The chemical characterization of the isolated and purified CPP was conducted using fourier-transform infrared spectroscopy, ultraviolet spectroscopy and scanning electron microscopy. COPD was induced in male BALB/c mice by intranasal infusion of LPS and exposure to cigarette smoke for 28 days. Lung tissues were then collected for subsequent histopathological and molecular analyses. The mechanism of CPP against COPD was investigated through transcriptomic data mining and Western blot analysis. Additionally, acute toxicity of CPP was assessed in mice following a single oral dose of 15 g/kg.
Results: Experimental evidence established that CPP consists of six monosaccharides: fucose, arabinose, rhamnose, galactose, glucose, and xylose. CPP treatment significantly reduced the levels of PCO2 and HCO3- in the blood of COPD mice, concurrently alleviating pulmonary inflammation. Mechanistic investigations have revealed that CPP exerts its anti-inflammatory effect by modulating the AhR/NF-κB pathway. In addition, CPP demonstrated safety at doses exceeding 100 times the effective level.
Conclusion: The results suggest that CPP holds promise as a potential therapeutic agent for the intervention of COPD. These findings provide a theoretical basis for the development of the ethnic medicinal herb Cyclocarya paliurus.
Ethnopharmacological relevance: Camellia japonica is recognized for its edible and therapeutic value in East Asia, and has anti-inflammatory, antioxidative, and antiasthmatic properties. However, the active compound and the modes of action are unclear.
Aim of the study: To evaluate the anti-AMD effect of hyperoside isolated from the leaves and twigs of Camellia japonica and to explore the underlying mechanisms using an ARPE-19 AMD cell model.
Material and methods: The hyperoside content in the extracts was evaluated using feature-based molecular network and UHPLC-MS/MS system. Network pharmacology was used to predict the interactions of hyperoside with AMD-related signaling pathways and the underlying mechanisms. For in vitro evaluation of the anti-AMD effects, ARPE-19 cells were divided into six treatment groups: CON, no treatment; A2E, AMD induction using 30 μM A2E and 20 mW/cm2 blue light treatment; Lutein, treatment with 25 μM lutein as a positive control; and three Hyperoside groups, treated with 37.5, 75, or 150 μM hyperoside. The antiapoptotic effect of hyperoside was evaluated using flow cytometry and TUNEL assays, and the intrinsic apoptotic pathway proteins (Bcl-xL, Bad, and Bim) were analyzed via western blotting. The interactions of hyperoside with JNK and p38 MAPKs were determined using western blotting, and molecular docking. The antioxidative effect of hyperoside was measured via DPPH and ABTS radical scavenging assays; Nrf2/HO-1 activation and SOD-1 stimulation were analyzed using western blotting and immunofluorescence assay. The anticarbonyl effect (4-HNE and MDA) was measured using western blotting.
Results: Hyperoside was nontoxic to ARPE-19 cells up to 150 μM. It dose-dependently decreased A2E and blue light-induced AMD in ARPE-19 cells by upregulating the antiapoptotic Bcl-2 protein (Bcl-xL) and downregulating the proapoptotic Bcl-2 proteins (Bad and Bim). Hyperoside dephosphorylated JNK and p38 MAPKs in a dose-dependent manner, eradicated DPPH and ABTS radicals, and activated Nrf2/HO-1 and SOD-1. It also decreased the levels of 4-HNE and MDA.
Conclusion: We conclude that C. japonica hyperoside could be a promising anti-AMD drug.
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